Comparison of the ACC/AHA and Framingham algorithms to assess cardiovascular risk in HIV-infected patients.

PubMed

Pinto Neto, Lauro Ferreira da Silva; Dias, Fernanda Rezende; Bressan, Flavia Feres; Santos, Carolina Rocio Oliveira

The aim of this study was to compare the predictions of Framingham cardiovascular (CV) risk score (FRS) and the American College of Cardiology/American Heart Association (ACC/AHA) risk score in an HIV outpatient clinic in the city of Vitoria, Espirito Santo, Brazil. In a cross-sectional study 341 HIV infected patients over 40 years old consecutively recruited were interviewed. Cohen's kappa coefficient was used to assess agreement between the two algorithms. 61.3% were stratified as low risk by Framingham score, compared with 54% by ACC/AHA score (Spearman correlation 0.845; p<0.000). Only 26.1% were classified as cardiovascular high risk by Framingham compared to 46% by ACC/AHA score (Kappa=0.745; p<0.039). Only one out of eight patients had cardiovascular high risk by Framingham at the time of a myocardial infarction event registered up to five years before the study period. Both cardiovascular risk scores but especially Framingham underestimated high-risk patients in this HIV-infected population. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Bivariate Heritability of Total and Regional Brain Volumes: the Framingham Study

PubMed Central

DeStefano, Anita L.; Seshadri, Sudha; Beiser, Alexa; Atwood, Larry D.; Massaro, Joe M.; Au, Rhoda; Wolf, Philip A.; DeCarli, Charles

2009-01-01

Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging (MRI) who were free of stroke and other neurological disorders that might influence brain volumes and who were members of families with at least two Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile. Genetic and environmental correlations between traits were obtained from bivariate analysis. Heritability estimates ranging from 0.46 to 0.60, were observed for total brain, white matter hyperintensity, hippocampal, temporal lobe, and lateral ventricular volumes. Moderate, yet significant, heritability was observed for the other measures. Bivariate analyses demonstrated that relationships between brain volume measures, except for white matter hyperintensity, reflected both moderate to strong shared genetic and shared environmental influences. This study confirms strong genetic effects on brain and white matter hyperintensity volumes. These data extend current knowledge by showing that these two different types of MRI measures do not share underlying genetic or environmental influences. PMID:19812462

The Envy of Scholars: Applying the Lessons of the Framingham Heart Study to the Prevention of Chronic Kidney Disease.

PubMed

Wasser, Walter G; Gil, Amnon; Skorecki, Karl L

2015-07-30

During the past 50 years, a dramatic reduction in the mortality rate associated with cardiovascular disease has occurred in the US and other countries. Statistical modeling has revealed that approximately half of this reduction is the result of risk factor mitigation. The successful identification of such risk factors was pioneered and has continued with the Framingham Heart Study, which began in 1949 as a project of the US National Heart Institute (now part of the National Heart, Lung, and Blood Institute). Decreases in total cholesterol, blood pressure, smoking, and physical inactivity account for 24%, 20%, 12%, and 5% reductions in the mortality rate, respectively. Nephrology was designated as a recognized medical professional specialty a few years later. Hemodialysis was first performed in 1943. The US Medicare End-Stage Renal Disease (ESRD) Program was established in 1972. The number of patients in the program increased from 5,000 in the first year to more than 500,000 in recent years. Only recently have efforts for risk factor identification, early diagnosis, and prevention of chronic kidney disease (CKD) been undertaken. By applying the approach of the Framingham Heart Study to address CKD risk factors, we hope to mirror the success of cardiology; we aim to prevent progression to ESRD and to avoid the cardiovascular complications associated with CKD. In this paper, we present conceptual examples of risk factor modification for CKD, in the setting of this historical framework.

The use of simple indicators for detecting potential coronary heart disease susceptibility in the third-class airman population.

DOT National Transportation Integrated Search

1972-07-01

An analysis was made of an eight-year interval change in several Framingham Heart Study (FHS) indicators of coronary heart disease (CHD) susceptibility as measured on 475 male air traffic control (ATC) personnel. The initial measurements were obtaine...

The Framingham Disability Study: relationship of various coronary heart disease manifestations to disability in older persons living in the community.

PubMed Central

Pinsky, J L; Jette, A M; Branch, L G; Kannel, W B; Feinleib, M

1990-01-01

The relation between coronary heart disease and disability was examined in 2,576 community-dwelling women and men ages 55-88 years. These Framingham Study participants were originally recruited in 1948-51 for an examination of cardiovascular disease. Twenty-seven years later, remaining members of the cohort were interviewed to ascertain physical abilities, and a score on a disability scale was assigned. Multivariate logistic analyses examined disability in relation to uncomplicated angina pectoris (AP), complicated AP, and coronary heart disease other than AP, controlling for possible confounders. In younger and older women and men, uncomplicated and complicated AP were associated with disability. Coronary heart disease other than AP was associated with disability only in the younger men. Congestive heart failure predicted disability only in the women. These results suggest that onset of AP should be recognized as a critical point in the development of disability and that AP is a better predictor of disability than is myocardial infarction or coronary insufficiency. PMID:2240306

A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies

PubMed Central

Brautbar, Ariel; Pompeii, Lisa A.; Dehghan, Abbas; Ngwa, Julius S.; Nambi, Vijay; Virani, Salim S.; Rivadeneira, Fernando; Uitterlinden, André G.; Hofman, Albert; Witteman, Jacqueline C.M.; Pencina, Michael J.; Folsom, Aaron R.; Cupples, L. Adrienne; Ballantyne, Christie M.; Boerwinkle, Eric

2013-01-01

Objective Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs). Methods SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS. Results The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07–1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ= 0.007; 95% CI, 0.004–0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10–1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02–1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest. Conclusion Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies. PMID:22789513

Does adding information on job strain improve risk prediction for coronary heart disease beyond the standard Framingham risk score? The Whitehall II study.

PubMed

Kivimäki, Mika; Nyberg, Solja T; Batty, G David; Shipley, Martin J; Ferrie, Jane E; Virtanen, Marianna; Marmot, Michael G; Vahtera, Jussi; Singh-Manoux, Archana; Hamer, Mark

2011-12-01

Guidelines for coronary heart disease (CHD) prevention recommend using multifactorial risk prediction algorithms, particularly the Framingham risk score. We sought to examine whether adding information on job strain to the Framingham model improves its predictive power in a low-risk working population. Our analyses are based on data from the prospective Whitehall II cohort study, UK. Job strain among 5533 adults (mean age 48.9 years, 1666 women) was ascertained in Phases 1 (1985-88), 2 (1989-90) and 3 (1991-93). Variables comprising the Framingham score (blood lipids, blood pressure, diabetes and smoking) were measured at Phase 3. In men and women who were CHD free at baseline, CHD mortality and non-fatal myocardial infarction (MI) were ascertained from 5-yearly screenings and linkage to mortality and hospital records until Phase 7 (2002-04). A total of 160 coronary deaths and non-fatal MIs occurred during the mean follow-up period of 11.3 years. The addition of indicators of job strain to the Framingham score increased the C-statistics from 0.725 [95% confidence intervals (95% CIs): 0.575-0.854] to only 0.726 (0.577-0.855), corresponding to a net reclassification improvement of 0.7% (95% CIs: -4.2 to 5.6%). The findings were similar after inclusion of definite angina in the CHD outcome (352 total cases) and when using alternative operational definitions for job strain. In this middle-aged low-risk working population, job strain was associated with an increased risk of CHD. However, when compared with the Framingham algorithm, adding job strain did not improve the model's predictive performance.

Cardiovascular risk assessment: addition of CKD and race to the Framingham equation

PubMed Central

Drawz, Paul E.; Baraniuk, Sarah; Davis, Barry R.; Brown, Clinton D.; Colon, Pedro J.; Cujyet, Aloysius B.; Dart, Richard A.; Graumlich, James F.; Henriquez, Mario A.; Moloo, Jamaluddin; Sakalayen, Mohammed G.; Simmons, Debra L.; Stanford, Carol; Sweeney, Mary Ellen; Wong, Nathan D.; Rahman, Mahboob

2012-01-01

Background/Aims The value of the Framingham equation in predicting cardiovascular risk in African Americans and patients with chronic kidney disease (CKD) is unclear. The purpose of the study was to evaluate whether the addition of CKD and race to the Framingham equation improves risk stratification in hypertensive patients. Methods Participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) were studied. Those randomized to doxazosin, age greater than 74 years, and those with a history of coronary heart disease (CHD) were excluded. Two risk stratification models were developed using Cox proportional hazards models in a two-thirds developmental sample. The first model included the traditional Framingham risk factors. The second model included the traditional risk factors plus CKD, defined by eGFR categories, and stratification by race (Black vs. Non-Black). The primary outcome was a composite of fatal CHD, nonfatal MI, coronary revascularization, and hospitalized angina. Results There were a total of 19,811 eligible subjects. In the validation cohort, there was no difference in C-statistics between the Framingham equation and the ALLHAT model including CKD and race. This was consistent across subgroups by race and gender and among those with CKD. One exception was among Non-Black women where the C-statistic was higher for the Framingham equation (0.68 vs 0.65, P=0.02). Additionally, net reclassification improvement was not significant for any subgroup based on race and gender, ranging from −5.5% to 4.4%. Conclusion The addition of CKD status and stratification by race does not improve risk prediction in high-risk hypertensive patients. PMID:23194494

75 FR 25863 - Proposed Collection; Comment Request; The Framingham Heart Study (FHS)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

... studying the determinants of cardiovascular disease. Examinations will be conducted on the original, [[Page... data collection plans and instruments, contact Dr. Gina Wei, Division of Cardiovascular Sciences, NHLBI...

The Framingham function overestimates the risk of ischemic heart disease in HIV-infected patients from Barcelona.

PubMed

Herrera, Sabina; Guelar, Ana; Sorlì, Luisa; Vila, Joan; Molas, Ema; Grau, María; Marrugat, Jaume; Esteve, Erika; Güerri-Fernández, Roberto; Montero, Milagro; Knobel, Hernando

2016-07-01

Cardiovascular risk (CVR) assessment helps to identify patients at high CVR. The Framingham CVR score (FRS) is the most widely used methods but may overestimate risk in regions with low incidence of cardiovascular disease. The objective was to compare the 10-year performance of the original and the adapted REGICOR - Framingham CVR functions in HIV-infected individuals. We carried out a longitudinal study of HIV-infected patients with CVR evaluation in a hospital in Barcelona between 2003 and 2013. Risk probability was calculated using the FRAMINGHAM function and REGICOR adaptation to the Spanish population, and individuals were categorized in three groups (low, 0 < 5%; moderate, 5-10%; and high, >10%). For each risk group, the number of events over 10 years was calculated using the Kaplan-Meier method, and the expected number of events was calculated by multiplying the frequency of participants in the group by the mean of the probabilities from the risk function. We used the X(2) goodness-of-fit test to assess agreement between observed and expected. Six hundred and forty-one patients were followed up for a median of 10.2 years, and 20 ischemic heart events (IHE) were observed. The mean (95% CI) number of IHEs per 1000 person-years was 3.7 (2.06-5.27). The estimates from the Framingham and REGICOR functions were 40 and 14 IHEs, respectively. The estimate from the original Framingham function differed significantly from the observed incidence (p < 0.001), whereas that from the REGICOR-adapted function did not (p = 0.15). In terms of the number of cardiovascular events (38 events observed), the REGICOR function significantly underestimated risk (p = 0.01), whereas the estimate from the Framingham function was similar to observed (p:0.93). The FRS significantly overestimates risk of IHE events in our HIV-infected patients, while the REGICOR function is a better predictor of these events. In terms of cardiovascular events, the REGICOR function significantly underestimates risk, whereas the FRS is a better estimator. We recommend using CVR scales and adjusting them to the origin of the population being studied.

A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies.

PubMed

Brautbar, Ariel; Pompeii, Lisa A; Dehghan, Abbas; Ngwa, Julius S; Nambi, Vijay; Virani, Salim S; Rivadeneira, Fernando; Uitterlinden, André G; Hofman, Albert; Witteman, Jacqueline C M; Pencina, Michael J; Folsom, Aaron R; Cupples, L Adrienne; Ballantyne, Christie M; Boerwinkle, Eric

2012-08-01

Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs). SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS. The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07-1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ = 0.007; 95% CI, 0.004-0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10-1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02-1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest. Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Leisure-Time Physical Activity, but not Commuting Physical Activity, is Associated with Cardiovascular Risk among ELSA-Brasil Participants.

PubMed

Pitanga, Francisco José Gondim; Matos, Sheila M A; Almeida, Maria da Conceição; Barreto, Sandhi Maria; Aquino, Estela M L

2018-01-01

Despite reports in the literature that both leisure-time physical activity (LTPA) and commuting physical activity (CPA) can promote health benefits, the literature lacks studies comparing the associations of these domains of physical activity with cardiovascular risk scores. To investigate the association between LTPA and CPA with different cardiovascular risk scores in the cohort of the Longitudinal Study of Adult Health ELSA-Brasil. Cross-sectional study with data from 13,721 participants of both genders, aged 35-74 years, free of cardiovascular disease, from ELSA Brazil. Physical activity was measured using the International Physical Activity Questionnaire (IPAQ). Five cardiovascular risk scores were used: Framingham score - coronary heart disease (cholesterol); Framingham score - coronary heart disease (LDL-C); Framingham score - cardiovascular disease (cholesterol); Framingham score - cardiovascular disease (body mass index, BMI); and pooled cohort equations for atherosclerotic cardiovascular disease (ASCVD). Associations adjusted for confounding variables between physical activity and different cardiovascular risk scores were analyzed by logistic regression. Confidence interval of 95% (95%CI) was considered. LTPA is inversely associated with almost all cardiovascular risk scores analyzed, while CPA shows no statistically significant association with any of them. Dose-response effect in association between LTPA and cardiovascular risk scores was also found, especially in men. LTPA was shown to be associated with the cardiovascular risk scores analyzed, but CPA not. The amount of physical activity (duration and intensity) was more significantly associated, especially in men, with cardiovascular risk scores in ELSA-Brasil.

75 FR 54886 - Submission for OMB Review; Comment Request; the Framingham Heart Study (FHS)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... morbidity and mortality follow-up for the purpose of studying the determinants of cardiovascular disease... of Cardiovascular Sciences, NHLBI, NIH, Two Rockledge Center, 6701 Rockledge Drive, MSC 7936...

78 FR 26639 - Proposed Collection; 60-Day Comment Request: The Framingham Heart Study (FHS)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-07

... examinations, for the purpose of studying the determinants of cardiovascular disease. Morbidity and mortality... instruments, contact Dr. Gina Wei, Division of Cardiovascular Sciences, NHLBI, NIH, Two Rockledge Center, 6701...

Long‐term Cardiovascular Risks Associated With an Elevated Heart Rate: The Framingham Heart Study

PubMed Central

Ho, Jennifer E.; Larson, Martin G.; Ghorbani, Anahita; Cheng, Susan; Coglianese, Erin E.; Vasan, Ramachandran S.; Wang, Thomas J.

2014-01-01

Background Higher heart rate has been associated with an adverse prognosis, but most prior studies focused on individuals with known cardiovascular disease or examined a limited number of outcomes. We sought to examine the association of baseline heart rate with both fatal and nonfatal outcomes during 2 decades of follow‐up. Methods and Results Our study included 4058 Framingham Heart Study participants (mean age 55 years, 56% women). Cox models were performed with multivariable adjustment for clinical risk factors and physical activity. A total of 708 participants developed incident cardiovascular disease (303 heart failure, 343 coronary heart disease, and 216 stroke events), 48 received a permanent pacemaker, and 1186 died. Baseline heart rate was associated with incident cardiovascular disease (hazard ratio [HR] 1.15 per 1 SD [11 bpm] increase in heart rate, 95% CI 1.07 to 1.24, P=0.0002), particularly heart failure (HR 1.32, 95% CI 1.18 to 1.48, P<0.0001). Higher heart rate was also associated with higher all‐cause (HR 1.17, 95% CI 1.11 to 1.24, P<0.0001) and cardiovascular mortality (HR 1.18, 95% CI 1.04 to 1.33, P=0.01). Spline analyses did not suggest a lower threshold beyond which the benefit of a lower heart rate abated or increased. In contrast, individuals with a higher heart rate had a lower risk of requiring permanent pacemaker placement (HR 0.55, 95% CI 0.38 to 0.79, P=0.001). Conclusions Individuals with a higher heart rate are at elevated long‐term risk for cardiovascular events, in particular, heart failure, and all‐cause death. On the other hand, a higher heart rate is associated with a lower risk of future permanent pacemaker implantation. PMID:24811610

Lipoprotein(a) levels, apo(a) isoform size, and coronary heart disease risk in the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

The aim of this study was to assess the independent contributions of plasma levels of lipoprotein(a) [Lp(a)], Lp(a) cholesterol, and of apo(a) isoform size to prospective coronary heart disease (CHD) risk. Plasma Lp(a) and Lp(a) cholesterol levels, and apo(a) isoform size were measured at examinati...

78 FR 58318 - Submission for OMB Review; 30-day Comment Request: The Framingham Heart Study (FHS)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

..., as well as examinations, for the purpose of studying the determinants of cardiovascular disease... instruments, contact Dr. Gina Wei, Division of Cardiovascular Sciences, NHLBI, NIH, Two Rockledge Center, 6701...

Testing for Non-Random Mating: Evidence for Ancestry-Related Assortative Mating in the Framingham Heart Study

PubMed Central

Sebro, Ronnie; Hoffman, Thomas J.; Lange, Christoph; Rogus, John J.; Risch, Neil J.

2013-01-01

Population stratification leads to a predictable phenomenon—a reduction in the number of heterozygotes compared to that calculated assuming Hardy-Weinberg Equilibrium (HWE). We show that population stratification results in another phenomenon—an excess in the proportion of spouse-pairs with the same genotypes at all ancestrally informative markers, resulting in ancestrally related positive assortative mating. We use principal components analysis to show that there is evidence of population stratification within the Framingham Heart Study, and show that the first principal component correlates with a North-South European cline. We then show that the first principal component is highly correlated between spouses (r=0.58, p=0.0013), demonstrating that there is ancestrally related positive assortative mating among the Framingham Caucasian population. We also show that the single nucleotide polymorphisms loading most heavily on the first principal component show an excess of homozygotes within the spouses, consistent with similar ancestry-related assortative mating in the previous generation. This nonrandom mating likely affects genetic structure seen more generally in the North American population of European descent today, and decreases the rate of decay of linkage disequilibrium for ancestrally informative markers. PMID:20842694

Dietary guideline adherence index and kidney measures in the framingham heart study

USDA-ARS?s Scientific Manuscript database

BACKGROUND: No observational studies have directly considered dietary guidelines when examining the prospective association between dietary intake and kidney measures. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We examined participants who attended examinations 7 (1998-2001) a...

Vascular risk factor burden and new-onset depression in the community.

PubMed

Adams, Shayna; Conner, Sarah; Himali, Jayandra J; Beiser, Alexa; Vasan, Ramachandran S; Seshadri, Sudha; Pase, Matthew P

2018-06-01

Depression is associated with an increased likelihood of cardiac events and stroke. We hypothesized that the vascular risk factor burden might itself predispose to both cardiovascular events and depression. Therefore, we examined whether aggregate scores of vascular risk factor burden were associated with the new-onset of depression in the community. We studied 2023 depression- and dementia-free Framingham Heart Study (Framingham, USA) Offspring participants who attended both examination cycles 7 (1998-2001) and 8 (2005-2008). The American Heart Association Ideal Cardiovascular Health metric and the Framingham stroke risk profile were calculated at exam seven. New-onset depression was adjudicated at examination cycle eight as antidepressant medication use or Centre for Epidemiologic Studies Depression Scale scores ≥16, after a mean follow-up of 6.6years (standard deviation=0.7). Of the 2023 participants, 269 (13%) developed new-onset depression. Following adjustments for age, sex, education, and the time interval between baseline and follow-up, the odds of new-onset depression decreased by 10% for each one-point increase in ideal cardiovascular health scores (Odds Ratio [OR], 0.90; 95% confidence interval [CI] 0.81-0.99) and increased by 4% for each percentage point increase in the Framingham stroke risk profile (OR, 1.04; CI, 1.00-1.07). Results were not explained by interim clinical stroke or cerebral white matter injury. In conclusion, vascular risk factor burden was associated with the new onset of depression. Shared vascular risk factors may contribute to the increased risk of cardiovascular events observed in persons with depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Does consideration of either psychological or material disadvantage improve coronary risk prediction? Prospective observational study of Scottish men.

PubMed

Macleod, John; Metcalfe, Chris; Smith, George Davey; Hart, Carole

2007-09-01

To assess the value of psychosocial risk factors in discriminating between individuals at higher and lower risk of coronary heart disease, using risk prediction equations. Prospective observational study. Scotland. 5191 employed men aged 35 to 64 years and free of coronary heart disease at study enrollment Area under receiver operating characteristic (ROC) curves for risk prediction equations including different risk factors for coronary heart disease. During the first 10 years of follow up, 203 men died of coronary heart disease and a further 200 were admitted to hospital with this diagnosis. Area under the ROC curve for the standard Framingham coronary risk factors was 74.5%. Addition of "vital exhaustion" and psychological stress led to areas under the ROC curve of 74.5% and 74.6%, respectively. Addition of current social class and lifetime social class to the standard Framingham equation gave areas under the ROC curve of 74.6% and 74.9%, respectively. In no case was there strong evidence for improved discrimination of the model containing the novel risk factor over the standard model. Consideration of psychosocial risk factors, including those that are strong independent predictors of heart disease, does not substantially influence the ability of risk prediction tools to discriminate between individuals at higher and lower risk of coronary heart disease.

Validity of an adaptation of the Framingham cardiovascular risk function: the VERIFICA study

PubMed Central

Marrugat, Jaume; Subirana, Isaac; Comín, Eva; Cabezas, Carmen; Vila, Joan; Elosua, Roberto; Nam, Byung‐Ho; Ramos, Rafel; Sala, Joan; Solanas, Pascual; Cordón, Ferran; Gené‐Badia, Joan; D'Agostino, Ralph B

2007-01-01

Background To assess the reliability and accuracy of the Framingham coronary heart disease (CHD) risk function adapted by the Registre Gironí del Cor (REGICOR) investigators in Spain. Methods A 5‐year follow‐up study was completed in 5732 participants aged 35–74 years. The adaptation consisted of using in the function the average population risk factor prevalence and the cumulative incidence observed in Spain instead of those from Framingham in a Cox proportional hazards model. Reliability and accuracy in estimating the observed cumulative incidence were tested with the area under the curve comparison and goodness‐of‐fit test, respectively. Results The Kaplan–Meier CHD cumulative incidence during the follow‐up was 4.0% in men and 1.7% in women. The original Framingham function and the REGICOR adapted estimates were 10.4% and 4.8%, and 3.6% and 2.0%, respectively. The REGICOR‐adapted function's estimate did not differ from the observed cumulated incidence (goodness of fit in men, p = 0.078, in women, p = 0.256), whereas all the original Framingham function estimates differed significantly (p<0.001). Reliabilities of the original Framingham function and of the best Cox model fit with the study data were similar in men (area under the receiver operator characteristic curve 0.68 and 0.69, respectively, p = 0.273), whereas the best Cox model fitted better in women (0.73 and 0.81, respectively, p<0.001). Conclusion The Framingham function adapted to local population characteristics accurately and reliably predicted the 5‐year CHD risk for patients aged 35–74 years, in contrast with the original function, which consistently overestimated the actual risk. PMID:17183014

A Summary Score for the Framingham Heart Study Neuropsychological Battery

PubMed Central

Downer, Brian; Fardo, David W.; Schmitt, Frederick A.

2015-01-01

Objective To calculate three summary scores of the Framingham Heart Study neuropsychological battery and determine which score best differentiates between subjects classified as having normal cognition, test-based impaired learning and memory, test-based multidomain impairment, and dementia. Method The final sample included 2,503 participants. Three summary scores were assessed: (a) composite score that provided equal weight to each subtest, (b) composite score that provided equal weight to each cognitive domain assessed by the neuropsychological battery, and (c) abbreviated score comprised of subtests for learning and memory. Receiver operating characteristic analysis was used to determine which summary score best differentiated between the four cognitive states. Results The summary score that provided equal weight to each subtest best differentiated between the four cognitive states. Discussion A summary score that provides equal weight to each subtest is an efficient way to utilize all of the cognitive data collected by a neuropsychological battery. PMID:25804903

A Summary Score for the Framingham Heart Study Neuropsychological Battery.

PubMed

Downer, Brian; Fardo, David W; Schmitt, Frederick A

2015-10-01

To calculate three summary scores of the Framingham Heart Study neuropsychological battery and determine which score best differentiates between subjects classified as having normal cognition, test-based impaired learning and memory, test-based multidomain impairment, and dementia. The final sample included 2,503 participants. Three summary scores were assessed: (a) composite score that provided equal weight to each subtest, (b) composite score that provided equal weight to each cognitive domain assessed by the neuropsychological battery, and (c) abbreviated score comprised of subtests for learning and memory. Receiver operating characteristic analysis was used to determine which summary score best differentiated between the four cognitive states. The summary score that provided equal weight to each subtest best differentiated between the four cognitive states. A summary score that provides equal weight to each subtest is an efficient way to utilize all of the cognitive data collected by a neuropsychological battery. © The Author(s) 2015.

Small dense low density lipoprotein cholesterol and coronary heart disease: results from the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

We sought to establish reference values for a new direct assay for small dense LDL cholesterol (sdLDL-C) and to measure sdLDL-C concentrations in patients with established coronary heart disease (CHD) vs controls. Direct LDL-C and sdLDL-C were measured in samples from 3188 male and female participan...

Aortic Arch Width and Cardiovascular Disease in Men and Women in the Community.

PubMed

Chuang, Michael L; Gona, Philimon N; Qazi, Saadia; Musgrave, Rebecca M; Fox, Caroline S; Massaro, Joseph M; Hoffmann, Udo; O'Donnell, Christopher J

2018-06-16

We sought to determine whether increased aortic arch width (AAW) adds to standard Framingham risk factors and coronary artery calcium (CAC) for prediction of incident adverse cardiovascular disease (CVD) events in community-dwelling adults. A total of 3026 Framingham Heart Study Offspring and Third Generation cohort participants underwent noncontrast multidetector computed tomography from 2002 to 2005 to quantify CAC. We measured AAW as the distance between the centroids of the ascending and descending thoracic aorta, at the level of main pulmonary artery bifurcation or the right pulmonary artery. We determined sex, age group, and body size specific cut points for high (≥90th percentile) AAW from a healthy referent group (N=1471) and dichotomized AAW as high or not high across all study participants. Clinical covariates were obtained at Offspring cycle 7 (1998-2001) or Third Generation cycle 1 (2002-2005) examinations. The primary CVD outcome was a composite of myocardial infarction, coronary insufficiency, cerebrovascular accident, first hospitalization for heart failure, or CVD death. Cox proportional hazards models were used to estimate hazard ratio of high AAW on time-to-incident CVD after adjustment for Framingham risk factors and CAC. Net reclassification improvement was used to assess the effect of adding AAW to the baseline Framingham risk factor+CAC model. A total of 2826 participants (aged 51±11 years, 48% women) had complete covariates and were free of CVD at multidetector computed tomography. Over a median 8.9 years of follow-up, there were 135 incident CVD events. High AAW was independently predictive of CVD events (hazard ratio, 1.55; P =0.032) and appropriately reclassified participants at risk: net reclassification improvement, 0.31 (95% confidence interval, 0.15-0.48). AAW augments traditional CVD risk factors and CAC for prediction of incident adverse CVD events among community-dwelling adults. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

OBJECTIVES: The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND: Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying c...

Effect of eprosartan-based antihypertensive therapy on coronary heart disease risk assessed by Framingham methodology in Canadian patients: results of the POWER survey

PubMed Central

Petrella, Robert J; Tremblay, Guy; De Backer, Guy; Gill, Dawn P

2014-01-01

Purpose/introduction The Canadian Hypertension Education Program (CHEP) has identified blood pressure (BP) control as a key target for an overall reduction in cardiovascular disease risk. The POWER survey (Physicians’ Observational Work on Patient Education According to their Vascular Risk) used Framingham methodology to investigate the impact of an angiotensin-receptor-blocker-based regimen on arterial BP and total coronary heart disease (CHD) risk in a subset of patients recruited in Canada. Methods 309 Canadian practices screened for patients with either newly diagnosed or uncontrolled mild/moderate hypertension (sitting systolic blood pressure [SBP] >140 mmHg with diastolic blood pressure [DBP] <110 mmHg). Treatment comprised eprosartan 600 mg/day with add-on antihypertensive therapy after 1 month if required. The primary efficacy variable was change in SBP at 6 months; the secondary variable was the absolute change in the Framingham 10-year CHD risk score. Results 1,385 patients were identified, of whom 1,114 were included in the intention-to-treat (ITT) cohort. Thirty-eight point four percent of ITT patients were managed with monotherapy at 6 months, versus 35.2% and 13.7% with two-drug or multiple-drug therapy, respectively. SBP in the ITT cohort declined 22.4 (standard deviation [SD] 14.8) mmHg and DBP declined 10.5 (SD 10.3) mmHg during that time. The absolute mean Framingham score declined 2.1 (SD 3.1) points with significant age and sex variation (P<0.001) and differences between the various Framingham methods used. Discussion/conclusion Primary care physicians were able to use a strategy of BP lowering and CHD risk assessment to achieve significant reductions in BP and Framingham-assessed CHD risk. The effect size estimate of the different Framingham methods varied noticeably; reasons for those differences warrant further investigation. PMID:24493928

Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Objective: Because vitamin D deficiency is associated with a variety of chronic diseases, understanding the characteristics that promote vitamin D deficiency in otherwise healthy adults could have important clinical implications. Few studies relating vitamin D deficiency to obesity have included d...

Kennedy Space Center Coronary Heart Disease Risk Screening Program

NASA Technical Reports Server (NTRS)

Tipton, David A.; Scarpa, Philip J.

1999-01-01

Coronary heart disease (CHD) is the number one cause of death in the U.S. It is a likely cause of death and disability in the lives of employees at Kennedy Space Center (KSC) as well. The KSC Biomedical Office used a multifactorial formula developed by the Framingham Heart Study to calculate CHD risk probabilities for individuals in a segment of the KSC population who require medical evaluation for job certification. Those individuals assessed to have a high risk probability will be targeted for intervention.

Association of lifestyle factors with abdominal subcutaneous and visceral adiposity: The Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

The objective of the present study was to assess the relationship between lifestyle factors and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in a community-based setting. Cross-sectional associations between lifestyle factors (dietary quality, physical activity, smo...

Mapping loci influencing blood pressure in the Framingham pedigrees using model-free LOD score analysis of a quantitative trait.

PubMed

Knight, Jo; North, Bernard V; Sham, Pak C; Curtis, David

2003-12-31

This paper presents a method of performing model-free LOD-score based linkage analysis on quantitative traits. It is implemented in the QMFLINK program. The method is used to perform a genome screen on the Framingham Heart Study data. A number of markers that show some support for linkage in our study coincide substantially with those implicated in other linkage studies of hypertension. Although the new method needs further testing on additional real and simulated data sets we can already say that it is straightforward to apply and may offer a useful complementary approach to previously available methods for the linkage analysis of quantitative traits.

Mapping loci influencing blood pressure in the Framingham pedigrees using model-free LOD score analysis of a quantitative trait

PubMed Central

Knight, Jo; North, Bernard V; Sham, Pak C; Curtis, David

2003-01-01

This paper presents a method of performing model-free LOD-score based linkage analysis on quantitative traits. It is implemented in the QMFLINK program. The method is used to perform a genome screen on the Framingham Heart Study data. A number of markers that show some support for linkage in our study coincide substantially with those implicated in other linkage studies of hypertension. Although the new method needs further testing on additional real and simulated data sets we can already say that it is straightforward to apply and may offer a useful complementary approach to previously available methods for the linkage analysis of quantitative traits. PMID:14975142

Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring: The Framingham Heart Study.

PubMed

Andersson, Charlotte; Quiroz, Rene; Enserro, Danielle; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S

2016-09-01

High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We compared arterial tonometry measures in a sample of 1564 nonhypertensive Framingham Heart Study third-generation cohort participants (mean age: 38 years; 55% women) whose parents were enrolled in the Framingham Offspring Study. A total of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents with hypertension. Parental hypertension was associated with greater offspring mean arterial pressure (multivariable-adjusted estimate=2.9 mm Hg; 95% confidence interval, 1.9-3.9, and 4.2 mm Hg; 95% confidence interval, 2.9-5.5, for 1 and 2 parents with hypertension, respectively; P<0.001 for both) and with greater forward pressure wave amplitude (1.6 mm Hg; 95% confidence interval, 0.6-2.7, and 1.9 mm Hg; 95% confidence interval, 0.6-3.2, for 1 and 2 parents with hypertension, respectively; P=0.003 for both). Carotid-femoral pulse wave velocity and augmentation index displayed similar dose-dependent relations with parental hypertension in sex-, age-, and height-adjusted models, but associations were attenuated on further adjustment. Offspring with at least 1 parent in the upper quartile of augmentation index and carotid-femoral pulse wave velocity had significantly higher values themselves (P≤0.02). In conclusion, in this community-based sample of young, nonhypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension. © 2016 American Heart Association, Inc.

Epidemiology of coronary heart disease: the Puerto Rico heart health program revisted.

PubMed

García-Palmieri, Mario R

2013-01-01

Coronary heart disease (CHD) remains as the main cause of death in most countries of the world including Puerto Rico. Due to the importance of gathering knowledge regarding the harmful effects and risk factors associated with the development of CHD some basic information is reviewed to stimulate the institution of measures for reduction of the prevalence of clinical CHD and its ultimate consequences. Special attention is given in the manuscript of the Puerto Rico Heart Health Program conducted in men aged 45-64 residing in four rural and three urban areas. The Puerto Rico and the Honolulu Study confirmed the initial publication on the epidemiology of coronary heart disease by the Framingham study. The presentation of some data collected among the three studies strengthen the message of avoiding the development of CHD by installing preventive measures for control and reduction of the risk factors. Concurrent data obtained in the three studies is presented. Although the degree of the involvement of the populations is higher in Framingham than in Puerto Rico and Honolulu, the deleterious effects of specific risk factors are harmful in all the three populations. Difference in the prevalence of risk factors among the urban and rural males in Puerto Rico is also illustrated. It is our hope that more intense measures be instituted in Puerto Rico at all levels in order to control risk factors and reduce the incidence of coronary disease in Puerto Rico.

Contemporary trends in dyslipidemia in the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Recent cross-sectional population studies in the United States have shown an increase in obesity, a decrease in cholesterol values, but no changes in levels of high-density lipoprotein cholesterol (HDL-C) or triglycerides (TG). Plasma total cholesterol, HDL-C, and TG levels, measured by the same met...

Health Lines | NIH Medlineplus the Magazine

MedlinePlus

... that question and more in a new monthly series of "Time to Talk" tips. The easy-to-read information ... The monthly tips can be found on the "Time to Talk" web page at ... Researchers from the Framingham Heart Study say a diet low in omega-3 fatty ...

Impact of smoking cessation on estimated cardiovascular risk in Spanish type 2 diabetes mellitus patients: The DIABETES study.

PubMed

Luque-Ramírez, M; Sanz de Burgoa, V

2018-06-08

To assess the cardiovascular risk according to the UKPDS risk engine; Framingham function and score comparing clinical characteristics of diabetes mellitus type 2 (DM2) patients according to their habits status. A descriptive analysis was performed. A total of 890 Spanish patients with DM2 (444 smokers and 446 former-smokers) were included in a cross-sectional, observational, epidemiological multicenter nationwide study. Coronary heart disease risk at 10 years was calculated using the UKPDS risk score in both patient subgroups. Results were also compared with the Spanish calibrated (REGICOR) and updated Framingham risk scores. The estimated likelihood of coronary heart disease risk at 10 years according to the UKPDS score was significantly greater in smokers compared with former-smokers. This increased risk was greater in subjects with poorer blood glucose control, and was attenuated in women ≥60 years-old. The Framingham and UKPDS scores conferred a greater estimated risk than the REGICOR equation in Spanish diabetics. Quitting smoke in patients with DM2 is accompanied by a significant decrease in the estimated risk of coronary events as assessed by UKPDS. Our findings support the importance of quitting smoking among diabetic patients in order to reduce cardiovascular risk. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Alterations in cholesterol absorption and synthesis characterize Framingham offspring study participants with coronary heart disease

USDA-ARS?s Scientific Manuscript database

Data is limited on measures influencing cholesterol homeostasis in subjects at high risk of developing cardiovascular disease (CVD) relative to established risk factors. To address this, we quantified circulating indicators of cholesterol homeostasis (plasma phytosterols and cholesterol precursor co...

SRC-1 regulates blood pressure and aortic stiffness in female mice

USDA-ARS?s Scientific Manuscript database

Framingham Heart Study suggests that dysfunction of steroid receptor coactivator-1 may be involved in the development of hypertension. However, there is no functional evidence linking steroid receptor coactivator-1 to the regulation of blood pressure. We used immunohistochemistry to map the expressi...

A single serving of blueberry (V. corymbosum) modulates peripheral arterial dysfunction induced by acute cigarette smoking in young volunteers: a randomized-controlled trial.

PubMed

Del Bo', Cristian; Porrini, Marisa; Fracassetti, Daniela; Campolo, Jonica; Klimis-Zacas, Dorothy; Riso, Patrizia

2014-12-01

Cigarette smoking causes oxidative stress, hypertension and endothelial dysfunction. Polyphenol-rich foods may prevent these conditions. We investigated the effect of a single serving of fresh-frozen blueberry intake on peripheral arterial function and arterial stiffness in young smokers. Sixteen male smokers were recruited for a 3-armed randomized-controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300 g of blueberry) + smoking; control treatment (300 mL of water with sugar) + smoking. Each treatment was separated by one week of wash-out period. The blood pressure, heart rate, peripheral arterial function (reactive hyperemia and Framingham reactive hyperemia), and arterial stiffness (digital augmentation index, digital augmentation index normalized for a heart rate of 75 bpm) were measured before and 20 min after smoking with Endo-PAT2000. Smoking impaired the blood pressure, heart rate and peripheral arterial function, but did not affect the arterial stiffness. Blueberry consumption counteracted the impairment of the reactive hyperemia index induced by smoking (-4.4 ± 0.8% blueberry treatment vs. -22.0 ± 1.1% smoking treatment, p < 0.01) and Framingham reactive hyperemia (+28.3 ± 19.2% blueberry treatment vs. -42.8 ± 20.0% smoking treatment, p < 0.0001), and the increase of systolic blood pressure (+8.4 ± 0.02% blueberry treatment vs. +13.1 ± 0.02% smoking treatment, mmHg, p < 0.05) after cigarette smoking. No effect was observed for arterial stiffness and other vital signs. In conclusion, data obtained suggest a protective role of blueberry on reactive hyperemia, Framingham reactive hyperemia, and systolic blood pressure in subjects exposed to smoke of one cigarette. Future studies are necessary to elucidate the mechanisms involved.

Sugar-sweetened beverages and prevalence of the metabolically abnormal phenotype in the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to examine the relationship between usual sugar-sweetened beverage (SSB) consumption and prevalence of abnormal metabolic health across body mass index (BMI) categories. The metabolic health of 6,842 non-diabetic adults was classified using cross-sectional data from the...

Lifestyle factors and indices of kidney function in the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Background and objectives: Lifestyle characteristics are modifiable factors that could be targeted as part of chronic kidney disease (CKD) prevention. We sought to determine the association of lifestyle characteristics with incident estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2 and rap...

Can Particulate Pollution Affect Lung Function in Healthy Adults?

EPA Science Inventory

Accompanying editorial to paper from Harvard by Rice et al. entitled "Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart StudyBy almost any measure the Clean Air Act and its amendments has to be considered as one...

Hypertension, Obesity, Diabetes, and Heart Failure-Free Survival: The Cardiovascular Disease Lifetime Risk Pooling Project.

PubMed

Ahmad, Faraz S; Ning, Hongyan; Rich, Jonathan D; Yancy, Clyde W; Lloyd-Jones, Donald M; Wilkins, John T

2016-12-01

This study was designed to quantify the relationship between the absence of heart failure risk factors in middle age and incident heart failure, heart failure-free survival, and overall survival. Quantification of years lived free from heart failure in the context of risk factor burden in mid-life may improve risk communication and prevention efforts. We conducted a pooled, individual-level analysis sampling from communities across the United States as part of 4 cohort studies: the Framingham Heart, Framingham Offspring, Chicago Heart Association Detection Project in Industry, and ARIC (Atherosclerosis Risk In Communities) studies. Participants with and without hypertension (blood pressure ≥140/90 mm Hg or treatment), obesity (body mass index ≥30 kg/m 2 ), or diabetes (fasting glucose ≥126 mg/dl or treatment), and combinations of these factors, at index ages of 45 years and 55 years through 95 years. Competing risk-adjusted Cox models, a modified Kaplan-Meier estimator, and Irwin's restricted mean were used to estimate the association between the absence of risk factors at mid-life and incident heart failure, heart failure-free survival, and overall survival. For participants at age 45 years, over 516,537 person-years of follow-up, 1,677 incident heart failure events occurred. Men and women with no risk factors, compared to those with all 3, had 73% to 85% lower risks of incident heart failure. Men and women without hypertension, obesity, or diabetes at age 45 years lived on average 34.7 years and 38.0 years without incident heart failure, and they lived on average an additional 3 years to 15 years longer free of heart failure than those with 1, 2, or 3 risk factors. Similar trends were seen when stratified by race and at index age 55 years. Prevention of hypertension, obesity, and diabetes by ages 45 years and 55 years may substantially prolong heart failure-free survival, decrease heart failure-related morbidity, and reduce the public health impact of heart failure. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Inverse association between cancer and Alzheimer's disease: results from the Framingham Heart Study.

PubMed

Driver, Jane A; Beiser, Alexa; Au, Rhoda; Kreger, Bernard E; Splansky, Greta Lee; Kurth, Tobias; Kiel, Douglas P; Lu, Kun Ping; Seshadri, Sudha; Wolf, Phillip A

2012-03-12

To relate cancer since entry into the Framingham Heart Study with the risk of incident Alzheimer's disease and to estimate the risk of incident cancer among participants with and without Alzheimer's disease. Community based prospective cohort study; nested age and sex matched case-control study. Framingham Heart Study, USA. 1278 participants with and without a history of cancer who were aged 65 or more and free of dementia at baseline (1986-90). Hazard ratios and 95% confidence intervals for the risks of Alzheimer's disease and cancer. Over a mean follow-up of 10 years, 221 cases of probable Alzheimer's disease were diagnosed. Cancer survivors had a lower risk of probable Alzheimer's disease (hazard ratio 0.67, 95% confidence interval 0.47 to 0.97), adjusted for age, sex, and smoking. The risk was lower among survivors of smoking related cancers (0.26, 0.08 to 0.82) than among survivors of non-smoking related cancers (0.82, 0.57 to 1.19). In contrast with their decreased risk of Alzheimer's disease, survivors of smoking related cancer had a substantially increased risk of stroke (2.18, 1.29 to 3.68). In the nested case-control analysis, participants with probable Alzheimer's disease had a lower risk of subsequent cancer (0.39, 0.26 to 0.58) than reference participants, as did participants with any Alzheimer's disease (0.38) and any dementia (0.44). Cancer survivors had a lower risk of Alzheimer's disease than those without cancer, and patients with Alzheimer's disease had a lower risk of incident cancer. The risk of Alzheimer's disease was lowest in survivors of smoking related cancers, and was not primarily explained by survival bias. This pattern for cancer is similar to that seen in Parkinson's disease and suggests an inverse association between cancer and neurodegeneration.

Whole- and refined-grain intakes are differentially associated with abdominal visceral and subcutaneous adiposity in healthy adults: The Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Different aspects of diet may be differentially related to body fat distribution. The purpose of this study was to assess associations between whole- and refined- grain intake and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). We examined the cross-sectional associati...

Association of serum vitamin D with the risk of incident dementia and subclinical indices of brain aging the framingham heart study

USDA-ARS?s Scientific Manuscript database

Background: Identifying nutrition- and lifestyle-based risk factors for cognitive impairment and dementia may aid future primary prevention efforts. Objective: We aimed to examine the association of serum vitamin D levels with incident all-cause dementia, clinically characterized Alzheimer's disease...

Economic evaluation of Cardio inCode®, a clinical-genetic function for coronary heart disease risk assessment.

PubMed

Ramírez de Arellano, A; Coca, A; de la Figuera, M; Rubio-Terrés, C; Rubio-Rodríguez, D; Gracia, A; Boldeanu, A; Puig-Gilberte, J; Salas, E

2013-10-01

A clinical–genetic function (Cardio inCode®) was generated using genetic variants associated with coronary heart disease (CHD), but not with classical CHD risk factors, to achieve a more precise estimation of the CHD risk of individuals by incorporating genetics into risk equations [Framingham and REGICOR (Registre Gironí del Cor)]. The objective of this study was to conduct an economic analysis of the CHD risk assessment with Cardio inCode®, which incorporates the patient’s genetic risk into the functions of REGICOR and Framingham, compared with the standard method (using only the functions). A Markov model was developed with seven states of health (low CHD risk, moderate CHD risk, high CHD risk, CHD event, recurrent CHD, chronic CHD, and death). The reclassification of CHD risk derived from genetic information and transition probabilities between states was obtained from a validation study conducted in cohorts of REGICOR (Spain) and Framingham (USA). It was assumed that patients classified as at moderate risk by the standard method were the best candidates to test the risk reclassification with Cardio inCode®. The utilities and costs (€; year 2011 values) of Markov states were obtained from the literature and Spanish sources. The analysis was performed from the perspective of the Spanish National Health System, for a life expectancy of 82 years in Spain. An annual discount rate of 3.5 % for costs and benefits was applied. For a Cardio inCode® price of €400, the cost per QALY gained compared with the standard method [incremental cost-effectiveness ratio (ICER)] would be €12,969 and €21,385 in REGICOR and Framingham cohorts, respectively. The threshold price of Cardio inCode® to reach the ICER threshold generally accepted in Spain (€30,000/QALY) would range between €668 and €836. The greatest benefit occurred in the subgroup of patients with moderate–high risk, with a high-risk reclassification of 22.8 % and 12 % of patients and an ICER of €1,652/QALY and €5,884/QALY in the REGICOR and Framingham cohorts, respectively. Sensitivity analyses confirmed the stability of the study results. Cardio inCode® is a cost-effective risk score option in CHD risk assessment compared with the standard method.

Evidence for a gene influencing the TG/HDL-C ratio on chromosome 7q32.3-qter: a genome-wide scan in the Framingham study.

PubMed

Shearman, A M; Ordovas, J M; Cupples, L A; Schaefer, E J; Harmon, M D; Shao, Y; Keen, J D; DeStefano, A L; Joost, O; Wilson, P W; Housman, D E; Myers, R H

2000-05-22

Some studies show that plasma triglyceride (TG) levels are a significant independent risk factor for cardiovascular disease (CVD). TG levels are inversely correlated with high density lipoprotein cholesterol (HDL-C) levels, and their metabolism may be closely interrelated. Therefore, the TG/HDL-C ratio may be a relevant CVD risk factor. Our analysis of families in the Framingham Heart Study gave a genetic heritability estimate for log(TG) of 0.40 and for log(TG/HDL-C) of 0.49, demonstrating an important genetic component for both. A 10 cM genome-wide scan for log(TG) level and log(TG/HDL-C) was carried out for the largest 332 extended families of the Framingham Heart Study (1702 genotyped individuals). The highest multipoint variance component LOD scores obtained for both log(TG) and log(TG/HDL-C) were on chromosome 7 (at 155 cM), where the results for the two phenotypes were 1.8 and 2.5, respectively. The 7q32.3-qter region contains several candidate genes. Four other regions with multipoint LOD scores greater than one were identified on chromosome 3 [LOD score for log(TG/HDL-C) = 1.8 at 140 cM], chromosome 11 [LOD score for log(TG/HDL-C) = 1.1 at 125 cM], chromosome 16 [LOD score for log(TG) = 1.5 at 70 cM, LOD score for log(TG/HDL-C) = 1.1 at 75 cM] and chromosome 20 [LOD score for log(TG/HDL-C) = 1.7 at 35 cM, LOD score for log(TG) = 1.3 at 40 cM]. These results identify loci worthy of further study.

Prediction of morbidity and mortality in patients with type 2 diabetes.

PubMed

Wells, Brian J; Roth, Rachel; Nowacki, Amy S; Arrigain, Susana; Yu, Changhong; Rosenkrans, Wayne A; Kattan, Michael W

2013-01-01

Introduction. The objective of this study was to create a tool that accurately predicts the risk of morbidity and mortality in patients with type 2 diabetes according to an oral hypoglycemic agent. Materials and Methods. The model was based on a cohort of 33,067 patients with type 2 diabetes who were prescribed a single oral hypoglycemic agent at the Cleveland Clinic between 1998 and 2006. Competing risk regression models were created for coronary heart disease (CHD), heart failure, and stroke, while a Cox regression model was created for mortality. Propensity scores were used to account for possible treatment bias. A prediction tool was created and internally validated using tenfold cross-validation. The results were compared to a Framingham model and a model based on the United Kingdom Prospective Diabetes Study (UKPDS) for CHD and stroke, respectively. Results and Discussion. Median follow-up for the mortality outcome was 769 days. The numbers of patients experiencing events were as follows: CHD (3062), heart failure (1408), stroke (1451), and mortality (3661). The prediction tools demonstrated the following concordance indices (c-statistics) for the specific outcomes: CHD (0.730), heart failure (0.753), stroke (0.688), and mortality (0.719). The prediction tool was superior to the Framingham model at predicting CHD and was at least as accurate as the UKPDS model at predicting stroke. Conclusions. We created an accurate tool for predicting the risk of stroke, coronary heart disease, heart failure, and death in patients with type 2 diabetes. The calculator is available online at http://rcalc.ccf.org under the heading "Type 2 Diabetes" and entitled, "Predicting 5-Year Morbidity and Mortality." This may be a valuable tool to aid the clinician's choice of an oral hypoglycemic, to better inform patients, and to motivate dialogue between physician and patient.

Microvascular Function Contributes to the Relation Between Aortic Stiffness and Cardiovascular Events: The Framingham Heart Study.

PubMed

Cooper, Leroy L; Palmisano, Joseph N; Benjamin, Emelia J; Larson, Martin G; Vasan, Ramachandran S; Mitchell, Gary F; Hamburg, Naomi M

2016-12-01

Arterial dysfunction contributes to cardiovascular disease (CVD) progression and clinical events. Inter-relations of aortic stiffness and vasodilator function with incident CVD remain incompletely studied. We used proportional hazards models to relate individual measures of vascular function to incident CVD in 4547 participants (mean age, 51±11 years; 54% women) in 2 generations of Framingham Heart Study participants. During follow-up (0.02-13.83 years), 232 participants (5%) experienced new-onset CVD events. In multivariable models adjusted for cardiovascular risk factors, both higher carotid-femoral pulse wave velocity (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.07-1.63; P=0.01) and lower hyperemic mean flow velocity (HR, 0.84; 95% CI, 0.71-0.99; P=0.04) were associated significantly with incident CVD, whereas primary pressure wave amplitude (HR, 1.12; 95% CI, 0.99-1.27; P=0.06), baseline brachial diameter (HR, 1.09; 95% CI, 0.90-1.31; P=0.39), and flow-mediated vasodilation (HR, 0.85; 95% CI, 0.69-1.04; P=0.12) were not. In mediation analyses, 8% to 13% of the relation between aortic stiffness and CVD events was mediated by hyperemic mean flow velocity. Our results suggest that associations between aortic stiffness and CVD events are mediated by pathways that include microvascular damage and remodeling. © 2016 American Heart Association, Inc.

Physical activity assessed with three different methods and the Framingham Risk Score on 10-year coronary heart disease risk

USDA-ARS?s Scientific Manuscript database

Physical activity (PA) protects against coronary heart disease (CHD) by favorably altering several CHD risk factors. In order to best understand the true nature of the relationship between PA and CHD, the impact different PA assessment methods have on the relationships must first be clarified. The p...

Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index

PubMed Central

Minster, Ryan L.; Sanders, Jason L.; Singh, Jatinder; Kammerer, Candace M.; Barmada, M. Michael; Matteini, Amy M.; Zhang, Qunyuan; Wojczynski, Mary K.; Daw, E. Warwick; Brody, Jennifer A.; Arnold, Alice M.; Lunetta, Kathryn L.; Murabito, Joanne M.; Christensen, Kaare; Perls, Thomas T.; Province, Michael A.

2015-01-01

Background. The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems. Methods. We conducted a genome-wide association study and a genome-wide linkage analysis to map quantitative trait loci associated with the HAI and a modified HAI weighted for mortality risk in 3,140 individuals selected for familial longevity from the Long Life Family Study. The genome-wide association study used the Long Life Family Study as the discovery cohort and individuals from the Cardiovascular Health Study and the Framingham Heart Study as replication cohorts. Results. There were no genome-wide significant findings from the genome-wide association study; however, several single-nucleotide polymorphisms near ZNF704 on chromosome 8q21.13 were suggestively associated with the HAI in the Long Life Family Study (p < 10− 6) and nominally replicated in the Cardiovascular Health Study and Framingham Heart Study. Linkage results revealed significant evidence (log-odds score = 3.36) for a quantitative trait locus for mortality-optimized HAI in women on chromosome 9p24–p23. However, results of fine-mapping studies did not implicate any specific candidate genes within this region of interest. Conclusions. ZNF704 may be a potential candidate gene for studies of the genetic underpinnings of longevity. PMID:25758594

Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study.

PubMed

Stefanidou, Maria; Das, Rohit R; Beiser, Alexa S; Sundar, Banu; Kelly-Hayes, Margaret; Kase, Carlos S; Devinsky, Orrin; Seshadri, Sudha; Friedman, Daniel

2017-04-01

We examined the incidence of seizures following ischemic stroke in a community-based sample. All subjects with incident ischemic strokes in the Framingham Original and Offspring cohorts between 1982 and 2003 were identified and followed for up to 20 years to determine incidence of seizures. Seizure-type was based on the 2010 International League Against Epilepsy (ILAE) classification. Disability was stratified into mild/none, moderate and severe, based on post-stroke neurological deficit documentation according to the Framingham Heart Study (FHS) protocol and functional status was determined using the Barthel Index. An initial ischemic stroke occurred in 469 subjects in the cohort and seizures occurred in 25 (5.3%) of these subjects. Seizure incidence was similar in both large artery atherosclerosis (LAA) (6.8%) and cardio-embolic (CE) (6.2%) strokes. No seizures occurred following lacunar strokes. The predominant seizure type was focal seizure with or without evolution to bilateral convulsive seizure. One third of participants had seizures within the first 24h from stroke onset and half of all seizures occurred within the first 30days. On multivariate analysis, moderate and severe disability following stroke was associated with increased risk of incident seizure. Seizures occurred in approximately 5% of subjects after an ischemic stroke. One third of these seizures occurred in the first 24h after stroke and none followed lacunar strokes. Focal seizures with or without evolution in bilateral convulsive seizures were the most common seizure type. Moderate and severe disability was predictive of incident seizures. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Changes in the food environment over time: examining 40 years of data in the Framingham Heart Study.

PubMed

James, Peter; Seward, Michael W; James O'Malley, A; Subramanian, S V; Block, Jason P

2017-06-24

Research has explored associations between diet, body weight, and the food environment; however, few studies have examined historical trends in food environments. In the Framingham Heart Study Offspring (N = 3321) and Omni (N = 447) cohorts, we created food environment metrics in four Massachusetts towns utilizing geocoded residential, workplace, and food establishment addresses from 1971 to 2008. We created multilevel models adjusted for age, sex, education, and census tract poverty to examine trends in home, workplace, and commuting food environments. Proximity to and density of supermarkets, fast-food, full service restaurants, convenience stores, and bakeries increased over time for residential, workplace, and commuting environments; exposure to grocery stores decreased. The greatest increase in access was for supermarkets, with residential distance to the closest supermarket 1406 m closer (95% CI 1303 m, 1508 m) by 2005-2008 than in 1971-1975. Although poorer census tracts had higher access to fast-food restaurants consistently across follow-up, this disparity dissipated over time, due to larger increases in proximity to fast-food in wealthier neighborhoods. Access to most food establishment types increased over time, with similar trends across home, workplace, and commuter environments.

Prognostic Utility of Novel Biomarkers of Cardiovascular Stress: The Framingham Heart Study

PubMed Central

Wang, Thomas J.; Wollert, Kai C.; Larson, Martin G.; Coglianese, Erin; McCabe, Elizabeth L.; Cheng, Susan; Ho, Jennifer E.; Fradley, Michael G.; Ghorbani, Anahita; Xanthakis, Vanessa; Kempf, Tibor; Benjamin, Emelia J.; Levy, Daniel; Vasan, Ramachandran S.; Januzzi, James L.

2013-01-01

Background Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. Methods and Results To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3,428 participants (mean age 59, 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a “multimarker” score composed of the 3 biomarkers, in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each endpoint (p<0.001) except for coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (adjusted hazard ratio, 3.2, 95% CI, 2.2–4.7; p<0.001), 6-fold risk of heart failure (6.2, 95% CI, 2.6–14.8; p<0.001), and 2-fold risk of cardiovascular events (1.9, 95% CI, 1.3–2.7; p=0.001). Addition of the multimarker score to clinical variables led to significant increases in the c-statistic (p=0.007 or lower) and net reclassification improvement (p=0.001 or lower). Conclusions Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals, and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure. PMID:22907935

Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.

PubMed

Wang, Thomas J; Wollert, Kai C; Larson, Martin G; Coglianese, Erin; McCabe, Elizabeth L; Cheng, Susan; Ho, Jennifer E; Fradley, Michael G; Ghorbani, Anahita; Xanthakis, Vanessa; Kempf, Tibor; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Januzzi, James L

2012-09-25

Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3428 participants (mean age, 59 years; 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a "multimarker" score composed of the 3 biomarkers in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each end point (P<0.001) except coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (adjusted hazard ratio, 3.2; 95% confidence interval, 2.2-4.7; P<0.001), 6-fold risk of heart failure (6.2; 95% confidence interval, 2.6-14.8; P<0.001), and 2-fold risk of cardiovascular events (1.9; 95% confidence interval, 1.3-2.7; P=0.001). Addition of the multimarker score to clinical variables led to significant increases in the c statistic (P=0.005 or lower) and net reclassification improvement (P=0.001 or lower). Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.

Cardiorespiratory Fitness and Long-Term Survival in “Low-Risk” Adults

PubMed Central

Barlow, Carolyn E.; DeFina, Laura F.; Radford, Nina B.; Berry, Jarett D.; Cooper, Kenneth H.; Haskell, William L.; Jones, Lee W.; Lakoski, Susan G.

2012-01-01

Background We sought to establish whether cardiorespiratory fitness had important implications for long-term cardiovascular risk among individuals classified as low risk by the Framingham Risk Score (10-year coronary heart disease risk <10%). Prognostic factors of long-term cardiovascular risk are needed for low-risk subjects who make up the largest percentage of the US population. Methods and Results The study population was composed of men and women, 30 to 50 years of age, who had a baseline medical exam at the Cooper Clinic, Dallas, TX, between 1970 and 1983. Eligible individuals were defined as at low risk for coronary heart disease by Framingham Risk Score at the time of study entry and had no history of diabetes (n=11 190). Cardiorespiratory fitness was determined by maximum graded exercise treadmill tests. Over an average 27±2-year period, 15% of low-fit (quintile 1) compared to 6% of high-fit (quintile 5) individuals died (P<0.001). A 1–metabolic equivalent level increase in baseline fitness was associated with an 11% reduction in all-cause deaths and an 18% reduction in deaths due to cardiovascular disease (CVD) after adjustment for age, sex, body mass index, systolic blood pressure, total cholesterol, blood glucose levels, smoking, and early family history of coronary disease. There was an incremental decrease in CVD risk with increasing fitness quintile, such that the high fit had the lowest adjusted 30-year CVD mortality rate (hazard ratio 0.29, 95% CI: 0.16–0.51) compared to the low fit. Conclusions Cardiorespiratory fitness is associated with a significant reduction in long-term CVD among individuals identified as low risk by Framingham Risk Score. These data suggest that preventive lifestyle interventions geared to optimize cardiorespiratory fitness, even among a “low-risk” subset, should be considered to improve CVD-free survival. (J Am Heart Assoc. 2012;1:e001354 doi: 10.1161/JAHA.112.001354.) PMID:23130161

Integrated genetic and epigenetic prediction of coronary heart disease in the Framingham Heart Study.

PubMed

Dogan, Meeshanthini V; Grumbach, Isabella M; Michaelson, Jacob J; Philibert, Robert A

2018-01-01

An improved method for detecting coronary heart disease (CHD) could have substantial clinical impact. Building on the idea that systemic effects of CHD risk factors are a conglomeration of genetic and environmental factors, we use machine learning techniques and integrate genetic, epigenetic and phenotype data from the Framingham Heart Study to build and test a Random Forest classification model for symptomatic CHD. Our classifier was trained on n = 1,545 individuals and consisted of four DNA methylation sites, two SNPs, age and gender. The methylation sites and SNPs were selected during the training phase. The final trained model was then tested on n = 142 individuals. The test data comprised of individuals removed based on relatedness to those in the training dataset. This integrated classifier was capable of classifying symptomatic CHD status of those in the test set with an accuracy, sensitivity and specificity of 78%, 0.75 and 0.80, respectively. In contrast, a model using only conventional CHD risk factors as predictors had an accuracy and sensitivity of only 65% and 0.42, respectively, but with a specificity of 0.89 in the test set. Regression analyses of the methylation signatures illustrate our ability to map these signatures to known risk factors in CHD pathogenesis. These results demonstrate the capability of an integrated approach to effectively model symptomatic CHD status. These results also suggest that future studies of biomaterial collected from longitudinally informative cohorts that are specifically characterized for cardiac disease at follow-up could lead to the introduction of sensitive, readily employable integrated genetic-epigenetic algorithms for predicting onset of future symptomatic CHD.

Reduced Kidney Function Is Associated With Cardiometabolic Risk Factors, Prevalent and Predicted Risk of Cardiovascular Disease in Chinese Adults: Results From the REACTION Study.

PubMed

Lu, Jieli; Mu, Yiming; Su, Qing; Shi, Lixin; Liu, Chao; Zhao, Jiajun; Chen, Lulu; Li, Qiang; Yang, Tao; Yan, Li; Wan, Qin; Wu, Shengli; Liu, Yan; Wang, Guixia; Luo, Zuojie; Tang, Xulei; Chen, Gang; Huo, Yanan; Gao, Zhengnan; Ye, Zhen; Wang, Youmin; Qin, Guijun; Deng, Huacong; Yu, Xuefeng; Shen, Feixia; Chen, Li; Zhao, Liebin; Sun, Jichao; Sun, Wanwan; Wang, Tiange; Du, Rui; Lin, Lin; Dai, Meng; Xu, Yu; Xu, Min; Bi, Yufang; Lai, Shenghan; Li, Donghui; Wang, Weiqing; Ning, Guang

2016-07-22

Chronic kidney disease (CKD) increases cardiovascular disease (CVD) risk. However, the association of mildly reduced kidney function with CVD risk is unclear. This study investigated the association of estimated glomerular filtration rate (eGFR) with prevalent CVDs, 10-year Framingham risk for coronary heart disease (CHD), and 10-year risk of atherosclerotic cardiovascular diseases (ASCVD) in 239 832 participants from the baseline of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study. With an interviewer-assisted questionnaire, we collected information on CVD, including reported CHD, stroke, or myocardial infarction. Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. Compared with individuals with normal eGFR (≥90 mL/min per 1.73 m(2)), those with decreased eGFR (75-89, 60-74, and <60 mL/min per 1.73 m(2)) had higher risk of prevalent obesity, diabetes mellitus, hypertension, and dyslipidemia in both men and women (P for trend all <0.001). Moreover, a significantly higher 10-year Framingham risk for CHD and 10-year risk for ASCVD was observed in both men and women with mildly decreased eGFR (60-89 mL/min per 1.73 m(2)). Even mildly reduced eGFR (under 90 mL/min per 1.73 m(2)) is associated with elevated 10-year Framingham risk for CHD and 10-year ASCVD risk among Chinese adults. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham Heart Study.

PubMed

Arya, Rector; Lehman, Donna; Hunt, Kelly J; Schneider, Jennifer; Almasy, Laura; Blangero, John; Stern, Michael P; Duggirala, Ravindranath

2003-12-31

Epidemiological studies have indicated that obesity and low high-density lipoprotein (HDL) levels are strong cardiovascular risk factors, and that these traits are inversely correlated. Despite the belief that these traits are correlated in part due to pleiotropy, knowledge on specific genes commonly affecting obesity and dyslipidemia is very limited. To address this issue, we first conducted univariate multipoint linkage analysis for body mass index (BMI) and HDL-C to identify loci influencing variation in these phenotypes using Framingham Heart Study data relating to 1702 subjects distributed across 330 pedigrees. Subsequently, we performed bivariate multipoint linkage analysis to detect common loci influencing covariation between these two traits. We scanned the genome and identified a major locus near marker D6S1009 influencing variation in BMI (LOD = 3.9) using the program SOLAR. We also identified a major locus for HDL-C near marker D2S1334 on chromosome 2 (LOD = 3.5) and another region near marker D6S1009 on chromosome 6 with suggestive evidence for linkage (LOD = 2.7). Since these two phenotypes have been independently mapped to the same region on chromosome 6q, we used the bivariate multipoint linkage approach using SOLAR. The bivariate linkage analysis of BMI and HDL-C implicated the genetic region near marker D6S1009 as harboring a major gene commonly influencing these phenotypes (bivariate LOD = 6.2; LODeq = 5.5) and appears to improve power to map the correlated traits to a region, precisely. We found substantial evidence for a quantitative trait locus with pleiotropic effects, which appears to influence both BMI and HDL-C phenotypes in the Framingham data.

Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the Framingham Heart Study.

PubMed

Jasuja, Guneet Kaur; Travison, Thomas G; Davda, Maithili; Murabito, Joanne M; Basaria, Shehzad; Zhang, Anqi; Kushnir, Mark M; Rockwood, Alan L; Meikle, Wayne; Pencina, Michael J; Coviello, Andrea; Rose, Adam J; D'Agostino, Ralph; Vasan, Ramachandran S; Bhasin, Shalender

2013-06-01

Age trends in estradiol and estrone levels in men and how lifestyle factors, comorbid conditions, testosterone, and sex hormone-binding globulin affect these age trends remain poorly understood, and were examined in men of the Framingham Heart Study. Estrone and estradiol concentrations were measured in morning fasting samples using liquid chromatography tandem mass spectrometry in men of Framingham Offspring Generation. Free estradiol was calculated using a law of mass action equation. There were 1,461 eligible men (mean age [±SD] 61.1±9.5 years and body mass index [BMI] 28.8±4.5kg/m(2)). Total estradiol and estrone were positively associated with age, but free estradiol was negatively associated with age. Age-related increase in total estrone was greater than that in total estradiol. Estrone was positively associated with smoking, BMI, and testosterone, and total and free estradiol with diabetes, BMI, testosterone, and comorbid conditions; additionally, free estradiol was associated negatively with smoking. Collectively, age, BMI, testosterone, and other health and behavioral factors explained only 18% of variance in estradiol, and 9% of variance in estrone levels. Men in the highest quintile of estrone levels had significantly higher age and BMI, and a higher prevalence of smoking, diabetes, and cardiovascular disease than others, whereas those in the highest quintile of estradiol had higher BMI than others. Total estrone and estradiol levels in men, measured using liquid chromatography tandem mass spectrometry, revealed significant age-related increases that were only partially accounted for by cross-sectional differences in BMI, diabetes status, and other comorbidities and health behaviors. Longitudinal studies are needed to confirm these findings.

Revised Framingham Stroke Risk Profile to Reflect Temporal Trends.

PubMed

Dufouil, Carole; Beiser, Alexa; McLure, Leslie A; Wolf, Philip A; Tzourio, Christophe; Howard, Virginia J; Westwood, Andrew J; Himali, Jayandra J; Sullivan, Lisa; Aparicio, Hugo J; Kelly-Hayes, Margaret; Ritchie, Karen; Kase, Carlos S; Pikula, Aleksandra; Romero, Jose R; D'Agostino, Ralph B; Samieri, Cécilia; Vasan, Ramachandran S; Chêne, Genevieve; Howard, George; Seshadri, Sudha

2017-03-21

Age-adjusted stroke incidence has decreased over the past 50 years, likely as a result of changes in the prevalence and impact of various stroke risk factors. An updated version of the Framingham Stroke Risk Profile (FSRP) might better predict current risks in the FHS (Framingham Heart Study) and other cohorts. We compared the accuracy of the standard (old) and of a revised (new) version of the FSRP in predicting the risk of all-stroke and ischemic stroke and validated this new FSRP in 2 external cohorts, the 3C (3 Cities) and REGARDS (Reasons for Geographic and Racial Differences in Stroke) studies. We computed the old FSRP as originally described and a new model that used the most recent epoch-specific risk factor prevalence and hazard ratios for individuals ≥55 years of age and for the subsample ≥65 years of age (to match the age range in REGARDS and 3C studies, respectively) and compared the efficacy of these models in predicting 5- and 10-year stroke risks. The new FSRP was a better predictor of current stroke risks in all 3 samples than the old FSRP (calibration χ 2 of new/old FSRP: in men: 64.0/12.1, 59.4/30.6, and 20.7/12.5; in women: 42.5/4.1, 115.4/90.3, and 9.8/6.5 in FHS, REGARDS, and 3C, respectively). In the REGARDS, the new FSRP was a better predictor among whites compared with blacks. A more contemporaneous, new FSRP better predicts current risks in 3 large community samples and could serve as the basis for examining geographic and racial differences in stroke risk and the incremental diagnostic utility of novel stroke risk factors. © 2017 American Heart Association, Inc.

Vitamin B-12 and folate status in relation to decline in scores on the Mini-Mental State Examination in the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Biochemical evidence of low vitamin B-12 status is common in seniors, but its clinical relevance is unclear. Vitamin B-12 deficiency can result in rapid, irreversible cognitive decline – a phenomenon that has been linked to high folate status. Our objective was to investigate the cognitive significa...

Maintenance of Ideal Cardiovascular Health and Coronary Artery Calcium Progression in Low-Risk Men and Women in the Framingham Heart Study.

PubMed

Hwang, Shih-Jen; Onuma, Oyere; Massaro, Joseph M; Zhang, Xiaoling; Fu, Yi-Ping; Hoffmann, Udo; Fox, Caroline S; O'Donnell, Christopher J

2018-01-01

Ideal cardiovascular health (CVH) is associated with a lower risk of cardiovascular disease and freedom from coronary artery calcium (CAC). Prospective data on the association between maintenance of optimal CVH and the progression of subclinical coronary atherosclerosis are limited. We assessed the influence of unfavorable versus favorable CVH on the incidence of CAC progression. The study population consisted of 1119 FHS (Framingham Heart Study) participants who attended the serial FHS MDCT I and MDCT II study (Multi-Detector Computed Tomography) and had a zero Agatston CAC score at baseline. CVH status was defined using 6 CVH metrics from the American Heart Association definition. CAC progression was defined by an increase in Agatston CAC score to ≥3.4. Generalized estimating equations were applied to identify significant associations of CAC progression with both the baseline measurement of CVH and the longitudinal maintenance of CVH. After follow-up (mean, 6.1 years), we observed CAC progression in 191 participants (17.1%). Participants with unfavorable CVH at baseline had a greater risk of CAC progression (odds ratio, 2.43; 95% confidence interval, 1.40-4.23; P =0.0017). In addition, each unit decrease in ideal CVH metric was associated with an increase in CAC progression (odds ratio, 1.15; 95% confidence interval, 0.99-1.34; P =0.067), after adjustment for baseline ideal CVH metrics. Significant associations between an unfavorable CVH profile and CAC progression support public health measures that seek to prevent cardiovascular disease by promoting favorable CVH profiles in persons free of clinical and subclinical cardiovascular disease. © 2018 American Heart Association, Inc.

Arterial stiffness and cardiovascular events: the Framingham Heart Study.

PubMed

Mitchell, Gary F; Hwang, Shih-Jen; Vasan, Ramachandran S; Larson, Martin G; Pencina, Michael J; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Benjamin, Emelia J

2010-02-02

Various measures of arterial stiffness and wave reflection have been proposed as cardiovascular risk markers. Prior studies have not assessed relations of a comprehensive panel of stiffness measures to prognosis in the community. We used proportional hazards models to analyze first-onset major cardiovascular disease events (myocardial infarction, unstable angina, heart failure, or stroke) in relation to arterial stiffness (pulse wave velocity [PWV]), wave reflection (augmentation index, carotid-brachial pressure amplification), and central pulse pressure in 2232 participants (mean age, 63 years; 58% women) in the Framingham Heart Study. During median follow-up of 7.8 (range, 0.2 to 8.9) years, 151 of 2232 participants (6.8%) experienced an event. In multivariable models adjusted for age, sex, systolic blood pressure, use of antihypertensive therapy, total and high-density lipoprotein cholesterol concentrations, smoking, and presence of diabetes mellitus, higher aortic PWV was associated with a 48% increase in cardiovascular disease risk (95% confidence interval, 1.16 to 1.91 per SD; P=0.002). After PWV was added to a standard risk factor model, integrated discrimination improvement was 0.7% (95% confidence interval, 0.05% to 1.3%; P<0.05). In contrast, augmentation index, central pulse pressure, and pulse pressure amplification were not related to cardiovascular disease outcomes in multivariable models. Higher aortic stiffness assessed by PWV is associated with increased risk for a first cardiovascular event. Aortic PWV improves risk prediction when added to standard risk factors and may represent a valuable biomarker of cardiovascular disease risk in the community.

Height and weight errors in aeromedical certification data.

DOT National Transportation Integrated Search

1973-06-01

The Framingham Relative Weight Index (FRWI) of obesity was described in previous reports as a screening aid for detecting susceptibility to coronary heart disease (CHD). FRWI calculation requires measured values of height and weight but the height an...

Advantages and disadvantages of using intravenous tissue Plasminogen activator as salvage therapy for inoperable HeartWare thrombosis.

PubMed

Basken, Robyn; Bazzell, Charles M; Smith, Richard; Janardhanan, Rajesh; Khalpey, Zain

2017-07-01

Device thrombosis is a devastating complication of left ventricular assist devices. The definitive treatment has been device exchange or explant. Evidence of increasing morbidity and mortality with device exchange has shifted strategies toward conservative management. In this report, we detail the use of thrombolytics as salvage therapy in a patient with an occlusive HeartWare ventricular assist device (HeartWare Inc., Framingham, MA) thrombus, resulting in long-term survival without further intervention. © 2017 Wiley Periodicals, Inc.

Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

PubMed

Speliotes, Elizabeth K; Yerges-Armstrong, Laura M; Wu, Jun; Hernaez, Ruben; Kim, Lauren J; Palmer, Cameron D; Gudnason, Vilmundur; Eiriksdottir, Gudny; Garcia, Melissa E; Launer, Lenore J; Nalls, Michael A; Clark, Jeanne M; Mitchell, Braxton D; Shuldiner, Alan R; Butler, Johannah L; Tomas, Marta; Hoffmann, Udo; Hwang, Shih-Jen; Massaro, Joseph M; O'Donnell, Christopher J; Sahani, Dushyant V; Salomaa, Veikko; Schadt, Eric E; Schwartz, Stephen M; Siscovick, David S; Voight, Benjamin F; Carr, J Jeffrey; Feitosa, Mary F; Harris, Tamara B; Fox, Caroline S; Smith, Albert V; Kao, W H Linda; Hirschhorn, Joel N; Borecki, Ingrid B

2011-03-01

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.

Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (The Framingham Heart Study).

PubMed

Morshedi-Meibodi, Ali; Larson, Martin G; Levy, Daniel; O'Donnell, Christopher J; Vasan, Ramachandran S

2002-10-15

A delayed heart rate (HR) recovery after graded exercise testing has been associated with increased all-cause mortality in clinic-based samples. No prior study has examined the association of HR recovery after exercise with the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) events. We evaluated 2,967 Framingham study subjects (1,400 men, mean age 43 years) who were free of CVD and underwent a treadmill exercise test (Bruce protocol) at a routine examination. We examined the relations of HR recovery indexes (decrease in HR from peak exercise) to the incidence of a first CHD or CVD event and all-cause mortality, adjusting for established CVD risk factors. During follow-up (mean 15 years), 214 subjects experienced a CHD event (156 men), 312 developed a CVD event (207 men), and 167 died (105 men). In multivariable models, continuous HR recovery indexes were not associated with the incidence of CHD or CVD events, or with all-cause mortality. However, in models evaluating quintile-based cut points, the top quintile of HR recovery (greatest decline in HR) at 1-minute after exercise was associated with a lower risk of CHD (hazards ratio vs bottom 4 quintiles 0.54, 95% confidence interval [CI], 0.32 to 0.93) and CVD (hazards ratio 0.61, 95% CI 0.41 to 0.93), but not all-cause mortality (hazards ratio 0.99, 95% CI 0.60 to 1.62). In our community-based sample, HR recovery indexes were not associated with all-cause mortality. A very rapid HR recovery immediately after exercise was associated with lower risk of CHD and CVD events. These findings should be confirmed in other settings.

Aortic-Brachial Arterial Stiffness Gradient and Cardiovascular Risk in the Community: The Framingham Heart Study.

PubMed

Niiranen, Teemu J; Kalesan, Bindu; Larson, Martin G; Hamburg, Naomi M; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S

2017-06-01

A recent study reported that the aortic-brachial arterial stiffness gradient, defined as carotid-radial/carotid-femoral pulse wave velocity (PWV ratio), predicts all-cause mortality better than carotid-femoral pulse wave velocity (CFPWV) alone in dialysis patients. However, the prognostic significance of PWV ratio for cardiovascular disease (CVD) in the community remains unclear. Accordingly, we assessed the correlates and prognostic value of the PWV ratio in 2114 Framingham Heart Study participants (60±10 years; 56% women) free of overt CVD. Mean PWV ratio decreased from 1.36±0.19 in participants aged <40 years to 0.73±0.21 in those aged ≥80 years. In multivariable linear regression, older age, male sex, higher body mass index, diabetes mellitus, lower high-density lipoprotein cholesterol, higher mean arterial pressure, and higher heart rate were associated with lower PWV ratio ( P <0.001 for all). During a median follow-up of 12.6 years, 248 first CVD events occurred. In Cox regression models adjusted for standard CVD risk factors, 1-SD changes in CFPWV (hazard ratio, 1.33; 95% confidence interval, 1.10-1.61) and PWV ratio (hazard ratio, 1.32; 95% confidence interval, 1.09-1.59) were associated with similar CVD risks. Models that included conventional CVD risk factors plus CFPWV or PWV ratio gave the same C statistics (C=0.783). Although PWV ratio has been reported to provide incremental predictive value over CFPWV in dialysis patients, we could not replicate these findings in our community-based sample. Our findings suggest that the prognostic significance of PWV ratio may vary based on baseline CVD risk, and CFPWV should remain the criterion standard for assessing vascular stiffness in the community. © 2017 American Heart Association, Inc.

Social networks and inflammatory markers in the Framingham Heart Study.

PubMed

Loucks, Eric B; Sullivan, Lisa M; D'Agostino, Ralph B; Larson, Martin G; Berkman, Lisa F; Benjamin, Emelia J

2006-11-01

Lack of social integration predicts coronary heart disease mortality in prospective studies; however, the biological pathways that may be responsible are poorly understood. The specific aims of this study were to examine whether social networks are associated with serum concentrations of the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Participants in the Framingham Study attending examinations from 1998 to 2001 (n=3267) were eligible for inclusion in the study. Social networks were assessed using the Berkman-Syme Social Network Index (SNI). Concentrations of IL-6, CRP, sICAM-1 and MCP-1 were measured in fasting serum samples. Multivariable linear regression analyses were used to assess the association of social networks with inflammatory markers adjusting for potential confounders including age, smoking, blood pressure, total:HDL cholesterol ratio, body mass index, lipid-lowering and antihypertensive medication, diabetes, cardiovascular disease, depression and socioeconomic status. Results found that the SNI was significantly inversely associated with IL-6 in men (p=0.03) after adjusting for potential confounders. In age-adjusted analyses, social networks also were significantly inversely associated with IL-6 for women (p=0.03) and were marginally to modestly associated with CRP and sICAM-1 for men (p=0.08 and 0.02, respectively), but these associations were not significant in the multivariate analyses. In conclusion, social networks were found to be inversely associated with interleukin-6 levels in men. The possibility that inflammatory markers may be potential mediators between social integration and coronary heart disease merits further investigation.

Relationship between lower urinary tract symptoms and cardiovascular risk scores including Framingham risk score and ACC/AHA risk score.

PubMed

Lee, Bora; Lee, Sang Wook; Kang, Hye Rim; Kim, Dae In; Sun, Hwa Yeon; Kim, Jae Heon

2018-01-01

This study attempted to investigate the association between lower urinary tract symptoms (LUTS) and cardiovascular disease (CVD) risk using International Prostate Symptom Score (IPSS) and CVD risk scores and to overcome the limitations of previous relevant studies. A total of 2994 ostensibly healthy males, who participated in a voluntary health check in a health promotion center from January 2010 to December 2014, were reviewed. CVD risk scores were calculated using Framingham risk score and American College of Cardiology (ACC)/American Heart Association (AHA) score. Correlation and multivariate logistic regression analysis to predict the CVD risk severity were performed. Correlation between total IPSS with CVD risk scores demonstrated significant positive associations, which showed higher correlation with ACC/AHA score than the Framingham score (r = 0.18 vs 0.09, respectively). For ACC/AHA score, the partial correlation after adjustment of body mass index (BMI) showed significant positive correlations between all LUTS parameters and PSA. For the Framingham score, all variables, except IPSS Q2 and IPSS Q6, showed significant positive correlations. After adjustment of BMI, prostate volume and PSA, only the severe LUTS group showed significant relationship with intermediate-high CVD risk severity, as compared with normal LUTS group (OR = 2.97, 95%CI (1.35-6.99)). Using two validated CVD risk calculators, we observed that LUTS is closely associated with future CVD risk. To predict the intermediate-high CVD risk severity, severe LUTS was a sentinel sign, the presence of which warrants the importance of an earlier screening for CVD. © 2017 Wiley Periodicals, Inc.

Stroke as the Initial Manifestation of Atrial Fibrillation: The Framingham Heart Study.

PubMed

Lubitz, Steven A; Yin, Xiaoyan; McManus, David D; Weng, Lu-Chen; Aparicio, Hugo J; Walkey, Allan J; Rafael Romero, Jose; Kase, Carlos S; Ellinor, Patrick T; Wolf, Philip A; Seshadri, Sudha; Benjamin, Emelia J

2017-02-01

To prevent strokes that may occur as the first manifestation of atrial fibrillation (AF), screening programs have been proposed to identify patients with undiagnosed AF who may be eligible for treatment with anticoagulation. However, the frequency with which patients with AF present with stroke as the initial manifestation of the arrhythmia is unknown. We estimated the frequency with which AF may present as a stroke in 1809 community-based Framingham Heart Study participants with first-detected AF and without previous strokes, by tabulating the frequencies of strokes occurring on the same day, within 30 days before, 90 days before, and 365 days before first-detected AF. Using previously reported AF incidence rates, we estimated the incidence of strokes that may represent the initial manifestation of AF. We observed 87 strokes that occurred ≤1 year before AF detection, corresponding to 1.7% on the same day, 3.4% within 30 days before, 3.7% within 90 days before, and 4.8% ≤1 year before AF detection. We estimated that strokes may present as the initial manifestation of AF at a rate of 2 to 5 per 10 000 person-years, in both men and women. We observed that stroke is an uncommon but measureable presenting feature of AF. Our data imply that emphasizing cost-effectiveness of population-wide AF-screening efforts will be important given the relative infrequency with which stroke represents the initial manifestation of AF. © 2017 American Heart Association, Inc.

Marital status, marital strain, and risk of coronary heart disease or total mortality: the Framingham Offspring Study.

PubMed

Eaker, Elaine D; Sullivan, Lisa M; Kelly-Hayes, Margaret; D'Agostino, Ralph B; Benjamin, Emelia J

2007-01-01

To determine if marriage and marital strain are related to the 10-year coronary heart disease (CHD) incidence or total mortality. Research has demonstrated associations between marital strain and prognosis of heart disease, but little research has addressed the association between specific aspects of marital strain and incident CHD. From 1984 to 1987, 3682 participants (mean age 48.5 +/- 10.1 (standard deviation) years; 52% women) of the Framingham Offspring Study were examined; measures of marital status, marital strain, and risk factors for CHD were collected at the baseline examination. The present study describes the 10-year follow-up for incident CHD and total mortality. After adjusting for age, systolic blood pressure, body mass index, cigarette smoking, diabetes, and total cholesterol/high density cholesterol, the married men compared with unmarried men were almost half as likely to die during follow-up (hazard ratio (HR) = 0.54; 95% confidence interval (CI): 0.34-0.83). Women who "self-silenced" during conflict with their spouse, compared with women who did not, had four times the risk of dying (HR = 4.01; 95% CI: 1.75-9.20). Men with wives who were upset by work were 2.7 times more likely to develop CHD (HR = 2.71; 95% CI: 1.22-6.03). Marital happiness, satisfaction, and disagreements were not related to the development of CHD or death in men or women. Our study suggests that marital communication, conflict, and strain are associated with adverse health outcomes. Further research into the influence of marital stress on health is merited.

Cardiovascular Risk and Serum Hyaluronic Acid: A Preliminary Study in a Healthy Population of Low/Intermediate Risk.

PubMed

Papanastasopoulou, Chrysanthi; Papastamataki, Maria; Karampatsis, Petros; Anagnostopoulou, Eleni; Papassotiriou, Ioannis; Sitaras, Nikolaos

2017-01-01

Hyaluronic acid (HA) has been found to be an important trigger of atherosclerosis. In this study, we investigate the possible association of serum HA with cardiovascular disease risk in a population of low/intermediate risk for cardiovascular events. We enrolled 200 subjects with low/intermediate risk for developing cardiovascular disease. High specific C-reactive protein (hsCRP) was used as an indicator of preclinical atherosclerosis. The Framingham score was used to calculate the cardiovascular risk. Participants with dyslipidemia had significantly higher levels of serum HA than those without dyslipidemia (t-test, P = 0.05), higher levels of hsCRP (Kruskal-Wallis test, P = 0.04), and higher cardiovascular risk according to the Framingham score (Kruskal-Wallis test, P = 0.05). Serum HA concentration correlated significantly with the Framingham score for risk for coronary heart disease over the next 10 years (Spearman r = 0.152, P = 0.02). Diabetic volunteers had significantly higher HA than those without diabetes (t-test, P = 0.02). Participants with metabolic syndrome had higher serum HA levels and higher hsCRP (Kruskal-Wallis test, P = 0.01) compared to volunteers without metabolic syndrome (t-test, P = 0.03). Serum HA should be explored as an early marker of atheromatosis and cardiovascular risk. © 2016 Wiley Periodicals, Inc.

Non-alcoholic fatty liver disease (NAFLD) and 10-year risk of cardiovascular diseases.

PubMed

Motamed, Nima; Rabiee, Behnam; Poustchi, Hossein; Dehestani, Babak; Hemasi, Gholam Reza; Khonsari, Mahmood Reza; Maadi, Mansooreh; Saeedian, Fatemeh Sima; Zamani, Farhad

2017-02-01

The association between cardiovascular diseases (CVD) and non-alcoholic fatty liver disease (NAFLD) was confirmed by a large body of evidence. This study was conducted to determine the association between NAFLD and 10-year CVD risk. This study utilized the data of 2804 subjects aged 40-74 years from a cohort study of northern Iran. Two CVD risk assessment tools, American College of Cardiology/American Heart Association and Framingham general cardiovascular risk profile for use in primary care, were utilized to determine the 10-year CVD risk in patients with NAFLD and the individuals without this condition. The mean risks were compared between these two groups. Using ACC/AHA approach, the mean risk in male participants suffering NAFLD was 14.2%, while in men without NAFLD was 11.7% (P-value < 0.0001). Using Framingham approach, the mean risks were 16.0 and 12.7% in men with and without NAFLD, respectively (P-value < 0.0001). Using ACC/AHA approach, the mean risks in female participants with and without NAFLD were 6.7 and 4.6%, respectively (P-value < 0.0001). Applying Framingham approach, the mean risk was 8.2% in women with NAFLD and 5.4% in women without NAFLD (P-value < 0.0001). The individuals with NAFLD had a higher risk of 10-year CVD events than individuals without NAFLD, according to both ACC/AHA tool and primary care version of Framingham tool. A large proportion of NAFLD patients fulfill the criteria of statin therapy recommendation, suggesting that statin therapy could reduce 10-year CVD risk in NAFLD patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Right Ventricular Volumes and Systolic Function by Cardiac Magnetic Resonance and the Impact of Sex, Age, and Obesity in a Longitudinally Followed Cohort Free of Pulmonary and Cardiovascular Disease: The Framingham Heart Study.

PubMed

Foppa, Murilo; Arora, Garima; Gona, Philimon; Ashrafi, Arman; Salton, Carol J; Yeon, Susan B; Blease, Susan J; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J; Chuang, Michael L

2016-03-01

Cardiac magnetic resonance is uniquely well suited for noninvasive imaging of the right ventricle. We sought to define normal cardiac magnetic resonance reference values and to identify the main determinants of right ventricular (RV) volumes and systolic function using a modern imaging sequence in a community-dwelling, longitudinally followed cohort free of clinical cardiovascular and pulmonary disease. The Framingham Heart Study Offspring cohort has been followed since 1971. We scanned 1794 Offspring cohort members using steady-state free precession cardiac magnetic resonance and identified a reference group of 1336 adults (64±9 years, 576 men) free of prevalent cardiovascular and pulmonary disease. RV trabeculations and papillary muscles were considered cavity volume. Men had greater RV volumes and cardiac output before and after indexation to body size (all P<0.001). Women had higher RV ejection fraction than men (68±6% versus 64±7%; P<0.0001). RV volumes and cardiac output decreased with advancing age. There was an increase in raw and height-indexed RV measurements with increasing body mass index, but this trend was weakly inverted after indexation of RV volumes to body surface area. Sex, age, height, body mass index, and heart rate account for most of the variability in RV volumes and function in this community-dwelling population. We report sex-specific normative values for RV measurements among principally middle-aged and older adults. RV ejection fraction is greater in women. RV volumes increase with body size, are greater in men, and are smaller in older people. Body surface area seems to be appropriate for indexation of cardiac magnetic resonance-derived RV volumes. © 2016 American Heart Association, Inc.

The development of a simulation model of primary prevention strategies for coronary heart disease.

PubMed

Babad, Hannah; Sanderson, Colin; Naidoo, Bhash; White, Ian; Wang, Duolao

2002-11-01

This paper describes the present state of development of a discrete-event micro-simulation model for coronary heart disease prevention. The model is intended to support health policy makers in assessing the impacts on health care resources of different primary prevention strategies. For each person, a set of times to disease events, conditional on the individual's risk factor profile, is sampled from a set of probability distributions that are derived from a new analysis of the Framingham cohort study on coronary heart disease. Methods used to model changes in behavioural and physiological risk factors are discussed and a description of the simulation logic is given. The model incorporates POST (Patient Oriented Simulation Technique) simulation routines.

Association of physical activity and heart failure with preserved vs. reduced ejection fraction in the elderly: the Framingham Heart Study.

PubMed

Kraigher-Krainer, Elisabeth; Lyass, Asya; Massaro, Joseph M; Lee, Douglas S; Ho, Jennifer E; Levy, Daniel; Kannel, William B; Vasan, Ramachandran S

2013-07-01

Reduced physical activity is associated with increased risk of heart failure (HF) in middle-aged individuals. We hypothesized that physical inactivity is also associated with greater HF risk in older individuals, and examined if the association was consistent for HF with preserved ejection fraction (HFPEF) vs. HF with a reduced ejection fraction (HFREF). We evaluated 1142 elderly participants (mean age 76 years) from the Framingham Study without prior myocardial infarction and who attended a routine examination when daily physical activity was assessed systematically with a questionnaire. A composite score, the physical activity index (PAI), was calculated and modelled as tertiles, and related to incidence of HF, HFPEF, and HFREF on follow-up using proportional hazards regression models adjusting for age and sex, and then additionally for standard HF risk factors. Participants with HF and EF <45% vs. ≥45% were categorized as HFREF and HFPEF, respectively. On follow-up (mean 10 years), 250 participants developed HF (108 with HFPEF, 106 with HFREF, 36 with unavailable EF). In age- and sex-adjusted models, the middle and highest PAI tertiles were associated with a 15-56% lower risk of any HF, of HFREF, and of HFPEF, with a graded response across tertiles. In multivariable models, the association of higher PAI with lower risk of any HF and with HFPEF was maintained, whereas the association with HFREF was attenuated. Our study of an older community-based sample extends to the elderly and to HFPEF previous findings of a protective effect of physical activity on HF risk.

Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index.

PubMed

Minster, Ryan L; Sanders, Jason L; Singh, Jatinder; Kammerer, Candace M; Barmada, M Michael; Matteini, Amy M; Zhang, Qunyuan; Wojczynski, Mary K; Daw, E Warwick; Brody, Jennifer A; Arnold, Alice M; Lunetta, Kathryn L; Murabito, Joanne M; Christensen, Kaare; Perls, Thomas T; Province, Michael A; Newman, Anne B

2015-08-01

The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems. We conducted a genome-wide association study and a genome-wide linkage analysis to map quantitative trait loci associated with the HAI and a modified HAI weighted for mortality risk in 3,140 individuals selected for familial longevity from the Long Life Family Study. The genome-wide association study used the Long Life Family Study as the discovery cohort and individuals from the Cardiovascular Health Study and the Framingham Heart Study as replication cohorts. There were no genome-wide significant findings from the genome-wide association study; however, several single-nucleotide polymorphisms near ZNF704 on chromosome 8q21.13 were suggestively associated with the HAI in the Long Life Family Study (p < 10(-) (6)) and nominally replicated in the Cardiovascular Health Study and Framingham Heart Study. Linkage results revealed significant evidence (log-odds score = 3.36) for a quantitative trait locus for mortality-optimized HAI in women on chromosome 9p24-p23. However, results of fine-mapping studies did not implicate any specific candidate genes within this region of interest. ZNF704 may be a potential candidate gene for studies of the genetic underpinnings of longevity. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Testing for genetic association taking into account phenotypic information of relatives.

PubMed

Uh, Hae-Won; Wijk, Henk Jan van der; Houwing-Duistermaat, Jeanine J

2009-12-15

We investigated efficient case-control association analysis using family data. The outcome of interest was coronary heart disease. We employed existing and new methods that take into account the correlations among related individuals to obtain the proper type I error rates. The methods considered for autosomal single-nucleotide polymorphisms were: 1) generalized estimating equations-based methods, 2) variance-modified Cochran-Armitage (MCA) trend test incorporating kinship coefficients, and 3) genotypic modified quasi-likelihood score test. Additionally, for X-linked single-nucleotide polymorphisms we proposed a two-degrees-of-freedom test. Performance of these methods was tested using Framingham Heart Study 500 k array data.

Proximity to Food Establishments and Body Mass Index in the Framingham Heart Study Offspring Cohort Over 30 Years

PubMed Central

Block, Jason P.; Christakis, Nicholas A.; O’Malley, A. James; Subramanian, S. V.

2011-01-01

Existing evidence linking residential proximity to food establishments with body mass index (BMI; weight (kg)/height (m)2) has been inconclusive. In this study, the authors assessed the relation between BMI and proximity to food establishments over a 30-year period among 3,113 subjects in the Framingham Heart Study Offspring Cohort living in 4 Massachusetts towns during 1971–2001. The authors used novel data that included repeated measures of BMI and accounted for residential mobility and the appearance and disappearance of food establishments. They calculated proximity to food establishments as the driving distance between each subject’s residence and nearby food establishments, divided into 6 categories. The authors used cross-classified linear mixed models to account for time-varying attributes of individuals and residential neighborhoods. Each 1-km increase in distance to the closest fast-food restaurant was associated with a 0.11-unit decrease in BMI (95% credible interval: −0.20, −0.04). In sex-stratified analyses, this association was present only for women. Other aspects of the food environment were either inconsistently associated or not at all associated with BMI. Contrary to much prior research, the authors did not find a consistent relation between access to fast-food restaurants and individual BMI, necessitating a reevaluation of policy discussions on the anticipated impact of the food environment on weight gain. PMID:21965186

Sugar-sweetened beverages and prevalence of the metabolically abnormal phenotype in the Framingham Heart Study.

PubMed

Green, Angela K; Jacques, Paul F; Rogers, Gail; Fox, Caroline S; Meigs, James B; McKeown, Nicola M

2014-05-01

The purpose of this study was to examine the relationship between usual sugar-sweetened beverage (SSB) consumption and prevalence of abnormal metabolic health across body mass index (BMI) categories. The metabolic health of 6,842 non-diabetic adults was classified using cross-sectional data from the Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-2005) cohorts. Adults were classified as normal weight, overweight or obese and, within these categories, metabolic health was defined based on five criteria-hypertension, elevated fasting glucose, elevated triglycerides, low HDL cholesterol, and insulin resistance. Individuals without metabolic abnormalities were considered metabolically healthy. Logistic regression was used to examine the associations between categories of SSB consumption and risk of metabolic health after stratification by BMI. Comparing the highest category of SSB consumers (median of 7 SSB per week) to the lowest category (non-consumers), odds ratios (95% confidence intervals) for metabolically abnormal phenotypes, compared to the metabolically normal, were 1.9 (1.1-3.4) among the obese, 2.0 (1.4-2.9) among the overweight, and 1.9 (1.4-2.6) among the normal weight individuals. In this cross-sectional analysis, it is observed that, irrespective of weight status, consumers of SSB were more likely to display metabolic abnormalities compared to non-consumers in a dose-dependent manner. Copyright © 2014 The Obesity Society.

Unique dietary patterns and chronic disease risk profiles of adult men: the Framingham nutrition studies.

PubMed

Millen, Barbara E; Quatromoni, Paula A; Pencina, Michael; Kimokoti, Ruth; Nam, Byung-H O; Cobain, Sonia; Kozak, Waldemar; Appugliese, Danielle P; Ordovas, Jose; D'Agostino, Ralph B

2005-11-01

To identify the dietary patterns of adult men and examine their relationships with nutrient intake and chronic disease risk over long-term follow-up. Baseline 145-item food frequency questionnaires from 1,666 Framingham Offspring-Spouse cohort men were used to identify comprehensive dietary patterns. Independent 3-day dietary records at baseline and 8 years later provided estimates of subjects' nutrient intake by dietary pattern. Chronic disease risk factor status was compared at baseline and 16-year follow-up across all male dietary patterns. Cluster analysis was applied to food frequency data to identify non-overlapping male dietary patterns. Analysis of covariance and logistic regression were used to compare nutrient intake, summary nutritional risk scores, and chronic disease risk status at baseline and follow-up by male dietary pattern. Five distinct and comprehensive dietary patterns of Framingham Offspring-Spouse men were identified and ordered according to overall nutritional risk: Transition to Heart Healthy, Higher Starch, Average Male, Lower Variety, and Empty Calories. Nutritional risk was high and varied by dietary pattern; key nutrient contrasts were stable over 8-year follow-up. Chronic disease risk also varied by dietary pattern and specific subgroup differences persisted over 16 years, notably rates of overweight/obesity and smoking. Quantitative cluster analysis applied to food frequency questionnaire data identified five distinct, comprehensive, and stable dietary patterns of adult Framingham Offspring-Spouse cohort men. The close associations between the dietary patterns, nutritional risk, and chronic disease profiles of men emphasize the importance of targeted preventive nutrition interventions to promote health in the male population.

A genome-wide search for genes affecting circulating fibrinogen levels in the Framingham Heart Study.

PubMed

Yang, Qiong; Tofler, Geoffrey H; Cupples, L Adrienne; Larson, Martin G; Feng, DaLi; Lindpaintner, Klaus; Levy, Daniel; D'Agostino, Ralph B; O'Donnell, Christopher J

2003-04-15

Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD=1.5 at 243 cM) and 10 (LOD=2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD=2.1 at 242 cM) and 10(LOD=1.4 at 86 cM), 17 (LOD=1.4 at 96 cM) and 20 (LOD=1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted.

Subclinical and clinical correlates of left ventricular wall motion abnormalities in the community.

PubMed

Tsao, Connie W; Gona, Philimon; Salton, Carol; Danias, Peter G; Blease, Susan; Hoffmann, Udo; Fox, Caroline S; Albert, Mark; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J; Yeon, Susan B

2011-03-15

The prevalence and clinical correlates of left ventricular (LV) wall motion abnormalities (WMAs), associated with morbidity and mortality, have not been well-characterized in the population. Framingham Heart Study Offspring Cohort participants (n = 1,794, 844 men, age 65 ± 9 years) underwent cine cardiovascular magnetic resonance for evaluation of LV function. A subset (n = 1,009, 460 men) underwent cardiac multidetector computed tomography for analysis of coronary artery calcium. The presence of coronary heart disease and heart failure (CHD-HF) were assessed in relation to the presence of WMAs. WMAs were present in 117 participants (6.5%) and were associated with male gender, elevated hemoglobin A1c, LV mass, LV end-diastolic volume, and lower LV ejection fraction. Of the 1,637 participants without CHD-HF, 68 (4.2%) had WMAs. In this group, WMAs were associated with obesity, hypertension, and Framingham coronary heart disease risk score in the age- and gender-adjusted analyses and were associated with male gender and hypertension on multivariate analysis. Most subjects with WMAs were in the greatest coronary artery calcium groups. The presence of coronary artery calcium greater than the seventy-fifth percentile and Agatston score >100 were associated with a greater than twofold risk of WMAs in the age- and gender-adjusted analysis but were no longer significant when additionally adjusted for CHD-HF. Previous Q-wave myocardial infarction was present in 29% of the 117 participants with WMAs. In conclusion, in the present longitudinally followed free-living population, 4.2% of the participants without CHD-HF had WMAs. WMAs were associated with the clinical parameters associated with cardiovascular disease risk. Aggressive risk factor modification may be prudent for subjects with WMAs, particularly those free of clinical CHD-HF. Copyright © 2011 Elsevier Inc. All rights reserved.

Risk factor differences in calcified and noncalcified aortic plaque: the Framingham Heart Study.

PubMed

Chuang, Michael L; Gona, Philimon; Oyama-Manabe, Noriko; Manders, Emily S; Salton, Carol J; Hoffmann, Udo; Manning, Warren J; O'Donnell, Christopher J

2014-07-01

The objective of this study was to determine the prevalence and risk factor (RF) correlates of aortic plaque (AP) detected by cardiovascular magnetic resonance (CMR), which mainly shows noncalcified plaques, and by noncontrast computed tomography (CT), which best depicts calcified plaques, in community-dwelling adults. A total of 1016 Framingham Heart Study Offspring cohort members (64 ± 9 years; 474 men) underwent CMR and CT of the aorta. Potential RFs for AP (age; sex; body mass index; blood pressure; low-density lipoprotein and high-density lipoprotein cholesterol; fasting glucose; C-reactive protein; prevalent hypertension, diabetes mellitus, smoking; use of antihypertensive, diabetes mellitus, or lipid-lowering drugs) were compared between participants, with zero versus nonzero AP by CMR and by CT. Candidate RFs attaining P<0.05 for difference with either imaging modality were entered into multivariable logistic regression models adjusting for age, sex, and other RFs. Odds ratios were calculated for modality-specific prevalence of AP. Associations between RFs and continuous measures of AP were assessed using Tobit regression. Prevalence of CMR and CT AP was 49% and 82%, respectively. AP burdens by CMR and CT were correlated, r=0.28, P<0.0001. Increasing age and smoking were associated with prevalent AP by both CMR and CT. Additionally, prevalent AP by CMR was associated with female sex and fasting glucose and prevalent AP by CT with hypertension treatment and adverse lipid profile. AP by CMR and CT are both associated with smoking and increasing age, but other RFs differ between calcified and noncalcified AP. The relative predictive value of AP detected by CMR versus by CT for incident cardiovascular events remains to be determined. © 2014 American Heart Association, Inc.

Left Ventricular Structure and Risk of Cardiovascular Events: A Framingham Heart Study Cardiac Magnetic Resonance Study

PubMed Central

Tsao, Connie W; Gona, Philimon N; Salton, Carol J; Chuang, Michael L; Levy, Daniel; Manning, Warren J; O’Donnell, Christopher J

2015-01-01

Background Elevated left ventricular mass index (LVMI) and concentric left ventricular (LV) remodeling are related to adverse cardiovascular disease (CVD) events. The predictive utility of LV concentric remodeling and LV mass in the prediction of CVD events is not well characterized. Methods and Results Framingham Heart Study Offspring Cohort members without prevalent CVD (n=1715, 50% men, aged 65±9 years) underwent cardiovascular magnetic resonance for LVMI and geometry (2002–2006) and were prospectively followed for incident CVD (myocardial infarction, coronary insufficiency, heart failure, stroke) or CVD death. Over 13 808 person-years of follow-up (median 8.4, range 0.0 to 10.5 years), 85 CVD events occurred. In multivariable-adjusted proportional hazards regression models, each 10-g/m2 increment in LVMI and each 0.1 unit in relative wall thickness was associated with 33% and 59% increased risk for CVD, respectively (P=0.004 and P=0.009, respectively). The association between LV mass/LV end-diastolic volume and incident CVD was borderline significant (P=0.053). Multivariable-adjusted risk reclassification models showed a modest improvement in CVD risk prediction with the incorporation of cardiovascular magnetic resonance LVMI and measures of LV concentricity (C-statistic 0.71 [95% CI 0.65 to 0.78] for the model with traditional risk factors only, improved to 0.74 [95% CI 0.68 to 0.80] for the risk factor model additionally including LVMI and relative wall thickness). Conclusions Among adults free of prevalent CVD in the community, greater LVMI and LV concentric hypertrophy are associated with a marked increase in adverse incident CVD events. The potential benefit of aggressive primary prevention to modify LV mass and geometry in these adults requires further investigation. PMID:26374295

Relations of Central Hemodynamics and Aortic Stiffness with Left Ventricular Structure and Function: The Framingham Heart Study.

PubMed

Kaess, Bernhard M; Rong, Jian; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Cheng, Susan; Aragam, Jayashree; Levy, Daniel; Benjamin, Emelia J; Vasan, Ramachandran S; Mitchell, Gary F

2016-03-25

The differing relations of steady and pulsatile components of central hemodynamics and aortic stiffness with cardiac dimensions and function have not been fully elucidated. Central hemodynamics and carotid-femoral pulse wave velocity (CFPWV, a measure of aortic stiffness) were measured by arterial tonometry in 5799 participants of the Framingham Heart Study (mean age 51 years, 54% women) and related to echocardiographic left ventricular (LV) dimensions and systolic and diastolic function using multivariable-adjusted partial Pearson correlations. Mean arterial pressure (MAP, steady component of central blood pressure) was associated positively with LV wall thickness (r=0.168; P<0.0001) but showed only a weak direct association with LV diastolic dimension (r=0.035, P=0.006). Central pulse pressure (pulsatile component of central blood pressure) showed a direct correlation with both LV diastolic dimension and LV wall thickness (r=0.08 and 0.044, both P<0.0001 in multivariable models that included MAP). CFPWV was not associated with LV structure (all P≥0.27) in MAP-adjusted models). Both MAP and CFPWV were associated inversely with LV diastolic function (E'; r=-0.140 and -0.153, respectively; both P<0.0001), and these associations persisted after additional adjustment for LV mass and central pulse pressure (r=-0.142 and -0.108, both P<0.0001). MAP and CFPWV were not associated with LV fractional shortening (P≥0.10), whereas central pulse pressure was positively related (r=0.064, P<0.0001). Pulsatile and steady components of central pressure are conjointly yet variably related to LV structure. CFPWV is related to LV diastolic function but not to systolic function. Additional studies are warranted to confirm these observations. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Cross-Sectional Associations of Flow Reversal, Vascular Function, and Arterial Stiffness in the Framingham Heart Study.

PubMed

Bretón-Romero, Rosa; Wang, Na; Palmisano, Joseph; Larson, Martin G; Vasan, Ramachandran S; Mitchell, Gary F; Benjamin, Emelia J; Vita, Joseph A; Hamburg, Naomi M

2016-12-01

Experimental studies link oscillatory flow accompanied by flow reversal to impaired endothelial cell function. The relation of flow reversal with vascular function and arterial stiffness remains incompletely defined. We measured brachial diastolic flow patterns along with vasodilator function in addition to tonometry-based central and peripheral arterial stiffness in 5708 participants (age 47±13 years, 53% women) in the Framingham Heart Study Offspring and Third Generation cohorts. Brachial artery diastolic flow reversal was present in 35% of the participants. In multivariable regression models, the presence of flow reversal was associated with lower flow-mediated dilation (3.9±0.2 versus 5.0±0.2%; P<0.0001) and reactive hyperemic flow velocity (50±0.99 versus 57±0.93 cm/s; P<0.0001). The presence of flow reversal (compared with absence) was associated with higher central aortic stiffness (carotid-femoral pulse wave velocity 9.3±0.1 versus 8.9±0.1 m/s), lower muscular artery stiffness (carotid-radial pulse wave velocity 9.6±0.1 versus 9.8±0.1 m/s), and higher forearm vascular resistance (5.32±0.03 versus 4.66±0.02 log dyne/s/cm 5 ; P<0.0001). The relations of diastolic flow velocity with flow-mediated dilation, aortic stiffness, and forearm vascular resistance were nonlinear, with a steeper decline in vascular function associated with increasing magnitude of flow reversal. In our large, community-based sample, brachial artery flow reversal was common and associated with impaired vasodilator function and higher aortic stiffness. Our findings are consistent with the concept that flow reversal may contribute to vascular dysfunction. © 2016 American Heart Association, Inc.

Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.

PubMed

Shaikh, Amir Y; Wang, Na; Yin, Xiaoyan; Larson, Martin G; Vasan, Ramachandran S; Hamburg, Naomi M; Magnani, Jared W; Ellinor, Patrick T; Lubitz, Steven A; Mitchell, Gary F; Benjamin, Emelia J; McManus, David D

2016-09-01

The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF. © 2016 American Heart Association, Inc.

Job strain and cardiovascular disease risk factors: meta-analysis of individual-participant data from 47,000 men and women.

PubMed

Nyberg, Solja T; Fransson, Eleonor I; Heikkilä, Katriina; Alfredsson, Lars; Casini, Annalisa; Clays, Els; De Bacquer, Dirk; Dragano, Nico; Erbel, Raimund; Ferrie, Jane E; Hamer, Mark; Jöckel, Karl-Heinz; Kittel, France; Knutsson, Anders; Ladwig, Karl-Heinz; Lunau, Thorsten; Marmot, Michael G; Nordin, Maria; Rugulies, Reiner; Siegrist, Johannes; Steptoe, Andrew; Westerholm, Peter J M; Westerlund, Hugo; Theorell, Töres; Brunner, Eric J; Singh-Manoux, Archana; Batty, G David; Kivimäki, Mika

2013-01-01

Job strain is associated with an increased coronary heart disease risk, but few large-scale studies have examined the relationship of this psychosocial characteristic with the biological risk factors that potentially mediate the job strain - heart disease association. We pooled cross-sectional, individual-level data from eight studies comprising 47,045 participants to investigate the association between job strain and the following cardiovascular disease risk factors: diabetes, blood pressure, pulse pressure, lipid fractions, smoking, alcohol consumption, physical inactivity, obesity, and overall cardiovascular disease risk as indexed by the Framingham Risk Score. In age-, sex-, and socioeconomic status-adjusted analyses, compared to those without job strain, people with job strain were more likely to have diabetes (odds ratio 1.29; 95% CI: 1.11-1.51), to smoke (1.14; 1.08-1.20), to be physically inactive (1.34; 1.26-1.41), and to be obese (1.12; 1.04-1.20). The association between job strain and elevated Framingham risk score (1.13; 1.03-1.25) was attributable to the higher prevalence of diabetes, smoking and physical inactivity among those reporting job strain. In this meta-analysis of work-related stress and cardiovascular disease risk factors, job strain was linked to adverse lifestyle and diabetes. No association was observed between job strain, clinic blood pressure or blood lipids.

CMR reference values for left ventricular volumes, mass, and ejection fraction using computer-aided analysis: the Framingham Heart Study.

PubMed

Chuang, Michael L; Gona, Philimon; Hautvast, Gilion L T F; Salton, Carol J; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J

2014-04-01

To determine sex-specific reference values for left ventricular (LV) volumes, mass, and ejection fraction (EF) in healthy adults using computer-aided analysis and to examine the effect of age on LV parameters. We examined data from 1494 members of the Framingham Heart Study Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a healthy reference group (without cardiovascular disease, hypertension, or LV wall motion abnormality) and determined sex-specific upper 95th percentile thresholds for LV volumes and mass, and lower 5th percentile thresholds for EF using computer-assisted border detection. In secondary analyses, we stratified participants by age-decade and tested for linear trend across age groups. The reference group comprised 685 adults (423F; 61 ± 9 years). Men had greater LV volumes and mass, before and after indexation to common measures of body size (all P = 0.001). Women had greater EF (73 ± 6 versus 71 ± 6%; P = 0.0002). LV volumes decreased with greater age in both sexes, even after indexation. Indexed LV mass did not vary with age. LV EF and concentricity increased with greater age in both sexes. We present CMR-derived LV reference values. There are significant age and sex differences in LV volumes, EF, and geometry, whereas mass differs between sexes but not age groups. Copyright © 2013 Wiley Periodicals, Inc.

CMR Reference Values for Left Ventricular Volumes, Mass and Ejection Fraction Using Computer-Aided Analysis: The Framingham Heart Study

PubMed Central

Chuang, Michael L.; Gona, Philimon; Hautvast, Gilion L.T.F.; Salton, Carol J.; Breeuwer, Marcel; O’Donnell, Christopher J.; Manning, Warren J.

2013-01-01

Purpose To determine sex-specific reference values for left ventricular (LV) volumes, mass and ejection fraction (EF) in healthy adults using computer-aided analysis and to examine the effect of age on LV parameters. Methods and Methods We examined data from 1494 members of the Framingham Heart Study Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a healthy reference group (without cardiovascular disease, hypertension, or LV wall motion abnormality) and determined sex-specific upper 95th percentile thresholds for LV volumes and mass, and lower 5th percentile thresholds for EF using computer-assisted border detection. In secondary analyses we stratified participants by age-decade and tested for linear trend across age groups. Results The reference group comprised 685 adults (423F; 61±9 years). Men had greater LV volumes and mass, before and after indexation to common measures of body size (all p<0.001). Women had greater EF (73±6 vs. 71±6%, p=0.0002). LV volumes decreased with greater age in both sexes, even after indexation. Indexed LV mass did not vary with age. LV EF and concentricity increased with greater age in both sexes. Conclusion We present CMR-derived LV reference values. There are significant age and sex differences in LV volumes, EF and geometry, while mass differs between sexes but not age groups. PMID:24123369

Left Ventricular Structure and Risk of Cardiovascular Events: A Framingham Heart Study Cardiac Magnetic Resonance Study.

PubMed

Tsao, Connie W; Gona, Philimon N; Salton, Carol J; Chuang, Michael L; Levy, Daniel; Manning, Warren J; O'Donnell, Christopher J

2015-09-15

Elevated left ventricular mass index (LVMI) and concentric left ventricular (LV) remodeling are related to adverse cardiovascular disease (CVD) events. The predictive utility of LV concentric remodeling and LV mass in the prediction of CVD events is not well characterized. Framingham Heart Study Offspring Cohort members without prevalent CVD (n=1715, 50% men, aged 65±9 years) underwent cardiovascular magnetic resonance for LVMI and geometry (2002-2006) and were prospectively followed for incident CVD (myocardial infarction, coronary insufficiency, heart failure, stroke) or CVD death. Over 13 808 person-years of follow-up (median 8.4, range 0.0 to 10.5 years), 85 CVD events occurred. In multivariable-adjusted proportional hazards regression models, each 10-g/m(2) increment in LVMI and each 0.1 unit in relative wall thickness was associated with 33% and 59% increased risk for CVD, respectively (P=0.004 and P=0.009, respectively). The association between LV mass/LV end-diastolic volume and incident CVD was borderline significant (P=0.053). Multivariable-adjusted risk reclassification models showed a modest improvement in CVD risk prediction with the incorporation of cardiovascular magnetic resonance LVMI and measures of LV concentricity (C-statistic 0.71 [95% CI 0.65 to 0.78] for the model with traditional risk factors only, improved to 0.74 [95% CI 0.68 to 0.80] for the risk factor model additionally including LVMI and relative wall thickness). Among adults free of prevalent CVD in the community, greater LVMI and LV concentric hypertrophy are associated with a marked increase in adverse incident CVD events. The potential benefit of aggressive primary prevention to modify LV mass and geometry in these adults requires further investigation. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits

PubMed Central

Palmer, Cameron D.; Gudnason, Vilmundur; Eiriksdottir, Gudny; Garcia, Melissa E.; Launer, Lenore J.; Nalls, Michael A.; Clark, Jeanne M.; Mitchell, Braxton D.; Shuldiner, Alan R.; Butler, Johannah L.; Tomas, Marta; Hoffmann, Udo; Hwang, Shih-Jen; Massaro, Joseph M.; O'Donnell, Christopher J.; Sahani, Dushyant V.; Salomaa, Veikko; Schadt, Eric E.; Schwartz, Stephen M.; Siscovick, David S.; Voight, Benjamin F.; Carr, J. Jeffrey; Feitosa, Mary F.; Harris, Tamara B.; Fox, Caroline S.

2011-01-01

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%–27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10−8) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT–assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits. PMID:21423719

Personalized Nutrition and Cardiovascular Disease Prevention: From Framingham to PREDIMED123

PubMed Central

Konstantinidou, Valentini; Ruiz, Lidia Angeles Daimiel; Ordovás, Jose M.

2014-01-01

Diet is considered the cornerstone for the prevention of age-related diseases, and a low-fat diet has been considered for decades as the most suitable alternative to achieve this goal. However, mounting evidence supports the efficacy of other alternatives, such as the Mediterranean diet. Nevertheless, it is well known that people present a dramatic range of responses to similar environmental challenges, and it has been shown that some of this variability is rooted in the genome. In fact, this knowledge is driving the field of nutrigenetics. The finding of interactions between diet and genetic variants has led to intense research and debate about the effectiveness of personalized nutrition as a more suitable tool for the prevention of chronic diseases than the traditional 1-size-fits-all recommendations. Here, we provide some of our own examples that illustrate the progression of nutrigenetics through the years, from the initial studies within the Framingham Heart Study, to the most recent use of large consortia, such as the Cohorts for Heart and Aging Research in Genomic Epidemiology, and ending up with large dietary intervention studies, such as the PREDIMED (Prevención con Dieta Mediterránea) study. These recent approaches are providing more robust and clinically relevant gene–diet interactions. Therefore, although the current evidence level of applying genomic information to tailoring is at its early stages, the prospect of widespread incorporation of nutrigenetics to the clinical practice is encouraging. PMID:24829490

A combined reference panel from the 1000 Genomes and UK10K projects improved rare variant imputation in European and Chinese samples

PubMed Central

Chou, Wen-Chi; Zheng, Hou-Feng; Cheng, Chia-Ho; Yan, Han; Wang, Li; Han, Fang; Richards, J. Brent; Karasik, David; Kiel, Douglas P.; Hsu, Yi-Hsiang

2016-01-01

Imputation using the 1000 Genomes haplotype reference panel has been widely adapted to estimate genotypes in genome wide association studies. To evaluate imputation quality with a relatively larger reference panel and a reference panel composed of different ethnic populations, we conducted imputations in the Framingham Heart Study and the North Chinese Study using a combined reference panel from the 1000 Genomes (N = 1,092) and UK10K (N = 3,781) projects. For rare variants with 0.01% < MAF ≤ 0.5%, imputation in the Framingham Heart Study with the combined reference panel increased well-imputed genotypes (with imputation quality score ≥0.4) from 62.9% to 76.1% when compared to imputation with the 1000 Genomes. For the North Chinese samples, imputation of rare variants with 0.01% < MAF ≤ 0.5% with the combined reference panel increased well-imputed genotypes by from 49.8% to 61.8%. The predominant European ancestry of the UK10K and the combined reference panels may explain why there was less of an increase in imputation success in the North Chinese samples. Our results underscore the importance and potential of larger reference panels to impute rare variants, while recognizing that increasing ethnic specific variants in reference panels may result in better imputation for genotypes in some ethnic groups. PMID:28004816

Validation of a Six Item Questionnaire for Assessing Type A Behavior.

ERIC Educational Resources Information Center

Perlman, Baron; And Others

Type A behavior is an aggregate of behaviors associated with increased risk of coronary heart disease. Two self-administered questionnaires used to determine the presence of Type A behavior, the Jenkins Activity Survey and Framingham Type A Behavior Pattern Scale, were administered to 150 undergraduate students at a midwestern university, along…

Changes in erectile dysfunction over time in relation to Framingham cardiovascular risk in the Boston Area Community Health (BACH) Survey.

PubMed

Fang, Shona C; Rosen, Raymond C; Vita, Joseph A; Ganz, Peter; Kupelian, Varant

2015-01-01

Erectile dysfunction (ED) is associated with cardiovascular disease (CVD); however, the association between change in ED status over time and future underlying CVD risk is unclear. The aim of this study was to investigate the association between change in ED status and Framingham CVD risk, as well change in Framingham risk. We studied 965 men free of CVD in the Boston Area Community Health (BACH) Survey, a longitudinal cohort study with three assessments. ED was assessed with the five-item International Index of Erectile Function at BACH I (2002-2005) and BACH II (2007-2010) and classified as no ED/transient ED/persistent ED. CVD risk was assessed with 10-year Framingham CVD risk algorithm at BACH I and BACH III (2010-2012). Linear regression models controlled for baseline age, socio-demographic and lifestyle factors, as well as baseline Framingham risk. Models were also stratified by age (≥/< 50 years). Framingham CVD risk and change in Framingham CVD risk were the main outcome measures. Transient and persistent ED was significantly associated with increased Framingham risk and change in risk over time in univariate and age-adjusted models. In younger men, persistent ED was associated with a Framingham risk that was 1.58 percentage points higher (95% confidence interval [CI]: 0.11, 3.06) and in older men, a Framingham risk that was 2.54 percentage points higher (95% CI: -1.5, 6.59), compared with those without ED. Change in Framingham risk over time was also associated with transient and persistent ED in men <50 years, but not in older men. Data suggest that even after taking into account other CVD risk factors, transient and persistent ED is associated with Framingham CVD risk and a greater increase in Framingham risk over time, particularly in younger men. Findings further support clinical assessment of CVD risk in men presenting with ED, especially those under 50 years. © 2014 International Society for Sexual Medicine.

Cardiovascular risk prediction tools for populations in Asia.

PubMed

Barzi, F; Patel, A; Gu, D; Sritara, P; Lam, T H; Rodgers, A; Woodward, M

2007-02-01

Cardiovascular risk equations are traditionally derived from the Framingham Study. The accuracy of this approach in Asian populations, where resources for risk factor measurement may be limited, is unclear. To compare "low-information" equations (derived using only age, systolic blood pressure, total cholesterol and smoking status) derived from the Framingham Study with those derived from the Asian cohorts, on the accuracy of cardiovascular risk prediction. Separate equations to predict the 8-year risk of a cardiovascular event were derived from Asian and Framingham cohorts. The performance of these equations, and a subsequently "recalibrated" Framingham equation, were evaluated among participants from independent Chinese cohorts. Six cohort studies from Japan, Korea and Singapore (Asian cohorts); six cohort studies from China; the Framingham Study from the US. 172,077 participants from the Asian cohorts; 25,682 participants from Chinese cohorts and 6053 participants from the Framingham Study. In the Chinese cohorts, 542 cardiovascular events occurred during 8 years of follow-up. Both the Asian cohorts and the Framingham equations discriminated cardiovascular risk well in the Chinese cohorts; the area under the receiver-operator characteristic curve was at least 0.75 for men and women. However, the Framingham risk equation systematically overestimated risk in the Chinese cohorts by an average of 276% among men and 102% among women. The corresponding average overestimation using the Asian cohorts equation was 11% and 10%, respectively. Recalibrating the Framingham risk equation using cardiovascular disease incidence from the non-Chinese Asian cohorts led to an overestimation of risk by an average of 4% in women and underestimation of risk by an average of 2% in men. A low-information Framingham cardiovascular risk prediction tool, which, when recalibrated with contemporary data, is likely to estimate future cardiovascular risk with similar accuracy in Asian populations as tools developed from data on local cohorts.

Self-reported stroke symptoms without a prior diagnosis of stroke or transient ischemic attack: a powerful new risk factor for stroke.

PubMed

Kleindorfer, Dawn; Judd, Suzanne; Howard, Virginia J; McClure, Leslie; Safford, Monika M; Cushman, Mary; Rhodes, David; Howard, George

2011-11-01

Previously in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, we found 18% of the stroke/transient ischemic attack-free study population reported ≥1 stroke symptom at baseline. We sought to evaluate the additional impact of these stroke symptoms on risk for subsequent stroke. REGARDS recruited 30,239 US blacks and whites, aged 45+ years in 2003 to 2007 who are being followed every 6 months for events. All stroke events are physician-verified; those with prior diagnosed stroke or transient ischemic attack are excluded from this analysis. At baseline, participants were asked 6 questions regarding stroke symptoms. Measured stroke risk factors were components of the Framingham Stroke Risk Score. After excluding those with prior stroke or missing data, there were 24,412 participants in this analysis with a median follow-up of 4.4 years. Participants were 39% black, 55% female, and had median age of 64 years. There were 381 physician-verified stroke events. The Framingham Stroke Risk Score explained 72.0% of stroke risk; individual components explained between 0.2% (left ventricular hypertrophy) and 5.7% (age+race) of stroke risk. After adjustment for Framingham Stroke Risk Score factors, stroke symptoms were significantly related to stroke risk: for each stroke symptom reported, the risk of stroke increased by 21% per symptom. Among participants without self-reported stroke or transient ischemic attack, prior stroke symptoms are highly predictive of future stroke events. Compared with Framingham Stroke Risk Score factors, the impact of stroke symptom on the prediction of future stroke was almost as large as the impact of smoking and hypertension and larger than the impact of diabetes and heart disease.

Accurate computer-aided quantification of left ventricular parameters: experience in 1555 cardiac magnetic resonance studies from the Framingham Heart Study.

PubMed

Hautvast, Gilion L T F; Salton, Carol J; Chuang, Michael L; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J

2012-05-01

Quantitative analysis of short-axis functional cardiac magnetic resonance images can be performed using automatic contour detection methods. The resulting myocardial contours must be reviewed and possibly corrected, which can be time-consuming, particularly when performed across all cardiac phases. We quantified the impact of manual contour corrections on both analysis time and quantitative measurements obtained from left ventricular short-axis cine images acquired from 1555 participants of the Framingham Heart Study Offspring cohort using computer-aided contour detection methods. The total analysis time for a single case was 7.6 ± 1.7 min for an average of 221 ± 36 myocardial contours per participant. This included 4.8 ± 1.6 min for manual contour correction of 2% of all automatically detected endocardial contours and 8% of all automatically detected epicardial contours. However, the impact of these corrections on global left ventricular parameters was limited, introducing differences of 0.4 ± 4.1 mL for end-diastolic volume, -0.3 ± 2.9 mL for end-systolic volume, 0.7 ± 3.1 mL for stroke volume, and 0.3 ± 1.8% for ejection fraction. We conclude that left ventricular functional parameters can be obtained under 5 min from short-axis functional cardiac magnetic resonance images using automatic contour detection methods. Manual correction more than doubles analysis time, with minimal impact on left ventricular volumes and ejection fraction. Copyright © 2011 Wiley Periodicals, Inc.

[Obesity and the prognosis of heart failure: the obesity paradox, myth or reality?].

PubMed

Bounhoure, Jean-Paul; Galinier, Michel; Roncalli, Jerôme; Massabuau, Pierre

2014-01-01

Obesity has now reached epidemic proportions worldwide. Obesity is associated with numerous comorbidities, including hypertension, lipid disorders and type II diabetes, and is also a major cause of cardiovascular disease, coronary disease, heart failure, atrial fibrillation, and sudden death. Obesity is the main cause of heart failure in respectively 11% and 14% of cases in men and women. The Framingham study showed that, after correction for other risk factors, each point increase in the body mass index raises the risk of heart failure by 5% in men and 7% in women. Obesity increases the heart workload, causes left ventricular hypertrophy, and impairs both diastolic and systolic function. The most common form of heart failure is diastolic dysfunction, and heart failure in obese individuals is associated with preserved systolic function. Despite these comorbidities and the severity of heart failure, numerous studies have revealed an "obesity paradox" in which overweight and obese individuals with heart failure appear to have a better prognosis than non overweight subjects. This review summarizes the adverse cardiac effects of this nutritional disease, the results of some studies supporting the obesity paradox, the better survival rate of obese patients with heart failure. Potential explanations for these surprising data include the possibility that a number of obese patients may simply not have heart failure, as well as methodological bias, and protective effects of adipose tissue. Further studies of large populations are needed to determine how obesity may improve the prognosis of heart failure.

Cardiovascular risk factors predictive for survival and morbidity-free survival in the oldest-old Framingham Heart Study participants.

PubMed

Terry, Dellara F; Pencina, Michael J; Vasan, Ramachandran S; Murabito, Joanne M; Wolf, Philip A; Hayes, Margaret Kelly; Levy, Daniel; D'Agostino, Ralph B; Benjamin, Emelia J

2005-11-01

To examine whether midlife cardiovascular risk factors predict survival and survival free of major comorbidities to the age of 85. Prospective community-based cohort study. Framingham Heart Study, Massachusetts. Two thousand five hundred thirty-one individuals (1,422 women) who attended at least two examinations between the ages of 40 and 50. Risk factors were classified at routine examinations performed between the ages of 40 and 50. Stepwise sex-adjusted logistic regression models predicting the outcomes of survival and survival free of morbidity to age 85 were selected from the following risk factors: systolic and diastolic blood pressure, total serum cholesterol, glucose intolerance, cigarette smoking, education, body mass index, physical activity index, pulse pressure, antihypertensive medication, and electrocardiographic left ventricular hypertrophy. More than one-third of the study sample survived to age 85, and 22% of the original study sample survived free of morbidity. Lower midlife blood pressure and total cholesterol levels, absence of glucose intolerance, nonsmoking status, higher educational attainment, and female sex predicted overall and morbidity-free survival. The predicted probability of survival to age 85 fell in the presence of accumulating risk factors: 37% for men with no risk factors to 2% with all five risk factors and 65% for women with no risk factors to 14% with all five risk factors. Lower levels of key cardiovascular risk factors in middle age predicted overall survival and major morbidity-free survival to age 85. Recognizing and modifying these factors may delay, if not prevent, age-related morbidity and mortality.

Cardiac risk stratification: Role of the coronary calcium score

PubMed Central

Sharma, Rakesh K; Sharma, Rajiv K; Voelker, Donald J; Singh, Vibhuti N; Pahuja, Deepak; Nash, Teresa; Reddy, Hanumanth K

2010-01-01

Coronary artery calcium (CAC) is an integral part of atherosclerotic coronary heart disease (CHD). CHD is the leading cause of death in industrialized nations and there is a constant effort to develop preventative strategies. The emphasis is on risk stratification and primary risk prevention in asymptomatic patients to decrease cardiovascular mortality and morbidity. The Framingham Risk Score predicts CHD events only moderately well where family history is not included as a risk factor. There has been an exploration for new tests for better risk stratification and risk factor modification. While the Framingham Risk Score, European Systematic Coronary Risk Evaluation Project, and European Prospective Cardiovascular Munster study remain excellent tools for risk factor modification, the CAC score may have additional benefit in risk assessment. There have been several studies supporting the role of CAC score for prediction of myocardial infarction and cardiovascular mortality. It has been shown to have great scope in risk stratification of asymptomatic patients in the emergency room. Additionally, it may help in assessment of progression or regression of coronary artery disease. Furthermore, the CAC score may help differentiate ischemic from nonischemic cardiomyopathy. PMID:20730016

Case Management to Reduce Cardiovascular Disease Risk in American Indians and Alaska Natives With Diabetes: Results From the Special Diabetes Program for Indians Healthy Heart Demonstration Project

PubMed Central

Jiang, Luohua; Manson, Spero M.; Beals, Janette; Henderson, William; Pratte, Katherine; Acton, Kelly J.; Roubideaux, Yvette

2014-01-01

Objectives. We evaluated cardiovascular disease (CVD) risk factors in American Indians/Alaska Natives (AI/ANs) with diabetes in the Special Diabetes Program for Indians Healthy Heart (SDPI-HH) Demonstration Project. Methods. Multidisciplinary teams implemented an intensive case management intervention among 30 health care programs serving 138 tribes. The project recruited 3373 participants, with and without current CVD, between 2006 and 2009. We examined data collected at baseline and 1 year later to determine whether improvements occurred in CVD risk factors and in Framingham coronary heart disease (CHD) risk scores, aspirin use, and smoking status. Results. A1c levels decreased an average of 0.2% (P < .001). Systolic and diastolic blood pressure, low-density lipoprotein (LDL) cholesterol, and triglyceride levels decreased, with the largest significant reduction in LDL cholesterol (∆ = −5.29 mg/dL; P < .001). Average Framingham CHD risk scores also decreased significantly. Aspirin therapy increased significantly, and smoking decreased. Participants with more case management visits had significantly greater reductions in LDL cholesterol and A1c values. Conclusions. SDPI-HH successfully translated an intensive case management intervention. Creative retention strategies and an improved understanding of organizational challenges are needed for future Indian health translational efforts. PMID:25211728

Metabolic Characterization of Adults with Binge Eating in the General Population: The Framingham Heart Study

PubMed Central

Abraham, Tobin M.; Massaro, Joseph M.; Hoffmann, D. Udo; Yanovski, Jack A.; Fox, Caroline S.

2014-01-01

OBJECTIVE To describe the metabolic profile of individuals with objective binge eating (OBE) and to evaluate whether associations between OBE and metabolic risk factors are mediated by body mass index (BMI). DESIGN AND METHODS Participants from the Framingham Heart Study, Third Generation and Omni 2 cohorts (n = 3551, 53.1% women, mean age 46.4 years) were screened for binge eating. We used multivariable-adjusted regression models to examine the associations of OBE with metabolic risk factors. RESULTS The prevalence of OBE was 4.8% in women and 4.9% in men. Compared to non-binge eating, OBE was associated with higher odds of hypertension (OR 1.85, 95% CI 1.32–2.60), hypertriglyceridemia (OR 1.42, 95% CI 1.01–2.01), low HDL (OR 1.70, 95% CI 1.18–2.44), insulin resistance (OR 3.18, 95% CI 2.25–4.50) and metabolic syndrome (OR 2.75, 95% CI 1.94–3.90). Fasting glucose was 7.2 mg/dl higher in those with OBE (p=0.0001). Individuals with OBE had more visceral, subcutaneous and liver fat. Most of these associations were attenuated with adjustment for BMI, with the exception of fasting glucose. CONCLUSIONS Binge eating is associated with a high burden of metabolic risk factors. Much of the associated risk appears to be mediated by BMI, with the exception of fasting glucose. PMID:25136837

Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study.

PubMed

Hruby, Adela; O'Donnell, Christopher J; Jacques, Paul F; Meigs, James B; Hoffmann, Udo; McKeown, Nicola M

2014-01-01

The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying cardiovascular disease. Little is known about the association of magnesium intake and atherosclerotic calcification in humans. We examined cross-sectional associations of self-reported total (dietary and supplemental) magnesium intake estimated by food frequency questionnaire with CAC and AAC in participants of the Framingham Heart Study who were free of cardiovascular disease and underwent Multi-Detector Computed Tomography (MDCT) of the heart and abdomen (n = 2,695; age: 53 ± 11 years), using multivariate-adjusted Tobit regression. CAC and AAC were quantified using modified Agatston scores (AS). Models were adjusted for age, sex, body mass index, smoking status, systolic blood pressure, fasting insulin, total-to-high-density lipoprotein cholesterol ratio, use of hormone replacement therapy (women only), menopausal status (women only), treatment for hyperlipidemia, hypertension, cardiovascular disease prevention, or diabetes, as well as self-reported intake of calcium, vitamins D and K, saturated fat, fiber, alcohol, and energy. Secondary analyses included logistic regressions of CAC and AAC outcomes as cut-points (AS >0 and AS ≥90th percentile for age and sex), as well as sex-stratified analyses. In fully adjusted models, a 50-mg/day increment in self-reported total magnesium intake was associated with 22% lower CAC (p < 0.001) and 12% lower AAC (p = 0.07). Consistent with these observations, the odds of having any CAC were 58% lower (p trend: <0.001) and any AAC were 34% lower (p trend: 0.01), in those with the highest compared to those with the lowest magnesium intake. Stronger inverse associations were observed in women than in men. In community-dwelling participants free of cardiovascular disease, self-reported magnesium intake was inversely associated with arterial calcification, which may play a contributing role in magnesium's protective associations in stroke and fatal coronary heart disease. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Assessment of the 10-year risk of coronary heart disease events for Qatar Petroleum's firefighters and non-firefighter staff in Qatar.

PubMed

Mochtar, I; Hooper, R W

2012-02-01

Coronary heart disease is a major public health problem worldwide and firefighters may be at particular occupational risk. In a cross-sectional study in Ras Laffan Industrial City, Qatar, we assessed the 10-year risk of coronary heart disease events for 369 Qatar Petroleum staff at their periodic medical examination. The subjects of the study (all males) were divided into firefighters and non-firefighters groups. Based on the Framingham risk score calculations, 69.9% of the subjects were categorized as low risk, 27.1% as intermediate risk and 2.9% as high risk. None of the firefighters was categorized as high risk, 15.5% were intermediate and the rest were low risk. In the whole group, low high-density lipoprotein cholesterol was the most prevalent risk factor (68.8%), followed by hypertension (32.0%) and smoking (15.4%). The mean risk of developing coronary heart disease in firefighters [6.5% (SD 3.7%)] was significantly lower than in non-firefighters 19.5% (SD 6.5%)].

Physical activity, the Framingham risk score and risk of coronary heart disease in men and women of the EPIC-Norfolk study.

PubMed

Arsenault, Benoit J; Rana, Jamal S; Lemieux, Isabelle; Després, Jean-Pierre; Wareham, Nicholas J; Kastelein, John J P; Boekholdt, S Matthijs; Khaw, Kay-Tee

2010-03-01

Test the hypothesis that considering leisure-time and work-related physical activity habits in addition to the Framingham risk score (FRS) would result into better classification of coronary heart disease (CHD) risk than FRS alone. Prospective, population-based study of 9564 men and 12165 women aged 45-79 years followed for an average of 11.4 years. A modified FRS which takes into account physical activity (evaluated using a validated lifestyle questionnaire taking into account leisure-time and work-related physical activity) was computed. During follow-up, 2191 CHD events occurred. Among 3369 men who were classified as intermediate risk (event rate of 12.4%) according to the FRS, 413 were reclassified into the low-risk category and 279 were reclassified into the high-risk category after modification of the FRS. After reclassification of these men, CHD event rate was of 5.3% and 18.6%, respectively for men classified at low and high CHD risk. Among 4766 women initially classified as intermediate risk (event rate of 8.4%), 1282 were reclassified into the low-risk category whereas 1071 women were reclassified into the high-risk category. After reclassification of these women, CHD event rate was of 6.8% and 12.2%, respectively for women classified at low and high CHD risk. Results of the present study suggest that asking simple questions about leisure-time and work-related physical activity which can be rapidly obtained by any physician at no cost could be helpful in the estimation of patients' CHD risk.

Relations of arterial stiffness with postural change in mean arterial pressure in middle-aged adults: The Framingham Heart Study

PubMed Central

Torjesen, Alyssa; Cooper, Leroy L.; Rong, Jian; Larson, Martin G.; Hamburg, Naomi M.; Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.; Mitchell, Gary F.

2017-01-01

Impaired regulation of blood pressure upon standing can lead to adverse outcomes, including falls, syncope, and disorientation. Mean arterial pressure typically increases upon standing; however, an insufficient increase or a decline in mean arterial pressure upon standing may result in decreased cerebral perfusion. Orthostatic hypotension has been reported in older people with increased arterial stiffness, whereas the association between orthostatic change in mean arterial pressure and arterial stiffness in young-to-middle aged individuals has not been examined. We analyzed orthostatic blood pressure response and comprehensive hemodynamic data in 3205 participants (1693 [53%] women) in the Framingham Heart Study Third Generation cohort. Participants were predominantly middle-aged (mean age: 46±9 years). Arterial stiffness was assessed using carotid-femoral pulse wave velocity, forward pressure wave amplitude, and characteristic impedance of the aorta. Adjusting for standard cardiovascular disease risk factors, orthostatic change in mean arterial pressure (6.9±7.7 mm Hg) was inversely associated with carotid-femoral pulse wave velocity (partial correlation, rp = −0.084, P<0.0001), forward wave amplitude (rp = −0.129, P<0.0001), and characteristic impedance (rp = −0.094, P<0.0001). The negative relation between forward wave amplitude and change in mean arterial pressure on standing was accentuated in women (P=0.002 for sex interaction). Thus, higher aortic stiffness was associated with a blunted orthostatic increase in mean arterial pressure, even in middle age. The clinical implications of these findings warrant further study. PMID:28264924

Genome-wide association and network analysis of lung function in the Framingham Heart Study.

PubMed

Liao, Shu-Yi; Lin, Xihong; Christiani, David C

2014-09-01

Single nucleotide polymorphisms have been found to be associated with pulmonary function using genome-wide association studies. However, lung function is a complex trait that is likely to be influenced by multiple gene-gene interactions besides individual genes. Our goal is to build a cellular network to explore the relationship between pulmonary function and genotypes by combining SNP level and network analyses using longitudinal lung function data from the Framingham Heart Study. We analyzed 2,698 genotyped participants from the Offspring cohort that had an average of 3.35 spirometry measurements per person for a mean length of 13 years. Repeated forced expiratory volume in one second (FEV1 ) and the ratio of FEV1 to forced vital capacity (FVC) were used as outcomes. Data were analyzed using linear-mixed models for the association between lung function and alleles by accounting for the correlation among repeated measures over time within the same subject and within-family correlation. Network analyses were performed using dmGWAS and validated with data from the Third Generation cohort. Analyses identified SMAD3, TGFBR2, CD44, CTGF, VCAN, CTNNB1, SCGB1A1, PDE4D, NRG1, EPHB1, and LYN as contributors to pulmonary function. Most of these genes were novel that were not found previously using solely SNP-level analysis. These novel genes are involving the transforming growth factor beta (TGFB)-SMAD pathway, Wnt/beta-catenin pathway, etc. Therefore, combining SNP-level and network analyses using longitudinal lung function data is a useful alternative strategy to identify risk genes. © 2014 WILEY PERIODICALS, INC.

A health economic model to determine the long-term costs and clinical outcomes of raising low HDL-cholesterol in the prevention of coronary heart disease.

PubMed

Roze, S; Liens, D; Palmer, A; Berger, W; Tucker, D; Renaudin, C

2006-12-01

The aim of this study was to describe a health economic model developed to project lifetime clinical and cost outcomes of lipid-modifying interventions in patients not reaching target lipid levels and to assess the validity of the model. The internet-based, computer simulation model is made up of two decision analytic sub-models, the first utilizing Monte Carlo simulation, and the second applying Markov modeling techniques. Monte Carlo simulation generates a baseline cohort for long-term simulation by assigning an individual lipid profile to each patient, and applying the treatment effects of interventions under investigation. The Markov model then estimates the long-term clinical (coronary heart disease events, life expectancy, and quality-adjusted life expectancy) and cost outcomes up to a lifetime horizon, based on risk equations from the Framingham study. Internal and external validation analyses were performed. The results of the model validation analyses, plotted against corresponding real-life values from Framingham, 4S, AFCAPS/TexCAPS, and a meta-analysis by Gordon et al., showed that the majority of values were close to the y = x line, which indicates a perfect fit. The R2 value was 0.9575 and the gradient of the regression line was 0.9329, both very close to the perfect fit (= 1). Validation analyses of the computer simulation model suggest the model is able to recreate the outcomes from published clinical studies and would be a valuable tool for the evaluation of new and existing therapy options for patients with persistent dyslipidemia.

Higher dietary anthocyanin and flavonol intakes are associated with anti-inflammatory effects in a population of US adults.

PubMed

Cassidy, Aedin; Rogers, Gail; Peterson, Julia J; Dwyer, Johanna T; Lin, Honghuang; Jacques, Paul F

2015-07-01

Although growing evidence from trials and population-based studies has supported a protective role for flavonoids in relation to risk of certain chronic diseases, the underlying mechanisms remain unclear. Several previous studies focused on individual inflammatory biomarkers, but because of the limited specificity of any individual marker, an assessment of a combination of biomarkers may be more informative. We used an inflammation score (IS) that integrated 12 individual inflammatory biomarkers for the examination of associations with intakes of different flavonoid classes. The study was a cross-sectional analysis of 2375 Framingham Heart Study Offspring Cohort participants. Intakes of total flavonoids and their classes (anthocyanins, flavonols, flavanones, flavan-3-ols, polymers, and flavones) were calculated from validated food-frequency questionnaires. Individual inflammatory biomarkers were ranked, standardized, and summed to derive an overall IS and subgroup scores of functionally related biomarkers. In multivariate analyses, an inverse association between higher anthocyanin and flavonol intakes and IS was observed with a mean ± SE difference between quintile categories 5 and 1 of -1.48 ± 0.32 (P-trend ≤ 0.001) and -0.72 ± 0.33 (P-trend = 0.01), respectively. Results remained significant after additional adjustment for physical activity and vitamin C and fruit and vegetable intakes. Higher anthocyanin intake was inversely associated with all biomarker subgroups, whereas higher flavonol intake was associated only with lower cytokine and oxidative stress biomarker concentrations. In food-based analyses, higher intakes of apples and pears, red wine, and strawberries were associated with a lower IS with differences between quintiles 5 and 1 of -1.02 ± 0.43 (P = 0.006), -1.73 ± 0.39 (P < 0.001), and -0.44 ± 0.88 (P = 0.02), respectively. Although intakes of other classes were not associated with a reduction in overall IS, higher intakes of flavan-3-ols and their polymers were associated with a significant reduction in oxidative stress biomarkers. These findings provide evidence to suggest that an anti-inflammatory effect may be a key component underlying the reduction in risk of certain chronic diseases associated with higher intakes of anthocyanins and flavonols. The Framingham Offspring Study was registered at clinicaltrials.gov as NCT00005121 (Framingham Heart Study). © 2015 American Society for Nutrition.

Long working hours may increase risk of coronary heart disease.

PubMed

Kang, Mo-Yeol; Cho, Soo-Hun; Yoo, Min-Sang; Kim, Taeshik; Hong, Yun-Chul

2014-11-01

To evaluate the association between long working hours and risk of coronary heart disease (CHD) estimated by Framingham risk score (FRS) in Korean adults. This study evaluated adult participants in Korean National Health and Nutrition Examination Survey IV (2007-2009). After inclusion and exclusion criteria were applied, the final sample size for this study model was 8,350. Subjects were asked about working hours and health status. Participants also completed physical examinations and biochemical measurement necessary for estimation of FRS. Multiple logistic regression was conducted to investigate the association between working hours and 10-year risk for CHD estimated by FRS. Compared to those who work 31-40 hr, significantly higher 10-year risk was estimated among subjects working longer hours. As working hours increased, odds ratio (OR) for upper 10 percent of estimated 10-year risk for CHD was increased up to 1.94. Long working hours are significantly related to risk of coronary heart disease. © 2014 Wiley Periodicals, Inc.

Strategy and model building in the fourth dimension: a null model for genotype x age interaction as a Gaussian stationary stochastic process.

PubMed

Diego, Vincent P; Almasy, Laura; Dyer, Thomas D; Soler, Júlia M P; Blangero, John

2003-12-31

Using univariate and multivariate variance components linkage analysis methods, we studied possible genotype x age interaction in cardiovascular phenotypes related to the aging process from the Framingham Heart Study. We found evidence for genotype x age interaction for fasting glucose and systolic blood pressure. There is polygenic genotype x age interaction for fasting glucose and systolic blood pressure and quantitative trait locus x age interaction for a linkage signal for systolic blood pressure phenotypes located on chromosome 17 at 67 cM.

Thoracic Kyphosis and Physical Function: The Framingham Study.

PubMed

Lorbergs, Amanda L; Murabito, Joanne M; Jarraya, Mohamed; Guermazi, Ali; Allaire, Brett T; Yang, Laiji; Kiel, Douglas P; Cupples, L Adrienne; Bouxsein, Mary L; Travison, Thomas G; Samelson, Elizabeth J

2017-10-01

To evaluate the association between thoracic kyphosis and physical function. Prospective cohort. Framingham, Massachusetts. Framingham Heart Study Offspring and Third Generation cohort members who had computed tomography (CT) performed between 2002 and 2005 and physical function assessed a mean 3.4 years later (N = 1,100; mean age 61 ± 8, range 50-85). Thoracic kyphosis (Cobb angle, T4-T12) was measured in degrees using supine CT scout images. Participants were categorized according to Cobb angle to compare those in the highest quartile (Q4, most-severe kyphosis) with those in the lowest quartiles (Q1-Q3). Quick walking speed (m/s), chair-stand time (seconds), grip strength (kg), and self-reported impairments were assessed using standardized procedures. Analyses were adjusted for age, height, weight, smoking, follow-up time, vertebral fractures, and prevalent spinal degeneration. Thoracic kyphosis was not associated with physical function in women or men, and these results were consistent in those younger than 65 and those aged 65 and older. For example, walking speed was similar in adults younger than 65 with and without severe kyphosis (women, Q4: 1.38 m/s, Q1-Q3: 1.40 m/s, P = .69; men, Q4: 1.65 m/s, Q1-Q3: 1.60 m/s; P = .39). In healthy relatively high-functioning women and men, kyphosis severity was not associated with subsequent physical function. Individuals at risk of functional decline cannot be targeted based on supine CT thoracic curvature measures alone. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

A Study of Correlation of Neck Circumference with Framingham Risk Score as a Predictor of Coronary Artery Disease.

PubMed

Koppad, Anand K; Kaulgud, Ram S; Arun, B S

2017-09-01

It has been observed that metabolic syndrome is risk factor for Coronary Artery Disease (CAD) and exerts its effects through fat deposition and vascular aging. CAD has been acknowledged as a leading cause of death. In earlier studies, the metabolic risk has been estimated by Framingham risk score. Recent studies have shown that Neck Circumference (NC) has a good correlation with other traditional anthropometric measurements and can be used as marker of obesity. It also correlates with Framingham risk score, which is slightly more sophisticated measure of CAD risk. To assess the risk of CAD in a subject based on NC and to correlate the NC to Framingham risk score. The present cross-sectional study, done at Karnataka Institute of Medical Sciences, Hubli, Karnataka, India, includes 100 subjects. The study duration was of one year from 1 st January 2015 to 31 st December 2015. Anthropometric indices Body Mass Index (BMI) and NC were correlated with 10 year CAD risk as calculated by Framingham risk score. The correlation between BMI, NC, vascular age and Framingham risk score was calculated using Karl Pearson's correlation method. NC has a strong correlation with 10 year CAD risk (p≤0.001). NC was significantly greater in males as compared to females (p≤0.001). Males had greater risk of cardiovascular disease as reflected by higher 10 year Framingham risk score (p≤0.0035). NC gives simple and easy prediction of CAD risk and is more reliable than traditional risk markers like BMI. NC correlates positively with 10 year Framingham risk score.

A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.

PubMed

Kalsbeek, Anya; Veenstra, Jenna; Westra, Jason; Disselkoen, Craig; Koch, Kristin; McKenzie, Katelyn A; O'Bott, Jacob; Vander Woude, Jason; Fischer, Karen; Shearer, Greg C; Harris, William S; Tintle, Nathan L

2018-01-01

Recent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Heart Study Offspring Cohort and FA levels, we used data from 2,400 of these individuals for whom red blood cell FA profiles, dietary information and genotypes are available, and then conducted a genome-wide evaluation of potential genetic variants associated with 22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our analysis found nine previously identified loci associated with FA levels (FADS, ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and RAB3GAP1/MCM6), while identifying four novel loci. The latter include an association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase activity, as well as two loci associated with less well understood proteins. Thus, the inclusion of dietary covariates had a modest impact, helping to uncover four additional loci. While genome-wide association studies continue to uncover additional genes associated with circulating FA levels, much of the heritable risk is yet to be explained, suggesting the potential role of rare genetic variation, epistasis and gene-environment interactions on FA levels as well. Further studies are needed to continue to understand the complex genetic picture of FA metabolism and synthesis.

A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort

PubMed Central

Veenstra, Jenna; Westra, Jason; Disselkoen, Craig; Koch, Kristin; McKenzie, Katelyn A.; O’Bott, Jacob; Vander Woude, Jason; Fischer, Karen; Shearer, Greg C.; Harris, William S.; Tintle, Nathan L.

2018-01-01

Recent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Heart Study Offspring Cohort and FA levels, we used data from 2,400 of these individuals for whom red blood cell FA profiles, dietary information and genotypes are available, and then conducted a genome-wide evaluation of potential genetic variants associated with 22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our analysis found nine previously identified loci associated with FA levels (FADS, ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and RAB3GAP1/MCM6), while identifying four novel loci. The latter include an association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase activity, as well as two loci associated with less well understood proteins. Thus, the inclusion of dietary covariates had a modest impact, helping to uncover four additional loci. While genome-wide association studies continue to uncover additional genes associated with circulating FA levels, much of the heritable risk is yet to be explained, suggesting the potential role of rare genetic variation, epistasis and gene-environment interactions on FA levels as well. Further studies are needed to continue to understand the complex genetic picture of FA metabolism and synthesis. PMID:29652918

Cardiovascular risk assessment of South Asians in a religious setting: a feasibility study.

PubMed

Rao, N; Eastwood, S V; Jain, A; Shah, M; Leurent, B; Harvey, D; Robertson, L; Walters, K; Persaud, J W; Mikhailidis, D P; Nair, D R

2012-03-01

South Asians in the UK have high cardiovascular disease (CVD) mortality. Therefore, this population is likely to benefit from screening programmes. To address this issue, an initiative was set up between the Royal Free Hampstead NHS Trust, H.E.A.R.T. UK and two Hindu temples in North London to provide screening for CVD risk factors in the community. A total of 434 individuals of Gujarati Indian origin were screened. Measurements included anthropometry, blood pressure and lipid profiles. Three different scoring systems: Framingham, Joint British Societies' 2 and QRISK2 were used to estimate CVD risk. At least one modifiable CVD risk factor was present in 92% of the individuals screened; 52% were hypertensive, 40% were obese, 75% had central adiposity and 10% had total cholesterol/high density lipoprotein cholesterol ratio > 6. In addition, 37% of a subset of 104 individuals with a fasting sample fulfilled the diagnostic criteria for metabolic syndrome. Overall, 15% of participants screened had a 10-year CV risk score > 20% using QRISK2. The three risk score calculators showed moderate agreement: QRISK2 and JBS2 (kappa 0.61, 95% CI 0.54-0.67), QRISK2 and Framingham (kappa 0.63, 95% CI 0.57-0.70) and JBS2 and Framingham (kappa 0.70, 95% CI 0.64-0.75). A high prevalence of modifiable risk factors for CVD was detected in the population screened. © 2011 Blackwell Publishing Ltd.

Performance of the Framingham and SCORE cardiovascular risk prediction functions in a non-diabetic population of a Spanish health care centre: a validation study

PubMed Central

Barroso, Lourdes Cañón; Muro, Eloísa Cruces; Herrera, Natalio Díaz; Ochoa, Gerardo Fernández; Hueros, Juan Ignacio Calvo; Buitrago, Francisco

2010-01-01

Objective To analyse the 10-year performance of the original Framingham coronary risk function and of the SCORE cardiovascular death risk function in a non-diabetic population of 40–65 years of age served by a Spanish healthcare centre. Also, to estimate the percentage of patients who are candidates for antihypertensive and lipid-lowering therapy. Design Longitudinal, observational study of a retrospective cohort followed up for 10 years. Setting Primary care health centre. Patients A total of 608 non-diabetic patients of 40–65 years of age (mean 52.8 years, 56.7% women), without evidence of cardiovascular disease were studied. Main outcome measures Coronary risk at 10 years from the time of their recruitment, using the tables based on the original Framingham function, and of their 10-year risk of fatal cardiovascular disease using the SCORE tables. Results The actual incidence rates of coronary and fatal cardiovascular events were 7.9% and 1.5%, respectively. The original Framingham equation over-predicted risk by 64%, while SCORE function over-predicted risk by 40%, but the SCORE model performed better than the Framingham one for discrimination and calibration statistics. The original Framingham function classified 18.3% of the population as high risk and SCORE 9.2%. The proportions of patients who would be candidates for lipid-lowering therapy were 31.0% and 23.8% according to the original Framingham and SCORE functions, respectively, and 36.8% and 31.2% for antihypertensive therapy. Conclusion The SCORE function showed better values than the original Framingham function for each of the discrimination and calibration statistics. The original Framingham function selected a greater percentage of candidates for antihypertensive and lipid-lowering therapy. PMID:20873973

Age at Natural Menopause and Risk of Ischemic Stroke: The Framingham Heart Study

PubMed Central

Lisabeth, Lynda D; Beiser, Alexa S; Brown, Devin L; Murabito, Joanne M; Kelly-Hayes, Margaret; Wolf, Philip A

2009-01-01

Background Women have increased lifetime stroke risk and more disabling strokes compared with men. Insights into the association between menopause and stroke could lead to new prevention strategies for women. The objective of this study was to examine the association of age at natural menopause with ischemic stroke risk in the Framingham Heart Study. Methods Participants included women who survived stroke-free until age 60, experienced natural menopause, did not use estrogen prior to menopause, and who had complete data (n=1,430). Participants were followed until first ischemic stroke, death, or end of follow-up (2006). Age at natural menopause was self-reported. Cox proportional hazards models were used to examine the association between age at natural menopause (<42, 42-54, ≥55) and ischemic stroke risk adjusted for age, systolic blood pressure, atrial fibrillation, diabetes, current smoking, cardiovascular disease and estrogen use. Results There were 234 ischemic strokes identified. Average age at menopause was 49 years (sd=4). Women with menopause at ages 42-54 (HR=0.50; 95% CI:0.29-0.89) and at ages ≥55 (HR=0.31; 95% CI:0.13-0.76) had lower stroke risk compared with those with menopause <42 years adjusted for covariates. Women with menopause before age 42 had twice the stroke risk compared to all other women (HR=2.03; 95% CI: 1.16-3.56). Conclusion In this prospective study, age at natural menopause before age 42 was associated with increased ischemic stroke risk. Future stroke studies with measures of endogenous hormones are needed to inform the underlying mechanisms so that novel prevention strategies for mid-life women can be considered. PMID:19233935

A Revised Framingham Stroke Risk Profile to Reflect Temporal Trends

PubMed Central

Dufouil, Carole; Beiser, Alexa; McLure, Leslie A.; Wolf, Philip A.; Tzourio, Christophe; Howard, Virginia J; Westwood, Andrew J.; Himali, Jayandra J.; Sullivan, Lisa; Aparicio, Hugo J.; Kelly-Hayes, Margaret; Ritchie, Karen; Kase, Carlos S.; Pikula, Aleksandra; Romero, Jose R.; D’Agostino, Ralph B.; Samieri, Cécilia; Vasan, Ramachandran S.; Chêne, Genevieve; Howard, George; Seshadri, Sudha

2017-01-01

Background Age-adjusted stroke incidence has decreased over the past 50 years, likely due to changes in the prevalence and impact of various stroke risk factors. An updated version of the Framingham Stroke Risk Profile (FSRP) might better predict current risks in the Framingham Heart Study (FHS) and other cohorts. We compared the accuracy of the standard (Old), and of a revised (New) version of the FSRP in predicting the risk of all-stroke and ischemic stroke, and validated this new FSRP in two external cohorts, the 3 Cities (3C) and REGARDS studies. Methods We computed the old FSRP as originally described, and a new model that used the most recent epoch-specific risk factors' prevalence and hazard-ratios for persons ≥ 55 years and for the subsample ≥ 65 years (to match the age range in REGARDS and 3C studies respectively), and compared the efficacy of these models in predicting 5- and 10-year stroke risks. Results The new FSRP was a better predictor of current stroke risks in all three samples than the old FSRP (Calibration chi-squares of new/old FSRP: in men 64.0/12.1, 59.4/30.6 and 20.7/12.5; in women 42.5/4.1, 115.4/90.3 and 9.8/6.5 in FHS, REGARDS and 3C, respectively). In the REGARDS, the new FSRP was a better predictor among whites compared to blacks. Conclusions A more contemporaneous, new FSRP better predicts current risks in 3 large community samples and could serve as the basis for examining geographic and racial differences in stroke risk and the incremental diagnostic utility of novel stroke risk factors. PMID:28159800

Growth mixture modelling in families of the Framingham Heart Study

PubMed Central

2009-01-01

Growth mixture modelling, a less explored method in genetic research, addresses unobserved heterogeneity in population samples. We applied this technique to longitudinal data of the Framingham Heart Study. We examined systolic blood pressure (BP) measures in 1060 males from 692 families and detected three subclasses, which varied significantly in their developmental trajectories over time. The first class consisted of 60 high-risk individuals with elevated BP early in life and a steep increase over time. The second group of 131 individuals displayed first normal BP, but showed a significant increase over time and reached high BP values late in their life time. The largest group of 869 individuals could be considered a normative group with normal BP on all exams. To identify genetic modulators for this phenotype, we tested 2,340 single-nucleotide polymorphisms on chromosome 8 for association with the class membership probabilities of our model. The probability of being in Class 1 was significantly associated with a very rare variant (rs1445404) present in only four individuals from four different families located in the coding region of the gene EYA (eyes absent homolog 1 in Drosophila) (p = 1.39 × 10-13). Mutations in EYA are known to cause brachio-oto-renal syndrome, as well as isolated renal malformations. Renal malformations could cause high BP early in life. This result awaits replication; however, it suggests that analyzing genetic data stratified for high-risk subgroups defined by a unique development over time could be useful for the detection of rare mutations in common multi-factorial diseases. PMID:20017979

Impact of Age, Sex and Indexation Method on MR Left Ventricular Reference Values in the Framingham Heart Study Offspring Cohort

PubMed Central

Yeon, Susan B.; Salton, Carol J.; Gona, Philimon; Chuang, Michael L.; Blease, Susan J.; Han, Yuchi; Tsao, Connie W.; Danias, Peter G.; Levy, Daniel; O’Donnell, Christopher J.; Manning, Warren J.

2014-01-01

Purpose To determine normative values for left ventricular (LV) volumes, mass, concentricity and ejection fraction (EF) and investigate associations between sex, age and body size with LV parameters in community dwelling adults. Materials and Methods 1794 Framingham Heart Study Offspring cohort members underwent LV short-axis oriented, contiguous multislice ciné SSFP MR of the left ventricle; from these a healthy referent group (N=852, 61±9 years, 40% men) free of clinical cardiac disease and hypertension (SBP<140, DBP<90 mmHg, never used antihypertensive medication ≥ 30 years prior to scanning) was identified. Referent participants were stratified by sex and age group (≤55, 56-65, >65 years); LV parameters were indexed to measures of body size. Results Men have greater LV volumes and mass than women both before and after indexation to height, powers of height, and body surface area (p<0.01 all), but indexation to fat-free mass yielded greater LV volume and mass in women. In both sexes, LV volumes and mass decrease with advancing age, though indexation attenuates this association. LVEF is greater in women than men (68±5% vs. 66±5%, p<0.01) and increases with age in both sexes (p<0.05). Conclusion Among non-hypertensive adults free of cardiac disease, men have greater LV volumes and mass with sex differences generally persisting after indexation to body size. LV volumes and mass tend to decrease with greater age in both sexes. Female sex and advanced age were both associated with greater LVEF. PMID:24817313

Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and alzheimer disease: results from the Framingham Heart Study.

PubMed

van Himbergen, Thomas M; Beiser, Alexa S; Ai, Masumi; Seshadri, Sudha; Otokozawa, Seiko; Au, Rhoda; Thongtang, Nuntakorn; Wolf, Philip A; Schaefer, Ernst J

2012-05-01

To investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A(2) levels) to the risk of developing Alzheimer disease (AD) and all-cause dementia. Prospective cohort study. Dementia-free Framingham Heart Study participants had sera measured for these biomarkers at the 19th biennial examination (1985-1988) and were followed up prospectively for the development of AD and all-cause dementia. Eight hundred forty (541 women, median age of 76 years) subjects participated in the study. We used sex-pooled and sex-specific multivariable Cox proportional hazards models adjusted for age, education, body mass index, recent change in weight, APOE ε4 allele status, and plasma docosahexaenoic acid levels to determine association of these biomarkers with the development of all-cause dementia and AD. Over a mean follow-up period of 13 years, 159 persons developed dementia (including 125 with AD). After adjustment for other risk factors, only adiponectin in women was associated with an increased risk of all-cause dementia (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.00-1.66; P=.054) and AD (HR, 1.33; 95% CI, 1.00-1.76; P=.050) per 1-SD increase in adiponectin level. Women with baseline adiponectin values more than the median had a higher risk of all-cause dementia (HR, 1.63; 95% CI, 1.03-2.56; P=.04) and AD (HR, 1.87; 95% CI, 1.13-3.10; P=.01) as compared with those with values less than the median. In women, increased plasma adiponectin levels are an independent risk factor for the development of both all-cause dementia and AD.

Relation of Pericardial Fat, Intrathoracic Fat, and Abdominal Visceral Fat with Incident Atrial Fibrillation (From the Framingham Heart Study)

PubMed Central

Lee, Jane J.; Yin, Xiaoyan; Hoffmann, Udo; Fox, Caroline S.; Benjamin, Emelia J.

2016-01-01

Obesity is associated with increased risk of developing atrial fibrillation (AF). Different fat depots may have differential associations with cardiac pathology. We examined the longitudinal associations between pericardial, intrathoracic, and visceral fat with incident AF. We studied Framingham Heart Study Offspring and Third Generation Cohorts who participated in the multi-detector computed tomography sub-study examination 1. We constructed multivariable-adjusted Cox proportional hazard models for risk of incident AF. Body mass index (BMI) was included in the multivariable-adjusted model as a secondary adjustment. We included 2,135 participants (53.3% women; mean age 58.8 years). During a median follow-up of 9.7 years, we identified 162 cases of incident AF. Across the increasing tertiles of pericardial fat volume, age- and sex-adjusted incident AF rate per 1000 person-years of follow-up were 8.4, 7.5, and 10.2. Based on an age- and sex-adjusted model, greater pericardial fat [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.03-1.34] and intrathoracic fat (HR 1.24, 95% CI 1.06-1.45) were associated with increased risk of incident AF. The HRs (95% CI) for incident AF were 1.13 (0.99-1.30) for pericardial fat, 1.19 (1.01-1.40) for intrathoracic fat, and 1.09 (0.93-1.28) for abdominal visceral fat after multivariable adjustment. After additional adjustment of BMI, none of the associations remained significant (all p>0.05). Our findings suggest that cardiac ectopic fat depots may share common risk factors with AF, which may have led to a lack of independence in the association between pericardial fat with incident AF. PMID:27666172

Ethnicity and the association between anthropometric indices of obesity and cardiovascular risk in women: a cross-sectional study

PubMed Central

Goh, Louise G H; Dhaliwal, Satvinder S; Welborn, Timothy A; Lee, Andy H; Della, Phillip R

2014-01-01

Objectives The objectives of this study were to determine whether the cross-sectional associations between anthropometric obesity measures, body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR), and calculated 10-year cardiovascular disease (CVD) risk using the Framingham and general CVD risk score models, are the same for women of Australian, UK and Ireland, North European, South European and Asian descent. This study would investigate which anthropometric obesity measure is most predictive at identifying women at increased CVD risk in each ethnic group. Design Cross-sectional data from the National Heart Foundation Risk Factor Prevalence Study. Setting Population-based survey in Australia. Participants 4354 women aged 20–69 years with no history of heart disease, diabetes or stroke. Most participants were of Australian, UK and Ireland, North European, South European or Asian descent (97%). Outcome measures Anthropometric obesity measures that demonstrated stronger predictive ability of identifying women at increased CVD risk and likelihood of being above the promulgated treatment thresholds of various risk score models. Results Central obesity measures, WC and WHR, were better predictors of cardiovascular risk. WHR reported a stronger predictive ability than WC and BMI in Caucasian women. In Northern European women, BMI was a better indicator of risk using the general CVD (10% threshold) and Framingham (20% threshold) risk score models. WC was the most predictive of cardiovascular risk among Asian women. Conclusions Ethnicity should be incorporated into CVD assessment. The same anthropometric obesity measure cannot be used across all ethnic groups. Ethnic-specific CVD prevention and treatment strategies need to be further developed. PMID:24852299

[Geriatric medicine].

PubMed

Lajoso, Sonia; Launay, Cyrille P; Poloni, Barbara; Büla, Christophe; Gold, Gabriel; Lang, Pierre-Olivier

2017-01-11

In 2016, consequences, contributing factors, and prevention of inappropriate drug prescribing were investigated. Two studies lift the veil on unexplained falls and syncope. A meta-analysis questions the need to adapting transfusion's threshold to comorbidities, and another one the performance of screening for swallowing disorders. The Framingham Heart Study reports the declining of the incidence of vascular dementia. The role played by microbleeds in cognitive deterioration was investigated and aducanumab showed encouraging effect in Alzheimer's disease. When vaccination against influenza for health workers in nursing home was challenged by a meta-analysis this recommendation must be followed. Vaccines against shingles are effective and safe, and a study confirms the efficacy of the HZ7su among 70+.

Genome-Wide Interaction Study of Omega-3 PUFAs and Other Fatty Acids on Inflammatory Biomarkers of Cardiovascular Health in the Framingham Heart Study.

PubMed

Veenstra, Jenna; Kalsbeek, Anya; Westra, Jason; Disselkoen, Craig; Smith, Caren; Tintle, Nathan

2017-08-18

Numerous genetic loci have been identified as being associated with circulating fatty acid (FA) levels and/or inflammatory biomarkers of cardiovascular health (e.g., C-reactive protein). Recently, using red blood cell (RBC) FA data from the Framingham Offspring Study, we conducted a genome-wide association study of over 2.5 million single nucleotide polymorphisms (SNPs) and 22 RBC FAs (and associated ratios), including the four Omega-3 FAs (ALA, DHA, DPA, and EPA). Our analyses identified numerous causal loci. In this manuscript, we investigate the extent to which polyunsaturated fatty acid (PUFA) levels moderate the relationship of genetics to cardiovascular health biomarkers using a genome-wide interaction study approach. In particular, we test for possible gene-FA interactions on 9 inflammatory biomarkers, with 2.5 million SNPs and 12 FAs, including all Omega-3 PUFAs. We identified eighteen novel loci, including loci which demonstrate strong evidence of modifying the impact of heritable genetics on biomarker levels, and subsequently cardiovascular health. The identified genes provide increased clarity on the biological functioning and role of Omega-3 PUFAs, as well as other common fatty acids, in cardiovascular health, and suggest numerous candidate loci for future replication and biological characterization.

Kennedy Space Center Coronary Heart Disease Risk Screening Program

NASA Technical Reports Server (NTRS)

Tipton, David A.; Scarpa, Philip J.

1999-01-01

The number one cause of death in the U.S. is coronary heart disease (CHD). It is probably a major cause of death and disability in the lives of employees at Kennedy Space Center (KSC) as well. The KSC Biomedical Office used a multifactorial mathematical formula from the Framingham Heart Study to calculate CHD risk probabilities for individuals in a segment of the KSC population that required medical evaluation for job certification. Those assessed to be high-risk probabilities will be targeted for intervention. Every year, several thousand KSC employees require medical evaluations for job related certifications. Most medical information for these evaluations is gathered on-site at one of the KSC or Cape Canaveral Air Station (CCAS) medical clinics. The formula used in the Framingham Heart Study allows calculation of a person's probability of acquiring CHD within 10 years. The formula contains the following variables: Age, Diabetes, Smoking, Left Ventricular Hypertrophy, Blood Pressure (Systolic or Diastolic), Cholesterol, and HDL cholesterol. The formula is also gender specific. It was used to calculate the 10-year probabilities of CHD in KSC employees who required medical evaluations for job certifications during a one-year time frame. This KSC population was profiled and CHD risk reduction interventions could be targeted to those at high risk. Population risk could also be periodically reevaluated to determine the effectiveness of intervention. A 10-year CHD risk probability can be calculated for an individual quite easily while gathering routine medical information. An employee population's CHD risk probability can be profiled graphically revealing high risk segments of the population which can be targeted for risk reduction intervention. The small audience of NASA/contractor physicians, nurses and exercise/fitness professionals at the breakout session received the lecture very well. Approximately one third indicated by a show of hands that they would be interested in implementing a similar program at their NASA Center. Questions were asked pertaining to standardization for age, the validity of using the idealized male values also for the female population, and indications of the screening test's sensitivity and specificity.

Guideline-Based Statin Eligibility, Cancer Events, and Noncardiovascular Mortality in the Framingham Heart Study.

PubMed

Pursnani, Amit; Massaro, Joseph M; D'Agostino, Ralph B; O'Donnell, Christopher J; Hoffmann, Udo

2017-09-01

Purpose Cancer and cardiovascular disease share risk factors, and there is some evidence that statins reduce cancer mortality. We sought to determine the accuracy of the 2013 American College of Cardiology/American Heart Association statin eligibility criteria to identify individuals at a higher risk of developing cancer or of dying as a result of cancer or other noncardiovascular causes. Methods We included 2,196 participants (50.5 ± 8.1 years of age; 55% female) who were statin naïve and free of cancer at baseline from the offspring and third-generation cohorts of the community-based longitudinal Framingham Heart Study. Statin eligibility was determined per American College of Cardiology/American Heart Association guidelines, and subclinical coronary atherosclerosis was assessed by computed tomography. The primary outcome was incident cancer at a median of 10.0 years (interquartile range, 9.1-10.6 years) of follow-up, and secondary outcomes were cancer mortality and noncardiovascular mortality. Results The incident cancer rate was 11.2% (247 of 2,196), with 58 noncardiovascular deaths, including 39 cancer deaths (1.8%). Overall, 37% (812 of 2,196) were statin eligible. Incident cancer occurred in 125 (15%) of the 812 statin-eligible participants versus 122 (8.8%) of the 1,384 of noneligible participants (subdistribution hazard ratio [SDHR], 1.8 [1.4 to 2.3]; P < .001). Cancer mortality occurred in 34 (4.2%) of the 812 statin-eligible participants versus five (0.4%) of the 1,384 noneligible participants (SDHR, 12.1 [4.7 to 31]; P < .001). Noncardiovascular mortality occurred in 49 (6.0%) of the 812 statin-eligible participants versus nine (0.7%) of the 1,384 noneligible participants (SDHR, 10.1 [5.0 to 21]; P < .001). In stratified analyses, these findings were independent of any individual causative risk factor such as body mass index, age, or smoking status. Conclusion In this community-based primary prevention cohort, guideline-based statin eligibility accurately identified patients at a higher risk of developing cancer and cancer-related mortality. Shared risk profiles and potential benefits of statins between cancer and cardiovascular outcomes may provide a unique opportunity to improve population health.

Clinical Utility of Multimarker Genetic Risk Scores for Prediction of Incident Coronary Heart Disease: A Cohort Study Among Over 51 Thousand Individuals of European Ancestry.

PubMed

Iribarren, Carlos; Lu, Meng; Jorgenson, Eric; Martínez, Manuel; Lluis-Ganella, Carla; Subirana, Isaac; Salas, Eduardo; Elosua, Roberto

2016-12-01

We evaluated whether including multilocus genetic risk scores (GRSs) into the Framingham Risk Equation improves the predictive capacity, discrimination, and reclassification of asymptomatic individuals with respect to coronary heart disease (CHD) risk. We performed a cohort study among 51 954 European-ancestry members of a Northern California integrated healthcare system (67% female; mean age 59) free of CHD at baseline (2007-2008). Four GRSs were constructed using between 8 and 51 previously identified genetic variants. After a mean (±SD) follow-up of 5.9 (±1.5) years, 1864 incident CHD events were documented. All GRSs were linearly associated with CHD in a model adjusted by individual risk factors: hazard ratio (95% confidence interval) per SD unit: 1.21 (1.15-1.26) for GRS_8, 1.20 (1.15-1.26) for GRS_12, 1.23 (1.17-1.28) for GRS_36, and 1.23 (1.17-1.28) for GRS_51. Inclusion of the GRSs improved the C statistic (ΔC statistic =0.008 for GRS_8 and GRS_36; 0.007 for GRS_12; and 0.009 for GRS_51; all P<0.001). The net reclassification improvement was 5% for GRS_8, GRS_12, and GRS_36 and 4% for GRS_51 in the entire cohort and was (after correcting for bias) 9% for GRS_8 and GRS_12 and 7% for GRS_36 and GRS_51 when analyzing those classified as intermediate Framingham risk (10%-20%). The number required to treat to prevent 1 CHD after selectively treating with statins up-reclassified subjects on the basis of genetic information was 36 for GRS_8 and GRS_12, 41 for GRS_36, and 43 for GRS_51. Our results demonstrate significant and clinically relevant incremental discriminative/predictive capability of 4 multilocus GRSs for incident CHD among subjects of European ancestry. © 2016 American Heart Association, Inc.

Early-adulthood cardiovascular disease risk factor profiles among individuals with and without diabetes in the Framingham Heart Study.

PubMed

Preis, Sarah Rosner; Pencina, Michael J; Mann, Devin M; D'Agostino, Ralph B; Savage, Peter J; Fox, Caroline S

2013-06-01

Many studies of diabetes have examined risk factors at the time of diabetes diagnosis instead of considering the lifetime burden of adverse risk factor levels. We examined the 30-year cardiovascular disease (CVD) risk factor burden that participants have up to the time of diabetes diagnosis. Among participants free of CVD, incident diabetes cases (fasting plasma glucose ≥ 126 mg/dL or treatment) occurring at examinations 2 through 8 (1979-2008) of the Framingham Heart Study Offspring cohort were age- and sex-matched 1:2 to controls. CVD risk factors (hypertension, high LDL cholesterol, low HDL cholesterol, high triglycerides, obesity) were measured at the time of diabetes diagnosis and at time points 10, 20, and 30 years prior. Conditional logistic regression was used to compare risk factor levels at each time point between diabetes cases and controls. We identified 525 participants with new-onset diabetes who were matched to 1,049 controls (mean age, 60 years; 40% women). Compared with those without diabetes, individuals who eventually developed diabetes had higher levels of hypertension (odds ratio [OR], 2.2; P = 0.003), high LDL (OR, 1.5; P = 0.04), low HDL (OR, 2.1; P = 0.0001), high triglycerides (OR, 1.7; P = 0.04), and obesity (OR, 3.3; P < 0.0001) at time points 30 years before diabetes diagnosis. After further adjustment for BMI, the ORs for hypertension (OR, 1.9; P = 0.02) and low HDL (OR, 1.7; P = 0.01) remained statistically significant. CVD risk factors are increased up to 30 years before diagnosis of diabetes. These findings highlight the importance of a life course approach to CVD risk factor identification among individuals at risk for diabetes.

Trends in Dietary Fat Intake and High-Fat Foods from 1991-2008 in the Framingham Heart Study participants

PubMed Central

Vadiveloo, Maya; Scott, Marc; Quatromoni, Paula; Jacques, Paul; Parekh, Niyati

2014-01-01

Few longitudinal studies among US adults have evaluated long-term dietary fat intakes and compared them to national recommendations during the 2-decade period when the prevalence of obesity and insulin resistance increased substantively. We examined trends in dietary fat intake and rich dietary sources of fats in the Framingham Heart Study Offspring Cohort over a 17-year period. The cohort was established in 1971-75 with follow-up examinations approximately every 4 years. Dietary data were collected using a semi-quantitative food frequency questionnaire beginning in 1991 (Exam 5). We included 2,732 adults ages ≥25y with complete dietary data in at least three exams from 1991-2008. Descriptive statistics were generated using SASv9.3 and a repeated measures model was used to examine trends in macronutrient and food intake using R. Over 17-years of follow-up, the %energy from total fat and protein increased (27.3-29.8% energy and 16.8-18.0% energy respectively) and %energy from carbohydrate decreased (51.0-46.8% energy;p-trend<0.001). Increases were seen in all fat subtypes except for trans-fats, which decreased over time (p-trend<0.001). Trends were similar between sexes, although women had a greater increase in %energy from saturated fats and less reduction in %energy from trans-fats (p-interaction<0.05). Trends of fat intakes were similar across BMI categories. Weekly servings of cheese, eggs, ice cream desserts, nuts, butter, and sausages/processed meats increased, whereas intake of milk, margarine, poultry, confectioneries, chips and breads decreased(p-trend<0.001). In this cohort of predominantly Caucasian older adults, %energy from dietary fat increased over time but remained within national recommendations of <35% of total energy, on average. PMID:24047827

Pericardial Fat is Associated With Atrial Conduction: The Framingham Heart Study

PubMed Central

Friedman, Daniel J.; Wang, Na; Meigs, James B.; Hoffmann, Udo; Massaro, Joseph M.; Fox, Caroline S.; Magnani, Jared W.

2014-01-01

Background Obesity is associated with altered atrial electrophysiology and a prominent risk factor for atrial fibrillation. Body mass index, the most widely used adiposity measure, has been related to atrial electrical remodeling. We tested the hypothesis that pericardial fat is independently associated with electrocardiographic measures of atrial conduction. Methods and Results We performed a cross‐sectional analysis of 1946 Framingham Heart Study participants (45% women) to determine the relation between pericardial fat and atrial conduction as measured by P wave indices (PWI): PR interval, P wave duration (P‐duration), P wave amplitude (P‐amplitude), P wave area (P‐area), and P wave terminal force (P‐terminal). We performed sex‐stratified linear regression analyses adjusted for relevant clinical variables and ectopic fat depots. Each 1‐SD increase in pericardial fat was significantly associated with PR interval (β=1.7 ms, P=0.049), P‐duration (β=2.3 ms, P<0.001), and P‐terminal (β=297 μV·ms, P<0.001) among women; and P‐duration (β=1.2 ms, P=0.002), P‐amplitude (β=−2.5 μV, P<0. 001), and P‐terminal (β=160 μV·ms, P=0.002) among men. Among both sexes, pericardial fat was significantly associated with P‐duration in analyses additionally adjusting for visceral fat or intrathoracic fat; a similar but non‐significant trend existed with P‐terminal. Among women, pericardial fat was significantly associated with P wave area after adjustment for visceral and intrathoracic fat. Conclusions Pericardial fat is associated with atrial conduction as quantified by PWI, even with adjustment for extracardiac fat depots. Further studies are warranted to identify the mechanisms through which pericardial fat may modify atrial electrophysiology and promote subsequent risk for arrhythmogenesis. PMID:24595189

Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts.

PubMed

Ma, Jiantao; Fox, Caroline S; Jacques, Paul F; Speliotes, Elizabeth K; Hoffmann, Udo; Smith, Caren E; Saltzman, Edward; McKeown, Nicola M

2015-08-01

Non-alcoholic fatty liver disease affects ∼30% of US adults, yet the role of sugar-sweetened beverages and diet soda on these diseases remains unknown. We examined the cross-sectional association between intake of sugar-sweetened beverages or diet soda and fatty liver disease in participants of the Framingham Offspring and Third Generation cohorts. Fatty liver disease was defined using liver attenuation measurements generated from computed tomography in 2634 participants. Alanine transaminase concentration, a crude marker of fatty liver disease, was measured in 5908 participants. Sugar-sweetened beverage and diet soda intake were estimated using a food frequency questionnaire. Participants were categorized as either non-consumers or consumers (3 categories: 1 serving/month to <1 serving/week, 1 serving/week to <1 serving/day, and ⩾1 serving/day) of sugar-sweetened beverages or diet soda. After adjustment for age, sex, smoking status, Framingham cohort, energy intake, alcohol, dietary fiber, fat (% energy), protein (% energy), diet soda intake, and body mass index, the odds ratios of fatty liver disease were 1, 1.16 (0.88, 1.54), 1.32 (0.93, 1.86), and 1.61 (1.04, 2.49) across sugar-sweetened beverage consumption categories (p trend=0.04). Sugar-sweetened beverage consumption was also positively associated with alanine transaminase levels (p trend=0.007). We observed no significant association between diet soda intake and measures of fatty liver disease. In conclusion, we observed that regular sugar-sweetened beverage consumption was associated with greater risk of fatty liver disease, particularly in overweight and obese individuals, whereas diet soda intake was not associated with measures of fatty liver disease. Copyright © 2015 European Association for the Study of the Liver. All rights reserved.

High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.

PubMed

Gordon, D J; Probstfield, J L; Garrison, R J; Neaton, J D; Castelli, W P; Knoke, J D; Jacobs, D R; Bangdiwala, S; Tyroler, H A

1989-01-01

The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.

Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative.

PubMed

den Ruijter, H M; Peters, S A E; Groenewegen, K A; Anderson, T J; Britton, A R; Dekker, J M; Engström, G; Eijkemans, M J; Evans, G W; de Graaf, J; Grobbee, D E; Hedblad, B; Hofman, A; Holewijn, S; Ikeda, A; Kavousi, M; Kitagawa, K; Kitamura, A; Koffijberg, H; Ikram, M A; Lonn, E M; Lorenz, M W; Mathiesen, E B; Nijpels, G; Okazaki, S; O'Leary, D H; Polak, J F; Price, J F; Robertson, C; Rembold, C M; Rosvall, M; Rundek, T; Salonen, J T; Sitzer, M; Stehouwer, C D A; Witteman, J C; Moons, K G; Bots, M L

2013-07-01

The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.

Microbial translocation in HIV infection is associated with dyslipidemia, insulin resistance, and risk of myocardial infarction.

PubMed

Pedersen, Karin K; Pedersen, Maria; Trøseid, Marius; Gaardbo, Julie C; Lund, Tamara T; Thomsen, Carsten; Gerstoft, Jan; Kvale, Dag; Nielsen, Susanne D

2013-12-15

Microbial translocation has been suggested to be a driver of immune activation and inflammation. It is hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals. Cross-sectional study of 60 HIV-infected patients on combination antiretroviral therapy with viral suppression >2 years and 31 healthy age-matched controls. Lipopolysaccharide (LPS) was analyzed by limulus amebocyte lysate colorimetric assay. Lipids, including cholesterol, low-density lipoprotein (LDL), and triglycerides, were measured. Glucose metabolism was determined using an oral glucose tolerance test. Body composition was determined using whole-body dual-energy x-ray absorptiometry scans and magnetic resonance imaging. The Framingham risk score was used to assess risk of cardiovascular disease and myocardial infarction. HIV-infected patients had higher level of LPS compared with controls (64 pg/mL vs. 50 pg/mL, P = 0.002). Likewise, HIV-infected patients had higher triglycerides, LDL, and fasting insulin as well as evidence of lower insulin sensitivity compared with controls. Among HIV-infected patients, high LPS was associated with a higher level of triglycerides and LDL and with lower insulin sensitivity. Importantly, among HIV-infected patients, high LPS was associated with a higher Framingham risk score. HIV-infected patients with suppressed viral replication had increased level of microbial translocation as measured by LPS. LPS was associated with cardiometabolic risk factors and increased Framingham risk score. Hence, the gastrointestinal mucosal barrier may be a potential therapeutic target to prevent dyslipidemia and future cardiovascular complications in HIV infection.

Lifetime risk of atrial fibrillation according to optimal, borderline, or elevated levels of risk factors: cohort study based on longitudinal data from the Framingham Heart Study

PubMed Central

Staerk, Laila; Wang, Biqi; Preis, Sarah R; Larson, Martin G; Lubitz, Steven A; Ellinor, Patrick T; McManus, David D; Ko, Darae; Weng, Lu-Chen; Lunetta, Kathryn L; Frost, Lars; Benjamin, Emelia J

2018-01-01

Abstract Objective To examine the association between risk factor burdens—categorized as optimal, borderline, or elevated—and the lifetime risk of atrial fibrillation. Design Community based cohort study. Setting Longitudinal data from the Framingham Heart Study. Participants Individuals free of atrial fibrillation at index ages 55, 65, and 75 years were assessed. Smoking, alcohol consumption, body mass index, blood pressure, diabetes, and history of heart failure or myocardial infarction were assessed as being optimal (that is, all risk factors were optimal), borderline (presence of borderline risk factors and absence of any elevated risk factor), or elevated (presence of at least one elevated risk factor) at index age. Main outcome measure Lifetime risk of atrial fibrillation at index age up to 95 years, accounting for the competing risk of death. Results At index age 55 years, the study sample comprised 5338 participants (2531 (47.4%) men). In this group, 247 (4.6%) had an optimal risk profile, 1415 (26.5%) had a borderline risk profile, and 3676 (68.9%) an elevated risk profile. The prevalence of elevated risk factors increased gradually when the index ages rose. For index age of 55 years, the lifetime risk of atrial fibrillation was 37.0% (95% confidence interval 34.3% to 39.6%). The lifetime risk of atrial fibrillation was 23.4% (12.8% to 34.5%) with an optimal risk profile, 33.4% (27.9% to 38.9%) with a borderline risk profile, and 38.4% (35.5% to 41.4%) with an elevated risk profile. Overall, participants with at least one elevated risk factor were associated with at least 37.8% lifetime risk of atrial fibrillation. The gradient in lifetime risk across risk factor burden was similar at index ages 65 and 75 years. Conclusions Regardless of index ages at 55, 65, or 75 years, an optimal risk factor profile was associated with a lifetime risk of atrial fibrillation of about one in five; this risk rose to more than one in three in individuals with at least one elevated risk factor. PMID:29699974

Clinical Utility of a Coronary Heart Disease Risk Prediction Gene Score in UK Healthy Middle Aged Men and in the Pakistani Population

PubMed Central

Beaney, Katherine E.; Cooper, Jackie A.; Ullah Shahid, Saleem; Ahmed, Waqas; Qamar, Raheel; Drenos, Fotios; Crockard, Martin A.; Humphries, Steve E.

2015-01-01

Background Numerous risk prediction algorithms based on conventional risk factors for Coronary Heart Disease (CHD) are available but provide only modest discrimination. The inclusion of genetic information may improve clinical utility. Methods We tested the use of two gene scores (GS) in the prospective second Northwick Park Heart Study (NPHSII) of 2775 healthy UK men (284 cases), and Pakistani case-control studies from Islamabad/Rawalpindi (321 cases/228 controls) and Lahore (414 cases/219 controls). The 19-SNP GS included SNPs in loci identified by GWAS and candidate gene studies, while the 13-SNP GS only included SNPs in loci identified by the CARDIoGRAMplusC4D consortium. Results In NPHSII, the mean of both gene scores was higher in those who went on to develop CHD over 13.5 years of follow-up (19-SNP p=0.01, 13-SNP p=7x10-3). In combination with the Framingham algorithm the GSs appeared to show improvement in discrimination (increase in area under the ROC curve, 19-SNP p=0.48, 13-SNP p=0.82) and risk classification (net reclassification improvement (NRI), 19-SNP p=0.28, 13-SNP p=0.42) compared to the Framingham algorithm alone, but these were not statistically significant. When considering only individuals who moved up a risk category with inclusion of the GS, the improvement in risk classification was statistically significant (19-SNP p=0.01, 13-SNP p=0.04). In the Pakistani samples, risk allele frequencies were significantly lower compared to NPHSII for 13/19 SNPs. In the Islamabad study, the mean gene score was higher in cases than controls only for the 13-SNP GS (2.24 v 2.34, p=0.04). There was no association with CHD and either score in the Lahore study. Conclusion The performance of both GSs showed potential clinical utility in European men but much less utility in subjects from Pakistan, suggesting that a different set of risk loci or SNPs may be required for risk prediction in the South Asian population. PMID:26133560

The 10-year Absolute Risk of Cardiovascular (CV) Events in Northern Iran: a Population Based Study

PubMed Central

Motamed, Nima; Mardanshahi, Alireza; Saravi, Benyamin Mohseni; Siamian, Hasan; Maadi, Mansooreh; Zamani, Farhad

2015-01-01

Background: The present study was conducted to estimate 10-year cardiovascular disease events (CVD) risk using three instruments in northern Iran. Material and methods: Baseline data of 3201 participants 40-79 of a population based cohort which was conducted in Northern Iran were analyzed. Framingham risk score (FRS), World Health Organization (WHO) risk prediction charts and American college of cardiovascular / American heart association (ACC/AHA) tool were applied to assess 10-year CVD events risk. The agreement values between the risk assessment instruments were determined using the kappa statistics. Results: Our study estimated 53.5%of male population aged 40-79 had a 10 –year risk of CVD events≥10% based on ACC/AHA approach, 48.9% based on FRS and 11.8% based on WHO risk charts. A 10 –year risk≥10% was estimated among 20.1% of women using the ACC/AHA approach, 11.9%using FRS and 5.7%using WHO tool. ACC/AHA and Framingham tools had closest agreement in the estimation of 10-year risk≥10% (κ=0.7757) in meanwhile ACC/AHA and WHO approaches displayed highest agreement (κ=0.6123) in women. Conclusion: Different estimations of 10-year risk of CVD event were provided by ACC/AHA, FRS and WHO approaches. PMID:26236160

The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%.

PubMed

Franco, Oscar H; Bonneux, Luc; de Laet, Chris; Peeters, Anna; Steyerberg, Ewout W; Mackenbach, Johan P

2004-12-18

Although the Polypill concept (proposed in 2003) is promising in terms of benefits for cardiovascular risk management, the potential costs and adverse effects are its main pitfalls. The objective of this study was to identify a tastier and safer alternative to the Polypill: the Polymeal. Data on the ingredients of the Polymeal were taken from the literature. The evidence based recipe included wine, fish, dark chocolate, fruits, vegetables, garlic, and almonds. Data from the Framingham heart study and the Framingham offspring study were used to build life tables to model the benefits of the Polymeal in the general population from age 50, assuming multiplicative correlations. Combining the ingredients of the Polymeal would reduce cardiovascular disease events by 76%. For men, taking the Polymeal daily represented an increase in total life expectancy of 6.6 years, an increase in life expectancy free from cardiovascular disease of 9.0 years, and a decrease in life expectancy with cardiovascular disease of 2.4 years. The corresponding differences for women were 4.8, 8.1, and 3.3 years. The Polymeal promises to be an effective, non-pharmacological, safe, cheap, and tasty alternative to reduce cardiovascular morbidity and increase life expectancy in the general population.

Ischemic heart disease in women: a focus on risk factors.

PubMed

Mehta, Puja K; Wei, Janet; Wenger, Nanette K

2015-02-01

Heart disease remains a major contributor to morbidity and mortality in women in the United States and worldwide. This review highlights known and emerging risk factors for ischemic heart disease (IHD) in women. Traditional Framingham risk factors such as hypertension, hyperlipidemia, diabetes, smoking, as well as lifestyle habits such as unhealthy diet and sedentary lifestyle are all modifiable. Health care providers should be aware of emerging cardiac risk factors in women such as adverse pregnancy outcomes, systemic autoimmune disorders, obstructive sleep apnea, and radiation-induced heart disease; psychosocial factors such as mental stress, depression, anxiety, low socioeconomic status, and work and marital stress play an important role in IHD in women. Appropriate recognition and management of an array of risk factors is imperative given the growing burden of IHD and need to deliver cost-effective, quality care for women. Copyright © 2015 Elsevier Inc. All rights reserved.

Hormones and heart disease.

PubMed

Kent, S

1979-06-01

Because the advantage that women have over men in a lower heart attack rate is gradually lost after menopause, it has been suggested that estrogen may exert a protective effect against heart disease. The situation is complex, and the available data are open to various interpretations. Available data show a gradual, predictable increase in the death rate from heart disease among women with advancing age, despite the apparent increase in cardiovascular events around the time of menopause. This suggests that men may be particularly susceptible to heart disease, rather than that women have an immunity to the disease. The theory that estrogen exerts a protective effect against heart disease was examined when men who had had heart attacks were treated with estrogen in the Coronary Drug Project. The practice was discontinued when it was found that men receiving estrogen had an elevated incidence of myocardial infarction, a finding that suggests that estrogen may promote heart disease. Additional evidence that estrogen may have a harmful effect on the cardiovascular system comes from a recent study by Gerald B. Phillips who found that men who had suffered heart attacks before age 43 had higher levels of estradiol in their blood than men who had not had heart attacks. A noteworthy finding from th e Framingham study was the fact that the relative risk of cardiovascular events in postmenopausal compared with premenopausal women seemed to decrease with age. Hans Selye identifies stress as "the final, decisive eliciting factor" in precipitating heart attack. Broda O. Barnes also maintains that stress is a major cause of heart attack, but adds that most stress-prone individuals suffer from thyroid deficiency, which is the underlying cause of their increased susceptibility to heart attacks.

Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index.

PubMed

Reynolds, Richard J; Vazquez, Ana I; Srinivasasainagendra, Vinodh; Klimentidis, Yann C; Bridges, S Louis; Allison, David B; Singh, Jasvinder A

2016-02-01

We hypothesized that serum urate-associated SNPs, individually or collectively, interact with BMI and renal disease to contribute to risk of incident gout. We measured the incidence of gout and associated comorbidities using the original and offspring cohorts of the Framingham Heart Study. We used direct and imputed genotypes for eight validated serum urate loci. We fit binomial regression models of gout incidence as a function of the covariates, age, type 2 diabetes, sex, and all main and interaction effects of the eight serum urate SNPs with BMI and renal disease. Models were also fit with a genetic risk score for serum urate levels which corresponds to the sum of risk alleles at the eight SNPs. Model covariates, age (P = 5.95E-06), sex (P = 2.46E-39), diabetes (P = 2.34E-07), BMI (P = 1.14E-11) and the SNPs, rs1967017 (P = 9.54E-03), rs13129697 (P = 4.34E-07), rs2199936 (P = 7.28E-03) and rs675209 (P = 4.84E-02) were all associated with incident gout. No BMI by SNP or BMI by serum urate genetic risk score interactions were statistically significant, but renal disease by rs1106766 was statistically significant (P = 6.12E-03). We demonstrated that minor alleles of rs1106766 (intergenic, INHBC) were negatively associated with the risk of incident gout in subjects without renal disease, but not for individuals with renal disease. These analyses demonstrate that a significant component of the risk of gout may involve complex interplay between genes and environment.

Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index

PubMed Central

Reynolds, Richard J.; Vazquez, Ana I.; Srinivasasainagendra, Vinodh; Klimentidis, Yann C.; Bridges, S. Louis; Allison, David B.; Singh, Jasvinder A.

2015-01-01

Introduction/objectives We hypothesized that serum urate-associated SNPs, individually or collectively, interact with BMI and renal disease to contribute to risk for incident gout. Method We measured the incidence of gout and associated comorbidities using the Original and Offspring cohorts of the Framingham Heart Study. We used direct and imputed genotypes for eight validated serum urate loci. We fit binomial regression models of gout incidence as a function of the covariates, age, type 2 diabetes, sex, and all main and interaction effects of the eight serum urate SNPs with BMI and renal disease. Models were also fit with a genetic risk score for serum urate levels which corresponds to the sum of risk alleles at the 8 SNPs. Results Model covariates, age (P = 5.95E-06), sex (P = 2.46E-39), diabetes (P = 2.34E-07), BMI (P = 1.14E-11) and the SNPs, rs1967017 (P = 9.54E-03), rs13129697 (P = 4.34E-07), rs2199936 (P = 7.28E-03) and rs675209 (P = 4.84E-02) were all associated with incident gout. No BMI by SNP or BMI by serum urate genetic risk score (GRS) interactions were statistically significant, but renal disease by rs1106766 was statistically significant (P=6.12E-03). Conclusions We demonstrated that minor alleles of rs1106766 (intergenic, INHBC) were negatively associated with the risk of incident gout in subjects without renal disease, but not for individuals with renal disease. These analyses demonstrate that a significant component of the risk for gout may involve complex interplay between genes and environment. PMID:26427508

Traditional Cardiovascular Risk Factors as Predictors of Cardiovascular Events in the U.S. Astronaut Corps

NASA Technical Reports Server (NTRS)

Halm, M. K.; Clark, A.; Wear, M. L.; Murray, J. D.; Polk, J. D.; Amirian, E.

2009-01-01

Risk prediction equations from the Framingham Heart Study are commonly used to predict the absolute risk of myocardial infarction (MI) and coronary heart disease (CHD) related death. Predicting CHD-related events in the U.S. astronaut corps presents a monumental challenge, both because astronauts tend to live healthier lifestyles and because of the unique cardiovascular stressors associated with being trained for and participating in space flight. Traditional risk factors may not hold enough predictive power to provide a useful indicator of CHD risk in this unique population. It is important to be able to identify individuals who are at higher risk for CHD-related events so that appropriate preventive care can be provided. This is of special importance when planning long duration missions since the ability to provide advanced cardiac care and perform medical evacuation is limited. The medical regimen of the astronauts follows a strict set of clinical practice guidelines in an effort to ensure the best care. The purpose of this study was to evaluate the utility of the Framingham risk score (FRS), low-density lipoprotein (LDL) and high-density lipoprotein levels, blood pressure, and resting pulse as predictors of CHD-related death and MI in the astronaut corps, using Cox regression. Of these factors, only two, LDL and pulse at selection, were predictive of CHD events (HR(95% CI)=1.12 (1.00-1.25) and HR(95% CI)=1.70 (1.05-2.75) for every 5-unit increase in LDL and pulse, respectively). Since traditional CHD risk factors may lack the specificity to predict such outcomes in astronauts, the development of a new predictive model, using additional measures such as electron-beam computed tomography and carotid intima-media thickness ultrasound, is planned for the future.

Short-Term Exposure to Air Pollution and Biomarkers of Oxidative Stress: The Framingham Heart Study.

PubMed

Li, Wenyuan; Wilker, Elissa H; Dorans, Kirsten S; Rice, Mary B; Schwartz, Joel; Coull, Brent A; Koutrakis, Petros; Gold, Diane R; Keaney, John F; Lin, Honghuang; Vasan, Ramachandran S; Benjamin, Emelia J; Mittleman, Murray A

2016-04-28

Short-term exposure to elevated air pollution has been associated with higher risk of acute cardiovascular diseases, with systemic oxidative stress induced by air pollution hypothesized as an important underlying mechanism. However, few community-based studies have assessed this association. Two thousand thirty-five Framingham Offspring Cohort participants living within 50 km of the Harvard Boston Supersite who were not current smokers were included. We assessed circulating biomarkers of oxidative stress including blood myeloperoxidase at the seventh examination (1998-2001) and urinary creatinine-indexed 8-epi-prostaglandin F2α (8-epi-PGF2α) at the seventh and eighth (2005-2008) examinations. We measured fine particulate matter (PM2.5), black carbon, sulfate, nitrogen oxides, and ozone at the Supersite and calculated 1-, 2-, 3-, 5-, and 7-day moving averages of each pollutant. Measured myeloperoxidase and 8-epi-PGF2α were loge transformed. We used linear regression models and linear mixed-effects models with random intercepts for myeloperoxidase and indexed 8-epi-PGF2α, respectively. Models were adjusted for demographic variables, individual- and area-level measures of socioeconomic position, clinical and lifestyle factors, weather, and temporal trend. We found positive associations of PM2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2- to 7-day moving averages of PM2.5 and sulfate were consistently positively associated with 8-epi-PGF2α. Stronger positive associations of black carbon and sulfate with myeloperoxidase were observed among participants with diabetes than in those without. Our community-based investigation supports an association of select markers of ambient air pollution with circulating biomarkers of oxidative stress. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Relations of insulin resistance and glycemic abnormalities to cardiovascular magnetic resonance measures of cardiac structure and function: the Framingham Heart Study.

PubMed

Velagaleti, Raghava S; Gona, Philimon; Chuang, Michael L; Salton, Carol J; Fox, Caroline S; Blease, Susan J; Yeon, Susan B; Manning, Warren J; O'Donnell, Christopher J

2010-05-01

Data regarding the relationships of diabetes, insulin resistance, and subclinical hyperinsulinemia/hyperglycemia with cardiac structure and function are conflicting. We sought to apply volumetric cardiovascular magnetic resonance (CMR) in a free-living cohort to potentially clarify these associations. A total of 1603 Framingham Heart Study Offspring participants (age, 64+/-9 years; 55% women) underwent CMR to determine left ventricular mass (LVM), LVM to end-diastolic volume ratio (LVM/LVEDV), relative wall thickness (RWT), ejection fraction, cardiac output, and left atrial size. Data regarding insulin resistance (homeostasis model, HOMA-IR) and glycemia categories (normal, impaired insulinemia or glycemia, prediabetes, and diabetes) were determined. In a subgroup (253 men, 290 women) that underwent oral glucose tolerance testing, we related 2-hour insulin and glucose with CMR measures. In both men and women, all age-adjusted CMR measures increased across HOMA-IR quartiles, but multivariable-adjusted trends were significant only for LVM/ht(2.7) and LVM/LVEDV. LVM/LVEDV and RWT were higher in participants with prediabetes and diabetes (in both sexes) in age-adjusted models, but these associations remained significant after multivariable adjustment only in men. LVM/LVEDV was significantly associated with 2-hour insulin in men only, and RWT was significantly associated with 2-hour glucose in women only. In multivariable stepwise selection analyses, the inclusion of body mass index led to a loss in statistical significance. Although insulin and glucose indices are associated with abnormalities in cardiac structure, insulin resistance and worsening glycemia are consistently and independently associated with LVM/LVEDV. These data implicate hyperglycemia and insulin resistance in concentric LV remodeling.

Impact of age, sex, and indexation method on MR left ventricular reference values in the Framingham Heart Study offspring cohort.

PubMed

Yeon, Susan B; Salton, Carol J; Gona, Philimon; Chuang, Michael L; Blease, Susan J; Han, Yuchi; Tsao, Connie W; Danias, Peter G; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J

2015-04-01

To determine normative values for left ventricular (LV) volumes, mass, concentricity, and ejection fraction (EF) and investigate associations between sex, age, and body size with LV parameters in community-dwelling adults. In all, 1794 Framingham Heart Study Offspring cohort members underwent LV short-axis oriented, contiguous multislice cine steady-state free precession MR of the left ventricle; from these a healthy referent group (n = 852, 61 ± 9 years, 40% men) free of clinical cardiac disease and hypertension (SBP < 140, DBP < 90 mmHg, never used antihypertensive medication ≥30 years prior to scanning) was identified. Referent participants were stratified by sex and age group (≤55, 56-65, >65 years); LV parameters were indexed to measures of body size. Men have greater LV volumes and mass than women both before and after indexation to height, powers of height, and body surface area (P < 0.01 all), but indexation to fat-free mass yielded greater LV volume and mass in women. In both sexes, LV volumes and mass decrease with advancing age, although indexation attenuates this association. LVEF is greater in women than men (68 ± 5% vs. 66 ± 5%, P < 0.01) and increases with age in both sexes (P < 0.05). Among nonhypertensive adults free of cardiac disease, men have greater LV volumes and mass with sex differences generally persisting after indexation to body size. LV volumes and mass tend to decrease with greater age in both sexes. Female sex and advanced age were both associated with greater LVEF. J. Magn. Reson. Imaging 2015;41:1038-1045. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Relations of Insulin Resistance and Glycemic Abnormalities to Cardiovascular Magnetic Resonance Measures of Cardiac Structure and Function: the Framingham Heart Study

PubMed Central

Velagaleti, Raghava S.; Gona, Philimon; Chuang, Michael L.; Salton, Carol J.; Fox, Caroline S.; Blease, Susan J.; Yeon, Susan B.; Manning, Warren J.; O’Donnell, Christopher J.

2011-01-01

Background Data regarding the relationships of diabetes, insulin resistance and sub-clinical hyperinsulinemia/hyperglycemia with cardiac structure and function are conflicting. We sought to apply volumetric cardiovascular magnetic resonance (CMR) in a free-living cohort to potentially clarify these associations. Methods and Results A total of 1603 Framingham Heart Study Offspring participants (age 64±9 years; 55% women) underwent CMR to determine left ventricular mass (LVM), LVM to end-diastolic volume ratio (LVM/LVEDV), relative wall thickness (RWT), ejection fraction (EF), cardiac output (CO) and left atrial size (LAD). Data regarding insulin resistance (homeostasis model, HOMA-IR) and glycemia categories (normal, impaired insulinemia or glycemia, pre-diabetes and diabetes) were determined. In a subgroup (253 men, 290 women) that underwent oral glucose tolerance testing, we related 2-hr insulin and glucose with CMR measures. In both men and women, all age-adjusted CMR measures increased across HOMA-IR quartiles, but multivariable-adjusted trends were significant only for LVM/ht2.7 and LVM/LVEDV. LVM/LVEDV and RWT were higher in participants with pre-diabetes and diabetes (in both sexes) in age-adjusted models, but these associations remained significant after multivariable-adjustment only in men. LVM/LVEDV was significantly associated with 2-hr insulin in men only, and RWT was significantly associated with 2-hr glucose in women only. In multivariable stepwise selection analyses, the inclusion of BMI led to a loss in statistical significance. Conclusions While insulin and glucose indices are associated with abnormalities in cardiac structure, insulin resistance and worsening glycemia are consistently and independently associated with LVM/LVEDV. These data implicate hyperglycemia and insulin resistance in concentric LV remodeling. PMID:20208015

Aortic Stiffness, Increased White Matter Free Water, and Altered Microstructural Integrity: A Continuum of Injury.

PubMed

Maillard, Pauline; Mitchell, Gary F; Himali, Jayandra J; Beiser, Alexa; Fletcher, Evan; Tsao, Connie W; Pase, Matthew P; Satizabal, Claudia L; Vasan, Ramachandran S; Seshadri, Sudha; DeCarli, Charles

2017-06-01

Previous reports from the Framingham Heart Study have identified cross-sectional associations of arterial stiffness, as reflected by carotid-femoral pulse wave velocity (CFPWV) and systolic blood pressure with vascular brain injury. The purpose of this study is to examine free water (FW), fractional anisotropy (FA), and white matter hyperintensities (WMH) in relation to arterial stiffness among subjects of the Framingham Offspring and Third-Generation cohorts. In 2422 participants aged 51.3±11.6 years, FA, FW, and WMH were related to CFPWV using voxel-based linear and generalized linear regressions, adjusting for relevant covariables. Mean FW, mean FA, and WMH burden (log transformed) were computed within white matter (WM) region and related to systolic blood pressure and CFPWV using multiple mediation analyses. CFPWV was found to be associated with higher FW, lower FA, and higher WMH incidence in WM areas covering, respectively, 356.1, 211.8, and 10.9 mL of the WM mask. Mediation analyses revealed that the effect of systolic blood pressure on FW was mediated by CFPWV (direct and indirect effects: a=0.040; P <0.001, and a'=0.020; P >0.05). Moreover, the effect of CFPWV on FA was mediated by FW (direct and indirect effects: b=-0.092; P <0.001, and b'=0.012; P >0.05), whose effect on WMH was, in turn, mediated by FA (direct and indirect effects: c=0.246; P <0.001, and c'=0.116; P >0.05). From these data, we propose a biomechanical hypothesis designed for future research experiments to explain how hemodynamic alteration may lead to WM injury by impacting cerebral water content and more subtly WM integrity, to finally lead to WMH development. © 2017 American Heart Association, Inc.

Advance Care Planning and Health Care Preferences of Community-Dwelling Elders: The Framingham Heart Study

PubMed Central

McCarthy, Ellen P.; Pencina, Michael J.; Kelly-Hayes, Margaret; Evans, Jane C.; Oberacker, Elizabeth J.; D’Agostino, Ralph B.; Burns, Risa B.; Murabito, Joanne M.

2009-01-01

Objectives To describe self-reported advance care planning, health care preferences, use of advance directives, and health perceptions in a very elderly community-dwelling sample. Methods Surviving participants of the original cohort of the Framingham Heart Study who were cognitively intact and attended a routine research exam between February 2004 and October 2005. Participants were queried about discussions about end of life care, preferences for care, documentation of advance directives, and health perceptions. Results Among 220 community-dwelling respondents, 67% were women with a mean age of 88 years (range 84-100). Overall 69% discussed their wishes for medical care at the end of life with someone, but only 17% discussed their wishes with a physician or health care provider. Two-thirds had a health care proxy, 55% had a living will, and 41% had both. Most (80%) respondents preferred comfort care over life-extending care, and 71% preferred to die at home; however, substantially fewer respondents said they would rather die than receive specific life-prolonging interventions [chronic ventilator (63%) or feeding tube (64%)]. Many were willing to endure distressing health states, with less than half indicating that they would rather die than live out their life in a great deal of pain (46%) or be confused/forgetful (45%) all of the time. Conclusions Although the vast majority of very elderly community-dwellers in this sample appear to prefer comfort measures at the end of life, many said they were willing to endure specific life-prolonging interventions and distressing health states to avoid death. Our results highlight the need for physicians better understand patients’ preferences and goals of care to help them make informed decisions at the end of life. PMID:18840800

Transfer function-derived central pressure and cardiovascular disease events: the Framingham Heart Study.

PubMed

Mitchell, Gary F; Hwang, Shih-Jen; Larson, Martin G; Hamburg, Naomi M; Benjamin, Emelia J; Vasan, Ramachandran S; Levy, Daniel; Vita, Joseph A

2016-08-01

Relations between central pulse pressure (PP) or pressure amplification and major cardiovascular disease (CVD) events are controversial. Estimates of central aortic pressure derived using radial artery tonometry and a generalized transfer function may better predict CVD risk beyond the predictive value of brachial SBP. Augmentation index, central SBP, central PP, and central-to-peripheral PP amplification were evaluated using radial artery tonometry and a generalized transfer function as implemented in the SphygmoCor device (AtCor Medical, Itasca, Illinois, USA). We used proportional hazards models to examine relations between central hemodynamics and first-onset major CVD events in 2183 participants (mean age 62 years, 58% women) in the Framingham Heart Study. During median follow-up of 7.8 (limits 0.2-8.9) years, 149 participants (6.8%) had an incident event. Augmentation index (P = 0.6), central aortic systolic pressure (P = 0.20), central aortic PP (P = 0.24), and PP amplification (P = 0.15) were not related to CVD events in multivariable models that adjusted for age, sex, brachial cuff systolic pressure, use of antihypertensive therapy, total and high-density lipoprotein cholesterol concentrations, smoking, and presence of diabetes. In a model that included standard risk factors, model fit was improved (P = 0.03) when brachial systolic pressure was added after central, whereas model fit was not improved (P = 0.30) when central systolic pressure was added after brachial. After considering standard risk factors, including brachial cuff SBP, augmentation index, central PP and PP amplification derived using radial artery tonometry, and a generalized transfer function were not predictive of CVD risk.

Association of Serum Vitamin D with the Risk of Incident Dementia and Subclinical Indices of Brain Aging: The Framingham Heart Study.

PubMed

Karakis, Ioannis; Pase, Matthew P; Beiser, Alexa; Booth, Sarah L; Jacques, Paul F; Rogers, Gail; DeCarli, Charles; Vasan, Ramachandran S; Wang, Thomas J; Himali, Jayandra J; Annweiler, Cedric; Seshadri, Sudha

2016-01-01

Identifying nutrition- and lifestyle-based risk factors for cognitive impairment and dementia may aid future primary prevention efforts. We aimed to examine the association of serum vitamin D levels with incident all-cause dementia, clinically characterized Alzheimer's disease (AD), MRI markers of brain aging, and neuropsychological function. Framingham Heart Study participants had baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations measured between 1986 and 2001. Vitamin D status was considered both as a continuous variable and dichotomized as deficient (<10 ng/mL), or at the cohort-specific 20th and 80th percentiles. Vitamin D was related to the 9-year risk of incident dementia (n = 1663), multiple neuropsychological tests (n = 1291) and MRI markers of brain volume, white matter hyperintensities and silent cerebral infarcts (n = 1139). In adjusted models, participants with vitamin D deficiency (n = 104, 8% of the cognitive sample) displayed poorer performance on Trail Making B-A (β= -0.03 to -0.05±0.02) and the Hooper Visual Organization Test (β= -0.09 to -0.12±0.05), indicating poorer executive function, processing speed, and visuo-perceptual skills. These associations remained when vitamin D was examined as a continuous variable or dichotomized at the cohort specific 20th percentile. Vitamin D deficiency was also associated with lower hippocampal volumes (β= -0.01±0.01) but not total brain volume, white matter hyperintensities, or silent brain infarcts. No association was found between vitamin D deficiency and incident all-cause dementia or clinically characterized AD. In this large community-based sample, low 25(OH)D concentrations were associated with smaller hippocampal volume and poorer neuropsychological function.

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study

PubMed Central

Horne, Benjamin D; Malhotra, Alka; Camp, Nicola J

2003-01-01

Background High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. Results Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. Conclusion Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions. PMID:14975161

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study.

PubMed

Horne, Benjamin D; Malhotra, Alka; Camp, Nicola J

2003-12-31

High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions.

Association of soda consumption with subclinical cardiac remodeling in the Framingham Heart Study

PubMed Central

Andersson, Charlotte; Sullivan, Lisa; Benjamin, Emelia J.; Aragam, Jayashri; Jacques, Paul; Cheng, Susan; Vasan, Ramachandran S.

2014-01-01

Objective Diet soda consumption increases cardiometabolic risk. The aim of this investigation was to assess the relations between self-reported soda consumption and subclinical cardiac remodeling. Methods We assessed the relations between self-reported soda consumption and left ventricular mass (LVM) and left atrial dimension (LAD) (both standardized within sex) in a sample of middle-aged attendees from the Framingham Heart Offspring cohort examination 5 and 6. Results The overall mean age was 55 years and 59% of the participants were women. Compared to non-consumers (n=1010), soda consumers (n=3192) had greater body weight (mean 86 vs. 82 kg among men, and 70 vs. 67 kg among women). Compared with non-consumers, age- and height-adjusted LAD was increased (standard deviation units) among soda consumers by 0.15 standard error 0.042, p<0.001) for those drinking >0–7 diet soda (n=1023), −0.010 (0.043, p=0.82) for people drinking >0–7 regular soda (n=907), 0.22 (0.057, p<0.0001) for individuals consuming >7 diet soda (n=372), and 0.20 (0.092, p=0.034) for participants drinking >7 regular soda (n=116) per week. LVM was increased among participants consuming diet soda (p<0.05), but not in regular soda consumers (p>0.05). Upon adjustment for weight, however, all aforementioned associations were attenuated. Conclusion The observed associations between soda consumption and LAD or LVM were likely related to the greater body weight of soda drinkers relative to non-drinkers. PMID:25456096

Association of soda consumption with subclinical cardiac remodeling in the Framingham heart study.

PubMed

Andersson, Charlotte; Sullivan, Lisa; Benjamin, Emelia J; Aragam, Jayashri; Jacques, Paul; Cheng, Susan; Vasan, Ramachandran S

2015-02-01

Diet soda consumption increases cardiometabolic risk. The aim of this investigation was to assess the relations between self-reported soda consumption and subclinical cardiac remodeling. We assessed the relations between self-reported soda consumption and left ventricular mass (LVM) and left atrial dimension (LAD) (both standardized within sex) in a sample of middle-aged attendees from the Framingham Heart Offspring cohort examination 5 and 6. The overall mean age was 55 years and 59% of the participants were women. Compared to non-consumers (n=1010), soda consumers (n=3192) had greater body weight (mean 86 vs. 82 kg among men, and 70 vs. 67 kg among women). Compared with non-consumers, age- and height-adjusted LAD was increased (standard deviation units) among soda consumers by 0.15 standard error 0.042, (p<0.001) for those drinking >0-7 diet soda (n=1023), -0.010 (0.043, p=0.82) for people drinking >0-7 regular soda (n=907), 0.22 (0.057, p<0.0001) for individuals consuming >7 diet soda (n=372), and 0.20 (0.092, p=0.034) for participants drinking >7 regular soda (n=116) per week. LVM was increased among participants consuming diet soda (p<0.05), but not in regular soda consumers (p>0.05). Upon adjustment for weight, however, all aforementioned associations were attenuated. The observed associations between soda consumption and LAD or LVM were likely related to the greater body weight of soda drinkers relative to non-drinkers. Copyright © 2015 Elsevier Inc. All rights reserved.

SCORE should be preferred to Framingham to predict cardiovascular death in French population.

PubMed

Marchant, Ivanny; Boissel, Jean-Pierre; Kassaï, Behrouz; Bejan, Theodora; Massol, Jacques; Vidal, Chrystelle; Amsallem, Emmanuel; Naudin, Florence; Galan, Pilar; Czernichow, Sébastien; Nony, Patrice; Gueyffier, François

2009-10-01

Numerous studies have examined the validity of available scores to predict the absolute cardiovascular risk. We developed a virtual population based on data representative of the French population and compared the performances of the two most popular risk equations to predict cardiovascular death: Framingham and SCORE. A population was built based on official French demographic statistics and summarized data from representative observational studies. The 10-year coronary and cardiovascular death risk and their ratio were computed for each individual by SCORE and Framingham equations. The resulting rates were compared with those derived from national vital statistics. Framingham overestimated French coronary deaths by 2.8 in men and 1.9 in women, and cardiovascular deaths by 1.5 in men and 1.3 in women. SCORE overestimated coronary death by 1.6 in men and 1.7 in women, and underestimated cardiovascular death by 0.94 in men and 0.85 in women. Our results revealed an exaggerated representation of coronary among cardiovascular death predicted by Framingham, with coronary death exceeding cardiovascular death in some individual profiles. Sensitivity analyses gave some insights to explain the internal inconsistency of the Framingham equations. Evidence is that SCORE should be preferred to Framingham to predict cardiovascular death risk in French population. This discrepancy between prediction scores is likely to be observed in other populations. To improve the validation of risk equations, specific guidelines should be issued to harmonize the outcomes definition across epidemiologic studies. Prediction models should be calibrated for risk differences in the space and time dimensions.

Ethnicity and prediction of cardiovascular disease: performance of QRISK2 and Framingham scores in a U.K. tri-ethnic prospective cohort study (SABRE--Southall And Brent REvisited).

PubMed

Tillin, Therese; Hughes, Alun D; Whincup, Peter; Mayet, Jamil; Sattar, Naveed; McKeigue, Paul M; Chaturvedi, Nish

2014-01-01

To evaluate QRISK2 and Framingham cardiovascular disease (CVD) risk scores in a tri-ethnic U.K. population. Cohort study. West London. Randomly selected from primary care lists. Follow-up data were available for 87% of traced participants, comprising 1866 white Europeans, 1377 South Asians, and 578 African Caribbeans, aged 40-69 years at baseline (1998-1991). First CVD events: myocardial infarction, coronary revascularisation, angina, transient ischaemic attack or stroke reported by participant, primary care or hospital records or death certificate. During follow-up, 387 CVD events occurred in men (14%) and 78 in women (8%). Both scores underestimated risk in European and South Asian women (ratio of predicted to observed risk: European women: QRISK2: 0.73, Framingham: 0.73; South Asian women: QRISK2: 0.52, Framingham: 0.43). In African Caribbeans, Framingham over-predicted in men and women and QRISK2 over-predicted in women. Framingham classified 28% of participants as high risk, predicting 54% of all such events. QRISK2 classified 19% as high risk, predicting 42% of all such events. Both scores performed poorly in identifying high risk African Caribbeans; QRISK2 and Framingham identified as high risk only 10% and 24% of those who experienced events. Neither score performed consistently well in all ethnic groups. Further validation of QRISK2 in other multi-ethnic datasets, and better methods for identifying high risk African Caribbeans and South Asian women, are required.

Localization of genes involved in the metabolic syndrome using multivariate linkage analysis.

PubMed

Olswold, Curtis; de Andrade, Mariza

2003-12-31

There are no well accepted criteria for the diagnosis of the metabolic syndrome. However, the metabolic syndrome is identified clinically by the presence of three or more of these five variables: larger waist circumference, higher triglyceride levels, lower HDL-cholesterol concentrations, hypertension, and impaired fasting glucose. We use sets of two or three variables, which are available in the Framingham Heart Study data set, to localize genes responsible for this syndrome using multivariate quantitative linkage analysis. This analysis demonstrates the applicability of using multivariate linkage analysis and how its use increases the power to detect linkage when genes are involved in the same disease mechanism.

Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts

PubMed Central

Ma, Jiantao; Fox, Caroline S.; Jacques, Paul F.; Speliotes, Elizabeth K.; Hoffmann, Udo; Smith, Caren E.; Saltzman, Edward; McKeown, Nicola M.

2016-01-01

Background & Aims Non-alcoholic fatty liver disease affects ~30% of US adults, yet the role of sugar-sweetened beverages and diet soda on these diseases remains unknown. We examined the cross-sectional association between intake of sugar-sweetened beverages or diet soda and fatty liver disease in participants of the Framingham Offspring and Third Generation cohorts. Methods Fatty liver disease was defined using liver attenuation measurements generated from computed tomography in 2634 participants. Alanine transaminase concentration, a crude marker of fatty liver disease, was measured in 5908 participants. Sugar-sweetened beverage and diet soda intake were estimated using a food frequency questionnaire. Participants were categorized as either non-consumers or consumers (3 categories: 1 serving/month to <1 serving/week, 1 serving/week to <1 serving/-day, and ⩾1 serving/day) of sugar-sweetened beverages or diet soda. Results After adjustment for age, sex, smoking status, Framingham cohort, energy intake, alcohol, dietary fiber, fat (% energy), protein (% energy), diet soda intake, and body mass index, the odds ratios of fatty liver disease were 1, 1.16 (0.88, 1.54), 1.32 (0.93, 1.86), and 1.61 (1.04, 2.49) across sugar-sweetened beverage consumption categories (p trend = 0.04). Sugar-sweetened beverage consumption was also positively associated with alanine transaminase levels (p trend = 0.007). We observed no significant association between diet soda intake and measures of fatty liver disease. Conclusion In conclusion, we observed that regular sugar-sweetened beverage consumption was associated with greater risk of fatty liver disease, particularly in overweight and obese individuals, whereas diet soda intake was not associated with measures of fatty liver disease. PMID:26055949

Gender disparities in the assessment and management of cardiovascular risk in primary care: the AusHEART study.

PubMed

Turnbull, Fiona; Arima, Hisatomi; Heeley, Emma; Cass, Alan; Chalmers, John; Morgan, Claire; Patel, Anushka; Peiris, David; Weekes, Andrew; Anderson, Craig

2011-06-01

Studies indicate ongoing gender-based differences in the prevention, detection and management of cardiovascular disease. The aims of this study were to determine whether there are differences in general practitioners' (GPs') perceptions of a patient's cardiovascular risk compared with the patient's estimated risk and in the patient's subsequent medical management according to patient sex. The Australian Hypertension and Absolute Risk Study (AusHEART) was a nationally representative, cluster-stratified, cross-sectional survey among 322 GPs. Each GP was asked to collect data on cardiovascular disease risk factors and their management in 15-20 consecutive patients (age ≥55 years) who presented between April and June, 2008. They were also asked to estimate each patient's absolute risk of a cardiovascular event in the next five years. The main outcomes were the Adjusted Framingham risk, GP estimated risk and proportion of patients receiving blood pressure-lowering, statin and antiplatelet therapy. A total of 5293 patients were recruited to the study, of whom 2968 (56%) were women. Among patients without established cardiovascular disease, the level of agreement between the GP estimated risk and the Adjusted Framingham risk was poor (<50%) and was similarly so for men (kappa coefficient 0.18; 95% confidence interval (CI) 0.14-0.21) and women (0.19; 95% CI 0.16-0.22; P homogeneity = 0.57). For patients with established cardiovascular disease, however, women were more likely to be assigned by the GP to a lower risk category (66% vs. 54%, P < 0.001) and less likely to be prescribed combination (blood pressure-lowering, statin and antiplatelet) (44% vs. 56%, P < 0.001) therapy compared with men, even after adjusting for patient age. Cardiovascular risk is underrecognized and undertreated in Australian primary care patients, with women apparently disproportionately affected. These findings underscore the importance of initiatives to raise awareness of cardiovascular disease in women.

Does load-induced ventricular hypertrophy progress to systolic heart failure?

PubMed

Berenji, Kambeez; Drazner, Mark H; Rothermel, Beverly A; Hill, Joseph A

2005-07-01

Ventricular hypertrophy develops in response to numerous forms of cardiac stress, including pressure or volume overload, loss of contractile mass from prior infarction, neuroendocrine activation, and mutations in genes encoding sarcomeric proteins. Hypertrophic growth is believed to have a compensatory role that diminishes wall stress and oxygen consumption, but Framingham and other studies established ventricular hypertrophy as a marker for increased risk of developing chronic heart failure, suggesting that hypertrophy may have maladaptive features. However, the relative contribution of comorbid disease to hypertrophy-associated systolic failure is unknown. For instance, coronary artery disease is induced by many of the same risk factors that cause hypertrophy and can itself lead to systolic dysfunction. It is uncertain, therefore, whether ventricular hypertrophy commonly progresses to systolic dysfunction without the contribution of intervening ischemia or infarction. In this review, we summarize findings from epidemiologic studies, preclinical experiments in animals, and clinical trials to lay out what is known-and not known-about this important question.

Gender differences and normal left ventricular anatomy in an adult population free of hypertension. A cardiovascular magnetic resonance study of the Framingham Heart Study Offspring cohort.

PubMed

Salton, Carol J; Chuang, Michael L; O'Donnell, Christopher J; Kupka, Michelle J; Larson, Martin G; Kissinger, Kraig V; Edelman, Robert R; Levy, Daniel; Manning, Warren J

2002-03-20

We sought to derive gender-specific cardiovascular magnetic resonance (CMR) reference values for normative left ventricular (LV) anatomy and function in a healthy adult population of clinically relevant age. Cardiovascular magnetic resonance imaging is increasingly applied in the clinical setting, but age-relevant, gender-specific normative values are currently unavailable. A representative sample of 318 Framingham Heart Study (FHS) Offspring participants free of clinically overt cardiovascular disease underwent CMR examination to determine LV end-diastolic and end-systolic volume (EDV and ESV, respectively), mass, ejection fraction (EF) and linear dimensions (wall thickness, cavity length). Subjects with a clinical history of hypertension or those with a systolic blood pressure > or =140 mm Hg or diastolic pressure > or =90 mm Hg at any FHS cycle examination were excluded, leaving 142 subjects (63 men, 79 women; age 57 +/- 9 years). All volumetric (EDV, ESV, mass) and unidimensional measures were significantly greater (p < 0.001) in men than in women and remained greater (p < 0.02) after adjustment for subject height. Volumetric measures were greater (p < 0.001) in men than in women after adjustment for body surface area (BSA), but there were increased linear dimensions in women after adjustment for BSA. In particular, end-diastolic dimension indexed to BSA was greater in women (p < 0.001) than in men. There were no gender differences in global LVEF (men = 0.69; women = 0.70). Cardiovascular magnetic resonance measures of LV volumes, mass and linear dimensions differ significantly according to gender and body size. This study provides gender-specific normal CMR reference values, uniquely derived from a population-based sample of persons free of cardiovascular disease and clinical hypertension. These data may serve as a reference to identify LV pathology in the adult population.

Relations of circulating GDF-15, soluble ST2, and troponin-I concentrations with vascular function in the community: The Framingham Heart Study.

PubMed

Andersson, Charlotte; Enserro, Danielle; Sullivan, Lisa; Wang, Thomas J; Januzzi, James L; Benjamin, Emelia J; Vita, Joseph A; Hamburg, Naomi M; Larson, Martin G; Mitchell, Gary F; Vasan, Ramachandran S

2016-05-01

Growth differentiation factor-15 (GDF-15), soluble (s)ST2, and high-sensitivity troponin-I (hs-TnI) are associated with incident cardiovascular disease (CVD) including heart failure, yet the underlying mechanisms are not fully understood. We investigated if GDF-15, sST2, and hs-TnI are related to subclinical vascular dysfunction in the community, which may explain the relations of these biomarkers with CVD. We evaluated 1823 Framingham Study participants (mean age 61 ± 10 years, 54% women) who underwent routine assessment of vascular function. We related circulating GDF-15, sST2, and hs-TnI concentrations to measures of arterial stiffness (carotid-femoral pulse wave velocity, CFPWV; augmentation index; and forward pressure wave amplitude, FW), endothelial-dependent vasodilation (flow-mediated dilation, FMD), and baseline and hyperemic brachial flow velocities using linear regression adjusting for standard risk factors. After multivariable adjustment, GDF-15 levels were positively associated with CFPWV (0.044 [95% confidence interval 0.007-0.081] standard deviation [SD] change per SD increase in loge[GDF-15], p = 0.02) and FW (0.076 [0.026-0.126] SD change per SD increase in loge[GDF-15], p = 0.003) and inversely related to FMD (-0.051 [-0.101-0.0003] SD change per SD increase in loge[GDF-15], p = 0.048). sST2 was positively associated with CFPWV (0.032 [0.0005-0.063] SD change per SD increase in loge[sST2], p = 0.046), and hs-TnI inversely associated with hyperemic flow velocity (-0.041 [-0.082-0.0004] SD change per SD increase in loge[hs-TnI], p = 0.048). In our community-based investigation, individual cardiac stress biomarkers were differentially related to select aspects of vascular function. These findings may contribute to the associations of circulating GDF-15, sST2, and hs-TnI with incident CVD and heart failure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dyslipidemias and Elevated Cardiovascular Risk on Lopinavir-Based Antiretroviral Therapy in Cambodia

PubMed Central

Ly, Sowath; Ouk, Vara; Chanroeurn, Hak; Thavary, Saem; Boroath, Ban; Canestri, Ana; Viretto, Gérald; Delfraissy, Jean-François; Ségéral, Olivier

2016-01-01

Background Lopinavir/ritonavir (LPV/r) is widely used in Cambodia with high efficacy but scarce data exist on long-term metabolic toxicity. Methods We carried out a cross-sectional and retrospective study evaluating metabolic disorders and cardiovascular risk in Cambodian patients on LPV/r-based antiretroviral therapy (ART) for > 1 year followed in Calmette Hospital, Phnom Penh. Data collected included cardiovascular risk factors, fasting blood lipids and glucose, and retrospective collection of bioclinical data. We estimated the 10-year risks of coronary heart disease with the Framingham, Ramathibodi-Electricity Generating Authority of Thailand (Rama-EGAT), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) risk equations. We identified patients with LDL above targets defined by the French expert group on HIV and by the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group (IDSA-AACTG). Results Of 115 patients enrolled—mean age 40.9 years, 69.2% male, mean time on LPV/r 3.8 years—40 (34.8%) had hypercholesterolemia (> 2.40 g/L), and 69 (60.0%) had low HDL cholesterol (< 0.40 g/L). Twelve (10.5%), 28 (24%) and 9 (7.7%) patients had a 10-year risk of coronary heart disease ≥ 10% according to the Framingham, D:A:D, and Rama-EGAT score, respectively. Fifty one (44.4%) and 36 (31.3%) patients had not reached their LDL target according to IDSA-AACTG and French recommendations, respectively. Conclusion Prevalence of dyslipidemia was high in this cohort of HIV-infected Cambodian patients on LPV/r. Roughly one third had high LDL levels requiring specific intervention. PMID:27579612

The joint associations of occupational, commuting, and leisure-time physical activity, and the Framingham risk score on the 10-year risk of coronary heart disease.

PubMed

Hu, Gang; Tuomilehto, Jaakko; Borodulin, Katja; Jousilahti, Pekka

2007-02-01

To determine joint associations of different kinds of physical activity and the Framingham risk score (FRS) with the 10-year risk of coronary heart disease (CHD) events. Study cohorts included 41 053 Finnish participants aged 25-64 years without history of CHD and stroke. The multivariable-adjusted 10-year hazard ratios (HRs) of coronary events associated with low, moderate, and high occupational physical activity were 1.00, 0.66, and 0.74 (Ptrend<0.001) for men, and 1.00, 0.53, and 0.58 (Ptrend<0.001) for women, respectively. The multivariable-adjusted 10-year HRs of coronary events associated with low, moderate, and high leisure-time physical activity were 1.00, 0.97, and 0.66 (Ptrend=0.002) for men, and 1.00, 0.74, and 0.54 (Ptrend=0.003) for women, respectively. Active commuting had a significant inverse association with 10-year risk of coronary events in women only. The FRS predicted 10-year risk of coronary events among both men and women. The protective effects of occupational, commuting, or leisure-time physical activity were consistent in subjects with a very low (<6%), low (6-9%), intermediate (10-19%), or high (>or=20%) risk of the FRS. Moderate or high levels of occupational or leisure-time physical activity among both men and women, and daily walking or cycling to and from work among women are associated with a reduced 10-year risk of CHD events. These favourable effects of physical activity on CHD risk are observed at all levels of CHD risk based on FRS assessment.

Obesity phenotype and coronary heart disease risk as estimated by the Framingham risk score.

PubMed

Park, Yong Soon; Kim, Jun-Su

2012-03-01

There are conflicting data as to whether general or abdominal obesity is a better predictor of cardiovascular risk. This cross-sectional study involved 4,573 subjects aged 30 to 74 yr who participated in the Fourth Korea National Health and Nutrition Examination Survey conducted in 2008. Obesity phenotype was classified by means of body mass index (BMI) and waist circumference (WC), and participants were categorized into 4 groups. Individuals' 10-yr risk of coronary heart diseases (CHD) was determined from the Framingham risk score. Subjects with obese WC had a higher proportion of high risk for CHD compared to the normal WC group, irrespective of BMI level. Relative to subjects with normal BMI/normal WC, the adjusted odds ratios (ORs) of normal BMI/obese WC group (OR 2.93 [1.70, 5.04] and OR 3.10 [1.49, 6.46]) for CHD risk in male were higher than obese BMI/obese WC group (OR 1.91 [1.40, 2.61] and OR 1.70 [1.16, 2.47]), whereas the adjusted ORs of obese BMI/obese WC group (OR 1.94 [1.24, 3.04] and OR 3.92 [1.75, 8.78]) were higher than the others in female. Subjects with obese BMI/normal WC were not significantly associated with 10-yr CHD risk in men (P = 0.449 and P = 0.067) and women (P = 0.702 and P = 0.658). WC is associated with increased CHD risk regardless of the level of BMI. Men with normal BMI and obese WC tend to be associated with CHD risk than those with obese BMI and obese WC.

The TyG index may predict the development of cardiovascular events.

PubMed

Sánchez-Íñigo, Laura; Navarro-González, David; Fernández-Montero, Alejandro; Pastrana-Delgado, Juan; Martínez, Jose Alfredo

2016-02-01

Cardiovascular disease (CVD) is the worldwide leading cause of morbidity and mortality. An early risk detection of apparently healthy people before CVD onset has clinical relevance in the prevention of cardiovascular events. We evaluated the association between the product of fasting plasma glucose and triglycerides (TyG index) and CVD. A total of 5014 patients of the Vascular Metabolic CUN cohort (VMCUN cohort) were followed up during a median period of 10 years. We used a Cox proportional-hazard ratio with repeated measures to estimate the risk of incidence of CVD across quintiles of the TyG index, calculated as ln[fasting triglycerides (mg/dL) × fasting plasma glucose (mg(dL)/2], and plotted a receiver-operating characteristics (ROC) curve to compare a prediction model fitted on the variables used in the Framingham risk score, a new model containing the Framingham variables with the TyG index, and the risk of coronary heart disease. A higher level of TyG index was significantly associated with an increased risk of developing CVD independent of confounding factors with a value of 2·32 (95% CI: 1·65-3·26) for those in the highest quintile and 1·52 (95% CI: 1·07-2·16) for those in the fourth quintile. The areas under the curve (AUC) of the ROC plots were 0·708 (0·68-0·73) for the Framingham model and 0·719 (0·70-0·74) for the Framingham + TyG index model (P = 0·014). The TyG index, a simple measure reflecting insulin resistance, might be useful to early identify individuals at a high risk of developing a cardiovascular event. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Rationale and design of the Karolinska-Rennes (KaRen) prospective study of dyssynchrony in heart failure with preserved ejection fraction.

PubMed

Donal, Erwan; Lund, Lars H; Linde, Cecilia; Edner, Magnus; Lafitte, Stéphane; Persson, Hans; Bauer, Fabrice; Ohrvik, John; Ennezat, Pierre-Vladimir; Hage, Camilla; Löfman, Ida; Juilliere, Yves; Logeart, Damien; Derumeaux, Geneviève; Gueret, Pascal; Daubert, Jean-Claude

2009-02-01

Heart failure with preserved ejection fraction (HFPEF) is common but not well understood. Electrical dyssynchrony in systolic heart failure is harmful. Little is known about the prevalence and the prognostic impact of dyssynchrony in HFPEF. We have designed a prospective, multicenter, international, observational study to characterize HFPEF and to determine whether electrical or mechanical dyssynchrony affects prognosis. Patients presenting with acute heart failure (HF) will be screened so as to identify 400 patients with HFPEF. Inclusion criteria will be: acute presentation with Framingham criteria for HF, left ventricular ejection fraction>or=45%, brain natriuretic peptide (BNP)>100 pg/mL or NT-proBNP>300 pg/mL. Once stabilized, 4-8 weeks after the index presentation, patients will return and undergo questionnaires, serology, ECG, and Doppler echocardiography. Thereafter, patients will be followed for mortality and HF hospitalization every 6 months for at least 18 months. Sub-studies will focus on echocardiographic changes from the acute presentation to the stable condition and on exercise echocardiography, cardiopulmonary exercise testing, and serological markers. KaRen aims to characterize electrical and mechanical dyssynchrony and to assess its prognostic impact in HFPEF. The results might improve our understanding of HFPEF and generate answers to the question whether dyssynchrony could be a target for therapy in HFPEF.

Relations of long-term and contemporary lipid levels and lipid genetic risk scores with coronary artery calcium in the framingham heart study.

PubMed

Tsao, Connie W; Preis, Sarah Rosner; Peloso, Gina M; Hwang, Shih-Jen; Kathiresan, Sekar; Fox, Caroline S; Cupples, L Adrienne; Hoffmann, Udo; O'Donnell, Christopher J

2012-12-11

This study evaluated the association of timing of lipid levels and lipid genetic risk score (GRS) with subclinical atherosclerosis. Atherosclerosis is a slowly progressive disorder influenced by suboptimal lipid levels. Long-term versus contemporary lipid levels may more strongly impact the development of coronary artery calcium (CAC). Framingham Heart Study (FHS) Offspring Cohort participants (n = 1,156, 44% male, 63 ± 9 years) underwent serial fasting lipids (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein, and triglycerides), Exam 1 (1971 to 1975) to Exam 7 (1998 to 2001). FHS Third Generation Cohort participants (n = 1,954, 55% male, 45 ± 6 years) had fasting lipid profiles assessed, 2002 to 2005. Computed tomography (2002 to 2005) measured CAC. Lipid GRSs were computed from significantly associated single-nucleotide polymorphisms. The association between early, long-term average, and contemporary lipids, and lipid GRS with elevated CAC was assessed using logistic regression. In FHS Offspring, Exam 1 and long-term average as compared with Exam 7 lipid measurements, including untreated lipid levels, were strongly associated with elevated CAC. In the FHS Third Generation, contemporary lipids were associated with CAC. The LDL-C GRS was associated with CAC (age-/sex-adjusted odds ratio: 1.14, 95% confidence interval: 1.00 to 1.29, p = 0.04). However, addition of the GRS to the lipid models did not result in a significant increase in the odds ratio or C-statistic for any lipid measure. Early and long-term average lipid levels, as compared with contemporary measures, are more strongly associated with elevated CAC. Lipid GRS was associated with lipid levels but did not predict elevated CAC. Adult early and long-term average lipid levels provide important information when assessing subclinical atherosclerosis and cardiovascular risk. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Duration and Degree of Weight Gain and Incident Diabetes in Younger Versus Middle-Aged Black and White Adults: ARIC, CARDIA, and the Framingham Heart Study.

PubMed

Wei, Gina S; Coady, Sean A; Reis, Jared P; Carnethon, Mercedes R; Coresh, Josef; D'Agostino, Ralph B; Goff, David C; Jacobs, David R; Selvin, Elizabeth; Fox, Caroline S

2015-11-01

To determine whether duration and degree of weight gain are differentially associated with diabetes risk in younger versus middle-aged black and white adults. We combined data from three cohort studies: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and the Framingham Heart Study. A total of 17,404 participants (56% women; 21% black) were stratified by baseline age (younger: ≥30 and <45 years; middle-aged: ≥45 and <60 years) and examined for incident diabetes (median follow-up 9 years). Duration and degree of gain in BMI were calculated as "BMI-years" above one's baseline BMI. Diabetes incidence per 1,000 person-years in the younger and middle-aged groups was 7.2 (95% CI 5.7, 8.7) and 24.4 (22.0, 26.8) in blacks, respectively, and 3.4 (2.8, 4.0) and 10.5 (9.9, 11.2) in whites, respectively. After adjusting for sex, baseline BMI and other cardiometabolic factors, and age and race interaction terms, gains in BMI-years were associated with higher risk of diabetes in the younger compared with middle-aged groups: hazard ratios for 1-unit increase in log BMI-years in younger versus middle-aged blacks were 1.18 (P = 0.02) and 1.02 (P = 0.39), respectively (P for interaction by age-group = 0.047), and in whites were 1.35 (P < 0.001) and 1.11 (P < 0.001), respectively (P for interaction by age-group = 0.008). Although middle-aged adults have higher rates of diabetes, younger adults are at greater relative risk of developing diabetes for a given level of duration and degree of weight gain. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Genetic and educational assortative mating among US adults.

PubMed

Domingue, Benjamin W; Fletcher, Jason; Conley, Dalton; Boardman, Jason D

2014-06-03

Understanding the social and biological mechanisms that lead to homogamy (similar individuals marrying one another) has been a long-standing issue across many fields of scientific inquiry. Using a nationally representative sample of non-Hispanic white US adults from the Health and Retirement Study and information from 1.7 million single-nucleotide polymorphisms, we compare genetic similarity among married couples to noncoupled pairs in the population. We provide evidence for genetic assortative mating in this population but the strength of this association is substantially smaller than the strength of educational assortative mating in the same sample. Furthermore, genetic similarity explains at most 10% of the assortative mating by education levels. Results are replicated using comparable data from the Framingham Heart Study.

Relations of mitochondrial genetic variants to measures of vascular function.

PubMed

Fetterman, Jessica L; Liu, Chunyu; Mitchell, Gary F; Vasan, Ramachandran S; Benjamin, Emelia J; Vita, Joseph A; Hamburg, Naomi M; Levy, Daniel

2018-05-01

Mitochondrial genetic variation with resultant alterations in oxidative phosphorylation may influence vascular function and contribute to cardiovascular disease susceptibility. We assessed relations of peptide-encoding variants in the mitochondrial genome with measures of vascular function in Framingham Heart Study participants. Of 258 variants assessed, 40 were predicted to have functional consequences by bioinformatics programs. A maternal pattern of heritability was estimated to contribute to the variability of aortic stiffness. A putative association with a microvascular function measure was identified that requires replication. The methods we have developed can be applied to assess the relations of mitochondrial genetic variation to other phenotypes. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

The Framingham study and treatment guidelines for stroke prevention.

PubMed

Grossi, Enzo

2008-06-01

In recent years, institutional bodies and scientific societies of principal Western countries have produced several guidelines dealing with risk assessment, primary prevention, and treatment of acute stroke. From a prospective, community-based, observational cohort of patients from the Framingham Heart Study, an absolute estimate of risk for stroke alone or stroke or death was determined based on several risk factors, including advanced age, female sex, increased systolic blood pressure, prior stroke or transient ischemic attack, and diabetes mellitus. This algorithm considers many variables and expresses their results as the percentage of risk of developing a fatal or nonfatal stroke in the following 5 years. The author has identified three major pitfalls of this algorithm, which are related to the limitation of the classic statistical approach in handling this kind of nonlinear and complex information: 1) the very large confidence interval of individual risk assessment, 2) the inability to capture the process dynamics, and 3) the inability to capture the disease complexity. The artificial intelligence armamentarium may provide an advantage in the attempt to overcome these limitations. The theoretic background and some application examples related to artificial neural networks (ANNs) and fuzzy logic are reviewed and discussed. Newer approaches linked to artificial intelligence, such as fuzzy logic and ANNs, seem better at addressing the challenge of the increasing complexity of the predisposing factors linked to cerebrovascular events and at predicting future events in an individual patient.

Validation of the Framingham general cardiovascular risk score in a multiethnic Asian population: a retrospective cohort study

PubMed Central

Gray, Sarah Yu Weng; Ching, Siew Mooi; Lim, Hooi Min; Chinna, Karuthan

2015-01-01

Objective This study aims to examine the validity of the Framingham general cardiovascular disease (CVD) risk chart in a primary care setting. Design This is a 10-year retrospective cohort study. Setting A primary care clinic in a teaching hospital in Malaysia. Participants 967 patients’ records were randomly selected from patients who were attending follow-up in the clinic. Main outcome measures Baseline demographic data, history of diabetes and smoking, blood pressure (BP), and serum lipids were captured from patient records in 1998. Each patient's Framingham CVD score was computed from these parameters. All atherosclerotic CVD events occurring between 1998 and 2007 were counted. Results In 1998, mean age was 57 years with 33.8% men, 6.1% smokers, 43.3% diabetics and 59.7% hypertensive. Median BP was 140/80 mm Hg and total cholesterol 6.0 mmol/L (1.3). The predicted median Framingham general CVD risk score for the study population was 21.5% (IQR 1.2–30.0) while the actual CVD events that occurred in the 10 years was 13.1% (127/967). The median CVD points for men was 30.0, giving them a CVD risk of more than 30%; for women it is 18.5, a CVD risk of 21.5%. Our study found that the Framingham general CVD risk score to have moderate discrimination with an area under the receiver operating characteristic curve (AUC) of 0.63. It also discriminates well for Malay (AUC 0.65, p=0.01), Chinese (AUC 0.60, p=0.03), and Indians (AUC 0.65, p=0.001). There was good calibration with Hosmer-Lemeshow test χ2=3.25, p=0.78. Conclusions Taking into account that this cohort of patients were already on treatment, the Framingham General CVD Risk Prediction Score predicts fairly accurately for men and overestimates somewhat for women. In the absence of local risk prediction charts, the Framingham general CVD risk prediction chart is a reasonable alternative for use in a multiethnic group in a primary care setting. PMID:25991451

Parental intermittent claudication as risk factor for claudication in adults.

PubMed

Prushik, Scott G; Farber, Alik; Gona, Philimon; Shrader, Peter; Pencina, Michael J; D'Agostino, Ralph B; Murabito, Joanne M

2012-03-01

Little is known about the familial aggregation of intermittent claudication (IC). Our objective was to examine whether parental IC increased the risk of IC in adult offspring, independent of the established cardiovascular risk factors. We evaluated the Offspring Cohort Participants of the Framingham Heart Study who were ≥30 years old, cardiovascular disease free, and had both parents enrolled in the Framingham Heart Study (n = 2,970 unique participants, 53% women). Pooled proportional hazards regression analysis was used to examine whether the 12-year risk of incident IC in offspring participants was associated with parental IC, adjusting for age, gender, diabetes, smoking, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, and antihypertensive and lipid treatment. Of the 909 person-examinations in the parental IC history group and 5,397 person-examinations in the no-parental IC history group, there were 101 incident IC events (29 with parental IC history and 72 without a parental IC history) during follow-up. The age- and gender-adjusted 12-year cumulative incidence rate per 1,000 person-years was 5.08 (95% confidence interval [CI] 2.74 to 7.33) and 2.34 (95% CI 1.46 to 3.19) in participants with and without a parental IC history. A parental history of IC significantly increased the risk of incident IC in the offspring (multivariable adjusted hazard ratio 1.81, 95% CI 1.14 to 2.88). The hazard ratio was unchanged, with an adjustment for the occurrence of cardiovascular disease (hazard ratio 1.83, 95% CI 1.15 to 2.91). In conclusion, IC in parents increases the risk of IC in adult offspring, independent of the established risk factors. These data suggest a genetic component of peripheral artery disease and support future research into genetic causes. Copyright © 2012 Elsevier Inc. All rights reserved.

Short-Term Exposure to Ambient Air Pollution and Biomarkers of Systemic Inflammation: The Framingham Heart Study.

PubMed

Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H; Rice, Mary B; Ljungman, Petter L; Schwartz, Joel D; Coull, Brent A; Koutrakis, Petros; Gold, Diane R; Keaney, John F; Vasan, Ramachandran S; Benjamin, Emelia J; Mittleman, Murray A

2017-09-01

The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation cohorts in the greater Boston area. We included 3996 noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived within 50 km from a central air pollution monitoring site in Boston, MA, and calculated the 1- to 7-day moving averages of fine particulate matter (diameter<2.5 µm), black carbon, sulfate, nitrogen oxides, and ozone before the examination visits. We used linear mixed effects models for C-reactive protein and tumor necrosis factor receptor 2, which were measured up to twice for each participant; we used linear regression models for interleukin-6, fibrinogen, and tumor necrosis factor α, which were measured once. We adjusted for demographics, socioeconomic position, lifestyle, time, and weather. The 3- to 7-day moving averages of fine particulate matter (diameter<2.5 µm) and sulfate were positively associated with C-reactive protein concentrations. A 5 µg/m 3 higher 5-day moving average fine particulate matter (diameter<2.5 µm) was associated with 4.2% (95% confidence interval: 0.8, 7.6) higher circulating C-reactive protein. Positive associations were also observed for nitrogen oxides with interleukin-6 and for black carbon, sulfate, and ozone with tumor necrosis factor receptor 2. However, black carbon, sulfate, and nitrogen oxides were negatively associated with fibrinogen, and sulfate was negatively associated with tumor necrosis factor α. Higher short-term exposure to relatively low levels of ambient air pollution was associated with higher levels of C-reactive protein, interleukin-6, and tumor necrosis factor receptor 2 but not fibrinogen or tumor necrosis factor α in individuals residing in the greater Boston area. © 2017 American Heart Association, Inc.

Haplotype Structure of the ENPP1 Gene and Nominal Association of the K121Q Missense Single Nucleotide Polymorphism With Glycemic Traits in the Framingham Heart Study

PubMed Central

Stolerman, Elliot S.; Manning, Alisa K.; McAteer, Jarred B.; Dupuis, Josée; Fox, Caroline S.; Cupples, L. Adrienne; Meigs, James B.; Florez, Jose C.

2008-01-01

OBJECTIVE—A recent meta-analysis demonstrated a nominal association of the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K→Q missense single nucleotide polymorphism (SNP) at position 121 with type 2 diabetes. We set out to confirm the association of ENPP1 K121Q with hyperglycemia, expand this association to insulin resistance traits, and determine whether the association stems from K121Q or another variant in linkage disequilibrium with it. RESEARCH DESIGN AND METHODS—We characterized the haplotype structure of ENPP1 and selected 39 tag SNPs that captured 96% of common variation in the region (minor allele frequency ≥5%) with an r2 value ≥0.80. We genotyped the SNPs in 2,511 Framingham Heart Study participants and used age- and sex-adjusted linear mixed effects (LME) models to test for association with quantitative metabolic traits. We also examined whether interaction between K121Q and BMI affected glycemic trait levels. RESULTS—The Q allele of K121Q (rs1044498) was associated with increased fasting plasma glucose (FPG), A1C, fasting insulin, and insulin resistance by homeostasis model assessment (HOMA-IR; all P = 0.01–0.006). Two noncoding SNPs (rs7775386 and rs7773477) demonstrated similar associations, but LME models indicated that their effects were not independent from K121Q. We found no association of K121Q with obesity, but interaction models suggested that the effect of the Q allele on FPG and HOMA-IR was stronger in those with a higher BMI (P = 0.008 and 0.01 for interaction, respectively). CONCLUSIONS—The Q allele of ENPP1 K121Q is associated with hyperglycemia and insulin resistance in whites. We found an adiposity-SNP interaction, with a stronger association of K121Q with diabetes-related quantitative traits in people with a higher BMI. PMID:18426862

Comparison of cystatin C- and creatinine-based estimated glomerular filtration rate to predict coronary heart disease risk in Japanese patients with obesity and diabetes.

PubMed

Ito, Ryo; Yamakage, Hajime; Kotani, Kazuhiko; Wada, Hiromichi; Otani, Sumire; Yonezawa, Kazuya; Ogo, Atsushi; Okajima, Taiichiro; Adachi, Masahiro; Araki, Rika; Yoshida, Kazuro; Saito, Miho; Nagaoka, Tadasu; Toyonaga, Tetsushi; Tanaka, Tsuyoshi; Yamada, Tsutomu; Ota, Itsuro; Oishi, Mariko; Miyanaga, Fumiko; Shimatsu, Akira; Satoh-Asahara, Noriko

2015-01-01

The aim of this study is to determine which indicator of chronic kidney disease most closely correlates with 10-year Framingham coronary heart disease (CHD) risk among serum creatinine, serum cystatin C (S-CysC), urine albumin-creatinine ratio (UACR), estimated creatinine-based GFRs (eGFRcre), and estimated CysC-based GFRs (eGFRcys) in patients with obesity and diabetes. Serum creatinine, S-CysC, UACR, and cardio-ankle vascular index (CAVI) were examined in 468 outpatients with obesity and type 2 diabetes, free of severe renal dysfunction or previous history of cardiovascular disease, as a cross-sectional survey using baseline data from the multi-centered Japan Diabetes and Obesity Study. S-CysC and eGFRcys had significantly stronger correlations with the 10-year Framingham CHD risk than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.318; S-CysC, ρ = 0.497; UACR, ρ = 0.174; eGFRcre, ρ = -0.291; eGFRcys, ρ = -0.521; P < 0.01 by Fisher's z-test). S-CysC and eGFRcys had significantly stronger correlations with CAVI than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.198; S-CysC, ρ = 0.383; UACR, ρ = 0.183; eGFRcre, ρ = -0.302; eGFRcys, ρ = -0.444; P < 0.05 by Fisher's z-test). The receiver operating characteristic curves to distinguish the high-risk patients for CHD revealed significantly larger areas under the curve of S-CysC and eGFRcys than those of serum creatinine, UACR, and eGFRcre (serum creatinine, 0.64; S-CysC, 0.75; UACR, 0.56; eGFRcre, 0.63; eGFRcys, 0.76; P < 0.01). The data suggested that eGFRcys can be more predictive of the 10-year CHD risk than eGFRcre in Japanese patients with obesity and diabetes.

Trends in Cardiovascular Disease Risk Factors in Individuals with and without Diabetes in the Framingham Heart Study

PubMed Central

Preis, Sarah Rosner; Pencina, Michael J.; Hwang, Shih-Jen; D’Agostino, Ralph B.; Savage, Peter J.; Levy, Daniel; Fox, Caroline S.

2009-01-01

Background Individuals with diabetes are at two to three-fold increased risk for cardiovascular disease (CVD) relative to those without diabetes. Our objective was to examine CVD risk factor level changes among individuals with and without type 2 diabetes from 1970–2005 in the Framingham Heart Study. Methods and Results We included 4,195 participants (3,990 non-diabetes/205 diabetes) aged 50 and 3,495 participants (3,178 non- diabetes/317 diabetes) aged 60. Contemporaneous CVD risk factor levels were measured; linear regression models were used to assess the interaction between diabetes status and calendar year on CVD risk factor levels. Among 50-year olds, for non-diabetes, there was an increase in body mass index (BMI) of 0.39 kg/m2 per 10 years whereas for diabetes there was an increase of 2.52 kg/m2 (p-value for the diabetes by calendar year interaction [p-interaction] <0.0001). For LDL cholesterol, the mean decrease was −7.43 mg/dL per decade [non-diabetes] and −15.5 mg/dL for diabetes (p-interaction=0.002). For systolic blood pressure, the mean decrease was −3.35 mmHg per decade [non-diabetes] and −3.50 mmHg for diabetes (p-interaction=0.97). The direction of the trends for those with diabetes relative to those without diabetes was similar for 60-year olds. Conclusions Individuals with diabetes experienced a greater increase in BMI, a greater decrease in LDL-C, and a similar magnitude of decline in systolic blood pressure as compared to those without diabetes. Individuals with diabetes have not experienced the necessary declines in CVD risk factors to overcome their increased risk of CVD. Further efforts are needed to aggressively control CVD risk factors among individuals with diabetes. PMID:19581493

Cardiovascular risk prediction in HIV-infected patients: comparing the Framingham, atherosclerotic cardiovascular disease risk score (ASCVD), Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk prediction models.

PubMed

Krikke, M; Hoogeveen, R C; Hoepelman, A I M; Visseren, F L J; Arends, J E

2016-04-01

The aim of the study was to compare the predictions of five popular cardiovascular disease (CVD) risk prediction models, namely the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, the Framingham Heart Study (FHS) coronary heart disease (FHS-CHD) and general CVD (FHS-CVD) models, the American Heart Association (AHA) atherosclerotic cardiovascular disease risk score (ASCVD) model and the Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) model. A cross-sectional design was used to compare the cumulative CVD risk predictions of the models. Furthermore, the predictions of the general CVD models were compared with those of the HIV-specific D:A:D model using three categories (< 10%, 10-20% and > 20%) to categorize the risk and to determine the degree to which patients were categorized similarly or in a higher/lower category. A total of 997 HIV-infected patients were included in the study: 81% were male and they had a median age of 46 [interquartile range (IQR) 40-52] years, a known duration of HIV infection of 6.8 (IQR 3.7-10.9) years, and a median time on ART of 6.4 (IQR 3.0-11.5) years. The D:A:D, ASCVD and SCORE-NL models gave a lower cumulative CVD risk, compared with that of the FHS-CVD and FHS-CHD models. Comparing the general CVD models with the D:A:D model, the FHS-CVD and FHS-CHD models only classified 65% and 79% of patients, respectively, in the same category as did the D:A:D model. However, for the ASCVD and SCORE-NL models, this percentage was 89% and 87%, respectively. Furthermore, FHS-CVD and FHS-CHD attributed a higher CVD risk to 33% and 16% of patients, respectively, while this percentage was < 6% for ASCVD and SCORE-NL. When using FHS-CVD and FHS-CHD, a higher overall CVD risk was attributed to the HIV-infected patients than when using the D:A:D, ASCVD and SCORE-NL models. This could have consequences regarding overtreatment, drug-related adverse events and drug-drug interactions. © 2015 British HIV Association.

[Carotid intima-media thickness distribution according to the stratification of cardiovascular risk by means of Framingham-REGICOR and score function charts].

PubMed

Hermida-Ameijeiras, Á; López-Paz, J E; Riveiro-Cruz, M A; Calvo-Gómez, C

2016-01-01

Carotid intima-media thickness (cIMT) has been suggested as a further tool for risk function charts. The aim of this study was to describethe relationship between cIMT and cardiovascular risk (CVR) estimation according to Framingham-REGICOR and SCORE equations. Observational, cross-sectional cohort study from 362 hypertensive subjects. Demographic and clinical information were collected as well as laboratory, ultrasonographic and CVR estimation by the Framingham-REGICOR and SCORE functions. Statistical analysis was performed using SPSS software (version 20,0). To analyze the data, statistical tests such as Chi-square, T-test, ANOVA, and Pearson correlation coefficient were used. According to both functions, differences on mean cIMT were found between low CVR group and intermediate to high groups. No differences were found between intermediate and high risk groups (cIMT: 0,73mm low risk patients vs. 0,89 or 0,88mm respectively according to SCORE function and cIMT: 0,73 vs. 0,85 or 0,87mm respectively according to Framingham-REGICOR function). cIMT correlated positively with CVR estimation according to both SCORE (r=0,421; P<.01), and Framingham-REGICOR functions (r=0,363; P<.01). cIMT correlates positively with CVR estimated by SCORE and Framingham-REGICOR functions. cIMT in those subjects at intermediate risk is similar to those at high risk. Our findings highlight the importance of carotid ultrasound in identifying silent target-organ damage in those patients at intermediate CVR. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

Contribution of the Arterial System and the Heart to Blood Pressure during Normal Aging - A Simulation Study.

PubMed

Maksuti, Elira; Westerhof, Nico; Westerhof, Berend E; Broomé, Michael; Stergiopulos, Nikos

2016-01-01

During aging, systolic blood pressure continuously increases over time, whereas diastolic pressure first increases and then slightly decreases after middle age. These pressure changes are usually explained by changes of the arterial system alone (increase in arterial stiffness and vascular resistance). However, we hypothesise that the heart contributes to the age-related blood pressure progression as well. In the present study we quantified the blood pressure changes in normal aging by using a Windkessel model for the arterial system and the time-varying elastance model for the heart, and compared the simulation results with data from the Framingham Heart Study. Parameters representing arterial changes (resistance and stiffness) during aging were based on literature values, whereas parameters representing cardiac changes were computed through physiological rules (compensated hypertrophy and preservation of end-diastolic volume). When taking into account arterial changes only, the systolic and diastolic pressure did not agree well with the population data. Between 20 and 80 years, systolic pressure increased from 100 to 122 mmHg, and diastolic pressure decreased from 76 to 55 mmHg. When taking cardiac adaptations into account as well, systolic and diastolic pressure increased from 100 to 151 mmHg and decreased from 76 to 69 mmHg, respectively. Our results show that not only the arterial system, but also the heart, contributes to the changes in blood pressure during aging. The changes in arterial properties initiate a systolic pressure increase, which in turn initiates a cardiac remodelling process that further augments systolic pressure and mitigates the decrease in diastolic pressure.

Validation of the pooled cohort risk score in an Asian population - a retrospective cohort study.

PubMed

Chia, Yook Chin; Lim, Hooi Min; Ching, Siew Mooi

2014-11-20

The Pooled Cohort Risk Equation was introduced by the American College of Cardiology (ACC) and American Heart Association (AHA) 2013 in their Blood Cholesterol Guideline to estimate the 10-year atherosclerotic cardiovascular disease (ASCVD) risk. However, absence of Asian ethnicity in the contemporary cohorts and limited studies to examine the use of the risk score limit the applicability of the equation in an Asian population. This study examines the validity of the pooled cohort risk score in a primary care setting and compares the cardiovascular risk using both the pooled cohort risk score and the Framingham General Cardiovascular Disease (CVD) risk score. This is a 10-year retrospective cohort study of randomly selected patients aged 40-79 years. Baseline demographic data, co-morbidities and cardiovascular (CV) risk parameters were captured from patient records in 1998. Pooled cohort risk score and Framingham General CVD risk score for each patient were computed. All ASCVD events (nonfatal myocardial infarction, coronary heart disease (CHD) death, fatal and nonfatal stroke) occurring from 1998-2007 were recorded. A total of 922 patients were studied. In 1998, mean age was 57.5 ± 8.8 years with 66.7% female. There were 47% diabetic patients and 59.9% patients receiving anti-hypertensive treatment. More than 98% of patients with pooled cohort risk score ≥7.5% had FRS >10%. A total of 45 CVD events occurred, 22 (7.2%) in males and 23 (3.7%) in females. The median pooled cohort risk score for the population was 10.1 (IQR 4.7-20.6) while the actual ASCVD events that occurred was 4.9% (45/922). Our study showed moderate discrimination with AUC of 0.63. There was good calibration with Hosmer-Lemeshow test χ2 = 12.6, P = 0.12. The pooled cohort risk score appears to overestimate CV risk but this apparent over-prediction could be a result of treatment. In the absence of a validated score in an untreated population, the pooled cohort risk score appears to be appropriate for use in a primary care setting.

The Cheer Study to Reduce BMI in Elementary School Students: A School-Based, Parent-Directed Study in Framingham, Massachusetts

ERIC Educational Resources Information Center

Resnick, Elissa A.; Bishop, Marilyn; O'Connell, Anne; Hugo, Beverly; Isern, Germinal; Timm, Alison; Ozonoff, Al; Geller, Alan C.

2009-01-01

Childhood obesity may be lessened by parent-focused interventions. A pilot parent-directed trial with 46 parents of overweight and obese elementary school students was conducted at two ethnically diverse public schools in Framingham, Massachusetts. Parents were randomly assigned to either the Materials Group, which received mailed educational…

Predicted 25-hydroxyvitamin D Score and incident type 2 diabetes in the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

Accumulating evidence suggests that vitamin D is involved in the development of type 2 diabetes (T2D). Our objective was to examine the relation between vitamin D status and incidence of T2D. We used a subsample of 1972 Framingham Offspring Study participants to develop a regression model to predict...

Predicted 25-hydroxyvitamin D score and incident type 2 diabetes in the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

Accumulating evidence suggests that vitamin D is involved in the development of type 2 diabetes (T2D). Our objective was to examine the relation between vitamin D status and incidence of T2D. We used a subsample of 1972 Framingham Offspring Study participants to develop a regression model to predict...

Appropriating Risk Factors: The Reception of an American Approach to Chronic Disease in the two German States, c. 1950–1990

PubMed Central

Timmermann, Carsten

2012-01-01

Summary Risk factors have become a dominant approach to the aetiology of chronic disease worldwide. The concept emerged in the new field of chronic disease epidemiology in the United States in the 1950s, around near-iconic projects such as the Framingham Heart Study. In this article I examine how chronic disease epidemiology and the risk factor concept were adopted and adapted in the two German states. I draw on case studies that illuminate the characteristics of the different contexts and different take on traditions in social hygiene, social medicine and epidemiology. I also look at critics of the risk factor approach in East and West Germany, who viewed risk factors as intellectually dishonest and a new surveillance tool.

Cost-effectiveness of the non-laboratory based Framingham algorithm in primary prevention of cardiovascular disease: A simulated analysis of a cohort of African American adults.

PubMed

Kariuki, Jacob K; Gona, Philimon; Leveille, Suzanne G; Stuart-Shor, Eileen M; Hayman, Laura L; Cromwell, Jerry

2018-06-01

The non-lab Framingham algorithm, which substitute body mass index for lipids in the laboratory based (lab-based) Framingham algorithm, has been validated among African Americans (AAs). However, its cost-effectiveness and economic tradeoffs have not been evaluated. This study examines the incremental cost-effectiveness ratio (ICER) of two cardiovascular disease (CVD) prevention programs guided by the non-lab versus lab-based Framingham algorithm. We simulated the World Health Organization CVD prevention guidelines on a cohort of 2690 AA participants in the Atherosclerosis Risk in Communities (ARIC) cohort. Costs were estimated using Medicare fee schedules (diagnostic tests, drugs & visits), Bureau of Labor Statistics (RN wages), and estimates for managing incident CVD events. Outcomes were assumed to be true positive cases detected at a data driven treatment threshold. Both algorithms had the best balance of sensitivity/specificity at the moderate risk threshold (>10% risk). Over 12years, 82% and 77% of 401 incident CVD events were accurately predicted via the non-lab and lab-based Framingham algorithms, respectively. There were 20 fewer false negative cases in the non-lab approach translating into over $900,000 in savings over 12years. The ICER was -$57,153 for every extra CVD event prevented when using the non-lab algorithm. The approach guided by the non-lab Framingham strategy dominated the lab-based approach with respect to both costs and predictive ability. Consequently, the non-lab Framingham algorithm could potentially provide a highly effective screening tool at lower cost to address the high burden of CVD especially among AA and in resource-constrained settings where lab tests are unavailable. Copyright © 2017 Elsevier Inc. All rights reserved.

Ambient air pollution, adipokines, and glucose homeostasis: The Framingham Heart Study.

PubMed

Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H; Rice, Mary B; Kloog, Itai; Schwartz, Joel D; Koutrakis, Petros; Coull, Brent A; Gold, Diane R; Meigs, James B; Fox, Caroline S; Mittleman, Murray A

2018-02-01

To examine associations of proximity to major roadways, sustained exposure to fine particulate matter (PM 2.5 ), and acute exposure to ambient air pollutants with adipokines and measures of glucose homeostasis among participants living in the northeastern United States. We included 5958 participants from the Framingham Offspring cohort examination cycle 7 (1998-2001) and 8 (2005-2008) and Third Generation cohort examination cycle 1 (2002-2005) and 2 (2008-2011), who did not have type 2 diabetes at the time of examination visit. We calculated 2003 annual average PM 2.5 at participants' home address, residential distance to the nearest major roadway, and daily PM 2.5 , black carbon (BC), sulfate, nitrogen oxides (NO x ), and ozone concentrations. We used linear mixed effects models for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) which were measured up to twice, and used linear regression models for adiponectin, resistin, leptin, and hemoglobin A1c (HbA1c) which were measured only once, adjusting for demographics, socioeconomic position, lifestyle, time, and seasonality. The mean age was 51years and 55% were women. Participants who lived 64m (25th percentile) from a major roadway had 0.28% (95% CI: 0.05%, 0.51%) higher fasting plasma glucose than participants who lived 413m (75th percentile) away, and the association appeared to be driven by participants who lived within 50m from a major roadway. Higher exposures to 3- to 7-day moving averages of BC and NO x were associated with higher glucose whereas the associations for ozone were negative. The associations otherwise were generally null and did not differ by median age, sex, educational attainment, obesity status, or prediabetes status. Living closer to a major roadway or acute exposure to traffic-related air pollutants were associated with dysregulated glucose homeostasis but not with adipokines among participants from the Framingham Offspring and Third Generation cohorts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trends in dietary carbohydrate consumption from 1991 to 2008 in the Framingham Heart Study Offspring Cohort.

PubMed

Makarem, Nour; Scott, Marc; Quatromoni, Paula; Jacques, Paul; Parekh, Niyati

2014-06-14

The intake of carbohydrates has been evaluated cross-sectionally, but not longitudinally in an ageing American adult population. The aim of the present study was to examine trends in the intake of dietary carbohydrates and their major food sources among the Framingham Heart Study Offspring (FOS) cohort, which had been uniquely tracked for 17 years in the study. The FOS cohort was recruited in 1971-1975. Follow-up examinations were conducted, on average, every 4 years. Dietary data collection began in 1991 (examination 5) using a validated semi-quantitative FFQ. The study included 2894 adults aged ≥ 25 years with complete dietary data in at least three examinations from 1991 to 2008. Descriptive statistics were generated using SAS version 9.3, and a repeated-measures model was used to examine trends in the intake of carbohydrates and their food sources in the whole sample, and by sex and BMI category. Over 17 years of follow-up, the percentage of energy from total carbohydrates (51·0-46·8 %; P for trend < 0·001) and total sugars (18·2-16·6 %; P for trend < 0·001) decreased. There was a decrease in the percentage of energy from fructose (5·4-4·7 %; P for trend < 0·001) and sucrose (9·8-8·8 %; P for trend < 0·001). Dietary fibre intake increased (18·0-19·2 g/d; P for trend < 0·001). The number of weekly servings of yeast bread, soft drinks/soda, cakes/cookies/quick breads/doughnuts, potatoes, milk, pasta, rice and cooked grains, fruit juice/drinks, potato chips/maize chips/popcorn, and lunch foods (e.g. pizzas and burgers) decreased significantly (P for trend < 0·001), while the intake of ready-to-eat cereals, legumes, fruits, dairy products, candy and ice cream/sherbet/frozen yogurt increased significantly (P for trend<0·04). Similar trends were observed when the analyses were stratified by sex and BMI. The present results suggest favourable trends in dietary carbohydrate consumption, but dietary guidelines for fruits, vegetables and fibre were not met in this cohort.

Chronic Kidney Disease as a Predictor of Cardiovascular Disease (From the Framingham Heart Study)

PubMed Central

Parikh, Nisha I.; Hwang, Shih-Jen; Larson, Martin G.; Levy, Daniel; Fox, Caroline S.

2008-01-01

Chronic kidney disease (CKD) is a risk factor for cardiovascular disease (CVD), although shared risk factors may mediate much of the association. We related CKD and CVD in the setting of specific CVD risk factors and determined whether more advanced CKD was a CVD risk equivalent. The Framingham Heart Study original cohort (n=2471, mean age 68 years, 58.9% women) was studied. Glomerular filtration rate (eGFR) was estimated using the simplified Modification of Diet in Renal Disease Study equation. CKD was defined as eGFR < 59 mL/min per 1.73 m2 (women) and < 64 (men) and Stage 3b CKD defined as eGFR 30-44 (women) and 30-50 (men). Cox Proportional Hazard models adjusting for CVD risk factors were used to relate CKD to CVD. We tested for effect modification by CVD risk factors. Overall, 23.2% of the study sample had CKD (n=574; mean eGFR 50 mL/min per 1.73 m2) and 5.3% had Stage 3b CKD (n=131; mean eGFR 42 mL/min per 1.73 m2). In multivariable models (mean follow-up time 16 years), Stage 3 CKD was marginally associated with CVD (HR=1.17, 95% CI 0.99-1.38, p=0.06), whereas Stage 3b CKD was associated with CVD [HR=1.41, 95% CI 1.05-1.91, p=0.02]. Upon testing CVD risk equivalency, the risk of CVD for Stage 3b CKD among participants with prior CVD was significantly lower as compared to participants with prior CVD and no Stage 3b CKD (age- and sex-adjusted HR for CVD = 0.66 [95% CI 0.47 to 0.91], p=0.01). Low HDL modified the association between CKD and CVD (p-value=0.004 for interaction). Stage 3b CKD is associated with CVD but is not a CVD risk equivalent. In conclusion, CVD risk in the setting of CKD is higher in the setting of low HDL cholesterol. PMID:18572034

Validation of the Framingham general cardiovascular risk score in a multiethnic Asian population: a retrospective cohort study.

PubMed

Chia, Yook Chin; Gray, Sarah Yu Weng; Ching, Siew Mooi; Lim, Hooi Min; Chinna, Karuthan

2015-05-19

This study aims to examine the validity of the Framingham general cardiovascular disease (CVD) risk chart in a primary care setting. This is a 10-year retrospective cohort study. A primary care clinic in a teaching hospital in Malaysia. 967 patients' records were randomly selected from patients who were attending follow-up in the clinic. Baseline demographic data, history of diabetes and smoking, blood pressure (BP), and serum lipids were captured from patient records in 1998. Each patient's Framingham CVD score was computed from these parameters. All atherosclerotic CVD events occurring between 1998 and 2007 were counted. In 1998, mean age was 57 years with 33.8% men, 6.1% smokers, 43.3% diabetics and 59.7% hypertensive. Median BP was 140/80 mm Hg and total cholesterol 6.0 mmol/L (1.3). The predicted median Framingham general CVD risk score for the study population was 21.5% (IQR 1.2-30.0) while the actual CVD events that occurred in the 10 years was 13.1% (127/967). The median CVD points for men was 30.0, giving them a CVD risk of more than 30%; for women it is 18.5, a CVD risk of 21.5%. Our study found that the Framingham general CVD risk score to have moderate discrimination with an area under the receiver operating characteristic curve (AUC) of 0.63. It also discriminates well for Malay (AUC 0.65, p=0.01), Chinese (AUC 0.60, p=0.03), and Indians (AUC 0.65, p=0.001). There was good calibration with Hosmer-Lemeshow test χ(2)=3.25, p=0.78. Taking into account that this cohort of patients were already on treatment, the Framingham General CVD Risk Prediction Score predicts fairly accurately for men and overestimates somewhat for women. In the absence of local risk prediction charts, the Framingham general CVD risk prediction chart is a reasonable alternative for use in a multiethnic group in a primary care setting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Assessment of risk factors for earlier onset of sporadic Alzheimer's disease dementia.

PubMed

de Oliveira, Fabricio Ferreira; Bertolucci, Paulo Henrique Ferreira; Chen, Elizabeth Suchi; Smith, Marilia Cardoso

2014-01-01

Pharmacological treatment has mild effects for patients with Alzheimer's disease dementia (AD); therefore, the search for modifiable risk factors is an important challenge. Though risk factors for AD are widely recognized, elements that influence the time of dementia onset have not been comprehensively reported. We aimed to investigate which risk factors might be related to the age of onset of AD in a sample of patients with highly variable educational levels, taking into account the Framingham risk scoring as the sole measure of vascular risk. We included 209 consecutive late-onset AD patients to find out which factors among educational levels, coronary heart disease risk estimated by way of Framingham risk scores, history of head trauma or depression, surgical procedures under general anesthesia, family history of neurodegenerative diseases, gender, marital status and APOE haplotypes might be related to the age of dementia onset in this sample of patients with low mean schooling. Mean age of AD onset was 73.38±6.5 years old, unaffected by schooling or family history of neurodegenerative diseases. Patients who were APOE-ε4 carriers, married, or with history of depression, had earlier onset of AD, particularly when they were women. Coronary heart disease risk was marginally significant for later onset of AD. APOE haplotypes, marital status and history of depression were the most important factors to influence the age of AD onset in this sample. While midlife cerebrovascular risk factors may increase incidence of AD, they may lead to later dementia onset when present in late life.

Risk factors for ischaemic heart disease in a Cretan rural population: a twelve year follow-up study.

PubMed

Karalis, Ioannis K; Alegakis, Athanasios K; Kafatos, Antonios G; Koutis, Antonios D; Vardas, Panos E; Lionis, Christos D

2007-12-18

Crete has been of great epidemiological interest ever since the publication of the Seven Countries Study. In 1988 a well-defined area of rural Crete was studied, with only scarce signs of coronary heart disease (CHD) despite the unfavorable risk profile. The same population was re-examined twelve years later aiming to describe the trends of CHD risk factors over time and discuss some key points on the natural course of coronary heart disease in a rural population of Crete. We re-examined 200 subjects (80.7% of those still living in the area, 62.4 +/- 17.0 years old). The prevalence of risk factors for CHD was high with 65.9% of men and 65.1% of women being hypertensive, 14.3% of men and 16.5% of women being diabetic, 44% of men being active smokers and more than 40% of both sexes having hyperlipidaemia. Accordingly, 77.5% of the population had a calculated Framingham Risk Score (FRS) > or = 15%, significantly higher compared to baseline (p < 0.001). The overall occurrence rate for CHD events was calculated at 7.1 per 1000 person-years (95% confidence interval: 6.8-7.3). The study confirms the unfavorable risk factor profile of a well defined rural population in Crete. Its actual effect on the observed incidence of coronary events in Cretans remains yet to be defined.

[Cardiovascular risk by Framingham and SCORE in patients 40-65 years old].

PubMed

González, Carmen; Rodilla, Enrique; Costa, José A; Justicia, Jorge; Pascual, José M

2006-04-15

The aim of this study was to compare the clinical and treatment implications of 2 cardiovascular risk stratification systems in a population of patients 40-65 years old. 929 non diabetic patients (40-65 years old) (51% female) with no evidence of previous cardiovascular disease were included in the study. The risk of cardiovascular death was assessed with the charts of the Systematic Coronary Risk Evaluation (SCORE), and coronary risk by the Framingham function (National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults -NCEP-ATP-III-). Patients were considered of high risk if risk of cardiovascular death was >or= 5% and coronary risk was > 20%, respectively. 4.1% of patients were considered as high risk by SCORE and 2.5% by Framingham. Only 0.2% of females were classified as high risk with either system. 8.2% and 4.8% of male population were considered as high risk by SCORE and Framingham, respectively. There was a low level of concordance between both systems. Patients classified as high risk by SCORE but not by Framingham were older, smoke less and had a better lipid profile. According to European Guidelines 28% of male and 23% of female were candidates to hypolipemic treatment, that proportion was higher, 43% of males and 28% of females, by NCEP-ATP-III guidelines. In Spanish patients 40-65 years old, SCORE charts almost duplicate the number of high risk individuals compared to Framingham. although the number of patients candidates to hypolipemic treatment is lower with the European than ATP-III guidelines. Differences were more evident in male.

APOE and mild cognitive impairment: the Framingham Heart Study

PubMed Central

Jefferson, Angela L.; Beiser, Alexa S.; Seshadri, Sudha; Wolf, Philip A.; Au, Rhoda

2015-01-01

Background: the risk apolipoprotein E-4 (APOE4) poses for mild cognitive impairment (MCI) may vary based on the neuropsychological definition of MCI. Setting: a community-based cohort study. Methods: using two psychometric neuropsychological impairment definitions, we examined APOE4 and prevalent MCI among older adults or pre-MCI among middle-aged adults. Neuropsychological, clinical and genetic data were collected on 2,239 Framingham Offspring Cohort participants free from clinical stroke or dementia (62 ± 9 years; 54% women). Prevalent amnestic MCI was defined from neuropsychological performances ≥1.5 SD below the mean based on (i) age and education or (ii) age and Wide Range Achievement Test-3 Reading (WRAT-3 Reading) performance adjustment. Results: in the entire sample, multivariable-adjusted logistic regressions found that APOE4 was associated with amnestic MCI when using the age and WRAT Reading definition (odds ratio [OR] = 1.7, P = 0.002) but not the age and education definition (OR = 1.0, P = 0.90). Results were modified by age, such that APOE4 was associated with amnestic MCI in participants ≥65 years using both the age and WRAT Reading definition (OR = 2.4, P < 0.001) and the age and education definition (OR = 1.7, P = 0.04). Conclusion: APOE4 risk for prevalent amnestic MCI varies depending on the definition of objective neuropsychological impairment for MCI. Our findings support existing literature emphasising the need to refine MCI neuropsychological profiling methods. PMID:25497326

Metabolic dysregulation of the insulin-glucose axis and risk of obesity-related cancers in the Framingham heart study-offspring cohort (1971-2008).

PubMed

Parekh, Niyati; Lin, Yong; Vadiveloo, Maya; Hayes, Richard B; Lu-Yao, Grace L

2013-10-01

Obesity-related dysregulation of the insulin-glucose axis is hypothesized in carcinogenesis. We studied impaired fasting glucose (IFG) and other markers of insulin-glucose metabolism in the Framingham Heart Study-Offspring Cohort, which uniquely tracks these markers and cancer >37 years. Participants were recruited between 1971 and 1975 and followed until 2008 (n = 4,615; mean age 66.8 years in 2008). Serum glucose, insulin, and hemoglobin A1c were determined from fasting blood in quart-annual exams. Lifestyle and demographic information was self-reported. HRs and 95% confidence intervals (CI) of cancer risk were computed using time-dependent survival analysis (SASv9.3), while accounting for temporal changes for relevant variables. We identified 787 obesity-related cancers, including 136 colorectal, 217 breast, and 219 prostate cancers. Absence versus presence of IFG 10 to 20 years and 20+ years before the event or last follow-up was associated with 44% (95% CI, 1.15-1.79) and 57% (95% CI, 1.17-2.11) increased risk of obesity-related cancers, respectively. When time-dependent variables were used, after adjusting for age, sex, smoking, alcohol, and body mass index, IFG was associated with a 27% increased risk of obesity-related cancer (HR = 1.27; CI, 1.1-1.5). Associations were stronger in smokers (HR = 1.41; CI, 1.13-1.76). Increased risk was noted among persons with higher insulin (HR = 1.47; CI, 1.15-1.88) and hemoglobin A1c (HR = 1.54; CI, 1.13-2.10) for the highest (≥ 5.73%) versus lowest (≤ 5.25%) category. A >2-fold increase in colorectal cancer risk was observed for all blood biomarkers of insulin-glucose metabolism, particularly with earlier IFG exposure. Nonsignificant increased risk of breast and prostate cancer was observed for blood biomarkers. Earlier IFG exposure (>10 years before) increased obesity-related cancer risk, particularly for colorectal cancer. Our study explicitly recognizes the importance of prolonged IFG exposure in identifying links between glucose dysregulation and obesity-related cancers.

Association Between Cardiovascular Risk Factors and Carpal Tunnel Syndrome in Pooled Occupational Cohorts.

PubMed

Hegmann, Kurt T; Thiese, Matthew Steven; Kapellusch, Jay; Merryweather, Andrew S; Bao, Stephen; Silverstein, Barbara; Wood, Eric M; Kendall, Richard; Wertsch, Jacqueline; Foster, James; Garg, Arun; Drury, David L

2016-01-01

The aim of the study was to ascertain if cardiovascular (CVD) risk factors are carpal tunnel syndrome (CTS) risk factors. Analysis of pooled baseline data from two large prospective cohort studies (n = 1824) assessed the relationships between a modified Framingham Heart Study CVD risk score both CTS and abnormal nerve conduction study prevalence. Quantified job exposures, personal and psychosocial confounders were statistically controlled. Odds ratio and 95% confidence intervals were calculated for individual risk scores. There was a strong relationship between CVD risk score and both CTS and abnormal nerve conduction study after adjustment for confounders, with odds ratios as high as 4.16 and 7.35, respectively. Dose responses were also observed. In this workplace population, there is a strong association between CVD risk scores and both CTS and abnormal nerve conduction study that persisted after controlling for confounders. These data suggest a potentially modifiable disease mechanism.

The position of the arm during blood pressure measurement in sitting position.

PubMed

Adiyaman, Ahmet; Verhoeff, Rutger; Lenders, Jacques W M; Deinum, Jaap; Thien, Theo

2006-12-01

Determining the influence of the position of the arm on blood pressure measurement in the sitting position. Blood pressure of 128 individuals (the majority being treated hypertensive patients) visiting the outpatient clinic was measured simultaneously on both arms with arms in two different positions. First, both arms were placed at the chair support level and blood pressure was measured three times on both arms after 10 min of rest. Subsequently, while still remaining in the same sitting position, five blood pressure measurements were made simultaneously at both arms with one arm placed on the desk and one arm placed and supported at heart level (mid-sternal). The arm placed at heart level served as the reference arm. The choice of which arm was placed at desk level and which arm was placed at heart level was randomized. Both at desk level and at chair support level, mean (+/-SD) systolic and diastolic blood pressures were higher than blood pressure at heart level by 6.1/5.7+/-4.6/3.1 and 9.3/9.4+/-5.4/3.4 mmHg, respectively. The effect of the height differences between the arm positions on the blood pressure readings was smaller than predicted (0.49 mmHg/cm systolic and 0.47 mmHg/cm diastolic). No significant correlation was found between blood pressure difference in the different arm positions (desk and heart level) and age, sex, weight or baseline blood pressure. Different arm positions below heart level have significant effects on blood pressure readings. The leading guidelines about arm position during blood pressure measurement are not in accordance with the arm position used in the Framingham study, the most frequently used study for risk estimations.

Concordance with World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines for cancer prevention and obesity-related cancer risk in the Framingham Offspring cohort (1991-2008)

USDA-ARS?s Scientific Manuscript database

Purpose: This prospective cohort study evaluates associations between healthful behaviors consistent with WCRF/AICR cancer prevention guidelines and obesity-related cancer risk, as a third of cancers are estimated to be preventable. Methods: The study sample consisted of adults from the Framingham O...

Cardiovascular Risk and Level of Statin Use Among Women With Breast Cancer in a Cardio-Oncology Clinic.

PubMed

Shum, Kelly; Solivan, Amber; Parto, Parham; Polin, Nichole; Jahangir, Eiman

2016-01-01

Because of the improvements in survival rates, patients with breast cancer are now more likely to die from cardiovascular disease than from cancer. Thus, providing appropriate preventive cardiovascular care to patients with cancer is of the utmost importance. We retrospectively compared the cardiovascular risk and management of 146 women treated at the Cardio-Oncology (Cardio-Onc) and the Obstetrics and Gynecology (Ob-Gyn) clinics. We calculated cardiovascular risk using the American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk calculator and the Framingham Risk Score Calculator. We also determined the prevalence of appropriate statin use according to both the 2013 ACC/AHA and the 2002 Adult Treatment Panel (ATP) III lipid guidelines. The 10-year ASCVD risk score was not significantly different between the 2 cohorts. More patients in the Ob-Gyn cohort with an ASCVD risk score >7.5% were already appropriately on statins compared to patients in the Cardio-Onc cohort (60.9% vs 31.0%, respectively, P=0.003), but after the first Cardio-Onc visit, 4 additional patients with breast cancer were prescribed statins (44.8% total). Fourteen (19.2%) Cardio-Onc patients had a high Framingham Risk Score compared to 6 (8.2%) Ob-Gyn patients. We demonstrated that the ASCVD risk is similar between women with breast cancer attending the Cardio-Onc clinic and the women without breast cancer attending the Ob-Gyn clinic, but the Cardio-Onc cohort had significantly more patients with a high Framingham Risk Score. Both clinics had similarly poor rates of appropriate statin prescribing rates according to the ATP III guidelines.

Cardiovascular Risk and Level of Statin Use Among Women With Breast Cancer in a Cardio-Oncology Clinic

PubMed Central

Shum, Kelly; Solivan, Amber; Parto, Parham; Polin, Nichole; Jahangir, Eiman

2016-01-01

Background: Because of the improvements in survival rates, patients with breast cancer are now more likely to die from cardiovascular disease than from cancer. Thus, providing appropriate preventive cardiovascular care to patients with cancer is of the utmost importance. Methods: We retrospectively compared the cardiovascular risk and management of 146 women treated at the Cardio-Oncology (Cardio-Onc) and the Obstetrics and Gynecology (Ob-Gyn) clinics. We calculated cardiovascular risk using the American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk calculator and the Framingham Risk Score Calculator. We also determined the prevalence of appropriate statin use according to both the 2013 ACC/AHA and the 2002 Adult Treatment Panel (ATP) III lipid guidelines. Results: The 10-year ASCVD risk score was not significantly different between the 2 cohorts. More patients in the Ob-Gyn cohort with an ASCVD risk score >7.5% were already appropriately on statins compared to patients in the Cardio-Onc cohort (60.9% vs 31.0%, respectively, P=0.003), but after the first Cardio-Onc visit, 4 additional patients with breast cancer were prescribed statins (44.8% total). Fourteen (19.2%) Cardio-Onc patients had a high Framingham Risk Score compared to 6 (8.2%) Ob-Gyn patients. Conclusion: We demonstrated that the ASCVD risk is similar between women with breast cancer attending the Cardio-Onc clinic and the women without breast cancer attending the Ob-Gyn clinic, but the Cardio-Onc cohort had significantly more patients with a high Framingham Risk Score. Both clinics had similarly poor rates of appropriate statin prescribing rates according to the ATP III guidelines. PMID:27660568

Usefulness of the Left Ventricular Myocardial Contraction Fraction in Healthy Men and Women to Predict Cardiovascular Morbidity and Mortality

PubMed Central

Chuang, Michael L.; Gona, Philimon; Salton, Carol J.; Yeon, Susan B.; Kissinger, Kraig V.; Blease, Susan J.; Levy, Daniel; O'Donnell, Christopher J.; Manning, Warren J.

2013-01-01

We sought to determine whether depressed myocardial contraction fraction (MCF, the ratio of left ventricular (LV) stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (N=318, 60±9 yrs, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance (CMR) imaging in 1998–1999. LV ejection fraction (EF), mass and MCF were determined. “Hard” CVD events comprised cardiovascular death, myocardial infarction, stroke or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score (FCRS) was used to estimate hazard ratios for incident hard CVD events for sex-specific quartiles of MCF, LV mass and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referent. Kaplan-Meier survival plots and the log rank test were used to compare event-free survival. MCF was greater in women (0.58±0.13) than men (0.52±0.11), p<0.01. Nearly all (99%) participants had EF ≥ 0.55. Over up to 9-year (median 5.2) follow-up, 31 participants (10%) experienced an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop hard CVD (hazard ratio 7.11, p=0.010) compared to the lowest quartile, and the elevated hazards persisted even after adjustment for LV mass (hazard ratio=6.09, p=0.020). The highest-quartile LV mass/height2.7 had nearly five-fold risk (hazard ratio 4.68, p=0.016). Event-free survival was shorter in lowest-quartile MCF, p = 0.0006, but not in lowest-quartile LVEF. Conclusion: In a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass. PMID:22381161

Usefulness of the left ventricular myocardial contraction fraction in healthy men and women to predict cardiovascular morbidity and mortality.

PubMed

Chuang, Michael L; Gona, Philimon; Salton, Carol J; Yeon, Susan B; Kissinger, Kraig V; Blease, Susan J; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J

2012-05-15

We sought to determine whether depressed myocardial contraction fraction (MCF; ratio of left ventricular [LV] stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (n = 318, 60 ± 9 years old, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance imaging in 1998 through 1999. LV ejection fraction (EF), mass, and MCF were determined. "Hard" CVD events consisted of cardiovascular death, myocardial infarction, stroke, or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score was used to estimate hazard ratios for incident hard CVD events for gender-specific quartiles of MCF, LV mass, and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referents. Kaplan-Meier survival plots and log-rank test were used to compare event-free survival. MCF was greater in women (0.58 ± 0.13) than in men (0.52 ± 0.11, p <0.01). Nearly all participants (99%) had EF ≥0.55. During an up to 9-year follow-up (median 5.2), 31 participants (10%) developed an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop a hard CVD (hazard ratio 7.11, p = 0.010) compared to the remaining quartiles, and increased hazards persisted even after adjustment for LV mass (hazard ratio 6.09, p = 0.020). The highest-quartile LV mass/height 2.7 had a nearly fivefold risk (hazard ratio 4.68, p = 0.016). Event-free survival was shorter in lowest-quartile MCF (p = 0.0006) but not in lowest-quartile LVEF. In conclusion, in a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass. Copyright © 2012 Elsevier Inc. All rights reserved.

Validity of the Framingham point scores in the elderly: results from the Rotterdam study.

PubMed

Koller, Michael T; Steyerberg, Ewout W; Wolbers, Marcel; Stijnen, Theo; Bucher, Heiner C; Hunink, M G Myriam; Witteman, Jacqueline C M

2007-07-01

The National Cholesterol Education Program recommends assessing 10-year risk of coronary heart disease (CHD) in individuals free of established CHD with the Framingham Point Scores (FPS). Individuals with a risk >20% are classified as high risk and are candidates for preventive intervention. We aimed to validate the FPS in a European population of elderly subjects. Subjects free of established CHD at baseline were selected from the Rotterdam study, a population-based cohort of subjects 55 years or older in The Netherlands. We studied calibration, discrimination (c-index), and the accuracy of high-risk classifications. Events consisted of fatal CHD and nonfatal myocardial infarction. Among 6795 subjects, 463 died because of CHD and 336 had nonfatal myocardial infarction. Predicted 10-year risk of CHD was on average well calibrated for women (9.9% observed vs 10.1% predicted) but showed substantial overestimation in men (14.3% observed vs 19.8% predicted), particularly with increasing age. This resulted in substantial number of false-positive classifications (specificity 70%) in men. In women, discrimination of the FPS was better than that in men (c-index 0.73 vs 0.63, respectively). However, because of the low baseline risk of CHD and limited discriminatory power, only 33% of all CHD events occurred in women classified as high risk. The FPS need recalibration for elderly men with better incorporation of the effect of age. In elderly women, FPS perform reasonably well. However, maintaining the rational of the high-risk threshold requires better performing models for a population with low incidence of CHD.

A comparison of time dependent Cox regression, pooled logistic regression and cross sectional pooling with simulations and an application to the Framingham Heart Study.

PubMed

Ngwa, Julius S; Cabral, Howard J; Cheng, Debbie M; Pencina, Michael J; Gagnon, David R; LaValley, Michael P; Cupples, L Adrienne

2016-11-03

Typical survival studies follow individuals to an event and measure explanatory variables for that event, sometimes repeatedly over the course of follow up. The Cox regression model has been used widely in the analyses of time to diagnosis or death from disease. The associations between the survival outcome and time dependent measures may be biased unless they are modeled appropriately. In this paper we explore the Time Dependent Cox Regression Model (TDCM), which quantifies the effect of repeated measures of covariates in the analysis of time to event data. This model is commonly used in biomedical research but sometimes does not explicitly adjust for the times at which time dependent explanatory variables are measured. This approach can yield different estimates of association compared to a model that adjusts for these times. In order to address the question of how different these estimates are from a statistical perspective, we compare the TDCM to Pooled Logistic Regression (PLR) and Cross Sectional Pooling (CSP), considering models that adjust and do not adjust for time in PLR and CSP. In a series of simulations we found that time adjusted CSP provided identical results to the TDCM while the PLR showed larger parameter estimates compared to the time adjusted CSP and the TDCM in scenarios with high event rates. We also observed upwardly biased estimates in the unadjusted CSP and unadjusted PLR methods. The time adjusted PLR had a positive bias in the time dependent Age effect with reduced bias when the event rate is low. The PLR methods showed a negative bias in the Sex effect, a subject level covariate, when compared to the other methods. The Cox models yielded reliable estimates for the Sex effect in all scenarios considered. We conclude that survival analyses that explicitly account in the statistical model for the times at which time dependent covariates are measured provide more reliable estimates compared to unadjusted analyses. We present results from the Framingham Heart Study in which lipid measurements and myocardial infarction data events were collected over a period of 26 years.

Clinical associations of total kidney volume: the Framingham Heart Study.

PubMed

Roseman, Daniel A; Hwang, Shih-Jen; Oyama-Manabe, Noriko; Chuang, Michael L; O'Donnell, Christopher J; Manning, Warren J; Fox, Caroline S

2017-08-01

Total kidney volume (TKV) is an imaging biomarker that may have diagnostic and prognostic utility. The relationships between kidney volume, renal function and cardiovascular disease (CVD) have not been characterized in a large community-dwelling population. This information is needed to advance the clinical application of TKV. We measured TKV in 1852 Framingham Heart Study participants (mean age 64.1 ± 9.2 years, 53% women) using magnetic resonance imaging. A healthy sample was used to define reference values. The associations between TKV, renal function and CVD risk factors were determined using multivariable logistic regression analysis. Overall, mean TKV was 278 ± 54 cm3 for women and 365 ± 66 cm3 for men. Risk factors for high TKV (>90% healthy referent size) were body surface area (BSA), diabetes, smoking and albuminuria, while age, female and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 were protective. Participants with high TKV had higher odds of diabetes [odds ratio (OR) 2.15, P < 0.001] and lower odds of eGFR <60 mL/min/1.73 m2 (OR 0.32, P = 0.007). Risk factors for low TKV (<10% healthy referent size) were age, female and eGFR <60 mL/min/1.73 m2, while BSA and diabetes were protective. Participants with low TKV had higher odds of eGFR <60 mL/min/1.73 m2 (OR 6.12, P < 0.001) and albuminuria (OR 1.56, P = 0.03). Low TKV is associated with markers of kidney damage including albuminuria and eGFR <60 mL/min/1.73 m2, while high TKV is associated with diabetes and decreased odds of eGFR <60 mL/min/1.73 m2. Prospective studies are needed to characterize the natural progression and clinical consequences of TKV. Published by Oxford University Press on behalf of ERA-EDTA 2016. This work is written by US Government employees and is in the public domain in the US.

Genomic variation associated with mortality among adults of European and African ancestry with heart failure: the cohorts for heart and aging research in genomic epidemiology consortium.

PubMed

Morrison, Alanna C; Felix, Janine F; Cupples, L Adrienne; Glazer, Nicole L; Loehr, Laura R; Dehghan, Abbas; Demissie, Serkalem; Bis, Joshua C; Rosamond, Wayne D; Aulchenko, Yurii S; Wang, Ying A; Haritunians, Talin; Folsom, Aaron R; Rivadeneira, Fernando; Benjamin, Emelia J; Lumley, Thomas; Couper, David; Stricker, Bruno H; O'Donnell, Christopher J; Rice, Kenneth M; Chang, Patricia P; Hofman, Albert; Levy, Daniel; Rotter, Jerome I; Fox, Ervin R; Uitterlinden, Andre G; Wang, Thomas J; Psaty, Bruce M; Willerson, James T; van Duijn, Cornelia M; Boerwinkle, Eric; Witteman, Jacqueline C M; Vasan, Ramachandran S; Smith, Nicholas L

2010-06-01

Prognosis and survival are significant concerns for individuals with heart failure (HF). To better understand the pathophysiology of HF prognosis, the association between 2,366,858 single-nucleotide polymorphisms (SNPs) and all-cause mortality was evaluated among individuals with incident HF from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Participants were 2526 individuals of European ancestry and 466 individuals of African ancestry who experienced an incident HF event during follow-up in the respective cohorts. Within each study, the association between genetic variants and time to mortality among individuals with HF was assessed by Cox proportional hazards models that included adjustment for sex and age at the time of the HF event. Prospective fixed-effect meta-analyses were conducted for the 4 study populations of European ancestry (N=1645 deaths) and for the 2 populations of African ancestry (N=281 deaths). Genome-wide significance was set at P=5.0x10(-7). Meta-analytic findings among individuals of European ancestry revealed 1 genome-wide significant locus on chromosome 3p22 in an intron of CKLF-like MARVEL transmembrane domain containing 7 (CMTM7, P=3.2x10(-7)). Eight additional loci in individuals of European ancestry and 4 loci in individuals of African ancestry were identified by high-signal SNPs (P<1.0x10(-5)) but did not meet genome-wide significance. This study identified a novel locus associated with all-cause mortality among individuals of European ancestry with HF. This finding warrants additional investigation, including replication, in other studies of HF.

Trade-offs in the effects of the apolipoprotein E polymorphism on risks of diseases of the heart, cancer, and neurodegenerative disorders: insights on mechanisms from the Long Life Family Study.

PubMed

Kulminski, Alexander M; Arbeev, Konstantin G; Culminskaya, Irina; Ukraintseva, Svetlana V; Stallard, Eric; Province, Michael A; Yashin, Anatoli I

2015-04-01

The lack of evolutionary established mechanisms linking genes to age-related traits makes the problem of genetic susceptibility to health span inherently complex. One complicating factor is genetic trade-off. Here we focused on long-living participants of the Long Life Family Study (LLFS), their offspring, and spouses to: (1) Elucidate whether trade-offs in the effect of the apolipoprotein E e4 allele documented in the Framingham Heart Study (FHS) are a more general phenomenon, and (2) explore potential mechanisms generating age- and gender-specific trade-offs in the effect of the e4 allele on cancer, diseases of the heart, and neurodegenerative disorders assessed retrospectively in the LLFS populations. The e4 allele can diminish risks of cancer and diseases of the heart and confer risks of diseases of the heart in a sex-, age-, and LLFS-population-specific manner. A protective effect against cancer is seen in older long-living men and, potentially, their sons (>75 years, relative risk [RR]>75=0.48, p=0.086), which resembles our findings in the FHS. The protective effect against diseases of the heart is limited to long-living older men (RR>76=0.50, p=0.016), as well. A detrimental effect against diseases of the heart is characteristic for a normal LLFS population of male spouses and is specific for myocardial infarction (RR=3.07, p=2.1×10(-3)). These trade-offs are likely associated with two inherently different mechanisms, including disease-specific (detrimental; characteristic for a normal male population) and systemic, aging-related (protective; characteristic for older long-living men) mechanisms. The e4 allele confers risks of neurological disorders in men and women (RR=1.98, p=0.046). The results highlight the complex role of the e4 allele in genetic susceptibility to health span.

Chronobiology of death in heart failure.

PubMed

Ribas, Nuria; Domingo, Maite; Gastelurrutia, Paloma; Ferrero-Gregori, Andreu; Rull, Pilar; Noguero, Mariana; Garcia, Carmen; Puig, Teresa; Cinca, Juan; Bayes-Genis, Antoni

2014-05-01

In the general population, heart events occur more often during early morning, on Mondays, and during winter. However, the chronobiology of death in heart failure has not been analyzed. The aim of this study was to determine the circadian, day of the week, and seasonal variability of all-cause mortality in chronic heart failure. This was an analysis of all consecutive heart failure patients followed in a heart failure unit from January 2003 to December 2008. The circadian moment of death was analyzed at 6-h intervals and was determined by reviewing medical records and by information provided by the relatives. Of 1196 patients (mean [standard deviation] age, 69 [13] years; 62% male), 418 (34.9%) died during a mean (standard deviation) follow-up of 29 (21) months. Survivors were younger, had higher body mass index, left ventricular ejection fraction, glomerular filtration rate, hemoglobin and sodium levels, and lower Framingham risk scores, amino-terminal pro-B type natriuretic peptide, troponin T, and urate values. They were more frequently treated with angiotensin receptor blockers, beta-blockers, mineralocorticoids receptor antagonists, digoxin, nitrates, hydralazine, statins, loop diuretics, and thiazides. The analysis of the circadian and weekly variability did not reveal significant differences between the four 6-h intervals or the days of the week. Mortality occurred more frequently during the winter (30.6%) compared with the other seasons (P = .024). All cause mortality does not follow a circadian pattern, but a seasonal rhythm in patients with heart failure. This finding is in contrast to the circadian rhythmicity of cardiovascular events reported in the general population. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Predicting survival in heart failure case and control subjects by use of fully automated methods for deriving nonlinear and conventional indices of heart rate dynamics

NASA Technical Reports Server (NTRS)

Ho, K. K.; Moody, G. B.; Peng, C. K.; Mietus, J. E.; Larson, M. G.; Levy, D.; Goldberger, A. L.

1997-01-01

BACKGROUND: Despite much recent interest in quantification of heart rate variability (HRV), the prognostic value of conventional measures of HRV and of newer indices based on nonlinear dynamics is not universally accepted. METHODS AND RESULTS: We have designed algorithms for analyzing ambulatory ECG recordings and measuring HRV without human intervention, using robust methods for obtaining time-domain measures (mean and SD of heart rate), frequency-domain measures (power in the bands of 0.001 to 0.01 Hz [VLF], 0.01 to 0.15 Hz [LF], and 0.15 to 0.5 Hz [HF] and total spectral power [TP] over all three of these bands), and measures based on nonlinear dynamics (approximate entropy [ApEn], a measure of complexity, and detrended fluctuation analysis [DFA], a measure of long-term correlations). The study population consisted of chronic congestive heart failure (CHF) case patients and sex- and age-matched control subjects in the Framingham Heart Study. After exclusion of technically inadequate studies and those with atrial fibrillation, we used these algorithms to study HRV in 2-hour ambulatory ECG recordings of 69 participants (mean age, 71.7+/-8.1 years). By use of separate Cox proportional-hazards models, the conventional measures SD (P<.01), LF (P<.01), VLF (P<.05), and TP (P<.01) and the nonlinear measure DFA (P<.05) were predictors of survival over a mean follow-up period of 1.9 years; other measures, including ApEn (P>.3), were not. In multivariable models, DFA was of borderline predictive significance (P=.06) after adjustment for the diagnosis of CHF and SD. CONCLUSIONS: These results demonstrate that HRV analysis of ambulatory ECG recordings based on fully automated methods can have prognostic value in a population-based study and that nonlinear HRV indices may contribute prognostic value to complement traditional HRV measures.

Management of pump thrombosis in patients with left ventricular assist devices.

PubMed

Stulak, John M; Sharma, Shashank; Maltais, Simon

2015-04-01

The gradual evolution of left ventricular assist device (LVAD) therapy has resulted in a durable option for patients as either a bridge to transplantation (BTT) or a destination therapy (DT). Outcomes with current continuous-flow devices continue to demonstrate significant patient benefit, not only in enhanced survival but also in improved functional capacity and quality of life. While the lessening of adverse events through time has resulted in more widespread adoption of this therapy, there continues to be unintended consequences, including, most notably, infection, bleeding, and thrombosis. Beginning in 2011, centers and collaborative groups began to observe a significant increase in the incidence of pump thrombosis with the HeartMate II LVAD (Thoratec Corp., Pleasanton, CA, USA). However, this clinical scourge is not limited to the HeartMate II, as the HeartWare Ventricular Assist System (HVAD; HeartWare Inc., Framingham, MA, USA) has also had these same issues, which led to pump modifications and the appreciation of more strict control of blood pressure and anticoagulation with this pump design. We review the current status of the field of mechanical circulatory support in its approach to diagnosis, management, and prevention of LVAD pump thrombosis.

Association Between Cardiovascular Disease Risk Factors and Rotator Cuff Tendinopathy: A Cross-Sectional Study.

PubMed

Applegate, Kara Arnold; Thiese, Matthew S; Merryweather, Andrew S; Kapellusch, Jay; Drury, David L; Wood, Eric; Kendall, Richard; Foster, James; Garg, Arun; Hegmann, Kurt T

2017-02-01

Recent evidence has found potential associations between cardiovascular disease (CVD) risk factors and common musculoskeletal disorders. We evaluated possible associations between risk factors and both glenohumeral joint pain and rotator cuff tendinopathy. Data from WISTAH hand study participants (n = 1226) were assessed for associations between Framingham Heart Study CVD risk factors and both health outcomes. A strong association was observed between CVD risk scores and both glenohumeral joint pain and rotator cuff tendinopathy. Peak odds ratios (ORs) of the adjusted models were 4.55 [95% confidence interval (95% CI) 1.97 to 10.31] and 5.97 (95% CI 2.12 to 16.83), respectively. The results show a dose-response trend of increasing risk. Individual risk factors were associated with both outcomes. Combined, CVD risk factors demonstrated a strong correlation with glenohumeral joint pain and an even stronger correlation with rotator cuff tendinopathy. Results suggest a potentially modifiable disease mechanism.

A longitudinal study of trunk muscle properties and severity of thoracic kyphosis in women and men: The Framingham Study.

PubMed

Lorbergs, Amanda L; Allaire, Brett T; Yang, Laiji; Kiel, Douglas P; Cupples, L Adrienne; Jarraya, Mohamed; Guermazi, Ali; Travison, Thomas G; Bouxsein, Mary L; Anderson, Dennis E; Samelson, Elizabeth J

2018-04-24

Cross-sectional studies suggest that trunk muscle morphology in the lumbar spine is an important determinant of kyphosis severity in older adults. The contribution of age-related changes in muscle morphology in the thoracic and lumbar spine to progression of kyphosis is not known. Our objective was to determine cross-sectional and longitudinal associations of thoracic and lumbar muscle size and density with kyphosis. Participants were 1,087 women and men (mean age 61y) of the Framingham Heart Study who underwent baseline and follow-up quantitative computed tomography (QCT) scanning 6y apart. We used QCT scans to measure trunk muscle cross-sectional area (CSA, cm2) and density (HU) at the thoracic and lumbar spine and Cobb angle (degrees) from T4 to T12. Linear regression models estimated the association between muscle morphology and kyphosis. At baseline, smaller muscle CSA and lower density of thoracic (but not lumbar) spine muscles were associated with a larger (worse) Cobb angle in women and men. For example, each standard deviation (SD) decrease in baseline thoracic paraspinal muscle CSA was associated with a larger baseline Cobb angle in women (3.7°, 95%CI:2.9, 4.5) and men (2.5°, 95%CI:1.6, 3.3). Longitudinal analyses showed that loss of muscle CSA and density at the thoracic and lumbar spine was not associated with progression of kyphosis. Our findings suggest that kyphosis severity is related to smaller and lower density trunk muscles at the thoracic spine. Future studies are needed to determine how strengthening mid-back musculature alters muscle properties and contributes to preventing kyphosis progression.

Does fibrinogen add to prediction of cardiovascular disease? Results from the Scottish Heart Health Extended Cohort Study.

PubMed

Woodward, Mark; Tunstall-Pedoe, Hugh; Rumley, Ann; Lowe, Gordon D O

2009-08-01

Plasma fibrinogen is an established risk factor for cardiovascular disease (CVD), but it has not been established whether it adds predictive value to risk scores. In the Scottish Heart Health Extended Cohort Study, we measured plasma fibrinogen in 13 060 men and women, aged 30-74 years, initially free of CVD. After follow-up for a median of 19.2 years, 2626 subjects had at least one CVD event. After adjusting for classical CVD risk factors and socio-economic status, the hazard ratios (95% confidence interval) for a one unit (g/l) increase in plasma fibrinogen were 1.09 (1.02, 1.16) for men and 1.10 (1.02, 1.19) for women. Although fibrinogen added significantly to the discrimination of the Framingham risk score for women, it failed to do so for men. Fibrinogen did not add significantly to the ASSIGN risk score. Fibrinogen added between 1.3% and 3.2% to the classification of CVD status by the existing risk scores. We conclude that the added value of fibrinogen to two currently used risk scores is low; hence population screening with fibrinogen for this purpose is unlikely to be clinically useful or cost-effective.

Personal coronary risk profiles modify autonomic nervous system responses to air pollution.

PubMed

Chen, Jiu-Chiuan; Stone, Peter H; Verrier, Richard L; Nearing, Bruce D; MacCallum, Gail; Kim, Jee-Young; Herrick, Robert F; You, Jinhong; Zhou, Haibo; Christiani, David C

2006-11-01

We investigated whether PM2.5-mediated autonomic modulation depends on individual coronary risk profiles. Five-minute average heart rate (HR) and heart rate variability (HRV, including standard deviation of normal-to-normal intervals [SDNN], square root of the mean squared differences of successive NN intervals [rMSSD], high frequency [HF]) were measured from 24-hour ambulatory electrocardiograms, and personal PM(2.5) exposures were monitored in a prospective study of 10 male boilermakers (aged 34.3 +/- 8.1 years). We used the Framingham score to classify individuals into low (score = 1-3) and high (score = 5-6) risk categories. Mixed-effect models were used for statistical analyses. Each 1-mg/m(3) increase in the preceding 4-hour moving average PM(2.5) was associated with HR increase (5.3 beats/min) and HRV reduction (11.7%, confidence interval [CI] = 6.2-17.1% for SDNN; 11.1%, CI = 3.1-19.1% for rMSSD; 16.6%, CI = 1.5-31.7% for HF). Greater responses (2- to 4-fold differences) were observed in high-risk subjects than in low-risk subjects. Our study suggests that adverse autonomic responses to metal particulate are aggravated in workers with higher coronary risk profiles.

Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score.

PubMed

Souza-Nogueira, Andre de; Camargo, Alissana Ester; Remondi, Felipe Assan; Paoliello, Monica Maria Bastos; Richter, Rebecca J; Furlong, Clement E; Barbosa, Decio Sabbatini; Maes, Michael; Moreira, Estefania Gastaldello

2016-10-01

Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.

Left ventricular ejection time is an independent predictor of incident heart failure in a community-based cohort.

PubMed

Biering-Sørensen, Tor; Querejeta Roca, Gabriela; Hegde, Sheila M; Shah, Amil M; Claggett, Brian; Mosley, Thomas H; Butler, Kenneth R; Solomon, Scott D

2017-09-04

Systolic time intervals change in the progress of cardiac dysfunction. The usefulness of left ventricular ejection time (LVET) to predict cardiovascular morbidity, however, is unknown. We studied middle-aged African-Americans from one of four cohorts of the Atherosclerosis Risk in Communities study (Jackson cohort, n=1980) who underwent echocardiography between 1993 and 1995. Left ventricular ejection time was measured by pulsed-wave Doppler of the left ventricular outflow tract and related to outcomes. A shorter LVET was associated with younger age, male sex, higher diastolic blood pressure, higher proportion of diabetes, higher heart rate, higher blood glucose levels and worse fractional shortening. During a median follow-up of 17.6 years, 384 (19%) had incident heart failure (HF), 158 (8%) had a myocardial infarction, and 587 (30%) died. In univariable analysis, a lower LVET was significantly associated with increased risk of all events (P<0.05 for all). However, after multivariable adjustment for age, sex, hypertension, diabetes, body mass index, heart rate, systolic and diastolic blood pressure, fractional shortening and left atrial diameter, LVET remained an independent predictor only of incident HF [hazard ratio 1.07 (1.02-1.14), P=0.010 per 10 ms decrease]. In addition, LVET provided incremental prognostic information to the known risk factors included in the Framingham risk score, in regard to predicting all outcomes except for myocardial infarction. Left ventricular ejection time is an independent predictor of incident HF in a community-based cohort and provides incremental prognostic information on the risk of future HF and death when added to known risk prediction models. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Gastric Bypass Surgery Produces a Durable Reduction in Cardiovascular Disease Risk Factors and Reduces the Long-Term Risks of Congestive Heart Failure.

PubMed

Benotti, Peter N; Wood, G Craig; Carey, David J; Mehra, Vishal C; Mirshahi, Tooraj; Lent, Michelle R; Petrick, Anthony T; Still, Christopher; Gerhard, Glenn S; Hirsch, Annemarie G

2017-05-23

Obesity and its association with reduced life expectancy are well established, with cardiovascular disease as one of the major causes of fatality. Metabolic surgery is a powerful intervention for severe obesity, resulting in improvement in comorbid diseases and in cardiovascular risk factors. This study investigates the relationship between metabolic surgery and long-term cardiovascular events. A cohort of Roux-en-Y gastric bypass surgery (RYGB) patients was tightly matched by age, body mass index, sex, Framingham Risk Score, smoking history, use of antihypertension medication, diabetes mellitus status, and calendar year with a concurrent cohort of nonoperated control patients. The primary study end points of major cardiovascular events (myocardial infarction, stroke, and congestive heart failure) were evaluated using Cox regression. Secondary end points of longitudinal cardiovascular risk factors were evaluated using repeated-measures regression. The RYGB and matched controls (N=1724 in each cohort) were followed for up to 12 years after surgery (overall median of 6.3 years). Kaplan-Meier analysis revealed a statistically significant reduction in incident major composite cardiovascular events ( P =0.017) and congestive heart failure (0.0077) for the RYGB cohort. Adjusted Cox regression models confirmed the reductions in severe composite cardiovascular events in the RYGB cohort (hazard ratio=0.58, 95% CI=0.42-0.82). Improvements of cardiovascular risk factors (eg, 10-year cardiovascular risk score, total cholesterol, high-density lipoprotein, systolic blood pressure, and diabetes mellitus) were observed within the RYGB cohort after surgery. Gastric bypass is associated with a reduced risk of major cardiovascular events and the development of congestive heart failure. © 2017 The Authors and Geisinger Clinic. Published on behalf of the American Heart Association, Inc., by Wiley.

Relationship between two indicators of coronary risk estimated by the Framingham Risk Score and the number of metabolic syndrome components in Japanese male manufacturing workers.

PubMed

Kawada, Tomoyuki; Otsuka, Toshiaki; Inagaki, Hirofumi; Wakayama, Yoko; Li, Qing; Katsumata, Masao

2009-10-01

The Framingham Risk Score (FRS) has frequently been used in the United States to predict the 10-year risk of coronary heart disease (CHD). Components of the metabolic syndrome and several lifestyle factors have also been evaluated to estimate the risk of CHD. To determine the relationship between the FRS and components of metabolic syndrome as coronary risk indicators, the authors conducted a cross-sectional study of 2,619 Japanese male workers, ranging in age from 40 to 64 years, at a single workplace. Although the estimation by the FRS and metabolic syndrome involved some different factors, significant association of the risk estimated by the 2 methods was observed. When logistic regression analysis was conducted with adjustment for several lifestyle factors, the FRS and serum insulin were found to be significantly associated with the risk of likelihood of metabolic syndrome. The odds ratios and 95% confidence intervals of FRS by per standard deviation increment and serum insulin by increasing 1 microIU/mL for the prediction of metabolic syndrome were 2.50 (2.17-2.88) and 1.24 (1.20-1.27), respectively. A preventive effect of abstaining from drinking every day and eating breakfast almost daily against the likelihood of metabolic syndrome was also observed. In conclusion, the FRS and insulin were found to be significantly associated with the risk of likelihood of metabolic syndrome, even after controlling for weight change.

Cardiac index is associated with brain aging: the Framingham Heart Study.

PubMed

Jefferson, Angela L; Himali, Jayandra J; Beiser, Alexa S; Au, Rhoda; Massaro, Joseph M; Seshadri, Sudha; Gona, Philimon; Salton, Carol J; DeCarli, Charles; O'Donnell, Christopher J; Benjamin, Emelia J; Wolf, Philip A; Manning, Warren J

2010-08-17

Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community. Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, or dementia (age, 61+/-9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent cardiovascular disease were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post hoc comparisons revealed that participants in the bottom cardiac index tertile (values <2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values >2.92). Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.

Cardiac index is associated with brain aging: The Framingham Heart Study

PubMed Central

Jefferson, Angela L.; Himali, Jayandra J.; Beiser, Alexa S.; Au, Rhoda; Massaro, Joseph M.; Seshadri, Sudha; Gona, Philimon; Salton, Carol J.; DeCarli, Charles; O’Donnell, Christopher J.; Benjamin, Emelia J.; Wolf, Philip A.; Manning, Warren J.

2010-01-01

Background Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease (CVD), theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with pre-clinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer’s disease in the community. Methods and Results Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free from clinical stroke, transient ischemic attack, or dementia (61±9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent CVD were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post-hoc comparisons revealed that participants in the bottom cardiac index tertile (values<2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values>2.92). Conclusions Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging. PMID:20679552

Trajectories of the Framingham general cardiovascular risk profile in midlife and poor motor function later in life: the Whitehall II study.

PubMed

Elbaz, Alexis; Shipley, Martin J; Nabi, Hermann; Brunner, Eric J; Kivimaki, Mika; Singh-Manoux, Archana

2014-03-01

Vascular risk factors are associated with increased risk of cognitive impairment and dementia, but their association with motor function, another key feature of aging, has received little research attention. We examined the association between trajectories of the Framingham general cardiovascular disease risk score (FRS) over midlife and motor function later in life. A total of 5376 participants of the Whitehall II cohort study (29% women) who had up to four repeat measures of FRS between 1991-1993 (mean age=48.6 years) and 2007-2009 (mean age=65.4 years) and without history of stroke or coronary heart disease in 2007-2009 were included. Motor function was assessed in 2007-2009 through objective tests (walking speed, chair rises, balance, finger tapping, grip strength). We used age- and sex-adjusted linear mixed models. Participants with poorer performances for walking speed, chair rises, and balance in 2007-2009 had higher FRS concurrently and also in 1991-1993, on average 16 years earlier. These associations were robust to adjustment for cognition, socio-economic status, height, and BMI, and not explained by incident mobility limitation prior to motor assessment. No association was found with finger tapping and grip strength. Cardiovascular risk early in midlife is associated with poor motor performances later in life. Vascular risk factors play an important and under-recognized role in motor function, independently of their impact on cognition, and suggest that better control of vascular risk factors in midlife may prevent physical impairment and disability in the elderly. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Longtime napping is associated with cardiovascular risk estimation according to Framingham risk score in postmenopausal women.

PubMed

Li, Feng; Sun, Kan; Lin, Diaozhu; Qi, Yiqin; Li, Yan; Yan, Li; Ren, Meng

2016-09-01

Menopause can affect the physiological timing system, which could result in circadian rhythm changes and development of napping habits. Whether longtime napping in postmenopausal women is associated with cardiovascular disease is, however, still debated. The present study aims to investigate this association. We conducted a population-based study in 4,616 postmenopausal Chinese women. Information on sleep duration was self-reported. The Framingham General Cardiovascular Risk Score was calculated and used to identify participants at high risk of coronary heart disease (CHD). Increased daytime napping hours were positively associated with cardiovascular disease risk factors in postmenopausal women, such as age, waist circumference, systolic blood pressure, triglycerides, fasting glucose, postload glucose, and hemoglobin A1C (all P for trend <0.05). The prevalence of high risk of CHD increased with daytime napping hours, and was 3.7%, 4.3%, and 6.9% in the no daytime napping group, the 0.1 to 1 hour group, and the more than 1 hour group, respectively (P for trend = 0.005). Compared with the no daytime napping group, postmenopausal women with daytime napping more than 1 hour had higher risk of CHD in both univariate (odds ratio 1.94, 95% CI, 1.29-2.95) and multivariate (odds ratio 1.61, 95% CI, 1.03-2.52) logistic regression analyses. No statistically significant association was detected between night sleeping hours and high risk of CHD in postmenopausal participants. Daytime napping is positively associated with estimated 10-year CHD risk in postmenopausal Chinese women.

Ten years cardiovascular risk estimation according to Framingham score and non HDL-cholesterol in blood donors.

PubMed

Graffigna, Mabel Nora; Berg, Gabriela; Migliano, Marta; Salgado, Pablo; Soutelo, Jimena; Musso, Carla

2015-01-01

Cardiovascular disease (CVD) is currently the primary cause of morbidity and mortality. (1) Assess the 10 years risk for CVD in Argentinean blood donors, according to Framingham score (updated by ATP III), (2) evaluate the prevalence of the MS, (3) evaluate non HDL-cholesterol level in this population as other risk for CVD. A prospective, epidemiological, transversal study was performed to evaluate 585 volunteer blood donors for two years. Non HDL-C was calculated as total cholesterol minus HDL-C and we evaluated the 10 years risk for CVD according to Framingham score (updated by ATP III). Metabolic syndrome prevalence was estimated according to ATP III and IDF criteria. Non HDL-C was (media±SD) 178.3±48.0 mg/dl in participants with MS and 143.7±39.3 mg/dl without MS (ATPIII) and 160.1±43.6 mg/dl in participants with MS and 139.8±43.1 mg/dl without MS (IDF). Participants with MS presented an OR of 3.1; IC 95% (2-5) of CVD according to de Framingham score. Individuals with MS and elevated non HDL-C are at a higher estimated risk for cardiovascular events in the next 10 years according to the Framingham risk score. Copyright © 2014. Published by Elsevier Ltd.

Low Serum Magnesium and the Development of Atrial Fibrillation in the Community: The Framingham Heart Study

PubMed Central

Khan, Abigail May; Lubitz, Steven A.; Sullivan, Lisa M.; Sun, Jenny X.; Levy, Daniel; Vasan, Ramachandran S.; Magnani, Jared W.; Ellinor, Patrick T.; Benjamin, Emelia J.; Wang, Thomas J.

2012-01-01

Background Low serum magnesium has been linked to increased risk of atrial fibrillation (AF) following cardiac surgery. It is unknown whether hypomagnesemia predisposes to AF in the community. Methods and Results We studied 3,530 participants (mean age, 44 years; 52% women) from the Framingham Offspring Study who attended a routine examination, and were free of AF and cardiovascular disease. We used Cox proportional hazard regression analysis to examine the association between serum magnesium at baseline and risk of incident AF. Analyses were adjusted for conventional AF risk factors, use of antihypertensive medications, and serum potassium. During up to 20 years of follow-up, 228 participants developed AF. Mean serum magnesium was 1.88 mg/dl. The age- and sex-adjusted incidence rate of AF was 9.4 per 1,000 person-years (95% confidence interval, 6.7 to 11.9) in the lowest quartile of serum magnesium (≤1.77 mg/dl), compared with 6.3 per 1,000 person-years (95% confidence interval, 4.1 to 8.4) in the highest quartile (≥1.99 mg/dl). In multivariable-adjusted models, individuals in the lowest quartile of serum magnesium were approximately 50% more likely to develop AF (adjusted hazard ratio, 1.52, 1.00 to 2.31; P=0.05), compared with those in the upper quartiles. Results were similar after excluding individuals on diuretics. Conclusion Low serum magnesium is moderately associated with the development of AF in individuals without cardiovascular disease. Because hypomagnesemia is common in the general population, a link with AF may have potential clinical implications. Further studies are warranted to confirm our findings and elucidate the underlying mechanisms. PMID:23172839

Dietary factors and incident atrial fibrillation: the Framingham Heart Study123

PubMed Central

Shen, Jian; Johnson, Victor M; Sullivan, Lisa M; Jacques, Paul F; Magnani, Jared W; Lubitz, Steven A; Pandey, Shivda; Levy, Daniel; Vasan, Ramachandran S; Quatromoni, Paula A; Junyent, Mireia; Ordovas, Jose M; Benjamin, Emelia J

2011-01-01

Background: There have been conflicting reported associations between dietary factors and incident atrial fibrillation (AF). Objective: We evaluated associations between consumption of alcohol, caffeine, fiber, and polyunsaturated fatty acids (PUFAs) and incident AF in the Framingham Heart Study. Design: Participants without AF (n = 4526; 9640 examinations; mean age: 62 y; 56% women) from the original and offspring cohorts completed food-frequency questionnaires and were followed prospectively for 4 y. We examined the associations between dietary exposures and AF with Cox proportional hazards regression. Results: A total of 296 individuals developed AF (177 men, 119 women). In multivariable analyses, there were no significant associations between examined dietary exposures and AF risk. Hazard ratios (HRs) for increasing quartiles of dietary factors were as follows: for alcohol, 0.73 (95% CI: 0.5, 1.05), 0.85 (95% CI: 0.61, 1.18), and 1.12 (95% CI: 0.83, 1.51) (P for trend = 0.48); for caffeine, 0.84 (95% CI: 0.62, 1.15), 0.87 (95% CI: 0.64, 1.2), and 0.98 (95% CI: 0.7, 1.39) (P for trend = 0.84); for total fiber, 0.86 (95% CI: 0.61, 1.2), 0.64 (95% CI: 0.44, 0.92), and 0.81 (95% CI: 0.54, 1.2) (P for trend = 0.16); and for n−3 (omega-3) PUFAs, 1.11 (95% CI: 0.81, 1.54), 0.92 (95% CI: 0.65, 1.29), and 1.18 (95% CI: 0.85, 1.64) (P for trend = 0.57; quartile 1 was the reference group). In exploratory analyses, consumption of >4 servings of dark fish/wk (5 cases and 21 individuals at risk) was significantly associated with AF risk compared with the consumption of <1 serving of dark fish/wk (HR: 6.53; 95% CI: 2.65, 16.06; P < 0.0001). Conclusions: Consumption of alcohol, caffeine, fiber, and fish-derived PUFAs was not significantly associated with AF risk. The observed adverse association between the consumption of dark fish and AF merits further investigation. Our findings suggest that the dietary exposures examined convey limited attributable risk of AF in the general population. PMID:21106919

Cardiovascular Risk among Older Women in a Havana Health Area.

PubMed

Armas, Nurys Bárbara; Hernández, Yesenia de la Caridad; Dueñas, Alfredo F; García, Reynaldo de la Noval; Castillo, Antonio

2008-04-01

Introduction Cardiovascular morbidity and mortality increase in women after menopause. Various scoring models assess qualitative risk of cardiovascular disease. The Framingham Heart Study global risk score is among the most widely used. Objective Determine level of coronary heart disease risk among women aged ≥60 years in a Havana health catchment area (geographic area whose residents are served by the M�rtires del Corynthia Polyclinic, in the Plaza de la Revoluci�n municipality of Havana). Methods A descriptive, cross-sectional study was conducted in 2006. Universe: all women (3,396) aged ≥60 years in the catchment area, attended at the primary care level by the Polyclinic and 42 neighborhood family doctor-and-nurse offices. Equal probability sample: 1,082 women meeting the inclusion criteria, chosen through single-stage cluster sampling considering a <10% error margin for estimates for this parameter, a 95% confidence interval (CI) and a design effect of 1.5. Absolute frequencies and percentages were calculated to summarize the qualitative data obtained. Results were presented as tables. Results The most common cardiovascular risk factors found in this study were: physical inactivity, 74.9%; hypertension (HTN), 70.6%; abdominal obesity, 53%; reported family history of coronary heart disease (CHD), 41.8%; diabetes mellitus (DM), 21.8%; and cigarette smoking, 17.2%. Scoring according to number of risk factors present in each individual, 79.3% of these women fell into the high- or moderate-risk categories. Conclusion The large number of women categorized as high- or moderate-risk for coronary heart disease in this population emphasizes the need for preventive actions aimed at reducing these figures. Cardiovascular diseases, vascular diseases, ischemic heart disease, coronary heart disease, postmenopause, woman, aged, risk factors, risk assessment, hypertension, high blood pressure, lifestyle, diabetes mellitus, obesity, abdominal adipose tissue, body mass index, physical inactivity, tobacco use.

Prediction of Cardiovascular Disease by the Framingham-REGICOR Equation in the High-Risk PREDIMED Cohort: Impact of the Mediterranean Diet Across Different Risk Strata.

PubMed

Amor, Antonio J; Serra-Mir, Mercè; Martínez-González, Miguel A; Corella, Dolores; Salas-Salvadó, Jordi; Fitó, Montserrat; Estruch, Ramón; Serra-Majem, Lluis; Arós, Fernando; Babio, Nancy; Ros, Emilio; Ortega, Emilio

2017-03-13

The usefulness of cardiovascular disease (CVD) predictive equations in different populations is debatable. We assessed the efficacy of the Framingham-REGICOR scale, validated for the Spanish population, to identify future CVD in participants, who were predefined as being at high-risk in the PREvención con DIeta MEDiterránea (PREDIMED) study-a nutrition-intervention primary prevention trial-and the impact of adherence to the Mediterranean diet on CVD across risk categories. In a post hoc analysis, we assessed the CVD predictive value of baseline estimated risk in 5966 PREDIMED participants (aged 55-74 years, 57% women; 48% with type 2 diabetes mellitus). Major CVD events, the primary PREDIMED end point, were an aggregate of myocardial infarction, stroke, and cardiovascular death. Multivariate-adjusted Cox regression was used to calculate hazard ratios for major CVD events and effect modification from the Mediterranean diet intervention across risk strata (low, moderate, high, very high). The Framingham-REGICOR classification of PREDIMED participants was 25.1% low risk, 44.5% moderate risk, and 30.4% high or very high risk. During 6-year follow-up, 188 major CVD events occurred. Hazard ratios for major CVD events increased in parallel with estimated risk (2.68, 4.24, and 6.60 for moderate, high, and very high risk), particularly in men (7.60, 13.16, and 15.85, respectively, versus 2.16, 2.28, and 3.51, respectively, in women). Yet among those with low or moderate risk, 32.2% and 74.3% of major CVD events occurred in men and women, respectively. Mediterranean diet adherence was associated with CVD risk reduction regardless of risk strata ( P >0.4 for interaction). Incident CVD increased in parallel with estimated risk in the PREDIMED cohort, but most events occurred in non-high-risk categories, particularly in women. Until predictive tools are improved, promotion of the Mediterranean diet might be useful to reduce CVD independent of baseline risk. URL: http://www.Controlled-trials.com. Unique identifier: ISRCTN35739639. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Trends in dietary carbohydrate consumption from 1991 to 2008 in the Framingham Heart Study Offspring Cohort

PubMed Central

Makarem, Nour; Scott, Marc; Quatromoni, Paula; Jacques, Paul; Parekh, Niyati

2014-01-01

The intake of carbohydrates has been evaluated cross-sectionally, but not longitudinally in an ageing American adult population. The aim of the present study was to examine trends in the intake of dietary carbohydrates and their major food sources among the Framingham Heart Study Offspring (FOS) cohort, which had been uniquely tracked for 17 years in the study. The FOS cohort was recruited in 1971–1975. Follow-up examinations were conducted, on average, every 4 years. Dietary data collection began in 1991 (examination 5) using a validated semi-quantitative FFQ. The study included 2894 adults aged ≥25 years with complete dietary data in at least three examinations from 1991 to 2008. Descriptive statistics were generated using SAS version 9.3, and a repeated-measures model was used to examine trends in the intake of carbohydrates and their food sources in the whole sample, and by sex and BMI category. Over 17 years of follow-up, the percentage of energy from total carbohydrates (51·0–46·8 %; P for trend<0·001) and total sugars (18·2–16·6 %; P for trend<0·001) decreased. There was a decrease in the percentage of energy from fructose (5·4–4·7 %; P for trend<0·001) and sucrose (9·8–8·8 %; P for trend<0·001). Dietary fibre intake increased (18·0–19·2 g/d; P for trend<0·001). The number of weekly servings of yeast bread, soft drinks/soda, cakes/cookies/quick breads/doughnuts, potatoes, milk, pasta, rice and cooked grains, fruit juice/drinks, potato chips/maize chips/popcorn, and lunch foods (e.g. pizzas and burgers) decreased significantly (P for trend<0·001), while the intake of ready-to-eat cereals, legumes, fruits, dairy products, candy and ice cream/sherbet/frozen yogurt increased significantly (P for trend<0·04). Similar trends were observed when the analyses were stratified by sex and BMI. The present results suggest favourable trends in dietary carbohydrate consumption, but dietary guidelines for fruits, vegetables and fibre were not met in this cohort. PMID:24661608

Circulating Estrogen Levels and Self-Reported Health and Mobility Limitation in Community-Dwelling Men of the Framingham Heart Study.

PubMed

Jasuja, Guneet Kaur; Travison, Thomas G; Murabito, Joanne M; Davda, Maithili N; Rose, Adam J; Basaria, Shehzad; Coviello, Andrea; Vasan, Ramachandran S; D'Agostino, Ralph; Bhasin, Shalender

2017-08-01

Self-rated health is a commonly used global indicator of health status. Few studies have examined the association of self-rated health and mobility with estrone and estradiol in men. Accordingly, we determined the cross-sectional, incident, and mediating relations between circulating estrone and estradiol levels with self-rated health, mobility limitation, and physical performance in community-dwelling men. The cross-sectional sample included 1,148 men, who attended Framingham Offspring Study Examinations 7 and 8. Estrone and estradiol levels were measured using liquid chromatography tandem mass spectrometry at Examination 7. Self-reported mobility limitation and self-rated health were assessed at Examinations 7 and 8. Additionally, short physical performance battery, usual walking speed, and grip strength were assessed at Examination 7. In incident analysis, estradiol levels at Examination 7 were associated with increased odds of fair or poor self-rated health at Examination 8, after adjusting for age, body mass index, comorbidities, and testosterone levels; in an individual with 50% greater estradiol than other, the odds of reporting "fair or poor" self-rated health increased by 1.78 (95% confidence interval: 1.25-2.55; p = .001). Neither estrone nor estradiol levels were associated with any physical performance measure at baseline. Higher circulating levels of estradiol are associated with increased risk of incident fair/poor self-rated health in community-dwelling men. The mechanisms by which circulating levels of estradiol are related to self-rated health in men need further investigation. Published by Oxford University Press on behalf of The Gerontological Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The relation of red blood cell fatty acids with vascular stiffness, cardiac structure and left ventricular function: the Framingham Heart Study.

PubMed

Kaess, Bernhard M; Harris, William S; Lacey, Sean; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Robins, Sander J; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S

2015-02-01

Polyunsaturated fatty acids have been associated with beneficial influences on cardiovascular health. However, the underlying mechanisms are not clear, and data on the relations of polyunsaturated fatty acids to subclinical disease measures such as vascular stiffness and cardiac function are sparse and inconclusive. In a large community-based cohort, we examined the relations of omega-3 and other fatty acids to a comprehensive panel of vascular function measures (assessing microvascular function and large artery stiffness), cardiac structure and left ventricular function. Red blood cell (RBC) membrane fatty acid composition, a measure of long-term fatty acid intake, was assessed in participants of the Framingham Offspring Study and Omni cohorts and related to tonometry-derived measures of vascular stiffness and to a panel of echocardiographic traits using partial correlations. Up to n=3055 individuals (56% women, mean age 66 years) were available for analyses. In age- and sex-adjusted models, higher RBC omega-3 content was moderately associated (p≤0.002) with several measures of vascular stiffness and function in a protective direction. However, after multivariable adjustment, only an association of higher RBC omega-3 content with lower carotid-femoral pulse wave velocity (a measure of aortic stiffness) remained significant (r = -0.06, p=0.002). In secondary analyses, higher linoleic acid, the major nutritional omega-6 fatty acid, was associated with smaller left atrial size, even after multivariable adjustment (r = -0.064, p<0.001). In conclusion, in our cross-sectional community-based study, we found several associations consistent with the notion of protective effects of omega-3 and linoleic acid. The clinical significance of these modest associations remains to be elucidated. © The Author(s) 2014.

Metabolic factors and genetic risk mediate familial type 2 diabetes risk in the Framingham Heart Study

PubMed Central

Raghavan, Sridharan; Porneala, Bianca; McKeown, Nicola; Fox, Caroline S.; Dupuis, Josée; Meigs, James B.

2015-01-01

Aims/hypothesis Type 2 diabetes mellitus in parents is a strong determinant of diabetes risk in their offspring. We hypothesise that offspring diabetes risk associated with parental diabetes is mediated by metabolic risk factors. Methods We studied initially non-diabetic participants of the Framingham Offspring Study. Metabolic risk was estimated using beta cell corrected insulin response (CIR), HOMA-IR or a count of metabolic syndrome components (metabolic syndrome score [MSS]). Dietary risk and physical activity were estimated using questionnaire responses. Genetic risk score (GRS) was estimated as the count of 62 type 2 diabetes risk alleles. The outcome of incident diabetes in offspring was examined across levels of parental diabetes exposure, accounting for sibling correlation and adjusting for age, sex and putative mediators. The proportion mediated was estimated by comparing regression coefficients for parental diabetes with (βadj) and without (βunadj) adjustments for CIR, HOMA-IR, MSS and GRS (percentage mediated = 1 – βadj / βunadj). Results Metabolic factors mediated 11% of offspring diabetes risk associated with parental diabetes, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.96. GRS mediated 9% of risk, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.99. Conclusions/interpretation Metabolic risk factors partially mediated offspring type 2 diabetes risk conferred by parental diabetes to a similar magnitude as genetic risk. However, a substantial proportion of offspring diabetes risk associated with parental diabetes remains unexplained by metabolic factors, genetic risk, diet and physical activity, suggesting that important familial influences on diabetes risk remain undiscovered. PMID:25619168

[Assessment of cardiovascular risk in population groups. Comparison of Score system and Framingham in hypertensive patients].

PubMed

Cosín Aguilar, J; Hernándiz Martínez, A; Rodríguez Padial, L; Zamorano Gómez, J L; Arístegui Urrestarazu, R; Armada Peláez, B; Aguilar Llopis, A; Masramon Morell, X

2006-04-01

Calculation of cardiovascular risk in populations allows for developing and assessing of intervention programs and adapting health resources. While the Framingham System has been used in the past, a group of European researchers have proposed a different method called the Score project. The purpose of this paper is to compare the value of both methods for assessing cardiovascular risk. In 6,775 evaluable hypertensive patients distributed over the 17 Spanish autonomous communities (ACs), the 10-year risk of experiencing a coronary event (CR) was calculated using the Framingham equation, while risk of coronary death (RCD) and vascular death (RVD) was calculated using the Score project system, both at baseline and after one year of blood pressure control with amlodipine at the required dose. A comparison was made of the capacity to detect risk differences by both methods between populations with known different risks, and in the same population as a result of blood pressure control. Both the Score and the Framingham systems detected the significant decrease in both CR and RCD or RVD at one year of application of the CORONARIA study protocol. Risk decrease measured by any of the two methods was significant (p < 0.05) overall, by genders, and by ACs. However, the Score System, unlike the Framingham system, could not detect the reported differences in the mortality risk for coronary and vascular disease between the ACs of the North and the South-East parts of Spain.

Ten-year cardiovascular risk assessment in university students.

PubMed

Uvacsek, Martina; Kneffel, Zs; Tóth, M; Johnson, A W; Vehrs, P; Myrer, J W; Hager, R

2014-09-01

Cardiovascular disease (CVD) is responsible for more than half of all deaths in the European region. The aim of the study was to compare body composition, blood pressure, total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C), family history, activity behaviors, and the 10-year risk of having a heart attack between 166 university students (21.62 ± 2.59 yrs) from Utah (USA) and 198 students (22.11 ± 2.51 yrs) from Hungary. Ninety-two percent of the Hungarian students and 100% of the Utah students had an estimated 10-year Framingham risk score of 1% or less. The high prevalence of low risk was primarily due to the young age of study participants, healthy body composition and non-smoking behavior. Hungarians who had higher 10-year risk of heart attack had significantly higher waist hip ratio (WHR), TC, diastolic blood pressure (DBP) and were smokers compared to those Hungarians with lower risk. The self-reported physical activity levels between the two groups of students were not different. In conclusion the young men and women who participated in this study were, for the most part healthy; however the smoking habits and the lower physical activity of the Hungarian students likely elevated their risk of CVD.

A Genome-Wide Association Study of the Human Metabolome in a Community-Based Cohort

PubMed Central

Rhee, Eugene P.; Ho, Jennifer E.; Chen, Ming-Huei; Shen, Dongxiao; Cheng, Susan; Larson, Martin G.; Ghorbani, Anahita; Shi, Xu; Helenius, Iiro T.; O’Donnell, Christopher J.; Souza, Amanda L.; Deik, Amy; Pierce, Kerry A.; Bullock, Kevin; Walford, Geoffrey A.; Vasan, Ramachandran S.; Florez, Jose C.; Clish, Clary; Yeh, J.-R. Joanna; Wang, Thomas J.; Gerszten, Robert E.

2014-01-01

SUMMARY Because metabolites are hypothesized to play key roles as markers and effectors of cardio-metabolic diseases, recent studies have sought to annotate the genetic determinants of circulating metabolite levels. We report a genome-wide association study (GWAS) of 217 plasma metabolites, including >100 not measured in prior GWAS, in 2,076 participants of the Framingham Heart Study. For the majority of analytes, we find that estimated heritability explains >20% of inter-individual variation, and that variation attributable to heritable factors is greater than that attributable to clinical factors. Further, we identify 31 genetic loci associated with plasma metabolites, including 23 that have not previously been reported. Importantly, we include GWAS results for all surveyed metabolites, and demonstrate how this information highlights a role for AGXT2 in cholesterol ester and triacylglycerol metabolism. Thus, our study outlines the relative contributions of inherited and clinical factors on the plasma metabolome and provides a resource for metabolism research. PMID:23823483

Born to Lead? A Twin Design and Genetic Association Study of Leadership Role Occupancy*

PubMed Central

De Neve, Jan-Emmanuel; Mikhaylov, Slava; Dawes, Christopher T.; Christakis, Nicholas A.; Fowler, James H.

2013-01-01

We address leadership emergence and the possibility that there is a partially innate predisposition to occupy a leadership role. Employing twin design methods on data from the National Longitudinal Study of Adolescent Health, we estimate the heritability of leadership role occupancy at 24%. Twin studies do not point to specific genes or neurological processes that might be involved. We therefore also conduct association analysis on the available genetic markers. The results show that leadership role occupancy is associated with rs4950, a single nucleotide polymorphism (SNP) residing on a neuronal acetylcholine receptor gene (CHRNB3). We replicate this family-based genetic association result on an independent sample in the Framingham Heart Study. This is the first study to identify a specific genotype associated with the tendency to occupy a leadership position. The results suggest that what determines whether an individual occupies a leadership position is the complex product of genetic and environmental influences; with a particular role for rs4950. PMID:23459689

Correlation of 6-min walk test with left ventricular function and quality of life in heart failure due to Chagas disease.

PubMed

Chambela, Mayara C; Mediano, Mauro F F; Ferreira, Roberto R; Japiassú, André M; Waghabi, Mariana C; da Silva, Gilberto M S; Saraiva, Roberto M

2017-10-01

To evaluate the correlation of the total distance walked during the six-minute walk test (6MWT) with left ventricular function and quality of life in patients with Chagas Disease (ChD) complicated by heart failure. This is a cross-sectional study of adult patients with ChD and heart failure diagnosed based on Framingham criteria. 6MWT was performed following international guidelines. New York Heart Association functional class, brain natriuretic peptide (BNP) serum levels, echocardiographic parameters and quality of life (SF-36 and MLHFQ questionnaires) were determined and their correlation with the distance covered at the 6MWT was tested. Forty adult patients (19 male; 60 ± 12 years old) with ChD and heart failure were included in this study. The mean left ventricular ejection fraction was 35 ± 12%. Only two patients (5%) ceased walking before 6 min had elapsed. There were no cardiac events during the test. The average distance covered was 337 ± 105 metres. The distance covered presented a negative correlation with BNP (r = -0.37; P = 0.02), MLHFQ quality-of-life score (r = -0.54; P = 0.002), pulmonary artery systolic pressure (r = -0.42; P = 0.02) and the degree of diastolic dysfunction (r = -0.36; P = 0.03) and mitral regurgitation (r = -0.53; P = 0.0006) and positive correlation with several domains of the SF-36 questionnaire. The distance walked during the 6MWT correlates with BNP, quality of life and parameters of left ventricular diastolic function in ChD patients with heart failure. We propose this test to be adopted in endemic areas with limited resources to aid in the identification of patients who need referral for tertiary centres for further evaluation and treatment. © 2017 John Wiley & Sons Ltd.

Haplotypes in the CRP gene associated with increased BMI and levels of CRP in subjects with type 2 diabetes or obesity from Southwestern Mexico.

PubMed

Martínez-Calleja, América; Quiróz-Vargas, Irma; Parra-Rojas, Isela; Muñoz-Valle, José Francisco; Leyva-Vázquez, Marco A; Fernández-Tilapa, Gloria; Vences-Velázquez, Amalia; Cruz, Miguel; Salazar-Martínez, Eduardo; Flores-Alfaro, Eugenia

2012-01-01

We evaluated the association between four polymorphisms in the CRP gene with circulating levels of C-reactive protein (CRP), type 2 diabetes (T2D), obesity, and risk score of coronary heart disease. We studied 402 individuals and classified them into four groups: healthy, obese, T2D obese, and T2D without obesity, from Guerrero, Southwestern Mexico. Blood levels of CRP, glucose, cholesterol, triglycerides, and leukocytes were measured. Genotyping was performed by PCR/RFLP, and the risk score for coronary heart disease was determined by the Framingham's methodology. The TT genotype of SNP rs1130864 was associated with increased body mass index and T2D patients with obesity. We found that the haplotype 2 (TGAG) was associated with increased levels of CRP (β = 0.3; 95%CI: 0.1, 0.5; P = 0.005) and haplotype 7 (TGGG) with higher body mass index (BMI) (β = 0.2; 95%CI: 0.1, 0.3; P < 0.001). The risk score for coronary heart disease was associated with increased levels of CRP, but not with any polymorphism or haplotype. The association between the TT genotype of SNP rs1130864 with obesity and the haplotype 7 with BMI may explain how obesity and genetic predisposition increase the risk of diseases such as T2D in the population of Southwestern Mexico.

Non-invasively measured structural and functional arterial characteristics and coronary heart disease risk in middle aged and elderly men.

PubMed

van Trijp, Marijke J C A; Bos, Willem J W; van der Schouw, Yvonne T; Muller, Majon; Grobbee, Diederick E; Bots, Michiel L

2006-07-01

In cardiovascular (CV) epidemiology, interest increases in studying etiologic and prognostic implications of early structural or functional changes of the large arteries. Examples of such measurements are pulse wave velocity (PWV), carotid intima-media thickness (CIMT) and augmentation index (AIx). PWV and CIMT are established markers of CV risk whereas the role of AIx as indicator of risk has not fully been established. Therefore, our aim was to relate AIx to CV risk and to compare the magnitude of relations of PWV, CIMT and AIx to CV risk. Two hundred and ninty-nine men free from cardiovascular disease (mean age 59.2 years), participated in this cross-sectional study. Cardiovascular risk profile was determined and 10-year coronary heart disease risk was estimated using the Framingham risk score (FRS). PWV, CIMT and AIx were measured and data were analyzed using linear regression models. PWV and CIMT were strongest related to FRS whereas AIx showed the weakest relation. Ten-year coronary heart disease risk increased 6.24%, 95% confidence interval (CI) [5.11;7.37] per standard deviation (S.D.) increase in PWV, 6.39% [5.24;7.54] per S.D. increase in CIMT and 2.50% [1.19;3.80] per S.D. increase in AIx. In middle aged and elderly men AIx is related to CV risk. However, compared with AIx, PWV and CIMT seem better markers of cardiovascular risk.

Association between parental history of diabetes and type 2 diabetes genetic risk scores in the PPP-Botnia and Framingham Offspring Studies.

PubMed

Vassy, Jason L; Shrader, Peter; Jonsson, Anna; Fox, Caroline S; Lyssenko, Valeriya; Isomaa, Bo; Groop, Leif; Meigs, James B; Franks, Paul W

2011-08-01

Parental history of diabetes and specific gene variants are risk factors for type 2 diabetes, but the extent to which these factors are associated is unknown. We examined the association between parental history of diabetes and a type 2 diabetes genetic risk score (GRS) in two cohort studies from Finland (population-based PPP-Botnia study) and the US (family-based Framingham Offspring Study). Mean (95% CI) GRS increased from 16.8 (16.8-16.9) to 16.9 (16.8-17.1) to 17.1 (16.8-17.4) among PPP-Botnia participants with 0, 1, and 2 parents with diabetes, respectively (p(trend)=0.03). The trend was similar among Framingham Offspring but was not statistically significant (p=0.07). The meta-analyzed p value for trend from the two studies was 0.005. The very modest associations reported above suggest that the increased risk of diabetes in offspring of parents with diabetes is largely the result of shared environmental/lifestyle factors and/or hitherto unknown genetic factors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Heinz Nixdorf Recall study and its potential impact on the adoption of atherosclerosis imaging in European primary prevention guidelines.

PubMed

Mahabadi, Amir A; Möhlenkamp, Stefan; Moebus, Susanne; Dragano, Nico; Kälsch, Hagen; Bauer, Marcus; Jöckel, Karl-Heinz; Erbel, Raimund

2011-10-01

Non-contrast-enhanced computed tomography (CT) imaging of the heart enables noninvasive quantification of coronary artery calcification (CAC), a surrogate marker of the atherosclerotic burden in the coronary artery tree. Multiple studies have underlined the ability of CAC score for individual risk stratification and, accordingly, the American Heart Association recommended cardiac CT for risk assessment in individuals with an intermediate risk of cardiovascular events as measured by Framingham Risk Score. However, limitations in transcribing risk stratification algorithms based on American cohort studies into European populations have been acknowledged in the past. Moreover, data on implications for reclassification into higher- or lower-risk groups based on CAC scores were lacking. The Heinz Nixdorf Recall (HNR) study is a population-based cohort study that investigated the ability of CAC scoring in risk prediction for major cardiovascular events above and beyond traditional cardiovascular risk factors. According to Heinz Nixdorf Recall findings, CAC can be used for reclassification, especially in those in the intermediate-risk group, to advise on lifestyle changes for the reclassified low-risk category, or to implement intensive treatments for the reclassified high-risk individuals. This article discusses the present findings of the Heinz Nixdorf Recall Study with respect to the current literature, risk stratification algorithms, and current European guidelines for risk prediction.

Association of parental obesity with concentrations of select systemic biomarkers in nonobese offspring: the Framingham Heart Study.

PubMed

Lieb, Wolfgang; Pencina, Michael J; Lanier, Katherine J; Tofler, Geoffrey H; Levy, Daniel; Fox, Caroline S; Wang, Thomas J; D'Agostino, Ralph B; Vasan, Ramachandran S

2009-01-01

Parental obesity is a risk factor for offspring obesity. It is unclear whether parental obesity also confers risk for obesity-associated conditions (e.g., a proinflammatory or prothrombotic state) in the absence of offspring obesity. We compared concentrations of multiple biomarkers representing distinct biological pathways (C-reactive protein [CRP], aldosterone, renin, B-type natriuretic peptide, NH(2)-terminal proatrial natriuretic peptide, fibrinogen, and plasminogen activator inhibitor-1) in nonobese Framingham Offspring Study participants with no parents (n = 665), one parent (n = 488), or two parents (n = 119) with obesity (BMI > or =30 kg/m(2)). Nonobese offspring with both parents with obesity had higher CRP levels (median 2.16 mg/l) than offspring with one parent (1.58 mg/l) or no parents (1.35 mg/l) with obesity. After multivariable adjustment, a nonlinear relationship with parental obesity became evident: compared with those without parental obesity, CRP levels were higher in offspring with two obese parents (P = 0.04) but not in offspring with only one obese parent (P = 0.76). Renin levels were more linearly related to parental obesity status, being significantly higher in offspring with one parent (P = 0.04) or two parents (P = 0.09) with obesity (P = 0.02 for trend). The other systemic biomarkers did not vary according to parental obesity status (all P > 0.05). Our findings suggest that offspring with a high risk of developing obesity have an altered biomarker profile, characterized by systemic inflammation and increased neurohormonal activity, even in the absence of obesity. This is consistent with the notion that parental obesity may confer an increased susceptibility to other adiposity-associated traits.

The Impact of Multipollutant Clusters on the Association Between Fine Particulate Air Pollution and Microvascular Function.

PubMed

Ljungman, Petter L; Wilker, Elissa H; Rice, Mary B; Austin, Elena; Schwartz, Joel; Gold, Diane R; Koutrakis, Petros; Benjamin, Emelia J; Vita, Joseph A; Mitchell, Gary F; Vasan, Ramachandran S; Hamburg, Naomi M; Mittleman, Murray A

2016-03-01

Prior studies including the Framingham Heart Study have suggested associations between single components of air pollution and vascular function; however, underlying mixtures of air pollution may have distinct associations with vascular function. We used a k-means approach to construct five distinct pollution mixtures from elemental analyses of particle filters, air pollution monitoring data, and meteorology. Exposure was modeled as an interaction between fine particle mass (PM2.5), and concurrent pollution cluster. Outcome variables were two measures of microvascular function in the fingertip in the Framingham Offspring and Third Generation cohorts from 2003 to 2008. In 1,720 participants, associations between PM2.5 and baseline pulse amplitude tonometry differed by air pollution cluster (interaction P value 0.009). Higher PM2.5 on days with low mass concentrations but high proportion of ultrafine particles from traffic was associated with 18% (95% confidence interval: 4.6%, 33%) higher baseline pulse amplitude per 5 μg/m and days with high contributions of oil and wood combustion with 16% (95% confidence interval: 0.2%, 34%) higher baseline pulse amplitude. We observed no variation in associations of PM2.5 with hyperemic response to ischemia observed across air pollution clusters. PM2.5 exposure from air pollution mixtures with large contributions of local ultrafine particles from traffic, heating oil, and wood combustion was associated with higher baseline pulse amplitude but not hyperemic response. Our findings suggest little association between acute exposure to air pollution clusters reflective of select sources and hyperemic response to ischemia, but possible associations with excessive small artery pulsatility with potentially deleterious microvascular consequences.

Comparison of the Framingham Risk Score, UKPDS Risk Engine, and SCORE for Predicting Carotid Atherosclerosis and Peripheral Arterial Disease in Korean Type 2 Diabetic Patients.

PubMed

Ahn, Hye-Ran; Shin, Min-Ho; Yun, Woo-Jun; Kim, Hye-Yeon; Lee, Young-Hoon; Kweon, Sun-Seog; Rhee, Jung-Ae; Choi, Jin-Su; Choi, Seong-Woo

2011-03-01

To compare the predictability of the Framingham Risk Score (FRS), United Kingdom Prospective Diabetes Study (UKPDS) risk engine, and the Systematic Coronary Risk Evaluation (SCORE) for carotid atherosclerosis and peripheral arterial disease in Korean type 2 diabetic patients. Among 1,275 registered type 2 diabetes patients in the health center, 621 subjects with type 2 diabetes participated in the study. Well-trained examiners measured the carotid intima-media thickness (IMT), carotid plaque, and ankle brachial index (ABI). The subject's 10-year risk of coronary heart disease was calculated according to the FRS, UKPDS, and SCORE risk scores. These three risk scores were compared to the areas under the curve (AUC). The odds ratios (ORs) of all risk scores increased as the quartiles increased for plaque, IMT, and ABI. For plaque and IMT, the UKPDS risk score provided the highest OR (95% confidence interval) at 3.82 (2.36, 6.17) and at 6.21 (3.37, 11.45). For ABI, the SCORE risk estimation provided the highest OR at 7.41 (3.20, 17.18). However, no significant difference was detected for plaque, IMT, or ABI (P = 0.839, 0.313, and 0.113, respectively) when the AUCs of the three risk scores were compared. When we graphed the Kernel density distribution of these three risk scores, UKPDS had a higher distribution than FRS and SCORE. No significant difference was observed when comparing the predictability of the FRS, UKPDS risk engine, and SCORE risk estimation for carotid atherosclerosis and peripheral arterial disease in Korean type 2 diabetic patients.

The Impact of Multi-pollutant Clusters on the Association between Fine Particulate Air Pollution and Microvascular Function

PubMed Central

Ljungman, Petter L.; Wilker, Elissa H.; Rice, Mary B.; Austin, Elena; Schwartz, Joel; Gold, Diane R.; Koutrakis, Petros; Benjamin, Emelia J.; Vita, Joseph A.; Mitchell, Gary F.; Vasan, Ramachandran S.

2016-01-01

Background Prior studies including the Framingham Heart Study have suggested associations between single components of air pollution and vascular function; however, underlying mixtures of air pollution may have distinct associations with vascular function. Methods We used a k-means approach to construct five distinct pollution mixtures from elemental analyses of particle filters, air pollution monitoring data, and meteorology. Exposure was modeled as an interaction between fine particle mass (PM2.5), and concurrent pollution cluster. Outcome variables were two measures of microvascular function in the fingertip in the Framingham Offspring and Third Generation cohorts from 2003-2008. Results In 1,720 participants, associations between PM2.5 and baseline pulse amplitude tonometry differed by air pollution cluster (interaction p value 0.009). Higher PM2.5 on days with low mass concentrations but high proportion of ultrafine particles from traffic was associated with 18% (95% CI 4.6%; 33%) higher baseline pulse amplitude per 5 μg/m3 and days with high contributions of oil and wood combustion with 16% (95% CI 0.2%; 34%) higher baseline pulse amplitude. We observed no variation in associations of PM2.5 with hyperemic response to ischemia observed across air pollution clusters. Conclusions PM2.5 exposure from air pollution mixtures with large contributions of local ultrafine particles from traffic, heating oil and wood combustion was associated with higher baseline pulse amplitude but not PAT ratio. Our findings suggest little association between acute exposure to air pollution clusters reflective of select sources and hyperemic response to ischemia, but possible associations with excessive small artery pulsatility with potentially deleterious microvascular consequences. PMID:26562062

Is the association between flow-mediated dilation and cardiovascular risk limited to low-risk populations?

PubMed

Witte, Daniel R; Westerink, Jan; de Koning, Eelco J; van der Graaf, Yolanda; Grobbee, Diederick E; Bots, Michiel L

2005-06-21

The aim of this research was to study whether the relation between endothelial function measured by flow-mediated dilation (FMD) of the brachial artery and cardiovascular risk factors is affected by the baseline cardiovascular risk. Flow-mediated dilation of the brachial artery is widely used as a measure of endothelial function. Relations between FMD and most cardiovascular risk factors have been described. We performed a meta-regression analysis of 211 selected articles (399 populations) reporting on FMD and cardiovascular risk factors. Mean values of FMD; age; proportion of men; proportion of smokers; blood pressure; lipids; glucose; and the presence of diabetes mellitus, of hyperlipidemia, and of hypertension were retrieved from the articles. The 10-year risk of coronary heart disease (CHD) for each population was estimated based on the Framingham risk score. The relation between FMD and cardiovascular risk factors was assessed within each risk category by linear regression analysis, adjusting for age and gender, and weighted for the study size. A relation between FMD and cardiovascular risk factors was most clear in the category with lowest baseline risk (below 2.8% per decade). In populations with low baseline risk, for each % increase in Framingham risk, FMD decreased by 1.42% (95% confidence interval: 0.65 to 2.19). In medium- and high-risk populations, FMD was not related to risk (-0.02% [-0.27 to 0.22] and 0.06% [-0.02 to 0.13], respectively). These findings were independent of differences in brachial lumen diameter and technical aspects of the FMD measurement. Only in populations at low risk, endothelial function measured by FMD is related to the principal cardiovascular risk factors, and to the estimated 10-year risk of CHD.

Performance of the UK Prospective Diabetes Study Risk Engine and the Framingham Risk Equations in Estimating Cardiovascular Disease in the EPIC- Norfolk Cohort

PubMed Central

Simmons, Rebecca K.; Coleman, Ruth L.; Price, Hermione C.; Holman, Rury R.; Khaw, Kay-Tee; Wareham, Nicholas J.; Griffin, Simon J.

2009-01-01

OBJECTIVE The purpose of this study was to examine the performance of the UK Prospective Diabetes Study (UKPDS) Risk Engine (version 3) and the Framingham risk equations (2008) in estimating cardiovascular disease (CVD) incidence in three populations: 1) individuals with known diabetes; 2) individuals with nondiabetic hyperglycemia, defined as A1C ≥6.0%; and 3) individuals with normoglycemia defined as A1C <6.0%. RESEARCH DESIGN AND METHODS This was a population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk). Participants aged 40–79 years recruited from U.K. general practices attended a health examination (1993–1998) and were followed for CVD events/death until April 2007. CVD risk estimates were calculated for 10,137 individuals. RESULTS Over 10.1 years, there were 69 CVD events in the diabetes group (25.4%), 160 in the hyperglycemia group (17.7%), and 732 in the normoglycemia group (8.2%). Estimated CVD 10-year risk in the diabetes group was 33 and 37% using the UKPDS and Framingham equations, respectively. In the hyperglycemia group, estimated CVD risks were 31 and 22%, respectively, and for the normoglycemia group risks were 20 and 14%, respectively. There were no significant differences in the ability of the risk equations to discriminate between individuals at different risk of CVD events in each subgroup; both equations overestimated CVD risk. The Framingham equations performed better in the hyperglycemia and normoglycemia groups as they did not overestimate risk as much as the UKPDS Risk Engine, and they classified more participants correctly. CONCLUSIONS Both the UKPDS Risk Engine and Framingham risk equations were moderately effective at ranking individuals and are therefore suitable for resource prioritization. However, both overestimated true risk, which is important when one is using scores to communicate prognostic information to individuals. PMID:19114615

Impact of using a non-diabetes-specific risk calculator on eligibility for statin therapy in type 2 diabetes.

PubMed

Price, H C; Coleman, R L; Stevens, R J; Holman, R R

2009-03-01

The aim of this study was to investigate the impact of using a non-diabetes-specific cardiovascular disease (CVD) risk calculator to determine eligibility for statin therapy according to current UK National Institute for Health and Clinical Excellence (NICE) guidelines for those patients with type 2 diabetes who are at an increased risk of CVD (10 year risk >or=20%). The 10 year CVD risks were estimated using the UK Prospective Diabetes Study (UKPDS) Risk Engine and the Framingham equation for 4,025 patients enrolled in the Lipids in Diabetes Study who had established type 2 diabetes and LDL-cholesterol <4.1 mmol/l. The mean (SD) age of the patients was 60.7 (8.6) years, blood pressure 141/83 (17/10) mmHg and the total cholesterol:HDL-cholesterol ratio was 3.9 (1.0). The median (interquartile range) diabetes duration was 6 (3-11) years and the HbA(1c) level was 8.0% (7.2-9.0%). The cohort comprised 65% men, 91% whites, 4% Afro-Caribbeans, 5% Asian Indians and 15% current smokers. More patients were classified as being at high risk by the UKPDS Risk Engine (65%) than by the Framingham CVD equation (63%) (p < 0.0001). The Framingham CVD equation classified fewer men and people aged <50 years old as high risk (p < 0.0001). There was no difference between the UKPDS Risk Engine and Framingham classification of women at high risk (p = 0.834). These results suggest that the use of Framingham-derived rather than UKPDS Risk Engine-derived CVD risk estimates would deny about one in 25 patients statin therapy when applying current NICE guidelines. Thus, under these guidelines the choice of CVD risk calculator is important when assessing CVD risk in patients with type 2 diabetes, particularly for the identification of the relatively small proportion of younger people who require statin therapy.

Risk Factor Differences in Calcified and Non-Calcified Aortic Plaque: The Framingham Heart Study

PubMed Central

Chuang, Michael L.; Gona, Philimon; Oyama-Manabe, Noriko; Manders, Emily S.; Salton, Carol J.; Hoffmann, Udo; Manning, Warren J.; O'Donnell, Christopher J.

2014-01-01

Objective Determine the prevalence and risk factor (RF) correlates of aortic plaque (AP) detected by cardiovascular magnetic resonance (CMR), which mainly shows noncalcified plaques, and by noncontrast computed tomography (CT), which best depicts calcified plaques, in community-dwelling adults. Approach and Results 1016 Framingham Offspring cohort members (64±9y, 474 men) underwent CMR and CT of the aorta. Potential RFs for AP (age; sex; BMI; blood pressure; LDL and HDL cholesterol; fasting glucose; C-reactive protein; prevalent hypertension, diabetes, smoking; use of antihypertensive, diabetes or lipid-lowering drugs) were compared between participants with zero versus nonzero AP by CMR and by CT. Candidate RFs attaining p<0.05 for difference with either imaging modality were entered into multivariable logistic regression models adjusting for age, sex and other RFs. Odds ratios were calculated for modality-specific prevalence of AP. Associations between RFs and continuous measures of AP were assessed using Tobit regression. Prevalences of CMR and CT AP were 49% and 82% respectively. AP burdens by CMR and CT were correlated, r=0.28, p<0.0001. Increasing age and smoking were associated with prevalent AP by both CMR and CT. Additionally, prevalent AP by CMR was associated with female sex and fasting glucose, prevalent AP by CT with hypertension treatment and with adverse lipid profile. Conclusions AP by CMR and CT are both associated with smoking and increasing age, but other risk factors differ between calcified and noncalcified AP. The relative predictive value of AP detected by CMR versus by CT for incident cardiovascular events remains to be determined. PMID:24833796

Risk factors of coronary heart disease among medical students in King Abdulaziz University, Jeddah, Saudi Arabia.

PubMed

Ibrahim, Nahla Khamis; Mahnashi, Morooj; Al-Dhaheri, Amal; Al-Zahrani, Borooj; Al-Wadie, Ebtihal; Aljabri, Mydaa; Al-Shanketi, Rajaa; Al-Shehri, Rawiah; Al-Sayes, Fatin M; Bashawri, Jamil

2014-04-28

Nowadays, Cardiovascular Diseases (CVDs) represents an escalating worldwide public health problem. Providing consistent data on the magnitude and risk factors of CVDs among young population will help in controlling the risks and avoiding their consequences. The objective was to estimate the prevalence of risk factors of Coronary Heart Disease (CHD) among medical students during their clinical clerkship (4th - 6th years). A cross-sectional study was done during the educational year 2012-2013 at King Abdulaziz University (KAU), Jeddah. Ethical standards were followed and a multistage stratified random sample method was used for selection of 214 medical students. Data was collected through an interviewing questionnaire, measurements and laboratory investigations. Both descriptive and analytical statistics were done by SPSS version 21. CHD risk percent in thirty years was calculated using Framingham algorithm for each student, then the risk among all students was determined. The commonest risk factors of CHDs were daily intake of high fat diet (73.4%), physical inactivity (57.9%), overweight/or obesity (31.2%) and daily consumption of fast food (13.1%). Hyper-cholesterolemia (17.2%) and hypertension (9.3%) were also prevalent risk factors. Smoking prevalence was low (2.8%). Males had significantly higher mean scores for most of CHD risk factors compared to females (p < 0.05). Systolic Blood pressure was higher among males (119.47 ± 11.17) compared to females (112.26 ± 9.06). A highly statistical significant difference was present (Students't test = 4.74, p < 0.001). Framingham Risk Score revealed that CHD risk percent in thirty-years among all students was 10.7%, 2.3% and 0.5% for mild, moderate and severe risk, respectively. An alarmingly high prevalence of CHD risk factors was prevailed among medical students, especially among males. However, a low prevalence of smoking may indicate the success of "Smoke-free Campus" program. Screening risk factors of CHD among medical students and implementation of intervention programs are recommended. Programs to raise awareness about CHD risk factors, encourage young adult students to adopt a healthy dietary behavior and promote physical exercise should be initiated.

Ambient hemolysis and activation of coagulation is different between HeartMate II and HeartWare left ventricular assist devices.

PubMed

Birschmann, Ingvild; Dittrich, Marcus; Eller, Thomas; Wiegmann, Bettina; Reininger, Armin J; Budde, Ulrich; Strüber, Martin

2014-01-01

Thromboembolic and bleeding events in patients with a left ventricular assist device (LVAD) are still a major cause of complications. Therefore, the balance between anti-coagulant and pro-coagulant factors needs to be tightly controlled. The principle hypothesis of this study is that different pump designs may have an effect on hemolysis and activation of the coagulation system. Referring to this, the HeartMate II (HMII; Thoratec Corp, Pleasanton, CA) and the HeartWare HVAD (HeartWare International Inc, Framingham, MA) were investigated. For 20 patients with LVAD support (n = 10 each), plasma coagulation, full blood count, and clinical chemistry parameters were measured. Platelet function was monitored using platelet aggregometry, platelet function analyzer-100 system ( Siemens, Marburg, Germany), vasodilator-stimulated phosphoprotein phosphorylation assay, immature platelet fraction, platelet-derived microparticles, and von Willebrand diagnostic. Acquired von Willebrand syndrome could be detected in all patients. Signs of hemolysis, as measured by lactate dehydrogenase levels (mean, 470 U/liter HMII, 250 U/liter HVAD; p < 0.001), were more pronounced in the HMII patients. In contrast, D-dimer analysis indicated a significantly higher activation of the coagulation system in HVAD patients (mean, 0.94 mg/liter HMII, 2.01 mg/liter HVAD; p < 0.01). The efficacy of anti-platelet therapy using clopidogrel was not sufficient in more than 50% of the patients. Our results support the finding that all patients with rotary blood pumps suffered from von Willebrand syndrome. In addition, a distinct footprint of effects on hemolysis and the coagulation system can be attributed to different devices. As a consequence, the individual status of the coagulation system needs to be controlled in long-term patients. © 2013 Published by International Society for the Heart and Lung Transplantation on behalf of International Society for Heart and Lung Transplantation.

Predicting the impact of population level risk reduction in cardio-vascular disease and stroke on acute hospital admission rates over a 5 year period--a pilot study.

PubMed

Whitfield, Malcolm D; Gillett, Michael; Holmes, Michael; Ogden, Elaine

2006-12-01

The brief for this study was to produce a practical, evidence based, financial planning tool, which could be used to present an economic argument for funding a public health-based prevention programme in coronary heart disease (CHD) related illness on the same basis as treatment interventions. To explore the possibility of using multivariate risk prediction equations, derived from the Framingham and other studies, to estimate how many people in a population are likely to be admitted to hospital in the next 5-10 years with cardio vascular disease (CVD) related events such as heart attacks, strokes, heart failure and kidney disease. To estimate the potential financial impact of reductions in hospital admissions, on an 'invest to save' basis, if primary care trusts (PCTs) were to invest in public health based interventions to reduce cardiovascular risk at a population level. The populations of five UK PCTs were entered into a spreadsheet based decision tree model, in terms of age and sex (this equated to around 620,000 adults). An estimation was made to determine how many people, in each age group, were likely to be diabetic. Population risk factors such as smoking rates, mean body mass index (BMI), mean total cholesterol and mean systolic blood pressure were entered by age group. The spreadsheet then used a variant of the Framingham equation to calculate how many non-diabetic people in each age group were likely to have a heart attack or stroke in the next 5 years. In addition heart failure and dialysis admission rates were estimated based upon risk factors for incidence. The United Kingdom Prospective Diabetes Study (UKPDS) risk engines 56 and 60 were used to calculate the risk of CHD and stroke, respectively, in people with type 2 diabetes. The spreadsheet deducted the number of people likely to die before reaching hospital and produced a predicted number of hospital admissions for each category over a 5-year period. The final part of the calculation attached a cost to the hospital activity using the UK Health Resource Grouping (HRG) tariffs. The predicted number of events in each of the primary care trusts was then compared with the actual number of events the previous year (2004/2005). The study used a decision tree type model, which was populated with data from the research literature. The model applied the risk equations to population data from five primary care trusts to estimate how many people would suffer from an acute CVD related event over the next 5 years. The predicted number of events was then compared with the actual number of acute admissions for heart attacks, strokes, heart failure, acute hypoglycaemic attacks, renal failure and coronary bypass surgery the previous year. The first outcome of the model was to compare the estimated number of people in each PCT likely to suffer from a heart attack, a stroke, heart failure or chronic kidney failure with the actual number the previous year 2004/2005. The predicted number was remarkably accurate in the case of heart attack and stroke. There was some over-prediction of chronic kidney disease (CKD) which could be accounted for by known under-diagnosis in this illness group and the inability of the model to pick up, at this stage, the fact that many CKD patients die of a CHD related event before they reach the stage of requiring renal replacement. The second outcome of the model was to estimate the financial consequence of risk reduction. Moderate reductions in risk in the order of around 2-4% were estimated to lead to saving in acute admission costs or around pounds sterling 5.4 million over 5 years. More ambitious targets of risk reduction in the order of 5-6% led to estimated savings of around pounds sterling 8.7 million. This study is not presented as the definitive approach to predicting the economic consequences of investment in public health on the cost of secondary care. It is simply a logical, systematic approach to quantifying these issues in order to present a business case for such investment. The research team do not know if the predicted savings would accrue from such investments; it is theoretical at this stage. The point is, however, that if the predictions are correct then the savings will accrue from over 4000 people, from an adult population of around 185,000 not having a heart attack or a stroke or an acute exacerbation of heart failure.

Observational and Genetic Associations of Resting Heart Rate With Aortic Valve Calcium.

PubMed

Whelton, Seamus P; Mauer, Andreas C; Pencina, Karol M; Massaro, Joseph M; D'Agostino, Ralph B; Fox, Caroline S; Hoffmann, Udo; Michos, Erin D; Peloso, Gina M; Dufresne, Line; Engert, James C; Kathiresan, Sekar; Budoff, Matthew; Post, Wendy S; Thanassoulis, George; O'Donnell, Christopher J

2018-05-15

It is unknown if lifelong exposure to increased hemodynamic stress from an elevated resting heart rate (HR) may contribute to aortic valve calcium (AVC). We performed multivariate regression analyses using data from 1,266 Framingham Heart Study (FHS) Offspring cohort participants and 6,764 Multi-Ethnic Study of Atherosclerosis (MESA) participants. We constructed a genetic risk score (GRS) for HR using summary-level data in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) AVC Consortium to investigate if there was evidence in favor of a causal relation. AVC was present in 39% of FHS Offspring cohort participants and in 13% of MESA cohort participants. In multivariate adjusted models, participants in the highest resting HR quartiles had significantly greater prevalence of AVC, with a prevalence ratio of 1.19 (95% confidence interval [CI] 0.99 to 1.44) for the FHS Offspring cohort and 1.32 (95% CI 1.12 to 1.63) for the MESA cohort, compared with those in the lowest quartile. There was a similar increase in the prevalence of AVC per standard deviation increase in resting HR in both FHS Offspring (prevalence ratio 1.08, 95% CI 1.01 to 1.15) and MESA (1.10, 95% CI 1.03 to 1.17). In contrast with these observational findings, a HR associated GRS was not significantly associated with AVC. Although our observational analysis indicates that a higher resting HR is associated with AVC, our genetic results do not support a causal relation. Unmeasured environmental and/or lifestyle factors associated with both increased resting HR and AVC that are not fully explained by covariates in our observational models may account for the association between resting HR and AVC. Copyright © 2018. Published by Elsevier Inc.

Association of Rare Loss-Of-Function Alleles in HAL, Serum Histidine: Levels and Incident Coronary Heart Disease.

PubMed

Yu, Bing; Li, Alexander H; Muzny, Donna; Veeraraghavan, Narayanan; de Vries, Paul S; Bis, Joshua C; Musani, Solomon K; Alexander, Danny; Morrison, Alanna C; Franco, Oscar H; Uitterlinden, André; Hofman, Albert; Dehghan, Abbas; Wilson, James G; Psaty, Bruce M; Gibbs, Richard; Wei, Peng; Boerwinkle, Eric

2015-04-01

Histidine is a semiessential amino acid with antioxidant and anti-inflammatory properties. Few data are available on the associations between genetic variants, histidine levels, and incident coronary heart disease (CHD) in a population-based sample. By conducting whole exome sequencing on 1152 African Americans in the Atherosclerosis Risk in Communities (ARIC) study and focusing on loss-of-function (LoF) variants, we identified 3 novel rare LoF variants in HAL, a gene that encodes histidine ammonia-lyase in the first step of histidine catabolism. These LoF variants had large effects on blood histidine levels (β=0.26; P=1.2×10(-13)). The positive association with histidine levels was replicated by genotyping an independent sample of 718 ARIC African Americans (minor allele frequency=1%; P=1.2×10(-4)). In addition, high blood histidine levels were associated with reduced risk of developing incident CHD with an average of 21.5 years of follow-up among African Americans (hazard ratio=0.18; P=1.9×10(-4)). This finding was validated in an independent sample of European Americans from the Framingham Heart Study (FHS) Offspring Cohort. However, LoF variants in HAL were not directly significantly associated with incident CHD after meta-analyzing results from the CHARGE Consortium. Three LoF mutations in HAL were associated with increased histidine levels, which in turn were shown to be inversely related to the risk of CHD among both African Americans and European Americans. Future investigations on the association between HAL gene variation and CHD are warranted. © 2015 American Heart Association, Inc.

Micro RNAs from DNA Viruses are Found Widely in Plasma in a Large Observational Human Population.

PubMed

Koupenova, Milka; Mick, Eric; Corkrey, Heather A; Huan, Tianxiao; Clancy, Lauren; Shah, Ravi; Benjamin, Emelia J; Levy, Daniel; Kurt-Jones, Evelyn A; Tanriverdi, Kahraman; Freedman, Jane E

2018-04-23

Viral infections associate with disease risk and select families of viruses encode miRNAs that control an efficient viral cycle. The association of viral miRNA expression with disease in a large human population has not been previously explored. We sequenced plasma RNA from 40 participants of the Framingham Heart Study (FHS, Offspring Cohort, Visit 8) and identified 3 viral miRNAs from 3 different human Herpesviridae. These miRNAs were mostly related to viral latency and have not been previously detected in human plasma. Viral miRNA expression was then screened in the plasma of 2763 participants of the remaining cohort utilizing high-throughput RT-qPCR. All 3 viral miRNAs associated with combinations of inflammatory or prothrombotic circulating biomarkers (sTNFRII, IL-6, sICAM1, OPG, P-selectin) but did not associate with hypertension, coronary heart disease or cancer. Using a large observational population, we demonstrate that the presence of select viral miRNAs in the human circulation associate with inflammatory biomarkers and possibly immune response, but fail to associate with overt disease. This study greatly extends smaller singular observations of viral miRNAs in the human circulation and suggests that select viral miRNAs, such as those for latency, may not impact disease manifestation.

Abuse, Nocturnal Stress Hormones, and Coronary Heart Disease Risk Among Women with HIV

PubMed Central

Dale, Sannisha K.; Weber, Kathleen M.; Cohen, Mardge H.; Brody, Leslie R.

2017-01-01

This study investigated the relationships among abuse, nocturnal levels of cortisol and norepinephrine (NE), and coronary heart disease (CHD) risk as measured by the Framingham Risk Score (FRS) among women with HIV. Participants (n=53) from the Chicago Women's Interagency HIV Study, a longitudinal prospective cohort study initiated in 1994, were enrolled in this study during 2012. At WIHS baseline and annual follow-up visits women were asked about recent experiences of abuse. Summary variables captured the proportion of visits for which women reported recent (past 12 months) physical, sexual, and domestic abuse. Cortisol and NE were assayed in overnight urine samples and adjusted for creatinine levels. Recent abuse was not significantly associated with levels of cortisol, NE, or NE/cortisol ratio. However, higher NE/cortisol ratio was significantly related to higher CHD risk score, higher cortisol was significantly related to lower CHD risk score, and NE was not associated with CHD risk score. In addition, higher proportions of visits with recent sexual abuse, physical abuse, and domestic abuse were significantly related to higher CHD risk score. The association between abuse exposure and CHD risk in the context of HIV infection is likely complex and may involve dysregulation of multiple neurobiological systems. Future research is needed to better understand these relationships and prevention and intervention efforts are needed to address abuse among women with HIV. PMID:27733045

Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.

PubMed

Smith, Nicholas L; Felix, Janine F; Morrison, Alanna C; Demissie, Serkalem; Glazer, Nicole L; Loehr, Laura R; Cupples, L Adrienne; Dehghan, Abbas; Lumley, Thomas; Rosamond, Wayne D; Lieb, Wolfgang; Rivadeneira, Fernando; Bis, Joshua C; Folsom, Aaron R; Benjamin, Emelia; Aulchenko, Yurii S; Haritunians, Talin; Couper, David; Murabito, Joanne; Wang, Ying A; Stricker, Bruno H; Gottdiener, John S; Chang, Patricia P; Wang, Thomas J; Rice, Kenneth M; Hofman, Albert; Heckbert, Susan R; Fox, Ervin R; O'Donnell, Christopher J; Uitterlinden, Andre G; Rotter, Jerome I; Willerson, James T; Levy, Daniel; van Duijn, Cornelia M; Psaty, Bruce M; Witteman, Jacqueline C M; Boerwinkle, Eric; Vasan, Ramachandran S

2010-06-01

Although genetic factors contribute to the onset of heart failure (HF), no large-scale genome-wide investigation of HF risk has been published to date. We have investigated the association of 2,478,304 single-nucleotide polymorphisms with incident HF by meta-analyzing data from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Eligible participants for these analyses were of European or African ancestry and free of clinical HF at baseline. Each study independently conducted genome-wide scans and imputed data to the approximately 2.5 million single-nucleotide polymorphisms in HapMap. Within each study, Cox proportional hazards regression models provided age- and sex-adjusted estimates of the association between each variant and time to incident HF. Fixed-effect meta-analyses combined results for each single-nucleotide polymorphism from the 4 cohorts to produce an overall association estimate and P value. A genome-wide significance P value threshold was set a priori at 5.0x10(-7). During a mean follow-up of 11.5 years, 2526 incident HF events (12%) occurred in 20 926 European-ancestry participants. The meta-analysis identified a genome-wide significant locus at chromosomal position 15q22 (1.4x10(-8)), which was 58.8 kb from USP3. Among 2895 African-ancestry participants, 466 incident HF events (16%) occurred during a mean follow-up of 13.7 years. One genome-wide significant locus was identified at 12q14 (6.7x10(-8)), which was 6.3 kb from LRIG3. We identified 2 loci that were associated with incident HF and exceeded genome-wide significance. The findings merit replication in other community-based settings of incident HF.

Cardiovascular risk assessment according to the Framingham score and abdominal obesity in individuals seen by a clinical school of nutrition.

PubMed

Oliveira, Alane Cabral Menezes de; Ferreira, Raphaela Costa; Santos, Arianne Albuquerque

2016-04-01

To analyze the relation of abdominal obesity on cardiovascular risk in individuals seen by a clinic school of nutrition, classifying them based on Framingham score. Cross-sectional study, conducted at the nutrition clinic of a private college in the city of Maceió, Alagoas. We included randomly selected adults and elderly individuals with abdominal obesity, of both sexes, treated from August to December of 2009, with no history of cardiomyopathy or cardiovascular events. To determine the cardiovascular risk, the Framingham score was calculated. All analyzes were performed with SPSS software version 20.0, with p <0.05 as significative. We studied 54 subjects, 83% female, the mean age was 48 years old, ranging from 31 to 73 years. No correlation was observed between measurements of waist circumference and cardiovascular risk in the subjects studied (r=0.065, p=0.048), and there was no relationship between these parameters. Abdominal fat distribution was weakly related to cardiovascular risk in patients seen by a clinical school of nutrition.

Quantifying the impact of using Coronary Artery Calcium Score for risk categorization instead of Framingham Score or European Heart SCORE in lipid lowering algorithms in a Middle Eastern population.

PubMed

Isma'eel, Hussain A; Almedawar, Mohamad M; Harbieh, Bernard; Alajaji, Wissam; Al-Shaar, Laila; Hourani, Mukbil; El-Merhi, Fadi; Alam, Samir; Abchee, Antoine

2015-10-01

The use of the Coronary Artery Calcium Score (CACS) for risk categorization instead of the Framingham Risk Score (FRS) or European Heart SCORE (EHS) to improve classification of individuals is well documented. However, the impact of reclassifying individuals using CACS on initiating lipid lowering therapy is not well understood. We aimed to determine the percentage of individuals not requiring lipid lowering therapy as per the FRS and EHS models but are found to require it using CACS and vice versa; and to determine the level of agreement between CACS, FRS and EHS based models. Data was collected for 500 consecutive patients who had already undergone CACS. However, only 242 patients met the inclusion criteria and were included in the analysis. Risk stratification comparisons were conducted according to CACS, FRS, and EHS, and the agreement (Kappa) between them was calculated. In accordance with the models, 79.7% to 81.5% of high-risk individuals were down-classified by CACS, while 6.8% to 7.6% of individuals at intermediate risk were up-classified to high risk by CACS, with slight to moderate agreement. Moreover, CACS recommended treatment to 5.7% and 5.8% of subjects untreated according to European and Canadian guidelines, respectively; whereas 75.2% to 81.2% of those treated in line with the guidelines would not be treated based on CACS. In this simulation, using CACS for risk categorization warrants lipid lowering treatment for 5-6% and spares 70-80% from treatment in accordance with the guidelines. Current strong evidence from double randomized clinical trials is in support of guideline recommendations. Our results call for a prospective trial to explore the benefits/risks of a CACS-based approach before any recommendations can be made.

Quantifying the impact of using Coronary Artery Calcium Score for risk categorization instead of Framingham Score or European Heart SCORE in lipid lowering algorithms in a Middle Eastern population

PubMed Central

Isma’eel, Hussain A.; Almedawar, Mohamad M.; Harbieh, Bernard; Alajaji, Wissam; Al-Shaar, Laila; Hourani, Mukbil; El-Merhi, Fadi; Alam, Samir; Abchee, Antoine

2015-01-01

Background The use of the Coronary Artery Calcium Score (CACS) for risk categorization instead of the Framingham Risk Score (FRS) or European Heart SCORE (EHS) to improve classification of individuals is well documented. However, the impact of reclassifying individuals using CACS on initiating lipid lowering therapy is not well understood. We aimed to determine the percentage of individuals not requiring lipid lowering therapy as per the FRS and EHS models but are found to require it using CACS and vice versa; and to determine the level of agreement between CACS, FRS and EHS based models. Methods Data was collected for 500 consecutive patients who had already undergone CACS. However, only 242 patients met the inclusion criteria and were included in the analysis. Risk stratification comparisons were conducted according to CACS, FRS, and EHS, and the agreement (Kappa) between them was calculated. Results In accordance with the models, 79.7% to 81.5% of high-risk individuals were down-classified by CACS, while 6.8% to 7.6% of individuals at intermediate risk were up-classified to high risk by CACS, with slight to moderate agreement. Moreover, CACS recommended treatment to 5.7% and 5.8% of subjects untreated according to European and Canadian guidelines, respectively; whereas 75.2% to 81.2% of those treated in line with the guidelines would not be treated based on CACS. Conclusion In this simulation, using CACS for risk categorization warrants lipid lowering treatment for 5–6% and spares 70–80% from treatment in accordance with the guidelines. Current strong evidence from double randomized clinical trials is in support of guideline recommendations. Our results call for a prospective trial to explore the benefits/risks of a CACS-based approach before any recommendations can be made. PMID:26557741

Elevated blood lipids are uncommon in patients with post-polio syndrome--a cross sectional study.

PubMed

Melin, Eva; Kahan, Thomas; Borg, Kristian

2015-04-29

The post-polio syndrome occurs in people who previously have had poliomyelitis. After the initial recovery, new or increasing neurologic symptoms occur. Inflammation and dyslipidaemia may play an important role in the development of atherosclerotic complications, for example myocardial infarction and angina pectoris. Previous studies on cardiovascular risk factors in the post-polio syndrome have found a higher prevalence of hypertension, ischemic heart disease, hyperlipidaemia, and stroke in these patients. The present study was undertaken in order to evaluate whether post-polio patients have elevated lipid values, and if blood lipid abnormalities could be correlated to signs of inflammation. Cross-sectional study of 89 consecutive post-polio patients, (53 women, mean age 65 years) from the Post-Polio Outpatient Clinic, Danderyd University Hospital, Stockholm, Sweden. The lipid profiles of post-polio patients were compared to age and sex matched reference values from two earlier studies. Statistical analyses were performed by the Student's t-test, and linear regression analyses were assessed by Pearson's correlation coefficient. Mean total cholesterol levels (5.7 mmol/L) were low or normal in post-polio patients, whereas low density lipoprotein levels (3.6 mmol/L) were normal, and high density lipoprotein (1.5 mmol/L) and triglycerides (1.4 mmol/L) lower than reference values. The prevalence of diabetes (7%), hypertension (38%), concomitant cardiovascular disease, (including angina pectoris, myocardial infarction, heart failure, atrial fibrillation and stroke) (7%), and calculated 10 year risk of coronary heart disease according to Framingham risk score algorithm (8%) was not increased in post-polio patients. Compared to reference populations, post-polio patients in Sweden appear to have low or normal total cholesterol and low density lipoprotein levels, whereas high density lipoprotein and triglyceride levels are low. Hence, a possible persisting inflammatory process in post-polio syndrome does not seem to be associated with increased lipids and an increased risk for coronary heart disease events.

Comparison of self-perceived cardiovascular disease risk among smokers with Framingham and PROCAM scores: a cross-sectional analysis of baseline data from a randomised controlled trial.

PubMed

Desgraz, Benoît; Collet, Tinh-Hai; Rodondi, Nicolas; Cornuz, Jacques; Clair, Carole

2017-01-06

Previous studies suggest that smokers have a misperception of their 10-year cardiovascular risk. We aimed to compare 10-year cardiovascular risk self-perception and calculated risk among smokers willing to quit and assess the determinants of a possible misperception. Cross-sectional secondary analysis of baseline data from a randomised controlled trial of smoking cessation. 514 participants, mean age 51.1 years, 46% women, 98% Caucasian. Eligible participants were regular smokers, aged between 40 and 70 years, with a consumption of at least 10 cigarettes per day for at least a year. None of them had experienced cardiovascular disease before. Exclusion criteria comprised a history of myocardial infarction, coronary heart disease, stroke, heart failure, peripheral vascular disease, carotid atherosclerosis or cardiac arrhythmia. Participants with renal or liver failure, psychiatric disorders, substance and alcohol abuse and with smoking cessation therapies were excluded. Participants were asked to estimate their 10-year cardiovascular risk using a 3-item scale corresponding to high-risk, moderate-risk and low-risk categories. We compared their risk perception with Framingham and Prospective Cardiovascular Munster Study (PROCAM) scores. We used multivariable-adjusted logistic regression models to determine characteristics of participants who underestimate their risk versus those who correctly estimate or overestimate it. Between 38% and 42% of smokers correctly perceived their 10-year cardiovascular risk, and 39-50% overestimated their 10-year cardiovascular risk while 12-19% underestimated it compared with their calculated 10-year cardiovascular risk depending on the score used. Underestimation of 10-year cardiovascular risk was associated with male gender (OR 8.16; CI 3.83 to 17.36), older age (OR 1.06; CI 1.02 to 1.09), and the presence of hyperlipidaemia (OR 2.71; CI 1.47 to 5.01) and diabetes mellitus (OR 13.93; CI 3.83 to 50.66). Among smokers, misperception of their 10-year cardiovascular risk is common, with one-fifth underestimating it. These findings may help physicians target patients with such characteristics to help them change their health behaviour and adherence to risk-reduction therapy. NCT00548665; Post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

New Zealand Diabetes Cohort Study cardiovascular risk score for people with Type 2 diabetes: validation in the PREDICT cohort.

PubMed

Robinson, Tom; Elley, C Raina; Wells, Sue; Robinson, Elizabeth; Kenealy, Tim; Pylypchuk, Romana; Bramley, Dale; Arroll, Bruce; Crengle, Sue; Riddell, Tania; Ameratunga, Shanthi; Metcalf, Patricia; Drury, Paul L

2012-09-01

New Zealand (NZ) guidelines recommend treating people for cardiovascular disease (CVD) risk on the basis of five-year absolute risk using a NZ adaptation of the Framingham risk equation. A diabetes-specific Diabetes Cohort Study (DCS) CVD predictive risk model has been developed and validated using NZ Get Checked data. To revalidate the DCS model with an independent cohort of people routinely assessed using PREDICT, a web-based CVD risk assessment and management programme. People with Type 2 diabetes without pre-existing CVD were identified amongst people who had a PREDICT risk assessment between 2002 and 2005. From this group we identified those with sufficient data to allow estimation of CVD risk with the DCS models. We compared the DCS models with the NZ Framingham risk equation in terms of discrimination, calibration, and reclassification implications. Of 3044 people in our study cohort, 1829 people had complete data and therefore had CVD risks calculated. Of this group, 12.8% (235) had a cardiovascular event during the five-year follow-up. The DCS models had better discrimination than the currently used equation, with C-statistics being 0.68 for the two DCS models and 0.65 for the NZ Framingham model. The DCS models were superior to the NZ Framingham equation at discriminating people with diabetes who will have a cardiovascular event. The adoption of a DCS model would lead to a small increase in the number of people with diabetes who are treated with medication, but potentially more CVD events would be avoided.

NT-proBNP is associated with coronary heart disease risk in healthy older women but fails to enhance prediction beyond established risk factors: results from the British Women's Heart and Health Study.

PubMed

Sattar, Naveed; Welsh, Paul; Sarwar, Nadeem; Danesh, John; Di Angelantonio, Emanuele; Gudnason, Vilmundur; Davey Smith, George; Ebrahim, Shah; Lawlor, Debbie A

2010-03-01

Limited evidence suggests NT-proBNP improves prediction of coronary heart disease (CHD) events but further data are needed, especially in people without pre-existing CHD and in women. We measured NT-proBNP in serum from 162 women with incident CHD events and 1226 controls (60-79 years) in a case-control study nested within the prospective British Women's Heart and Health Study. All cases and controls were free from CHD at baseline. We related NT-proBNP to CHD event risk, and determined to what extent NT-proBNP enhanced CHD risk prediction beyond established risk factors. The odds ratio for CHD per 1 standard deviation increase in log(e)NT-proBNP was 1.37 (95% CI: 1.13-1.68) in analyses adjusted for established CHD risk factors, social class, CRP and insulin. However, addition of log(e)NT-proBNP did not improve the discrimination of a prediction model including age, social class, smoking, physical activity, lipids, fasting glucose, waist:hip ratio, hypertension, statin and aspirin use, nor a standard Framingham risk score model; area under the receiver operator curve for the former model increased from 0.676 to 0.687 on inclusion of NT-proBNP (p=0.3). Furthermore, adding NT-proBNP did not improve calibration of a prediction model containing established risk factors, nor did inclusion more appropriately re-classify participants in relation to their final outcome. Findings were similar (independent associations, but no prediction improvement) for fasting insulin and CRP. These results caution against use of NT-proBNP for CHD risk prediction in healthy women and suggest a need for larger studies in both genders to resolve outstanding uncertainties.

Haplotypes in the CRP Gene Associated with Increased BMI and Levels of CRP in Subjects with Type 2 Diabetes or Obesity from Southwestern Mexico

PubMed Central

Martínez-Calleja, América; Quiróz-Vargas, Irma; Parra-Rojas, Isela; Muñoz-Valle, José Francisco; Leyva-Vázquez, Marco A.; Fernández-Tilapa, Gloria; Vences-Velázquez, Amalia; Cruz, Miguel; Salazar-Martínez, Eduardo; Flores-Alfaro, Eugenia

2012-01-01

Objective. We evaluated the association between four polymorphisms in the CRP gene with circulating levels of C-reactive protein (CRP), type 2 diabetes (T2D), obesity, and risk score of coronary heart disease. Methods. We studied 402 individuals and classified them into four groups: healthy, obese, T2D obese, and T2D without obesity, from Guerrero, Southwestern Mexico. Blood levels of CRP, glucose, cholesterol, triglycerides, and leukocytes were measured. Genotyping was performed by PCR/RFLP, and the risk score for coronary heart disease was determined by the Framingham's methodology. Results. The TT genotype of SNP rs1130864 was associated with increased body mass index and T2D patients with obesity. We found that the haplotype 2 (TGAG) was associated with increased levels of CRP (β = 0.3; 95%CI: 0.1, 0.5; P = 0.005) and haplotype 7 (TGGG) with higher body mass index (BMI) (β = 0.2; 95%CI: 0.1, 0.3; P < 0.001). The risk score for coronary heart disease was associated with increased levels of CRP, but not with any polymorphism or haplotype. Conclusions. The association between the TT genotype of SNP rs1130864 with obesity and the haplotype 7 with BMI may explain how obesity and genetic predisposition increase the risk of diseases such as T2D in the population of Southwestern Mexico. PMID:23049543

Relationship Between Central and Peripheral Atherosclerosis and Left Ventricular Dysfunction in a Community Population

PubMed Central

Tsao, Connie W.; Gona, Philimon; Salton, Carol; Murabito, Joanne M.; Oyama, Noriko; Danias, Peter G.; O’Donnell, Christopher J.; Manning, Warren J.; Yeon, Susan B.

2011-01-01

We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and PAD in a community cohort. 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65±9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional LV systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at Examination 7. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p<0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p<0.001) and volume of aortic plaque were associated with decreased ABI (p<0.001). After multivariable adjustment, ABI≤0.9 or prior revascularization was associated with a three-fold odds of aortic plaque (p=0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p<0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment suggesting shared mechanisms beyond those captured by traditional risk factors. PMID:21708875

Beyond Framingham risk factors and coronary calcification: does aortic valve calcification improve risk prediction? The Heinz Nixdorf Recall Study.

PubMed

Kälsch, Hagen; Lehmann, Nils; Mahabadi, Amir A; Bauer, Marcus; Kara, Kaffer; Hüppe, Patricia; Moebus, Susanne; Möhlenkamp, Stefan; Dragano, Nico; Schmermund, Axel; Stang, Andreas; Jöckel, Karl-Heinz; Erbel, Raimund

2014-06-01

Aortic valve calcification (AVC) is considered a manifestation of atherosclerosis. In this study, we investigated whether AVC adds to cardiovascular risk prediction beyond Framingham risk factors and coronary artery calcification (CAC). A total of 3944 subjects from the population based Heinz Nixdorf Recall Study (59.3±7.7 years; 53% females) were evaluated for coronary events, stroke, and cardiovascular disease (CVD) events (including all plus CV death) over 9.1±1.9 years. CT scans were performed to quantify AVC. Cox proportional hazards regressions and Harrell's C were used to examine AVC as event predictor in addition to risk factors and CAC. During follow-up, 138 (3.5%) subjects experienced coronary events, 101 (2.6%) had a stroke, and 257 (6.5%) experienced CVD events. In subjects with AVC>0 versus AVC=0 the incidence of coronary events was 8.0% versus 3.0% (p<0.001) and the incidence of CVD events was 13.0% versus 5.7% (p<0.001). The frequency of events increased significantly with increasing AVC scores (p<0.001). After adjustment for Framingham risk factors, high AVC scores (3rd tertile) remained independently associated with coronary events (HR 2.21, 95% CI 1.28 to 3.81) and CVD events (HR 1.67, 95% CI 1.08 to 2.58). After further adjustment for CAC score, HRs were attenuated (coronary events 1.55, 95% CI 0.89 to 2.69; CVD events 1.29, 95% CI 0.83 to 2.00). When adding AVC to the model containing traditional risk factors and CAC, Harrell's C indices did not increase for coronary events (from 0.744 to 0.744) or CVD events (from 0.759 to 0.759). AVC is associated with incident coronary and CVD events independent of Framingham risk factors. However, AVC fails to improve cardiovascular event prediction over Framingham risk factors and CAC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Association of Parental Obesity and Diabetes Mellitus With Circulating Adipokines in Nonobese Nondiabetic Offspring.

PubMed

Zachariah, Justin P; Quiroz, Rene; Enserro, Danielle; Andersson, Charlotte; Keaney, John F; Sullivan, Lisa M; Vasan, Ramachandran S

2017-07-16

Adipokines are implicated in the development of obesity-related traits. We hypothesized that nonobese participants without diabetes mellitus (DM) whose parents were obese or had DM would have altered circulating adipokines compared with those without parental history of these conditions. Participants in the community-based Framingham Third Generation cohort who were not obese (body mass index <30) and not diabetic with both parents in the Framingham Offspring cohort were included in this analysis (n=2034, mean age 40 years, 54% women). Circulating concentrations of fetuin A, RBP4 (retinol binding protein 4), FABP4 (fatty acid binding protein 4), leptin, LEP-R (leptin receptor), and adiponectin were assayed. Parental DM was defined as occurring before age 60 years, and obesity was defined as body mass index ≥30 before age 60 years. General estimating equations were used to compare concentrations of adipokines among participants with 0, 1, or 2 parents affected by obesity or DM (separate analyses for each), adjusting for known correlates of adipokines. Overall, 44% had at least 1 parent who was obese and 15% had parents with DM. Parental obesity was associated with higher serum levels of FABP4 and LEP-R in their offspring ( P =0.02 for both). Parental DM was associated with lower adiponectin but higher RBP4 concentrations in offspring ( P ≤0.02 for both). In our community-based sample, a parental history of DM or obesity was associated with an altered adipokine profile in nonobese nondiabetic offspring. Additional studies are warranted to evaluate whether such preclinical biomarker alterations presage future risk of disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes.

PubMed

Colombo, Marco; Looker, Helen C; Farran, Bassam; Agakov, Felix; Brosnan, M Julia; Welsh, Paul; Sattar, Naveed; Livingstone, Shona; Durrington, Paul N; Betteridge, D John; McKeigue, Paul M; Colhoun, Helen M

2018-05-21

Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded. Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction. Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745. The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Dietary patterns and the metabolic syndrome in obese and non-obese Framingham women.

PubMed

Sonnenberg, Lillian; Pencina, Michael; Kimokoti, Ruth; Quatromoni, Paula; Nam, Byung-Ho; D'Agostino, Ralph; Meigs, James B; Ordovas, Jose; Cobain, Mark; Millen, Barbara

2005-01-01

To examine the relationship between habitual dietary patterns and the metabolic syndrome (MetS) in women and to identify foci for preventive nutrition interventions. Dietary patterns, nutrient intake, cardiovascular disease (CVD), and MetS risk factors were characterized in 1615 Framingham Offspring-Spouse Study (FOS) women. Dietary pattern subgroups were compared for MetS prevalence and CVD risk factor status using logistic regression and analysis of covariance. Analyses were performed overall in women and stratified on obesity status; multivariate models controlled for age, apolipoprotein E (APOE) genotypes, and CVD risk factors. Food and nutrient profiles and overall nutritional risk of five non-overlapping habitual dietary patterns of women were identified including Heart Healthier, Lighter Eating, Wine and Moderate Eating, Higher Fat, and Empty Calories. Rates of hypertension and low high-density lipoprotein levels were high in non-obese women, but individual MetS risk factor levels were substantially increased in obese women. Overall MetS risk varied by dietary pattern and obesity status, independently of APOE and CVD risk factors. Compared with obese or non-obese women and women overall with other dietary patterns, MetS was highest in those with the Empty Calorie pattern (contrast p value: p<0.05). This research shows the independent relationship between habitual dietary patterns and MetS risk in FOS women and the influence of obesity status. High overall MetS risk and the varying prevalence of individual MetS risk factors in female subgroups emphasize the importance of preventive nutrition interventions and suggest potential benefits of targeted behavior change in both obese and non-obese women by dietary pattern.

Evidence for increased cardiovascular events in the fathers but not mothers of women with polycystic ovary syndrome.

PubMed

Taylor, Mary C; Reema Kar, A; Kunselman, Allen R; Stetter, Christy M; Dunaif, Andrea; Legro, Richard S

2011-08-01

Polycystic ovary syndrome (PCOS) is a familial syndrome, associated with multiple cardiovascular disease (CVD) risk factors. Thus, parents of affected women may have a higher prevalence of CVD events than the general population. PCOS probands (n = 410) and their participating parents (n = 180 fathers and 211 mothers) were queried for CVD events in themselves and non-participating family members. In order to include the family CVD history of all parents, agreement between the proband and parental reports of CVD events was assessed. Estimated 10-year coronary heart disease (CHD) risk was calculated using the Framingham risk calculator. The National Health and Nutrition Examination Survey (NHANES) 2001-2002 database was used to generate gender, age and body mass index-relevant population parameters of CVD prevalence in the USA population. Ninety-eight percent of the parents' self-reporting of CVD events agreed with the proband's report of parental heart attack history [Kappa = 0.82; 95% CI: (0.69, 0.94)] and 99% with parental stroke history [Kappa = 0.79; 95% CI: (0.62, 0.97)]. Fathers of women with PCOS had a higher prevalence of heart attack and stroke compared with the reference NHANES population (heart attack: 11.1 versus 5.3%, P < 0.0001; stroke: 3.0 versus 1.0%, P = 0.002). Fathers of women with PCOS had an elevated 10-year risk for CHD (11.5 versus 9.9% in NHANES, P = 0.03). No statistically significant increased prevalence of CVD events or 10-year risk was noted in probands or mothers. Fathers, and not mothers, may be disproportionately burdened with CVD in PCOS families. The strengths of this study include the size of our cohort, the consistent phenotyping and the validation of proband's reporting of parental CVD events.

Exercise in the prevention of coronary heart disease.

PubMed

Paffenbarger, R S; Hyde, R T

1984-01-01

Epidemiological studies have left no doubt as to the existence of a strong inverse relationship between physical exercise and coronary heart disease (CHD) risk. British studies of transport workers and civil servants, together with American studies of stevedores and college alumni, have provided persuasive evidence that contemporary vigorous activity is accompanied by lower risk of both fatal and nonfatal CHD. The relationship is largely independent of influential characteristics of high risk such as cigarette smoking, hypertension, obesity, and family history of hypertensive--atherosclerotic disease. Recent studies of occupational or leisure physical exercise among residents of Framingham, Massachusetts, the state of Iowa, four residential areas of Holland, urban--rural sections of Puerto Rico, Seattle--King County, Washington, city employees in Los Angeles, and various regions of Finland and Norway support the likelihood that the inverse relationship of exercise and CHD is causal, signifying a protective effect of exercise rather than an incidental contrast due to a selective influence of precursive CHD symptoms. Experimental studies in monkeys have added laboratory evidence that endurance exercise inhibits the development of CHD. The questions we need to address are not whether exercise is a real element for cardiovascular health, but what kind of exercise is needed, and how much, i.e., with what frequency, intensity, timing, and duration. An understanding of the ways and means by which exercise alters CHD risk is only beginning to emerge, but there is wide acceptance that its benefits are vitally needed in the sedentary Western world.

Comparative assessment of absolute cardiovascular disease risk characterization from non-laboratory-based risk assessment in South African populations

PubMed Central

2013-01-01

Background All rigorous primary cardiovascular disease (CVD) prevention guidelines recommend absolute CVD risk scores to identify high- and low-risk patients, but laboratory testing can be impractical in low- and middle-income countries. The purpose of this study was to compare the ranking performance of a simple, non-laboratory-based risk score to laboratory-based scores in various South African populations. Methods We calculated and compared 10-year CVD (or coronary heart disease (CHD)) risk for 14,772 adults from thirteen cross-sectional South African populations (data collected from 1987 to 2009). Risk characterization performance for the non-laboratory-based score was assessed by comparing rankings of risk with six laboratory-based scores (three versions of Framingham risk, SCORE for high- and low-risk countries, and CUORE) using Spearman rank correlation and percent of population equivalently characterized as ‘high’ or ‘low’ risk. Total 10-year non-laboratory-based risk of CVD death was also calculated for a representative cross-section from the 1998 South African Demographic Health Survey (DHS, n = 9,379) to estimate the national burden of CVD mortality risk. Results Spearman correlation coefficients for the non-laboratory-based score with the laboratory-based scores ranged from 0.88 to 0.986. Using conventional thresholds for CVD risk (10% to 20% 10-year CVD risk), 90% to 92% of men and 94% to 97% of women were equivalently characterized as ‘high’ or ‘low’ risk using the non-laboratory-based and Framingham (2008) CVD risk score. These results were robust across the six risk scores evaluated and the thirteen cross-sectional datasets, with few exceptions (lower agreement between the non-laboratory-based and Framingham (1991) CHD risk scores). Approximately 18% of adults in the DHS population were characterized as ‘high CVD risk’ (10-year CVD death risk >20%) using the non-laboratory-based score. Conclusions We found a high level of correlation between a simple, non-laboratory-based CVD risk score and commonly-used laboratory-based risk scores. The burden of CVD mortality risk was high for men and women in South Africa. The policy and clinical implications are that fast, low-cost screening tools can lead to similar risk assessment results compared to time- and resource-intensive approaches. Until setting-specific cohort studies can derive and validate country-specific risk scores, non-laboratory-based CVD risk assessment could be an effective and efficient primary CVD screening approach in South Africa. PMID:23880010

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

PubMed Central

Ljungman, Petter L.; Wilker, Elissa H.; Gold, Diane R.; Schwartz, Joel D.; Koutrakis, Petros; Washko, George R.; O’Connor, George T.; Mittleman, Murray A.

2013-01-01

Rationale: Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U.S. Environmental Protection Agency (EPA) standards. Objectives: To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study. Methods: We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995–2011) who were not current smokers, with previous-day pollutant levels in compliance with EPA standards. We compared lung function (FEV1 and FVC) after previous-day exposure to particulate matter less than 2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in the “moderate” range of the EPA Air Quality Index to exposure in the “good” range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function. Measurements and Main Results: Exposure to pollutant concentrations in the “moderate” range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV1 for PM2.5 (95% confidence interval [CI], −33.4, −6.9), a 30.6-ml lower FEV1 for NO2 (95% CI, −60.9, −0.2), and a 55.7-ml lower FEV1 for O3 (95% CI, −100.7, −10.8) compared with the “good” range. The 1- and 2-day moving averages of PM2.5, NO2, and O3 before testing were negatively associated with FEV1 and FVC. Conclusions: Short-term exposure to PM2.5, NO2, and O3 within current EPA standards was associated with lower lung function in this cohort of adults. PMID:24200465

Height Loss Predicts Subsequent Hip Fracture in Men and Women of the Framingham Study

PubMed Central

Hannan, Marian T.; Broe, Kerry E.; Cupples, L. Adrienne; Dufour, Alyssa B.; Rockwell, Margo; Kiel, Douglas P.

2013-01-01

Background Although height is a risk factor for osteoporotic fracture, current risk assessments do not consider height loss. Height loss may be a simple measurement that clinicians could use to predict fracture or need for further testing. Objective To examine height loss and subsequent hip fracture, evaluating both long-term adult height loss and recent height loss. Methods Prospective cohort of 3,081 adults from the Framingham Heart Study. Height was measured biennially since 1948, and cohort followed for hip fracture through 2005. Adult height loss from middle-age years across 24 years and recent height loss in elderly years were considered. Cox proportional hazard regression was used to estimate association between height loss and risk of hip fracture. Results Of 1,297 men and 1,784 women, mean baseline age was 66y (SD7.8). Average height loss for men was 1.06 inches (0.76), and for women was 1.12 inches (0.84). 11% of men and 15% of women lost ≤ 2 inches of height. Mean follow-up was 17y during which 71 men and 278 women had incident hip fractures. For each 1-inch of height loss, HR=1.4 in men (95%CI: 1.00, 1.99), and 1.04 in women (95%CI: 0.88, 1.23). Men and women who lost ≤ 2 inches of height had increased fracture risk (compared to 0 to <2 inches) of borderline significance: men HR=1.8, 95%CI: 0.86, 3.61; women HR=1.3, 95%CI: 0.90, 1.76. Recent height loss in elders significantly increased the risk of hip fracture, 54% in men and 21% in women (95%CI: 1.14, 2.09; 1.03, 1.42, respectively). Conclusions Adult height loss predicted hip fracture risk in men in our study. Recent height loss in elderly men and women predicted risk of hip fracture. PMID:22072590

Prognostic significance of hemoglobin level in patients with congestive heart failure and normal ejection fraction.

PubMed

Varadarajan, Padmini; Gandhi, Siddharth; Sharma, Sanjay; Umakanthan, Branavan; Pai, Ramdas G

2006-10-01

Previous studies have shown low hemoglobin (Hb) to have an adverse effect on survival in patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction (EF); but its effect on survival in patients with CHF and normal EF is not known. This study sought to determine whether low Hb has an effect on survival in patients with both CHF and normal EF. Detailed chart reviews were performed by medical residents on 2,246 patients (48% with normal EF) with a discharge diagnosis of CHF in a large tertiary care hospital from 1990 to 1999. The CHF diagnosis was validated using the Framingham criteria. Mortality data were obtained from the National Death Index. Survival analysis was performed using Kaplan-Meier and Cox regression models. By Kaplan-Meier analysis, low Hb (< 12 gm/dl) compared with normal hemoglobin was associated with a lower 5-year survival in patients with CHF and both normal (38 vs. 50%, p = 0.0008) and reduced (35 vs. 48%, p = 0.0009) EF. Using the Cox regression model, low Hb was an independent predictor of mortality after adjusting for age, gender, renal dysfunction, diabetes mellitus, hypertension, and EF in both groups of patients. Low Hb has an independent adverse effect on survival in patients with CHF and both normal and reduced EF in both groups of patients.

Toward the identification of causal genes in complex diseases: a gene-centric joint test of significance combining genomic and transcriptomic data.

PubMed

Charlesworth, Jac C; Peralta, Juan M; Drigalenko, Eugene; Göring, Harald Hh; Almasy, Laura; Dyer, Thomas D; Blangero, John

2009-12-15

Gene identification using linkage, association, or genome-wide expression is often underpowered. We propose that formal combination of information from multiple gene-identification approaches may lead to the identification of novel loci that are missed when only one form of information is available. Firstly, we analyze the Genetic Analysis Workshop 16 Framingham Heart Study Problem 2 genome-wide association data for HDL-cholesterol using a "gene-centric" approach. Then we formally combine the association test results with genome-wide transcriptional profiling data for high-density lipoprotein cholesterol (HDL-C), from the San Antonio Family Heart Study, using a Z-transform test (Stouffer's method). We identified 39 genes by the joint test at a conservative 1% false-discovery rate, including 9 from the significant gene-based association test and 23 whose expression was significantly correlated with HDL-C. Seven genes identified as significant in the joint test were not independently identified by either the association or expression tests. This combined approach has increased power and leads to the direct nomination of novel candidate genes likely to be involved in the determination of HDL-C levels. Such information can then be used as justification for a more exhaustive search for functional sequence variation within the nominated genes. We anticipate that this type of analysis will improve our speed of identification of regulatory genes causally involved in disease risk.

The estimated risk for coronary heart disease and prevalence of dyslipidemia among workers of information technology industries in Taiwan.

PubMed

Yang, Shao-Chi; Chien, Kuo-Liong; Tsai, Wei-I; Ho, Yi-Lwun; Chen, Ming-Fong

2011-03-18

Individuals working in information technology (IT) industries suffer from high work stress, possibly causing adverse impacts on their health. However, studies of cardiovascular risk factors among these workers are lacking. The aims of this study were to evaluate the estimated risk for coronary heart disease (CHD) and prevalence of dyslipidemia among IT workers. A total of 941 employees from 11 IT companies were enrolled and the anthropometrics and serum lipid profiles were measured. The 10-year risk for CHD was calculated based on the Framingham risk score. Compared with lipid profiles in a representative sample (n=6589), IT workers had a significantly higher prevalence of obesity, hypercholesterolemia, low level of HDL-C, and high level of LDL-C in each age group. Their overall estimated 10-year risk for CHD was higher than the average risk of an age- and gender-matched population (2.91% vs. 2.79%, p=0.027). Working for more than 10h/day was associated with a higher estimated CHD risk (3.62% vs. 2.54%, p<0.01). A higher prevalence of hyperlipidemia was noted among IT workers. Their estimated 10-year CHD risk was also higher than average. More aggressive interventions to reduce the risk of CHD in this population are needed. Copyright © 2010 Elsevier B.V. All rights reserved.

Minimally Invasive Implantation of HeartWare Assist Device and Simultaneous Tricuspid Valve Reconstruction Through Partial Upper Sternotomy.

PubMed

Hillebrand, Julia; Hoffmeier, Andreas; Djie Tiong Tjan, Tonny; Sindermann, Juergen R; Schmidt, Christoph; Martens, Sven; Scherer, Mirela

2017-05-01

Left ventricular assist device (LVAD) implantation is a well-established therapy to support patients with end-stage heart failure. However, the operative procedure is associated with severe trauma. Third generation LVADs like the HeartWare assist device (HeartWare, Inc., Framingham, MA, USA) are characterized by enhanced technology despite smaller size. These devices offer new minimally invasive surgical options. Tricuspid regurgitation requiring valve repair is frequent in patients with the need for mechanical circulatory support as it is strongly associated with ischemic and nonischemic cardiomyopathy. We report on HeartWare LVAD implantation and simultaneous tricuspid valve reconstruction through minimally invasive access by partial upper sternotomy to the fifth left intercostal space. Four male patients (mean age 51.72 ± 11.95 years) suffering from chronic heart failure due to dilative (three patients) and ischemic (one patient) cardiomyopathy and also exhibiting concomitant tricuspid valve insufficiency due to annular dilation underwent VAD implantation and tricuspid valve annuloplasty. Extracorporeal circulation was established via the ascending aorta, superior vena cava, and right atrium. In all four cases the LVAD implantation and tricuspid valve repair via partial median sternotomy was successful. During the operative procedure, no conversion to full sternotomy was necessary. One patient needed postoperative re-exploration because of pericardial effusion. No postoperative focal neurologic injury was observed. New generation VADs are advantageous because of the possibility of minimally invasive implantation procedure which can therefore minimize surgical trauma. Concomitant tricuspid valve reconstruction can also be performed simultaneously through partial upper sternotomy. Nevertheless, minimally invasive LVAD implantation is a challenging operative technique. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study

PubMed Central

Petoumenos, Kathy; Worm, Signe W; Fontas, Eric; Weber, Rainer; De Wit, Stephane; Bruyand, Mathias; Reiss, Peter; El-Sadr, Wafaa; Monforte, Antonella D'Arminio; Friis-Møller, Nina; Lundgren, Jens D; Law, Matthew G

2012-01-01

Introduction HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV-positive populations and to compare the existing models developed in the general population. Methods All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined. Results Of 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person-years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of<200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower glucose and lower triglycerides, and for BMI levels below 25 kg/m2. Conclusions The D:A:D equation performed well in predicting the short-term onset of DM in the validation dataset and for specific subgroups provided better estimates of DM risk than the Framingham. PMID:23078769

What does my patient's coronary artery calcium score mean? Combining information from the coronary artery calcium score with information from conventional risk factors to estimate coronary heart disease risk

PubMed Central

Pletcher, Mark J; Tice, Jeffrey A; Pignone, Michael; McCulloch, Charles; Callister, Tracy Q; Browner, Warren S

2004-01-01

Background The coronary artery calcium (CAC) score is an independent predictor of coronary heart disease. We sought to combine information from the CAC score with information from conventional cardiac risk factors to produce post-test risk estimates, and to determine whether the score may add clinically useful information. Methods We measured the independent cross-sectional associations between conventional cardiac risk factors and the CAC score among asymptomatic persons referred for non-contrast electron beam computed tomography. Using the resulting multivariable models and published CAC score-specific relative risk estimates, we estimated post-test coronary heart disease risk in a number of different scenarios. Results Among 9341 asymptomatic study participants (age 35–88 years, 40% female), we found that conventional coronary heart disease risk factors including age, male sex, self-reported hypertension, diabetes and high cholesterol were independent predictors of the CAC score, and we used the resulting multivariable models for predicting post-test risk in a variety of scenarios. Our models predicted, for example, that a 60-year-old non-smoking non-diabetic women with hypertension and high cholesterol would have a 47% chance of having a CAC score of zero, reducing her 10-year risk estimate from 15% (per Framingham) to 6–9%; if her score were over 100, however (a 17% chance), her risk estimate would be markedly higher (25–51% in 10 years). In low risk scenarios, the CAC score is very likely to be zero or low, and unlikely to change management. Conclusion Combining information from the CAC score with information from conventional risk factors can change assessment of coronary heart disease risk to an extent that may be clinically important, especially when the pre-test 10-year risk estimate is intermediate. The attached spreadsheet makes these calculations easy. PMID:15327691

Estimates of Commercial Population at High Risk for Cardiovascular Events: Impact of Aggressive Cholesterol Reduction

PubMed Central

Fitch, Kathryn; Goldberg, Sara W.; Iwasaki, Kosuke; Pyenson, Bruce S.; Kuznik, Andreas; Solomon, Henry A.

2009-01-01

Objectives To model the financial and health outcomes impact of intensive statin therapy compared with usual care in a high-risk working-age population (actively employed, commercially insured health plan members and their adult dependents). The target population consists of working-age people who are considered high-risk for cardiovascular disease events because of a history of coronary heart disease. Study Design Three-year event forecast for a sample population generated from the National Health and Nutrition Examination Survey data. Methods Using Framingham risk scoring system, the probability of myocardial infarction or stroke events was calculated for a representative sample population, ages 35 to 69 years, of people at high risk for cardiovascular disease, with a history of coronary heart disease. The probability of events for each individual was used to project the number of events expected to be generated for this population. Reductions in cardiovascular and stroke events reported in clinical trials with aggressive statin therapy were applied to these cohorts. We used medical claims data to model the cohorts' event costs. All results are adjusted to reflect the demographics of a typical working-age population. Results The high-risk cohort (those with coronary heart disease) comprises 4% of the 35- to 69-year-old commercially insured population but generates 22% of the risk for coronary heart disease and stroke. Reduced event rates associated with intensive statin therapy yielded a $58 mean medical cost reduction per treated person per month; a typical payer cost for a 30-day supply of intensive statin therapy is approximately $57. Conclusions Aggressive low-density lipoprotein cholesterol–lowering therapy for working-age people at high risk for cardiovascular events and with a history of heart disease appears to have a significant potential to reduce the rate of clinical events and is cost-neutral for payers. PMID:25126293

Systolic blood pressure, arterial rigidity, and risk of stroke. The Framingham study.

PubMed

Kannel, W B; Wolf, P A; McGee, D L; Dawber, T R; McNamara, P; Castelli, W P

1981-03-27

Based on prospective data from the Framingham study relating systolic pressure, diastolic pressure, age, and pulse-wave configuration to future stroke incidence, it would appear that isolated systolic hypertension predisposes to stroke independent of arterial rigidity. The prevalence of isolated systolic hypertension increased with age and with the degree of blunting of the dicrotic notch in the pulse wave. Subjects with isolated systolic hypertension experienced two to four times as many strokes as did normotensive persons. While diastolic pressure is related to stroke incidence, in the subject with systolic hypertension, the diastolic component adds little to risk assessment and in men, in this subgroup, appears unrelated to stroke incidence.

Progress of statistical analysis in biomedical research through the historical review of the development of the Framingham score.

PubMed

Ignjatović, Aleksandra; Stojanović, Miodrag; Milošević, Zoran; Anđelković Apostolović, Marija

2017-12-02

The interest in developing risk models in medicine not only is appealing, but also associated with many obstacles in different aspects of predictive model development. Initially, the association of biomarkers or the association of more markers with the specific outcome was proven by statistical significance, but novel and demanding questions required the development of new and more complex statistical techniques. Progress of statistical analysis in biomedical research can be observed the best through the history of the Framingham study and development of the Framingham score. Evaluation of predictive models comes from a combination of the facts which are results of several metrics. Using logistic regression and Cox proportional hazards regression analysis, the calibration test, and the ROC curve analysis should be mandatory and eliminatory, and the central place should be taken by some new statistical techniques. In order to obtain complete information related to the new marker in the model, recently, there is a recommendation to use the reclassification tables by calculating the net reclassification index and the integrated discrimination improvement. Decision curve analysis is a novel method for evaluating the clinical usefulness of a predictive model. It may be noted that customizing and fine-tuning of the Framingham risk score initiated the development of statistical analysis. Clinically applicable predictive model should be a trade-off between all abovementioned statistical metrics, a trade-off between calibration and discrimination, accuracy and decision-making, costs and benefits, and quality and quantity of patient's life.

An estimating equation approach to dimension reduction for longitudinal data

PubMed Central

Xu, Kelin; Guo, Wensheng; Xiong, Momiao; Zhu, Liping; Jin, Li

2016-01-01

Sufficient dimension reduction has been extensively explored in the context of independent and identically distributed data. In this article we generalize sufficient dimension reduction to longitudinal data and propose an estimating equation approach to estimating the central mean subspace. The proposed method accounts for the covariance structure within each subject and improves estimation efficiency when the covariance structure is correctly specified. Even if the covariance structure is misspecified, our estimator remains consistent. In addition, our method relaxes distributional assumptions on the covariates and is doubly robust. To determine the structural dimension of the central mean subspace, we propose a Bayesian-type information criterion. We show that the estimated structural dimension is consistent and that the estimated basis directions are root-\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$n$\\end{document} consistent, asymptotically normal and locally efficient. Simulations and an analysis of the Framingham Heart Study data confirm the effectiveness of our approach. PMID:27017956

Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study.

PubMed

Dehghan, Abbas; Köttgen, Anna; Yang, Qiong; Hwang, Shih-Jen; Kao, Wh Linda; Rivadeneira, Fernando; Boerwinkle, Eric; Levy, Daniel; Hofman, Albert; Astor, Brad C; Benjamin, Emelia J; van Duijn, Cornelia M; Witteman, Jacqueline C; Coresh, Josef; Fox, Caroline S

2008-12-06

Hyperuricaemia, a highly heritable trait, is a key risk factor for gout. We aimed to identify novel genes associated with serum uric acid concentration and gout. Genome-wide association studies were done for serum uric acid in 7699 participants in the Framingham cohort and in 4148 participants in the Rotterdam cohort. Genome-wide significant single nucleotide polymorphisms (SNPs) were replicated in white (n=11 024) and black (n=3843) individuals who took part in the study of Atherosclerosis Risk in Communities (ARIC). The SNPs that reached genome-wide significant association with uric acid in either the Framingham cohort (p<5.0 x 10(-8)) or the Rotterdam cohort (p<1.0 x 10(-7)) were evaluated with gout. The results obtained in white participants were combined using meta-analysis. Three loci in the Framingham cohort and two in the Rotterdam cohort showed genome-wide association with uric acid. Top SNPs in each locus were: missense rs16890979 in SLC2A9 (p=7.0 x 10(-168) and 2.9 x 10(-18) for white and black participants, respectively); missense rs2231142 in ABCG2 (p=2.5 x 10(-60) and 9.8 x 10(-4)), and rs1165205 in SLC17A3 (p=3.3 x 10(-26) and 0.33). All SNPs were direction-consistent with gout in white participants: rs16890979 (OR 0.59 per T allele, 95% CI 0.52-0.68, p=7.0 x 10(-14)), rs2231142 (1.74, 1.51-1.99, p=3.3 x 10(-15)), and rs1165205 (0.85, 0.77-0.94, p=0.002). In black participants of the ARIC study, rs2231142 was direction-consistent with gout (1.71, 1.06-2.77, p=0.028). An additive genetic risk score of high-risk alleles at the three loci showed graded associations with uric acid (272-351 mumol/L in the Framingham cohort, 269-386 mumol/L in the Rotterdam cohort, and 303-426 mumol/L in white participants of the ARIC study) and gout (frequency 2-13% in the Framingham cohort, 2-8% in the Rotterdam cohort, and 1-18% in white participants in the ARIC study). We identified three genetic loci associated with uric acid concentration and gout. A score based on genes with a putative role in renal urate handling showed a substantial risk for gout.

Anthropometric measures and absolute cardiovascular risk estimates in the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study.

PubMed

Chen, Lei; Peeters, Anna; Magliano, Dianna J; Shaw, Jonathan E; Welborn, Timothy A; Wolfe, Rory; Zimmet, Paul Z; Tonkin, Andrew M

2007-12-01

Framingham risk functions are widely used for prediction of future cardiovascular disease events. They do not, however, include anthropometric measures of overweight or obesity, now considered a major cardiovascular disease risk factor. We aimed to establish the most appropriate anthropometric index and its optimal cutoff point for use as an ancillary measure in clinical practice when identifying people with increased absolute cardiovascular risk estimates. Analysis of a population-based, cross-sectional survey was carried out. The 1991 Framingham prediction equations were used to compute 5 and 10-year risks of cardiovascular or coronary heart disease in 7191 participants from the Australian Diabetes, Obesity and Lifestyle Study (1999-2000). Receiver operating characteristic curve analysis was used to compare measures of body mass index (BMI), waist circumference, and waist-to-hip ratio in identifying participants estimated to be at 'high', or at 'intermediate or high' absolute risk. After adjustment for BMI and age, waist-to-hip ratio showed stronger correlation with absolute risk estimates than waist circumference. The areas under the receiver operating characteristic curve for waist-to-hip ratio (0.67-0.70 in men, 0.64-0.74 in women) were greater than those for waist circumference (0.60-0.65, 0.59-0.71) or BMI (0.52-0.59, 0.53-0.66). The optimal cutoff points of BMI, waist circumference and waist-to-hip ratio to predict people at 'high', or at 'intermediate or high' absolute risk estimates were 26 kg/m2, 95 cm and 0.90 in men, and 25-26 kg/m2, 80-85 cm and 0.80 in women, respectively. Measurement of waist-to-hip ratio is more useful than BMI or waist circumference in the identification of individuals estimated to be at increased risk for future primary cardiovascular events.

Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke: The Framingham Study.

PubMed

Saber, Hamidreza; Himali, Jayandra J; Beiser, Alexa S; Shoamanesh, Ashkan; Pikula, Aleksandra; Roubenoff, Ronenn; Romero, Jose R; Kase, Carlos S; Vasan, Ramachandran S; Seshadri, Sudha

2017-07-01

Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09-5.06; P =0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist-hip ratio for the association between IGF-1 and ischemic stroke ( P <0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist-hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P =0.007) and 41% (hazard ratio, 0.59; 95% confidence interval, 0.37-0.95; P =0.031) lower risk of incident ischemic stroke, respectively. IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance. © 2017 American Heart Association, Inc.

Whole genome sequence analyses of brain imaging measures in the Framingham Study.

PubMed

Sarnowski, Chloé; Satizabal, Claudia L; DeCarli, Charles; Pitsillides, Achilleas N; Cupples, L Adrienne; Vasan, Ramachandran S; Wilson, James G; Bis, Joshua C; Fornage, Myriam; Beiser, Alexa S; DeStefano, Anita L; Dupuis, Josée; Seshadri, Sudha

2018-01-16

We sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within the Trans-Omics for Precision Medicine Program. We performed association analyses of cerebral and hippocampal volumes and white matter hyperintensity (WMH) in up to 2,180 individuals by testing the association of rank-normalized residuals from mixed-effect linear regression models adjusted for sex, age, and total intracranial volume with individual variants while accounting for familial relatedness. We conducted gene-based tests for rare variants using (1) a sliding-window approach, (2) a selection of functional exonic variants, or (3) all variants. We detected new loci in 1p21 for cerebral volume (minor allele frequency [MAF] 0.005, p = 10 -8 ) and in 16q23 for hippocampal volume (MAF 0.05, p = 2.7 × 10 -8 ). Previously identified associations in 12q24 for hippocampal volume (rs7294919, p = 4.4 × 10 -4 ) and in 17q25 for WMH (rs7214628, p = 2.0 × 10 -3 ) were confirmed. Gene-based tests detected associations ( p ≤ 2.3 × 10 -6 ) in new loci for cerebral (5q13, 8p12, 9q31, 13q12-q13, 15q24, 17q12, 19q13) and hippocampal volumes (2p12) and WMH (3q13, 4p15) including Alzheimer disease- ( UNC5D ) and Parkinson disease-associated genes ( GBA ). Pathway analyses evidenced enrichment of associated genes in immunity, inflammation, and Alzheimer disease and Parkinson disease pathways. Whole genome sequence-wide search reveals intriguing new loci associated with brain measures. Replication of novel loci is needed to confirm these findings. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Strategies for reducing coronary risk factors in primary care: which is most cost effective?

PubMed Central

Field, K.; Thorogood, M.; Silagy, C.; Normand, C.; O'Neill, C.; Muir, J.

1995-01-01

OBJECTIVE--To examine the relative cost effectiveness of a range of screening and intervention strategies for preventing coronary heart disease in primary care. SUBJECTS--7840 patients aged 35-64 years who were participants in a trial of modifying coronary heart disease risk factors in primary care. DESIGN--Effectiveness of interventions assumed and the potential years of life gained estimated from a risk equation calculated from Framingham study data. MAIN OUTCOME MEASURE--The cost per year of life gained. RESULTS--The most cost effective strategy was minimal screening of blood pressure and personal history of vascular disease, which cost 310 pounds-930 pounds per year of life gained for men and 1100 pounds-3460 pounds for women excluding treatment of raised blood pressure. The extra cost per life year gained by adding smoking history to the screening was 400 pounds-6300 pounds in men. All strategies were more cost effective in men than in women and more cost effective in older age groups. Lipid lowering drugs accounted for at least 70% of the estimated costs of all strategies. Cost effectiveness was greatest when drug treatment was limited to those with cholesterol concentrations above 9.5 mmol/l. CONCLUSIONS--Universal screening and intervention strategies are an inefficient approach to reducing the coronary heart disease burden. A basic strategy for screening and intervention, targeted at older men with raised blood pressure and limiting the use of cholesterol lowering drugs to those with very high cholesterol concentrations would be most cost effective. PMID:7742678

Relationship between central and peripheral atherosclerosis and left ventricular dysfunction in a community population.

PubMed

Tsao, Connie W; Gona, Philimon; Salton, Carol; Murabito, Joanne M; Oyama, Noriko; Danias, Peter G; O'Donnell, Christopher J; Manning, Warren J; Yeon, Susan B

2011-08-01

We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and peripheral artery disease (PAD) in a community cohort. A total of 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65 ± 9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional left ventricular systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at the most contemporaneous examination visit. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p < 0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p < 0.001) and volume of aortic plaque were associated with decreased ABI (p < 0.001). After multivariable adjustment, an ABI ≤ 0.9 or prior revascularization was associated with a threefold odds of aortic plaque (p = 0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p < 0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment, suggesting shared mechanisms beyond those captured by traditional risk factors.

Assessment of the agreement between the Framingham and DAD risk equations for estimating cardiovascular risk in adult Africans living with HIV infection: a cross-sectional study.

PubMed

Noumegni, Steve Raoul; Ama, Vicky Jocelyne Moor; Assah, Felix K; Bigna, Jean Joel; Nansseu, Jobert Richie; Kameni, Jenny Arielle M; Katte, Jean-Claude; Dehayem, Mesmin Y; Kengne, Andre Pascal; Sobngwi, Eugene

2017-01-01

The Absolute cardiovascular disease (CVD) risk evaluation using multivariable CVD risk models is increasingly advocated in people with HIV, in whom existing models remain largely untested. We assessed the agreement between the general population derived Framingham CVD risk equation and the HIV-specific Data collection on Adverse effects of anti-HIV Drugs (DAD) CVD risk equation in HIV-infected adult Cameroonians. This cross-sectional study involved 452 HIV infected adults recruited at the HIV day-care unit of the Yaoundé Central Hospital, Cameroon. The 5-year projected CVD risk was estimated for each participant using the DAD and Framingham CVD risk equations. Agreement between estimates from these equations was assessed using the spearman correlation and Cohen's kappa coefficient. The mean age of participants (80% females) was 44.4 ± 9.8 years. Most participants (88.5%) were on antiretroviral treatment with 93.3% of them receiving first-line regimen. The most frequent cardiovascular risk factors were abdominal obesity (43.1%) and dyslipidemia (33.8%). The median estimated 5-year CVD risk was 0.6% (25th-75th percentiles: 0.3-1.3) using the DAD equation and 0.7% (0.2-2.0) with the Framingham equation. The Spearman correlation between the two estimates was 0.93 ( p  < 0.001). The kappa statistic was 0.61 (95% confident interval: 0.54-0.67) for the agreement between the two equations in classifying participants across risk categories defined as low, moderate, high and very high. Most participants had a low-to-moderate estimated CVD risk, with acceptable level of agreement between the general and HIV-specific equations in ranking CVD risk.

Carotid intima media thickness and plaques can predict the occurrence of ischemic cerebrovascular events.

PubMed

Prati, Patrizio; Tosetto, Alberto; Vanuzzo, Diego; Bader, Giovanni; Casaroli, Marco; Canciani, Luigi; Castellani, Sergio; Touboul, Pierre-Jean

2008-09-01

The clinical usefulness of noninvasive measurement of carotid intima media thickness and plaque visualization in the general population is still uncertain. We evaluated the age-specific incidence rates of cerebrovascular events in a cohort of 1348 subjects randomly taken from the census list of San Daniele Township and followed for a mean period of 12.7 years. The association among common carotid intima media thickness, measured at baseline, arterial risk factors, and incidence of ischemic cerebrovascular events was modeled using Poisson regression. The predictive ability of common carotid intima media thickness over arterial risk factors (summarized in the Framingham Stroke Risk Score) was evaluated by receiver operating characteristic curve analysis. During the follow-up, 115 subjects developed nonfatal ischemic stroke, transient ischemic attack, or vascular death, which were the predefined study end points. After adjustment for age and sex, hypertension, diabetes, common carotid intima media thickness above 1 mm, and carotid plaques were all independent risk factors for development of vascular events. Inclusion of carotid findings (presence of common carotid intima media thickness above 1 mm or carotid plaques) resulted in a predictive power higher than Framingham Stroke Risk Score alone only on for those subjects with a Framingham Stroke Risk Score over 20%. Although common carotid intima media thickness and presence of carotid plaques are known to be risk factors for the development of vascular events and to be independent from the conventional risk factors summarized in the Framingham Stroke Risk Score, their contribution to individual risk prediction is limited. Further studies will be required to address the role of carotid ultrasonography in the primary prevention of high-risk subjects.

White matter hyperintensities and vascular risk factors in monozygotic twins.

PubMed

Ten Kate, Mara; Sudre, Carole H; den Braber, Anouk; Konijnenberg, Elles; Nivard, Michel G; Cardoso, M Jorge; Scheltens, Philip; Ourselin, Sébastien; Boomsma, Dorret I; Barkhof, Frederik; Visser, Pieter Jelle

2018-06-01

Cerebral white matter hyperintensities (WMHs) have been associated with vascular risk factors, both of which are under genetic influence. We examined in a monozygotic twin sample whether the association between vascular risk and WMHs is influenced by overlapping genetic factors. We included 195 cognitively normal monozygotic twins (age = 70 ± 7 years), including 94 complete pairs. Regional WMH load was estimated using an automated algorithm. Vascular risk was summarized with the Framingham score. The within-twin pair correlation for total WMHs was 0.76 and for Framingham score was 0.77. Within participants, Framingham score was associated with total and periventricular WMHs (r = 0.32). Framingham score in 1 twin was also associated with total WMHs in the co-twin (r = 0.26). Up to 83% of the relation between both traits could be explained by shared genetic effects. In conclusion, monozygotic twins have highly similar vascular risk and WMH burden, confirming a genetic background for these traits. The association between both traits is largely driven by overlapping genetic factors. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

A functional variant in NEPH3 gene confers high risk of renal failure in primary hematuric glomerulopathies. Evidence for predisposition to microalbuminuria in the general population

PubMed Central

Voskarides, Konstantinos; Stefanou, Charalambos; Pieri, Myrtani; Demosthenous, Panayiota; Felekkis, Kyriakos; Arsali, Maria; Athanasiou, Yiannis; Xydakis, Dimitris; Stylianou, Kostas; Daphnis, Eugenios; Goulielmos, Giorgos; Loizou, Petros; Savige, Judith; Höhne, Martin; Völker, Linus A.; Benzing, Thomas; Maxwell, Patrick H.; Gale, Daniel P.; Gorski, Mathias; Böger, Carsten; Kollerits, Barbara; Kronenberg, Florian; Paulweber, Bernhard; Zavros, Michalis; Pierides, Alkis; Deltas, Constantinos

2017-01-01

Background Recent data emphasize that thin basement membrane nephropathy (TBMN) should not be viewed as a form of benign familial hematuria since chronic renal failure (CRF) and even end-stage renal disease (ESRD), is a possible development for a subset of patients on long-term follow-up, through the onset of focal and segmental glomerulosclerosis (FSGS). We hypothesize that genetic modifiers may explain this variability of symptoms. Methods We looked in silico for potentially deleterious functional SNPs, using very strict criteria, in all the genes significantly expressed in the slit diaphragm (SD). Two variants were genotyped in a cohort of well-studied adult TBMN patients from 19 Greek-Cypriot families, with a homogeneous genetic background. Patients were categorized as “Severe” or “Mild”, based on the presence or not of proteinuria, CRF and ESRD. A larger pooled cohort (HEMATURIA) of 524 patients, including IgA nephropathy patients, was used for verification. Additionally, three large general population cohorts [Framingham Heart Study (FHS), KORAF4 and SAPHIR] were used to investigate if the NEPH3-V353M variant has any renal effect in the general population. Results and conclusions Genotyping for two high-scored variants in 103 TBMN adult patients with founder mutations who were classified as mildly or severely affected, pointed to an association with variant NEPH3-V353M (filtrin). This promising result prompted testing in the larger pooled cohort (HEMATURIA), indicating an association of the 353M variant with disease severity under the dominant model (p = 3.0x10-3, OR = 6.64 adjusting for gender/age; allelic association: p = 4.2x10-3 adjusting for patients’ kinships). Subsequently, genotyping 6,531 subjects of the Framingham Heart Study (FHS) revealed an association of the homozygous 353M/M genotype with microalbuminuria (p = 1.0x10-3). Two further general population cohorts, KORAF4 and SAPHIR confirmed the association, and a meta-analysis of all three cohorts (11,258 individuals) was highly significant (p = 1.3x10-5, OR = 7.46). Functional studies showed that Neph3 homodimerization and Neph3-Nephrin heterodimerization are disturbed by variant 353M. Additionally, 353M was associated with differential activation of the unfolded protein response pathway, when overexpressed in stressed cultured undifferentiated podocyte cells, thus attesting to its functional significance. Genetics and functional studies support a “rare variant-strong effect” role for NEPH3-V353M, by exerting a negative modifier effect on primary glomerular hematuria. Additionally, genetics studies provide evidence for a role in predisposing homozygous subjects of the general population to micro-albuminuria. PMID:28334007

Coronary risk assessment by point-based vs. equation-based Framingham models: significant implications for clinical care.

PubMed

Gordon, William J; Polansky, Jesse M; Boscardin, W John; Fung, Kathy Z; Steinman, Michael A

2010-11-01

US cholesterol guidelines use original and simplified versions of the Framingham model to estimate future coronary risk and thereby classify patients into risk groups with different treatment strategies. We sought to compare risk estimates and risk group classification generated by the original, complex Framingham model and the simplified, point-based version. We assessed 2,543 subjects age 20-79 from the 2001-2006 National Health and Nutrition Examination Surveys (NHANES) for whom Adult Treatment Panel III (ATP-III) guidelines recommend formal risk stratification. For each subject, we calculated the 10-year risk of major coronary events using the original and point-based Framingham models, and then compared differences in these risk estimates and whether these differences would place subjects into different ATP-III risk groups (<10% risk, 10-20% risk, or >20% risk). Using standard procedures, all analyses were adjusted for survey weights, clustering, and stratification to make our results nationally representative. Among 39 million eligible adults, the original Framingham model categorized 71% of subjects as having "moderate" risk (<10% risk of a major coronary event in the next 10 years), 22% as having "moderately high" (10-20%) risk, and 7% as having "high" (>20%) risk. Estimates of coronary risk by the original and point-based models often differed substantially. The point-based system classified 15% of adults (5.7 million) into different risk groups than the original model, with 10% (3.9 million) misclassified into higher risk groups and 5% (1.8 million) into lower risk groups, for a net impact of classifying 2.1 million adults into higher risk groups. These risk group misclassifications would impact guideline-recommended drug treatment strategies for 25-46% of affected subjects. Patterns of misclassifications varied significantly by gender, age, and underlying CHD risk. Compared to the original Framingham model, the point-based version misclassifies millions of Americans into risk groups for which guidelines recommend different treatment strategies.

Screening for Cardiovascular Disease Risk With Electrocardiography: US Preventive Services Task Force Recommendation Statement.

PubMed

Curry, Susan J; Krist, Alex H; Owens, Douglas K; Barry, Michael J; Caughey, Aaron B; Davidson, Karina W; Doubeni, Chyke A; Epling, John W; Kemper, Alex R; Kubik, Martha; Landefeld, C Seth; Mangione, Carol M; Silverstein, Michael; Simon, Melissa A; Tseng, Chien-Wen; Wong, John B

2018-06-12

Cardiovascular disease (CVD), which encompasses atherosclerotic conditions such as coronary heart disease, cerebrovascular disease, and peripheral arterial disease, is the most common cause of death among adults in the United States. Treatment to prevent CVD events by modifying risk factors is currently informed by CVD risk assessment with tools such as the Framingham Risk Score or the Pooled Cohort Equations, which stratify individual risk to inform treatment decisions. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on screening for coronary heart disease with electrocardiography (ECG). The USPSTF reviewed the evidence on whether screening with resting or exercise ECG improves health outcomes compared with the use of traditional CVD risk assessment alone in asymptomatic adults. For asymptomatic adults at low risk of CVD events (individuals with a 10-year CVD event risk less than 10%), it is very unlikely that the information from resting or exercise ECG (beyond that obtained with conventional CVD risk factors) will result in a change in the patient's risk category as assessed by the Framingham Risk Score or Pooled Cohort Equations that would lead to a change in treatment and ultimately improve health outcomes. Possible harms are associated with screening with resting or exercise ECG, specifically the potential adverse effects of subsequent invasive testing. For asymptomatic adults at intermediate or high risk of CVD events, there is insufficient evidence to determine the extent to which information from resting or exercise ECG adds to current CVD risk assessment models and whether information from the ECG results in a change in risk management and ultimately reduces CVD events. As with low-risk adults, possible harms are associated with screening with resting or exercise ECG in asymptomatic adults at intermediate or high risk of CVD events. The USPSTF recommends against screening with resting or exercise ECG to prevent CVD events in asymptomatic adults at low risk of CVD events. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening with resting or exercise ECG to prevent CVD events in asymptomatic adults at intermediate or high risk of CVD events. (I statement).

Social contagion theory: examining dynamic social networks and human behavior

PubMed Central

Christakis, Nicholas A.; Fowler, James H.

2013-01-01

Here, we review the research we have conducted on social contagion. We describe the methods we have employed (and the assumptions they have entailed) to examine several datasets with complementary strengths and weaknesses, including the Framingham Heart Study, the National Longitudinal Study of Adolescent Health, and other observational and experimental datasets that we and others have collected. We describe the regularities that led us to propose that human social networks may exhibit a ‘three degrees of influence’ property, and we review statistical approaches we have used to characterize interpersonal influence with respect to phenomena as diverse as obesity, smoking, cooperation, and happiness. We do not claim that this work is the final word, but we do believe that it provides some novel, informative, and stimulating evidence regarding social contagion in longitudinally followed networks. Along with other scholars, we are working to develop new methods for identifying causal effects using social network data, and we believe that this area is ripe for statistical development as current methods have known and often unavoidable limitations. PMID:22711416

Interarm differences in systolic blood pressure and the risk of dementia and subclinical brain injury.

PubMed

Pase, Matthew P; Beiser, Alexa; Aparicio, Hugo; DeCarli, Charles; Vasan, Ramachandran S; Murabito, Joanne; Seshadri, Sudha

2016-04-01

This study examined whether interarm differences in systolic blood pressure (IDSBP) ≥10 mm Hg were associated with the risk of incident dementia and subclinical brain injury. Between 1992 and 1998, 2063 participants of the Framingham Heart Study underwent assessment of IDSBP with results related to the 10-year risk of incident dementia including clinically characterized Alzheimer's disease. Secondary outcomes included markers of subclinical brain injury on magnetic resonance imaging. High IDSBP were associated with a greater risk of incident dementia (hazard ratio [HR] 1.92; 95% confidence interval [CI], 1.09-3.40) and Alzheimer's disease (HR, 2.32; 95% CI, 1.29-4.18), but only in those who carried an apolipoprotein E (APOE) ε4 allele. IDSBP also predicted lower total brain volumes and more prevalent silent brain infarcts in those who were APOE ε4 positive. High IDSBP were associated with an increased risk of dementia, including clinical Alzheimer's disease, and subclinical brain injury in those who were APOE ε4 positive. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Women at Risk for Cardiovascular Disease Lack Knowledge of Heart Attack Symptoms

PubMed Central

Flink, Laura E; Sciacca, Robert R; Bier, Michael L; Rodriguez, Juviza; Giardina, Elsa-Grace V

2012-01-01

SUMMARY Background It is not known whether cardiovascular disease (CVD) risk level is related to knowledge of the leading cause of death of women, or heart attack symptoms. Hypothesis Women with higher CVD risk estimated by Framingham Risk Score (FRS) or Metabolic Syndrome (MS) have lower CVD knowledge. Methods Women visiting primary care clinics completed a standardized behavioral risk questionnaire. Blood pressure, weight, height, waist size, fasting glucose and lipid profile were assessed. Women were queried regarding CVD knowledge. Results Participants (n=823) were Hispanic women (46%), Non-Hispanic White (37%), Non-Hispanic Black (8%). FRS was determined in 278: low (63%), moderate (29%), and high (8%); 24% had ≥3 components of MS. The leading cause of death was answered correctly by 54%, heart attack symptoms by 67%. Knowledge was lowest among racial/ethnic minorities and those with less education (both p<0.001). Increasing FRS was inversely associated with knowing the leading cause of death (low 72%, moderate 68%, high 45%, p=0.045). After multivariable adjustment, moderate/high FRS was inversely associated with knowing symptoms (moderate OR 0.52, 95% CI 0.28–0.98, high OR 0.29, 95% CI 0.11–0.81), but not the leading cause of death. MS was inversely associated with knowing the leading cause of death (p<0.001) or heart attack symptoms (p=0.018), but not after multivariable adjustment. Conclusions Women with higher FRS were less likely to know heart attack symptoms. Efforts to target those at higher CVD risk must persist or the most vulnerable may suffer disproportionately, not only because of risk factors, but also inadequate knowledge. PMID:23338973

Women at risk for cardiovascular disease lack knowledge of heart attack symptoms.

PubMed

Flink, Laura E; Sciacca, Robert R; Bier, Michael L; Rodriguez, Juviza; Giardina, Elsa-Grace V

2013-03-01

It is not known whether cardiovascular disease (CVD) risk level is related to knowledge of the leading cause of death of women or heart attack symptoms. Women with higher CVD risk estimated by Framingham Risk Score (FRS) or metabolic syndrome (MS) have lower CVD knowledge. Women visiting primary care clinics completed a standardized behavioral risk questionnaire. Blood pressure, weight, height, waist size, fasting glucose, and lipid profile were assessed. Women were queried regarding CVD knowledge. Participants (N = 823) were Hispanic women (46%), non-Hispanic white (37%), and non-Hispanic black (8%). FRS was determined in 278: low (63%), moderate (29%), and high (8%); 24% had ≥3 components of MS. The leading cause of death was answered correctly by 54%, heart attack symptoms by 67%. Knowledge was lowest among racial/ethnic minorities and those with less education (both P< 0.001). Increasing FRS was inversely associated with knowing the leading cause of death (low 72%, moderate 68%, high 45%, P = 0.045). After multivariable adjustment, moderate/high FRS was inversely associated with knowing symptoms (moderate odds ratio [OR] 0.52, 95% confidence interval [CI]: 0.28-0.98; high OR 0.29, 95% CI: 0.11-0.81), but not the leading cause of death. MS was inversely associated with knowing the leading cause of death (P< 0.001) or heart attack symptoms (P = 0.018), but not after multivariable adjustment. Women with higher FRS were less likely to know heart attack symptoms. Efforts to target those at higher CVD risk must persist, or the most vulnerable may suffer disproportionately, not only because of risk factors but also inadequate knowledge. © 2013 Wiley Periodicals, Inc.

Relations of Metabolically Healthy and Unhealthy Obesity to Digital Vascular Function in Three Community-Based Cohorts: A Meta-Analysis.

PubMed

Brant, Luisa C C; Wang, Na; Ojeda, Francisco M; LaValley, Michael; Barreto, Sandhi M; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S; Palmisano, Joseph N; Münzel, Thomas; Blankenberg, Stefan; Wild, Philipp S; Zeller, Tanja; Ribeiro, Antonio L P; Schnabel, Renate B; Hamburg, Naomi M

2017-03-08

Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. We meta-analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19-90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated. Individuals were classified as normal-weight, overweight, or obese by body mass index (BMI) and stratified by healthy or unhealthy metabolic status based on metabolic syndrome using the ATP-III criteria. Male sex, BMI, and metabolic risk factors were associated with higher baseline pulse amplitude and lower PAT ratio. There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata. Metabolically healthy obese individuals had more impaired vascular function than metabolically healthy normal-weight individuals (baseline pulse amplitude 6.12±0.02 versus 5.61±0.01; PAT ratio 0.58±0.01 versus 0.76±0.01, all P <0.0001). Metabolically unhealthy obese individuals had more impaired vascular function than metabolically healthy obese individuals (baseline pulse amplitude 6.28±0.01 versus 6.12±0.02; PAT ratio 0.49±0.01 versus 0.58±0.01, all P <0.0001). Metabolically healthy obese individuals have impaired microvascular function, though the degree of impairment is less marked than in metabolically unhealthy obese individuals. Our findings suggest that obesity is detrimental to vascular health irrespective of metabolic status. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A Semiparametric Approach to Simultaneous Covariance Estimation for Bivariate Sparse Longitudinal Data

PubMed Central

Das, Kiranmoy; Daniels, Michael J.

2014-01-01

Summary Estimation of the covariance structure for irregular sparse longitudinal data has been studied by many authors in recent years but typically using fully parametric specifications. In addition, when data are collected from several groups over time, it is known that assuming the same or completely different covariance matrices over groups can lead to loss of efficiency and/or bias. Nonparametric approaches have been proposed for estimating the covariance matrix for regular univariate longitudinal data by sharing information across the groups under study. For the irregular case, with longitudinal measurements that are bivariate or multivariate, modeling becomes more difficult. In this article, to model bivariate sparse longitudinal data from several groups, we propose a flexible covariance structure via a novel matrix stick-breaking process for the residual covariance structure and a Dirichlet process mixture of normals for the random effects. Simulation studies are performed to investigate the effectiveness of the proposed approach over more traditional approaches. We also analyze a subset of Framingham Heart Study data to examine how the blood pressure trajectories and covariance structures differ for the patients from different BMI groups (high, medium and low) at baseline. PMID:24400941

Metabolic acidosis status and mortality in patients on the end stage of renal disease.

PubMed

Raikou, Vaia D

2016-12-01

Uncorrected metabolic acidosis leads to higher death risk in dialysis patients. We observed the relationship between metabolic acidosis status and mortality rate in patients on renal replacement therapy during a median follow up time of 60 months. We studied 76 patients on an on-line hemodiafiltration. The dialysis adequacy was defined by Kt/V for urea. The Framingham risk score (FRS) points were used to determine the 10-year risk for coronary heart disease. We examined the impact of high or low serum bicarbonate concentrations on mortality rate and on 10-year risk for coronary heart disease via the Kaplan-Meier method. Cox's model was used to evaluate a combination of prognostic variables, such as dialysis adequacy defined by Kt/V for urea, age and serum bicarbonate concentrations. We divided the enrolled patients in three groups according to serum bicarbonate concentrations (< 20 mmol/L, 20-22 mmol/L and > 22 mmol/L). Kaplan-Meier survival curve for the impact of serum bicarbonate concentrations on overall mortality was found significant (log-rank = 7.8, P = 0.02). The prevalence of serum bicarbonate less or more than 20 mmol/L on high FRS (> 20%) by Kaplan-Meier curve was also found significant (log-rank = 4.9, P = 0.02). Cox's model revealed the significant predictive effect of serum bicarbonate on overall mortality ( P = 0.006, OR = 1.5, 95% CI = 1.12-1.98) in combination to Kt/V for urea and age. Uncorrected severe metabolic acidosis, defined by serum bicarbonate concentrations less than 20 mmol/L, is associated with a 10-year risk for coronary heart disease more than 20% and high overall mortality in patients on renal replacement therapy.

Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults.

PubMed

Moore, Elizabeth E; Liu, Dandan; Pechman, Kimberly R; Terry, James G; Nair, Sangeeta; Cambronero, Francis E; Bell, Susan P; Gifford, Katherine A; Anderson, Adam W; Hohman, Timothy J; Carr, John Jeffrey; Jefferson, Angela L

2018-06-26

Left ventricular (LV) hypertrophy is associated with cerebrovascular disease and cognitive decline. Increased LV mass index is a subclinical imaging marker that precedes overt LV hypertrophy. This study relates LV mass index to white matter microstructure and cognition among older adults with normal cognition and mild cognitive impairment. Vanderbilt Memory & Aging Project participants free of clinical stroke, dementia, and heart failure (n=318, 73±7 years, 58% male, 39% mild cognitive impairment) underwent brain magnetic resonance imaging, cardiac magnetic resonance, and neuropsychological assessment. Voxelwise analyses related LV mass index (g/m 2 ) to diffusion tensor imaging metrics. Models adjusted for age, sex, education, race/ethnicity, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E-ε4 status. Secondary analyses included a LV mass index×diagnosis interaction term with follow-up models stratified by diagnosis. With identical covariates, linear regression models related LV mass index to neuropsychological performances. Increased LV mass index related to altered white matter microstructure ( P <0.05). In models stratified by diagnosis, associations between LV mass index and diffusion tensor imaging were present among mild cognitive impairment participants only ( P <0.05). LV mass index was related only to worse visuospatial memory performance (β=-0.003, P =0.036), an observation that would not withstand correction for multiple testing. In the absence of prevalent heart failure and clinical stroke, increased LV mass index corresponds to altered white matter microstructure, particularly among older adults with clinical symptoms of prodromal dementia. Findings highlight the potential link between subclinical LV remodeling and cerebral white matter microstructure vulnerability. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Lifetime Risk for Sudden Cardiac Death in the Community.

PubMed

Bogle, Brittany M; Ning, Hongyan; Mehrotra, Sanjay; Goldberger, Jeffrey J; Lloyd-Jones, Donald M

2016-06-29

Sudden cardiac death (SCD) is a leading cause of death in the United States and often occurs without previous cardiac symptoms. Lifetime risk for SCD and the influence of established risk factors on lifetime risks for SCD have not been estimated previously. We followed Framingham Heart Study participants who were free of cardiovascular disease before their earliest examination. SCD was defined as death attributed to coronary heart disease within 1 hour of symptom onset without another probable cause of death, as adjudicated by a panel of 3 physicians. Lifetime risk for SCD was estimated to 85 years of age for men and women, with death attributed to other causes as the competing risk, and stratified by risk factor levels. We followed 2294 men and 2785 women for 160 396 person-years; 375 experienced SCD. At 45 years of age, lifetime risks were 10.9% (95% CI, 9.4-12.5) for men and 2.8% (95% CI, 2.1-3.5) for women. Greater aggregate burden of established risk factors was associated with a higher lifetime risk for SCD. Categorizing men and women solely by blood pressure levels resulted in a clear stratification of lifetime risk curves. We present the first lifetime risk estimates for SCD. Greater aggregate risk factor burden, or blood pressure level alone, is associated with higher lifetime risks for SCD. This high risk of premature death attributed to SCD (approximately 1 in 9 men and 1 in 30 women) should serve as a motivator of public health efforts in preventing and responding to SCD. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Refractory Hypertension: Determination of Prevalence, Risk Factors and Comorbidities in a Large, Population-Based Cohort

PubMed Central

Calhoun, David A.; Booth, John N.; Oparil, Suzanne; Irvin, Marguerite R.; Shimbo, Daichi; Lackland, Daniel T.; Howard, George; Safford, Monika M.; Muntner, Paul

2014-01-01

Refractory hypertension is an extreme phenotype of antihypertensive treatment failure. Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a large (n=30,239), population-based cohort were evaluated to determine the prevalence of refractory hypertension and associated cardiovascular risk factors and comorbidities. Refractory hypertension was defined as uncontrolled blood pressure (systolic/diastolic ≥ 140/90 mm Hg) on ≥ 5 antihypertensive drug classes. Participants with resistant hypertension (systolic/diastolic ≥140/90 mm Hg on ≥ 3 or<140/90 mm Hg on ≥ 4 antihypertensive classes) and all treated hypertensive participants served as comparator groups. Of 14,809 REGARDS participants receiving antihypertensive treatment, 78 (0.5%) had refractory hypertension. The prevalence of refractory hypertension was 3.6% among participants with resistant hypertension(n=2,144) and 41.7% among participants on 5 or more antihypertensive drug classes. Among all hypertensive participants, African American race, male gender, living in the stroke belt or buckle, higher body mass index, lower heart rate, reduced estimated glomerular filtration rate, albuminuria, diabetes and history of stroke and coronary heart disease were associated with refractory hypertension. Compared to resistant hypertension, prevalence ratios for refractory hypertension were increased for African Americans (3.00, 95% CI 1.68 – 5.37) and those with albuminuria (2.22, 95% CI 1.40 – 3.52) and diabetes (2.09, 95% CI 1.32 – 3.31). The median 10-year Framingham risk for coronary heart disease and stroke was higher among participants with refractory hypertension compared to either comparator group. These data indicate that while resistant hypertension is relatively common among treated hypertensive patients, true antihypertensive treatment failure is rare. PMID:24324035

The Impact of Rheumatoid Arthritis Disease Characteristics on Heart Failure

PubMed Central

Myasoedova, Elena; Crowson, Cynthia S.; Nicola, Paulo J.; Maradit-Kremers, Hilal; Davis, John M.; Roger, Véronique L.; Therneau, Terry M.; Gabriel, Sherine E.

2011-01-01

Objective To examine the impact of rheumatoid arthritis (RA) characteristics and antirheumatic medications on the risk of heart failure (HF) in RA. Methods A population-based incidence cohort of RA patients aged ≥18 (1987 ACR criteria first met between 1/1/1980 and 1/1/2008) without a history of HF was followed until HF onset (defined by Framingham criteria), death, or 1/1/2008. We collected data on RA characteristics, antirheumatic medications and cardiovascular (CV) risk factors. Cox models adjusting for age, sex and calendar year were used to analyze the data. Results The study included 795 RA patients (mean age 55.3 years, 69% females, 66% rheumatoid factor [RF] positive). During the mean follow-up of 9.7 years, 92 patients developed HF. The risk of HF was associated with RF positivity (HR 1.6, 95%CI 1.0, 2.5), erythrocyte sedimentation rate (ESR) at RA incidence (HR 1.6, 95%CI 1.2, 2.0), repeatedly high ESR (HR 2.1, 95%CI 1.2, 3.5), severe extra-articular manifestations (HR 3.1, 95%CI 1.9, 5.1) and corticosteroid use (HR 2.0, 95%CI 1.3, 3.2), adjusting for CV risk factors and coronary heart disease (CHD). Methotrexate users were half as likely to have HF as non-users (HR 0.5, 95%CI 0.3, 0.9). Conclusion Several RA characteristics and the use of corticosteroids were associated with HF adjusting for CV risk factors and CHD. Methotrexate use appeared to be protective against HF. These findings suggest an independent impact of RA on HF which may be further modified by antirheumatic treatment. PMID:21572155

Noninvasive arterial measurements of vascular damage in healthy young adults: relation to coronary heart disease risk.

PubMed

Van Trijp, Marijke J C A; Uiterwaal, Cuno S P M; Bos, Willem J W; Oren, Anath; Grobbee, Diederick E; Bots, Michiel L

2006-02-01

There is an increasing interest in noninvasive measurements of early structural or functional changes in large arteries such as pulse wave velocity (PWV), carotid intima-media thickness (CIMT), and augmentation index (AIx). These measurements may be applied in etiologic or prognostic research. The role of the AIx as a marker of cardiovascular risk has not fully been established. Our aim was to study whether AIx is related to coronary heart disease (CHD) risk and to compare the strength of the relations of AIx, PWV, and CIMT with cardiovascular risk in healthy young adults. Our study included 224 men and 273 women (mean age 28 years, range 27-30 years) from the Atherosclerosis Risk in Young Adults (ARYA) study. Cardiovascular risk profile was determined and CHD risk was estimated using the Framingham risk score. AIx, PWV and CIMT were measured using standard methods. Data were analyzed in strata of gender using linear regression models. In men, PWV and CIMT were most strongly related to CHD risk. The increase in CHD risk per standard deviation increase in measurement was 0.24%/m/s, 95% CI (0.01;0.33) and 0.32%/mm, 95% CI (0.08;0.55), whereas the AIx was not significantly related to CHD risk (0.09 %/% 95% CI [-0.15;0.33]). In women, AIx, PWV, and CIMT were weakly but significantly related to CHD risk; there was no clear difference between the measurements. In young men, PWV and CIMT are better measures of CHD risk than AIx. In women, AIx, PWV and CIMT estimate CHD risk equally well.

Revised Framingham Stroke Risk Score, Nontraditional Risk Markers, and Incident Stroke in a Multiethnic Cohort.

PubMed

Flueckiger, Peter; Longstreth, Will; Herrington, David; Yeboah, Joseph

2018-02-01

Limited data exist on the performance of the revised Framingham Stroke Risk Score (R-FSRS) and the R-FSRS in conjunction with nontraditional risk markers. We compared the R-FSRS, original FSRS, and the Pooled Cohort Equation for stroke prediction and assessed the improvement in discrimination by nontraditional risk markers. Six thousand seven hundred twelve of 6814 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) were included. Cox proportional hazard, area under the curve, net reclassification improvement, and integrated discrimination increment analysis were used to assess and compare each stroke prediction risk score. Stroke was defined as fatal/nonfatal strokes (hemorrhagic or ischemic). After mean follow-up of 10.7 years, 231 of 6712 (3.4%) strokes were adjudicated (2.7% ischemic strokes). Mean stroke risks using the R-FSRS, original FSRS, and Pooled Cohort Equation were 4.7%, 5.9%, and 13.5%. The R-FSRS had the best calibration (Hosmer-Lemeshow goodness-of-fit, χ 2 =6.55; P =0.59). All risk scores were predictive of incident stroke. C statistics of R-FSRS (0.716) was similar to Pooled Cohort Equation (0.716), but significantly higher than the original FSRS (0.653; P =0.01 for comparison with R-FSRS). Adding nontraditional risk markers individually to the R-FSRS did not improve discrimination of the R-FSRS in the area under the curve analysis, but did improve category-less net reclassification improvement and integrated discrimination increment for incident stroke. The addition of coronary artery calcium to R-FSRS produced the highest category-less net reclassification improvement (0.36) and integrated discrimination increment (0.0027). Similar results were obtained when ischemic strokes were used as the outcome. The R-FSRS downgraded stroke risk but had better calibration and discriminative ability for incident stroke compared with the original FSRS. Nontraditional risk markers modestly improved the discriminative ability of the R-FSRS, with coronary artery calcium performing the best. © 2018 American Heart Association, Inc.

Fifty-Year Trends in Atrial Fibrillation Prevalence, Incidence, Risk Factors, and Mortality in the Community

PubMed Central

Schnabel, Renate B.; Yin, Xiaoyan; PhilimonGona; Larson, Martin G.; Beiser, Alexa S.; McManus, David D.; Newton-Cheh, Christopher; Lubitz, Steven A.; Magnani, Jared W.; Ellinor, Patrick T.; SudhaSeshadri; Wolf, Philip A; Vasan, Ramachandran S.; Benjamin, Emelia J.; Levy, Daniel

2015-01-01

Summary Background Comprehensive long-term data on atrial fibrillation trends in men and women are scant. Methods We investigated trends in atrial fibrillation incidence, prevalence, and risk factors, and in stroke and mortality following its onset in Framingham Heart Study participants (n=9511) from 1958 to 2007. To accommodate sex differences in atrial fibrillation risk factors and disease manifestations, sex-stratified analyses were performed. Findings During 50 years of observation (202,417 person-years), there were 1,544 new-onset atrial fibrillation cases (46.8% women). We observed about a fourfold increase in the age-adjusted prevalence and more than a tripling in age-adjusted incidence of atrial fibrillation (prevalence 20.4 versus 96.2 per 1000 person-years in men; 13.7 versus 49.4 in women; incidence rates in first versus last decade 3.7 versus 13.4 per 1000 person-years in men; 2.5 versus 8.6 in women, ptrend<0.0001). For atrial fibrillation diagnosed by ECG during routine Framingham examinations, age-adjusted prevalence increased (12.6versus 25.7 per 1000 person-years in men; 8.1 versus 11.8 in women, ptrend<0.0001). The age-adjusted incidence increased, but did not achieve statistical significance. Although the prevalence of most risk factors changed over time, their associated hazards for atrial fibrillation changed little. Multivariable-adjusted proportional hazards models revealed a 73.5% decline in stroke and a 25.4% decline in mortality following atrial fibrillation onset (ptrend=0.0001, ptrend=0.003, respectively). Interpretation Our data suggest that observed trends of increased incidence of atrial fibrillation in the community were partially due to enhanced surveillance. Stroke occurrence and mortality following atrial fibrillation onset declined over the decades, and prevalence increased approximately fourfold. The hazards for atrial fibrillation risk factors remained fairly constant. Our data indicate a need for measures to enhance early detection of atrial fibrillation through increased awareness coupled with targeted screening programs, and risk factor-specific prevention. PMID:25960110

Genetic markers enhance coronary risk prediction in men: the MORGAM prospective cohorts.

PubMed

Hughes, Maria F; Saarela, Olli; Stritzke, Jan; Kee, Frank; Silander, Kaisa; Klopp, Norman; Kontto, Jukka; Karvanen, Juha; Willenborg, Christina; Salomaa, Veikko; Virtamo, Jarmo; Amouyel, Phillippe; Arveiler, Dominique; Ferrières, Jean; Wiklund, Per-Gunner; Baumert, Jens; Thorand, Barbara; Diemert, Patrick; Trégouët, David-Alexandre; Hengstenberg, Christian; Peters, Annette; Evans, Alun; Koenig, Wolfgang; Erdmann, Jeanette; Samani, Nilesh J; Kuulasmaa, Kari; Schunkert, Heribert

2012-01-01

More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design. Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived. Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events. Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.

Psoriasis and cardiovascular risk. Assessment by different cardiovascular risk scores.

PubMed

Fernández-Torres, R; Pita-Fernández, S; Fonseca, E

2013-12-01

Psoriasis is an inflammatory disease associated with an increased risk of cardiovascular morbidity and mortality. However, very few studies determine cardiovascular risk by means of Framingham risk score or other indices more appropriate for countries with lower prevalence of cardiovascular risk factors. To determine multiple cardiovascular risk scores in psoriasis patients, the relation between cardiovascular risk and psoriasis features and to compare our results with those in the literature. We assessed demographic data, smoking status, psoriasis features, blood pressure and analytical data. Cardiovascular risk was determined by means of Framingham, SCORE, DORICA and REGICOR scores. A total of 395 patients (59.7% men and 40.3% women) aged 18-86 years were included. The proportion of patients at intermediate and high risk of suffering a major cardiovascular event in the next 10 years was 30.5% and 11.4%, respectively, based on Framingham risk score; 26.9% and 2.2% according to DORICA and 6.8% and 0% using REGICOR score. According to the SCORE index, 22.1% of patients had a high risk of death due to a cardiovascular event over the next 10 years. Cardiovascular risk was not related to psoriasis characteristics, except for the Framingham index, with higher risk in patients with more severe psoriasis (P = 0.032). A considerable proportion of patients had intermediate or high cardiovascular risk, without relevant relationship with psoriasis characteristics and treatment schedules. Therefore, systematic evaluation of cardiovascular risk scores in all psoriasis patients could be useful to identify those with increased cardiovascular risk, subsidiary of lifestyle changes or therapeutic interventions. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Effectiveness of User- and Expert-Driven Web-based Hypertension Programs: an RCT.

PubMed

Liu, Sam; Brooks, Dina; Thomas, Scott G; Eysenbach, Gunther; Nolan, Robert P

2018-04-01

The effectiveness of self-guided Internet-based lifestyle counseling (e-counseling) varies, depending on treatment protocol. Two dominant procedures in e-counseling are expert- and user-driven. The influence of these procedures on hypertension management remains unclear. The objective was to assess whether blood pressure improved with expert-driven or user-driven e-counseling over control intervention in patients with hypertension over a 4-month period. This study used a three-parallel group, double-blind randomized controlled design. In Toronto, Canada, 128 participants (aged 35-74 years) with hypertension were recruited. Participants were recruited using online and poster advertisements. Data collection took place between June 2012 and June 2014. Data were analyzed from October 2014 to December 2016. Controls received a weekly e-mail newsletter regarding hypertension management. The expert-driven group was prescribed a weekly exercise and diet plan (e.g., increase 1,000 steps/day this week). The user-driven group received weekly e-mail, which allowed participants to choose their intervention goals (e.g., [1] feel more confident to change my lifestyle, or [2] self-help tips for exercise or a heart healthy diet). Primary outcome was systolic blood pressure measured at baseline and 4-month follow-up. Secondary outcomes included cholesterol, 10-year Framingham cardiovascular risk, daily steps, and dietary habits. Expert-driven groups showed a greater systolic blood pressure decrease than controls at follow-up (expert-driven versus control: -7.5 mmHg, 95% CI= -12.5, -2.6, p=0.01). Systolic blood pressure reduction did not significantly differ between user- and expert-driven. Expert-driven compared with controls also showed a significant improvement in pulse pressure, cholesterol, and Framingham risk score. The expert-driven intervention was significantly more effective than both user-driven and control groups in increasing daily steps and fruit intake. It may be advisable to incorporate an expert-driven e-counseling protocol in order to accommodate participants with greater motivation to change their lifestyle behaviors, but more studies are needed. This study is registered at www.clinicaltrials.gov NCT03111836. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Leisure Time Physical Activity and Cardio-Metabolic Health: Results From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

Lin, Xiaochen; Alvim, Sheila M; Simoes, Eduardo J; Bensenor, Isabela M; Barreto, Sandhi M; Schmidt, Maria I; Ribeiro, Antonio L; Pitanga, Francisco; Almeida, Maria Conceição C; Liu, Simin; Lotufo, Paulo A

2016-06-13

Although increasing effort has been devoted to the promotion of a healthy lifestyle such as leisure time physical activity for cardio-metabolic health, specific evidence supporting health policy remains sparse, particularly in those ethnically diverse populations where cardio-metabolic diseases are reaching epidemic proportion and yet are grossly understudied. We conducted a cross-sectional analysis of the baseline data from 10 585 participants aged 35 to 74 free of cardiovascular diseases in the Brazilian Longitudinal Study of Adult Health. Leisure time physical activity status was defined by the American Heart Association and the World Health Organization recommendations (≥150 min/week moderate activities or 75 min/week vigorous activities). In total, 1183 (21%) women and 1387 (29%) men were active. After accounting for covariates, the favorable effects of leisure time physical activity on cardio-metabolic parameters were evident. Specifically, the average blood pressure, heart rate, and Framingham Risk Score for cardiovascular diseases of the active were significantly lower within each sex. The ORs comparing the active versus the inactive women were 0.78 (95% CI: 0.66-0.92) for hypertension and 0.78 (95% CI: 0.65-0.93) for cardiovascular diseases in 10 years. Among men, the ORs were 0.75 (95% CI: 0.65-0.87) for hypertension and 0.73 (95% CI: 0.61-0.87) for diabetes. The 10-year risk of cardiovascular diseases was significantly lower among the active men with a 33% reduction (OR=0.67, 95% CI: 0.57-0.78). We observed beneficial effects of leisure time physical activity on cardio-metabolic health in this large Brazilian population that are consistent with studies in North America and Europe. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Weight gain and 10-year cardiovascular risk with sustained tobacco abstinence in smokers with serious mental illness: a subgroup analysis of a randomized trial.

PubMed

Thorndike, Anne N; Achtyes, Eric D; Cather, Corinne; Pratt, Sarah; Pachas, Gladys N; Hoeppner, Susanne S; Evins, A Eden

2016-03-01

People with serious mental illness die earlier than those without mental illness, largely from cardiovascular disease due to high rates of smoking and obesity. The objective of this study was to determine whether the metabolic effects of postcessation weight gain among smokers with serious mental illness attenuated the cardiovascular benefit of tobacco abstinence. A subgroup analysis was conducted of 65 outpatient smokers with DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder from 10 community mental health centers in 6 states who enrolled between March 2008-April 2012 and completed a trial of varenicline for tobacco abstinence. The intervention included a 12-week open-label phase with varenicline followed by a 40-week randomized, placebo-controlled phase in 87 participants who achieved 12-week abstinence. Main outcome measures were smoking status and change from baseline in weight and 10-year Framingham cardiovascular risk score at end of intervention (week 52). At week 52, 65 participants completed follow-up (33 abstinent; 32 relapsed). At baseline, the 2 groups did not differ in body mass index (mean = 31 kg/m(2)), blood pressure, serum glucose, or diagnoses of diabetes (31%) and hypertension (34%). Abstinent participants were older and had a higher mean baseline Framingham risk score (14.2% vs 10.3%, P = .002). At week 52, abstinent participants gained more weight than relapsed participants (4.8 vs 1.2 kg, P = .048) and, as a result of quitting smoking, had a greater reduction in Framingham risk score (-7.6% vs 0.0%, P < .001). There was no effect of study drug assignment on weight or Framingham risk score. Sustained tobacco abstinence reduced 10-year cardiovascular risk in outpatients with serious mental illness despite significant postcessation weight gain and high prevalence of obesity, diabetes, and hypertension. Clinicaltrials.gov identifier: NCT00621777. © Copyright 2016 Physicians Postgraduate Press, Inc.

Racial discrimination & cardiovascular disease risk: my body my story study of 1005 US-born black and white community health center participants (US).

PubMed

Krieger, Nancy; Waterman, Pamela D; Kosheleva, Anna; Chen, Jarvis T; Smith, Kevin W; Carney, Dana R; Bennett, Gary G; Williams, David R; Thornhill, Gisele; Freeman, Elmer R

2013-01-01

To date, limited and inconsistent evidence exists regarding racial discrimination and risk of cardiovascular disease (CVD). Cross-sectional observational study of 1005 US-born non-Hispanic black (n = 504) and white (n = 501) participants age 35-64 randomly selected from community health centers in Boston, MA (2008-2010; 82.4% response rate), using 3 racial discrimination measures: explicit self-report; implicit association test (IAT, a time reaction test for self and group as target vs. perpetrator of discrimination); and structural (Jim Crow status of state of birth, i.e. legal racial discrimination prior 1964). Black and white participants both had adverse cardiovascular and socioeconomic profiles, with black participants most highly exposed to racial discrimination. Positive crude associations among black participants occurred for Jim Crow birthplace and hypertension (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.28, 2.89) and for explicit self-report and the Framingham 10 year CVD risk score (beta = 0.04; 95% CI 0.01, 0.07); among white participants, only negative crude associations existed (for IAT for self, for lower systolic blood pressure (SBP; beta = -4.86; 95% CI -9.08, -0.64) and lower Framingham CVD score (beta = -0.36, 95% CI -0.63, -0.08)). All of these associations were attenuated and all but the white IAT-Framingham risk score association were rendered null in analyses that controlled for lifetime socioeconomic position and additional covariates. Controlling for racial discrimination, socioeconomic position, and other covariates did not attenuate the crude black excess risk for SBP and hypertension and left unaffected the null excess risk for the Framingham CVD score. Despite worse exposures among the black participants, racial discrimination and socioeconomic position were not associated, in multivariable analyses, with risk of CVD. We interpret results in relation to constrained variability of exposures and outcomes and discuss implications for valid research on social determinants of health.

Microvascular function predicts cardiovascular events in primary prevention: long-term results from the Firefighters and Their Endothelium (FATE) study.

PubMed

Anderson, Todd J; Charbonneau, Francois; Title, Lawrence M; Buithieu, Jean; Rose, M Sarah; Conradson, Heather; Hildebrand, Kathy; Fung, Marinda; Verma, Subodh; Lonn, Eva M

2011-01-18

Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of endothelial function and other vascular markers in apparently healthy men. The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92; P=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90; P=0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83; P=0.002) but not C-reactive protein (P=0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% (P<0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (P=0.24). In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.

A family longevity selection score: ranking sibships by their longevity, size, and availability for study.

PubMed

Sebastiani, Paola; Hadley, Evan C; Province, Michael; Christensen, Kaare; Rossi, Winifred; Perls, Thomas T; Ash, Arlene S

2009-12-15

Family studies of exceptional longevity can potentially identify genetic and other factors contributing to long life and healthy aging. Although such studies seek families that are exceptionally long lived, they also need living members who can provide DNA and phenotype information. On the basis of these considerations, the authors developed a metric to rank families for selection into a family study of longevity. Their measure, the family longevity selection score (FLoSS), is the sum of 2 components: 1) an estimated family longevity score built from birth-, gender-, and nation-specific cohort survival probabilities and 2) a bonus for older living siblings. The authors examined properties of FLoSS-based family rankings by using data from 3 ongoing studies: the New England Centenarian Study, the Framingham Heart Study, and screenees for the Long Life Family Study. FLoSS-based selection yields families with exceptional longevity, satisfactory sibship sizes and numbers of living siblings, and high ages. Parameters in the FLoSS formula can be tailored for studies of specific populations or age ranges or with different conditions. The first component of the FLoSS also provides a conceptually sound survival measure to characterize exceptional longevity in individuals or families in various types of studies and correlates well with later-observed longevity.

Effect of Hyperbaric Carbon Dioxide on Spores and Vegetative Cells of Bacillus stearothermophilus

DTIC Science & Technology

1994-05-01

BACILLUS STEAROTHERMOPHILUS DTIC ELECTE JUN131994 D By Chester T. Roskey* Anthony Sikes *Framingham State College Framingham, MA 01701 94-18004...Spores and Vegetative Cells of Bacillus Stearothermophilus 6. AUTHOR(S) Dr. Chester T. Roskey* & Dr. Anthony Sikes 5 FUNDING NUMBERS PR: TB040...SUBJECT TERMS BACILLUS STEAROTHERMOPHILUS THERM0PHILIC BACTERIA THERM0PHILIC SPOILAGE 15. NUMBER OF PAGES 39 16 PRICE CODE 17. SECURITY

Ethnic differences in risk factors and total risk of cardiovascular disease based on the Norwegian CONOR study.

PubMed

Rabanal, Kjersti S; Lindman, Anja S; Selmer, Randi M; Aamodt, Geir

2013-12-01

Risk of cardiovascular disease varies between ethnic groups and the aim of this study was to investigate differences in cardiovascular risk factors, and total cardiovascular risk between ethnic groups in Norway. Cross-sectional study using data from the Cohort of Norway (CONOR). A sample of 62,145 participants, 40-65 years of age, originating from 11 geographical regions, were included in our study. Self-reported variables, blood samples and physical measurements were used to estimate age- and time-adjusted mean values of cardiovascular risk factors for different ethnic groups. The 10-year risks of cardiovascular mortality and cardiovascular events were calculated using the Framingham and NORRISK risk models. We observed differences between ethnic groups for cardiovascular risk factors and both Framingham and NORRISK risk scores. NORRISK showed significant differences by ethnicity in women only. Immigrants from the Indian subcontinent had the lowest high-density lipoprotein (HDL) levels, the highest levels of blood glucose, triglycerides, total cholesterol/HDL ratio, waist hip ratio and diabetes prevalence. Immigrants from the former Yugoslavia had the highest Framingham scores, high blood pressure, high total cholesterol/HDL ratio, overweight measures and smoking. Low cardiovascular risk was observed among East Asian immigrants. The previously reported excess cardiovascular risk among immigrants from the Indian subcontinent was supported in this study. We also showed that immigrants from the former Yugoslavian countries had a higher total 10-year risk of cardiovascular events than other ethnic groups. This study adds information about ethnic groups in Norway which needs to be addressed in further research and targeted prevention strategies.

Impact of Chronic Glucocorticoid Treatment on Cardiovascular Risk Profile in Patients with Systemic Lupus Erythematosus.

PubMed

Moya, Fernando Briceño; Pineda Galindo, Luis Francisco; García de la Peña, Maximiliano

2016-01-01

Systemic lupus erythematosus is highly associated with premature atherosclerosis and cardiovascular events. The origin of this subclinical atherosclerosis has been attributed mainly to the inflammatory nature of the disease. To assess the effect of long-term use of glucocorticoids on cardiovascular risk in patients with systemic lupus erythematosus. We conducted a registry-based retrospective cohort study. We determined 2 periods: (1) Time 0, that is, time of diagnosis and (2) time 1, that is, when the study was finalized. At both times, the cardiovascular risk was evaluated using the Framingham scale and their scores were compared. Afterward, the change magnitude between the 2 times was evaluated and associated with the cumulative glucocorticoids dose. One hundred one patients were included. The mean ± SD age was 26.5 ± 5 years. Length of disease evolution was of 7.8 ± 4.9 years. There was an 8-point increase in the Framingham score, from -8.1 ± 4 to 0.8 ± 7; P < 0.0001. The correlation between the magnitude of the increase in Framingham score and their corresponding cumulative dose showed a coefficient of 0.88; P < 0.001. The glucocorticoids are a primary factor that influences cardiovascular risk. There is a directly proportional relationship between the cumulative glucocorticoid dose and the increase in cardiovascular risk.

Implementation of health risk assessments with family health history: barriers and benefits.

PubMed

Wu, R Ryanne; Orlando, Lori A

2015-09-01

Health risk assessments provide an opportunity to emphasise health promotion and disease prevention for individuals and populations at large. A key component of health risk assessments is the detailed collection of family health history information. This information is helpful in determining risk both for common chronic conditions and more rare diseases as well. While the concept of health risk assessments has been around since the Framingham Heart Study was launched in the 1950s, and such assessments are commonly performed in the workplace today, the US healthcare system has been slow to embrace them and the emphasis on prevention that they represent. Before wider implementation of health risk assessments within healthcare can be seen, several concerns must be addressed: (1) provider impact, (2) patient impact, (3) validity of patient-entered data and (4) health outcomes effect. Here, we describe recent developments in health risk assessment design that are helping to address these issues. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Breaking Up is Hard to Do, Unless Everyone Else is Doing it Too: Social Network Effects on Divorce in a Longitudinal Sample

PubMed Central

McDermott, Rose; Fowler, James; Christakis, Nicholas

2014-01-01

Divorce represents the dissolution of a social tie, but it is also possible that attitudes about divorce flow across social ties. To explore how social networks influence divorce and vice versa, we exploit a longitudinal data set from the long-running Framingham Heart Study. The results suggest that divorce can spread between friends. Clusters of divorces extend to two degrees of separation in the network. Popular people are less likely to get divorced, divorcees have denser social networks, and they are much more likely to remarry other divorcees. Interestingly, the presence of children does not influence the likelihood of divorce, but each child reduces the susceptibility to being influenced by peers who get divorced. Overall, the results suggest that attending to the health of one’s friends’ marriages may serve to support and enhance the durability of one’s own relationship, and that, from a policy perspective, divorce should be understood as a collective phenomenon that extends beyond those directly affected. PMID:24748689

Sleep architecture and the risk of incident dementia in the community.

PubMed

Pase, Matthew P; Himali, Jayandra J; Grima, Natalie A; Beiser, Alexa S; Satizabal, Claudia L; Aparicio, Hugo J; Thomas, Robert J; Gottlieb, Daniel J; Auerbach, Sandford H; Seshadri, Sudha

2017-09-19

Sleep disturbance is common in dementia, although it is unclear whether differences in sleep architecture precede dementia onset. We examined the associations between sleep architecture and the prospective risk of incident dementia in the community-based Framingham Heart Study (FHS). Our sample comprised a subset of 321 FHS Offspring participants who participated in the Sleep Heart Health Study between 1995 and 1998 and who were aged over 60 years at the time of sleep assessment (mean age 67 ± 5 years, 50% male). Stages of sleep were quantified using home-based polysomnography. Participants were followed for a maximum of 19 years for incident dementia (mean follow-up 12 ± 5 years). We observed 32 cases of incident dementia; 24 were consistent with Alzheimer disease dementia. After adjustments for age and sex, lower REM sleep percentage and longer REM sleep latency were both associated with a higher risk of incident dementia. Each percentage reduction in REM sleep was associated with approximately a 9% increase in the risk of incident dementia (hazard ratio 0.91; 95% confidence interval 0.86, 0.97). The magnitude of association between REM sleep percentage and dementia was similar following adjustments for multiple covariates including vascular risk factors, depressive symptoms, and medication use, following exclusions for persons with mild cognitive impairment at baseline and following exclusions for early converters to dementia. Stages of non-REM sleep were not associated with dementia risk. Despite contemporary interest in slow-wave sleep and dementia pathology, our findings implicate REM sleep mechanisms as predictors of clinical dementia. © 2017 American Academy of Neurology.

[Diagnosis of acute heart failure and relevance of biomarkers in elderly patients].

PubMed

Ruiz Ortega, Raúl Antonio; Manzano, Luis; Montero-Pérez-Barquero, Manuel

2014-03-01

Diagnosis of acute heart failure (HF) is difficult in elderly patients with multiple comorbidities. Risk scales and classification criteria based exclusively on clinical manifestations, such as the Framingham scales, lack sufficient specificity. In addition to clinical manifestations, diagnosis should be based on two key factors: natriuretic peptides and echocardiographic study. When there is clinical suspicion of acute HF, a normal natriuretic peptide level will rule out this process. When a consistent clinical suspicion is present, an echocardiographic study should also be performed. Diagnosis of HF with preserved ejection fraction (HF/pEF) requires detection of an enlarged left atrium or the presence of parameters of diastolic dysfunction. Elevation of cardiac biomarkers seems to be due to myocardial injury and the compensatory mechanisms of the body against this injury (hormone and inflammatory response and repair mechanisms). Elevation of markers of cardiac damage (troponins and natriuretic peptides) have been shown to be useful both in the diagnosis of acute HF and in prediction of outcome. MMP-2 could be useful in the diagnosis of HF/pEF. In addition to biomarkers with diagnostic value, other biomarkers are helpful in prognosis in the acute phase of HF, such as biomarkers of renal failure (eGFR, cystatin and urea), inflammation (cytokines and CRP), and the cell regeneration marker, galectin-3. A promising idea that is under investigation is the use of panels of biomarkers, which could allow more accurate diagnosis and prognosis of acute HF. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Effect of diet and physical exercise intervention programmes on coronary heart disease risk in smoking and non-smoking men in Sweden.

PubMed Central

Näslund, G K; Fredrikson, M; Hellénius, M L; de Faire, U

1996-01-01

STUDY OBJECTIVE: To investigate differences between smokers and non-smokers in health behaviour, cardiovascular risk factors, coronary heart disease (CHD) risks, health knowledge, health attitudes, and compliance with a CHD prevention programme. DESIGN: Differences between smokers and non-smokers were studied via medical examinations, questionnaires, physical exercise activity logs, and food record sheets. Data were analysed using univariate and multivariate analyses. The five and 10 year CHD risks were assessed using the Framingham CHD risk estimate. SETTING: The Karolinska Hospital, Stockholm, and Sollentuna Primary Health Centre, Sollentuna, Sweden. PARTICIPANTS: The analyses were based on 158 healthy smoking and non-smoking men aged 35-60 years with raised cardiovascular risk factors who enrolled in controlled, randomised six month diet and exercise programmes. MAIN RESULTS: Discriminant analysis suggested that smokers, compared with non-smokers, were characterised by a higher alcohol energy percent, lower HDL cholesterol concentration, lower systolic blood pressure, and a higher plasminogen activator inhibitor-1 (PAI-1) value. Knowledge of the risk factors for CHD was not a discriminating factor. Both smokers and non-smokers increased the exercise taken, improved their diet, and lowered their CHD risk. Before, as well as after the intervention, smokers had a higher CHD risk than non-smokers. CONCLUSIONS: The best CHD prevention action that could be taken by smokers would of course be to quit smoking. Those who cannot stop should be encouraged to improve their diet and increase the amount of physical exercise they take in order to reduce the health hazards of their smoking behaviour. PMID:8762375

Hypertension and Diabetes Mellitus: Coprediction and Time Trajectories.

PubMed

Tsimihodimos, Vasilis; Gonzalez-Villalpando, Clicerio; Meigs, James B; Ferrannini, Ele

2018-03-01

Type 2 diabetes mellitus and hypertension overlap in the population. In many subjects, development of diabetes mellitus is characterized by a relatively rapid increase in plasma glucose values. Whether a similar phenomenon occurs during the development of hypertension is not known. We analyzed the pattern of blood pressure (BP) changes during the development of hypertension in patients with or without diabetes mellitus using data from the MCDS (Mexico City Diabetes Study; a population-based study of diabetes mellitus in Hispanic whites) and in the FOS (Framingham Offspring Study, a community-based study in non-Hispanic whites) during a 7-year follow-up. Diabetes mellitus at baseline was a significant predictor of incident hypertension (in FOS, odds ratio, 3.14; 95% confidence interval, 2.17-4.54) independently of sex, age, body mass index, and familial diabetes mellitus. Conversely, hypertension at baseline was an independent predictor of incident diabetes mellitus (in FOS, odds ratio, 3.33; 95% CI, 2.50-4.44). In >60% of the converters, progression from normotension to hypertension was characterized by a steep increase in BP values, averaging 20 mm Hg for systolic BP within 3.5 years (in MCDS). In comparison with the nonconverters group, hypertension and diabetes mellitus converters shared a metabolic syndrome phenotype (hyperinsulinemia, higher body mass index, waist girth, BP, heart rate and pulse pressure, and dyslipidemia). Overall, results were similar in the 2 ethnic groups. We conclude that (1) development of hypertension and diabetes mellitus track each other over time, (2) transition from normotension to hypertension is characterized by a sharp increase in BP values, and (3) insulin resistance is one common feature of both prediabetes and prehypertension and an antecedent of progression to 2 respective disease states. © 2018 American Heart Association, Inc.

Lipoprotein(a) is strongly associated with coronary artery calcification in type-2 diabetic women

PubMed Central

Qasim, Atif N.; Martin, Seth S.; Mehta, Nehal N.; Wolfe, Megan L.; Park, James; Schwartz, Stanley; Schutta, Mark; Iqbal, Nayyar; Reilly, Muredach P.

2011-01-01

Background Lp(a), implicated in both atherogenesis and thrombosis pathways, varies significantly by demographic and metabolic factors, providing challenges for its use in Coronary Heart Disease (CHD) risk. The purpose of this study was to investigate whether type-2 diabetic subjects, relative to non-diabetics, might benefit more from Lp(a) measurement in the prediction of CHD risk, as measured by coronary artery calcium (CAC). Methods We performed cross sectional analyses in two community-based studies: the Penn Diabetes Heart Study [N=1299 with type-2 diabetes] and the Study of Inherited Risk of Coronary Atherosclerosis [N=860 without diabetes]. Results Blacks had 2–3 fold higher Lp(a) levels than whites in diabetic and non-diabetic samples. There was significant difference by gender (interaction p<0.001), but not race, in the association of Lp(a) with CAC in type-2 diabetic subjects. In age and race adjusted analysis of diabetic women, Lp(a) was associated with CAC [Tobit regression ratio 2.76 (95% CI 1.73–4.40), p<0.001]. Adjustment for exercise, medications, Framingham risk score, metabolic syndrome, BMI, CRP and hemoglobin A1c attenuated this effect, but the association of Lp(a) with CAC remained significant [2.25, (1.34–3.79), p=0.002]. This relationship was further maintained in women stratified by race, or by the use of HRT or lipid lowering drugs. In contrast, Lp(a) was not associated with CAC in diabetic men, nor in non-diabetic men and women. Conclusions Lp(a) is a strong independent predictor of CAC in type-2 diabetic women, regardless of race, but not in men. Lp(a) does not relate to CAC in men or women without type-2 diabetes. PMID:20303190

Social Network Concordance in Food Choice Among Spouses, Friends, and Siblings

PubMed Central

Jacques, Paul F.; Christakis, Nicholas A.

2011-01-01

Objectives. We investigated whether eating behaviors were concordant among diverse sets of social ties. Methods. We analyzed the socioeconomic and demographic distribution of eating among 3418 members of the Framingham Heart Study observed from 1991 to 2001. We used a data-classification procedure to simplify choices into 7 nonoverlapping patterns that we matched with information on social network ties. We used correlation analysis to examine eating associations among 4 types of peers (spouses, friends, brothers, and sisters). Longitudinal multiple logistic regression was used to evaluate evidence for peer influences on eating. Results. Of all peer types, spouses showed the strongest concordances in eating patterns over time after adjustment for social contextual factors. Across all peers, the eating pattern most likely to be shared by socially connected individuals was “alcohol and snacks.” Models estimating one's current eating pattern on the basis of a peer's prior eating provided supportive evidence of a social influence process. Conclusions. Certain eating patterns appeared to be socially transmissible across different kinds of relationships. These findings represent an important step in specifying the relevant social environment in the study of health behaviors to include eating. PMID:21940920

Incorporating gene-environment interaction in testing for association with rare genetic variants.

PubMed

Chen, Han; Meigs, James B; Dupuis, Josée

2014-01-01

The incorporation of gene-environment interactions could improve the ability to detect genetic associations with complex traits. For common genetic variants, single-marker interaction tests and joint tests of genetic main effects and gene-environment interaction have been well-established and used to identify novel association loci for complex diseases and continuous traits. For rare genetic variants, however, single-marker tests are severely underpowered due to the low minor allele frequency, and only a few gene-environment interaction tests have been developed. We aimed at developing powerful and computationally efficient tests for gene-environment interaction with rare variants. In this paper, we propose interaction and joint tests for testing gene-environment interaction of rare genetic variants. Our approach is a generalization of existing gene-environment interaction tests for multiple genetic variants under certain conditions. We show in our simulation studies that our interaction and joint tests have correct type I errors, and that the joint test is a powerful approach for testing genetic association, allowing for gene-environment interaction. We also illustrate our approach in a real data example from the Framingham Heart Study. Our approach can be applied to both binary and continuous traits, it is powerful and computationally efficient.

Advanced age, cardiovascular risk burden, and timed up and go test performance in Parkinson disease.

PubMed

Kotagal, Vikas; Albin, Roger L; Müller, Martijn L T M; Koeppe, Robert A; Studenski, Stephanie; Frey, Kirk A; Bohnen, Nicolaas I

2014-12-01

Cardiovascular comorbidities are a known risk factor for impaired mobility in elderly individuals. Motor impairments in Parkinson disease are conventionally ascribed to nigrostriatal dopaminergic denervation although progressive gait and balance impairments become more common with aging and often show limited response to dopaminergic replacement therapies. We explored the association between elevated cardiovascular risk factors and performance on the Timed Up and Go test in cross-sectional of Parkinson disease subjects (n = 83). Cardiovascular risk factor status was estimated using the Framingham General Cardiovascular Disease risk-scoring algorithm in order to dichotomize the cohort into those with and without elevated modifiable cardiovascular risk compared with normative scores for age and gender. All subjects underwent clinical and neuroimaging evaluations including a 3-m Timed Up and Go test, [(11)C]dihydrotetrabenazine positron emission tomography imaging to estimate nigrostriatal dopamine terminal loss, and an magnetic resonance imaging assessment of leukoaraiosis. A similar analysis was performed in 49 healthy controls. After adjusting for disease duration, leukoaraiosis, and nigrostriatal dopaminergic denervation, Parkinson disease subjects with elevated Framingham risk scores (n = 61) displayed slower Timed Up and Go test performance (β = 1.86, t = 2.41, p = .018) compared with subjects with normal range Framingham risk scores (n = 22). When age ≥65 was added to the model in a post hoc analysis, the strength of effect seen with older age (β = 1.51, t = 2.44, p = .017) was similar to that of elevated Framingham risk scoring (β = 1.87, t = 2.51, p = .014). In a multivariable regression model studying the healthy control population, advanced age (t = 2.15, p = .037) was a significant predictor of Timed Up and Go speed though striatal [(11)C]dihydrotetrabenazine (t = -1.30, p = .19) and elevated Framingham risk scores (t = 1.32, p = .19) were not. Modifiable cardiovascular risk factors and older age may independently exacerbate balance-related disability in Parkinson disease and may exert additive or synergistic pathological effects. The pathophysiology of these impairments cannot be explained completely by nigrostriatal dopaminergic denervation or leukoaraiosis burden and may relate to systemic factors seen with accelerated aging. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Health-risk appraisal with or without disease management for worksite cardiovascular risk reduction.

PubMed

Maron, David J; Forbes, Barbara L; Groves, Jay R; Dietrich, Mary S; Sells, Patrick; DiGenio, Andres G

2008-01-01

Worksite health promotion programs use health risk appraisal (HRA) surveys to identify employees at increased risk, then provide a range of interventions to encourage high-risk individuals to improve their health. Our objective was to determine how the intensity of intervention after HRA affected cardiovascular risk after 1 year, comparing individual follow-up counseling with environmental supports. 133 employees of Vanderbilt University with cardiovascular risk factors were randomly assigned to worksite HRA plus targeted disease management (DM group) or HRA plus information about worksite health promotion programs (HRA group). The DM group received longitudinal individualized counseling for risk reduction, whereas the HRA group members received one feedback session about their risk factors and information about free worksite health promotion programs. The main outcome measure was the difference between groups in the change in average Framingham risk score from baseline to 1 year. There was no significant baseline difference between groups in the Framingham risk score. Among DM participants, the mean (SD) Framingham risk score decreased by 22.6%; among HRA participants, the mean score rose by 4.3% (P = .017 for the difference between groups). In this study of employees with cardiovascular risk factors, HRA followed by individual counseling was more effective than providing information about free worksite health promotion programs.

The systolic blood pressure difference between arms and cardiovascular disease in the Framingham Heart Study.

PubMed

Weinberg, Ido; Gona, Philimon; O'Donnell, Christopher J; Jaff, Michael R; Murabito, Joanne M

2014-03-01

An increased interarm systolic blood pressure difference is an easily determined physical examination finding. The relationship between interarm systolic blood pressure difference and risk of future cardiovascular disease is uncertain. We described the prevalence and risk factor correlates of interarm systolic blood pressure difference in the Framingham Heart Study (FHS) original and offspring cohorts and examined the association between interarm systolic blood pressure difference and incident cardiovascular disease and all-cause mortality. An increased interarm systolic blood pressure difference was defined as ≥ 10 mm Hg using the average of initial and repeat blood pressure measurements obtained in both arms. Participants were followed through 2010 for incident cardiovascular disease events. Multivariable Cox proportional hazards regression analyses were performed to investigate the effect of interarm systolic blood pressure difference on incident cardiovascular disease. We examined 3390 (56.3% female) participants aged 40 years and older, free of cardiovascular disease at baseline, mean age of 61.1 years, who attended a FHS examination between 1991 and 1994 (original cohort) and from 1995 to 1998 (offspring cohort). The mean absolute interarm systolic blood pressure difference was 4.6 mm Hg (range 0-78). Increased interarm systolic blood pressure difference was present in 317 (9.4%) participants. The median follow-up time was 13.3 years, during which time 598 participants (17.6%) experienced a first cardiovascular event, including 83 (26.2%) participants with interarm systolic blood pressure difference ≥ 10 mm Hg. Compared with those with normal interarm systolic blood pressure difference, participants with an elevated interarm systolic blood pressure difference were older (63.0 years vs 60.9 years), had a greater prevalence of diabetes mellitus (13.3% vs 7.5%,), higher systolic blood pressure (136.3 mm Hg vs 129.3 mm Hg), and a higher total cholesterol level (212.1 mg/dL vs 206.5 mg/dL). Interarm systolic blood pressure difference was associated with a significantly increased hazard of incident cardiovascular events in the multivariable adjusted model (hazard ratio 1.38; 95% CI, 1.09-1.75). For each 1-SD-unit increase in absolute interarm systolic blood pressure difference, the hazard ratio for incident cardiovascular events was 1.07 (95% CI, 1.00-1.14) in the fully adjusted model. There was no such association with mortality (hazard ratio 1.02; 95% CI 0.76-1.38). In this community-based cohort, an interarm systolic blood pressure difference is common and associated with a significant increased risk for future cardiovascular events, even when the absolute difference in arm systolic blood pressure is modest. These findings support research to expand clinical use of this simple measurement. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of Circulating Adipokines With Echocardiographic Measures of Cardiac Structure and Function in a Community-Based Cohort.

PubMed

von Jeinsen, Beatrice; Short, Meghan I; Xanthakis, Vanessa; Carneiro, Herman; Cheng, Susan; Mitchell, Gary F; Vasan, Ramachandran S

2018-06-21

Adipokines mediate cardiometabolic risk associated with obesity but their role in the pathogenesis of obesity-associated heart failure remains uncertain. We investigated the associations between circulating adipokine concentrations and echocardiographic measures in a community-based sample. We evaluated 3514 Framingham Heart Study participants (mean age 40 years, 53.8% women) who underwent routine echocardiography and had select circulating adipokines measured, ie, leptin, soluble leptin receptor, fatty acid-binding protein 4, retinol-binding protein 4, fetuin-A, and adiponectin. We used multivariable linear regression, adjusting for known correlates (including weight), to relate adipokine concentrations (independent variables) to the following echocardiographic measures (dependent variables): left ventricular mass index, left atrial diameter in end systole, fractional shortening, and E/e'. In multivariable-adjusted analysis, left ventricular mass index was inversely related to circulating leptin and fatty acid-binding protein 4 concentrations but positively related to retinol-binding protein 4 and leptin receptor levels ( P ≤0.002 for all). Left atrial end-systolic dimension was inversely related to leptin but positively related to retinol-binding protein 4 concentrations ( P ≤0.0001). E/e' was inversely related to leptin receptor levels ( P =0.0002). We observed effect modification by body weight for select associations (leptin receptor and fatty acid-binding protein 4 with left ventricular mass index, and leptin with left atrial diameter in end systole; P <0.05 for interactions). Fractional shortening was not associated with any of the adipokines. No echocardiographic trait was associated with fetuin-A or adiponectin concentrations. In our cross-sectional study of a large, young to middle-aged, relatively healthy community-based sample, key indices of subclinical cardiac remodeling were associated with higher or lower circulating concentrations of prohypertrophic and antihypertrophic adipokines in a context-specific manner. These observations may offer insights into the pathogenesis of the cardiomyopathy of obesity. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Can an Internet-based health risk assessment highlight problems of heart disease risk factor awareness? A cross-sectional analysis.

PubMed

Dickerson, Justin B; McNeal, Catherine J; Tsai, Ginger; Rivera, Cathleen M; Smith, Matthew Lee; Ohsfeldt, Robert L; Ory, Marcia G

2014-04-18

Health risk assessments are becoming more popular as a tool to conveniently and effectively reach community-dwelling adults who may be at risk for serious chronic conditions such as coronary heart disease (CHD). The use of such instruments to improve adults' risk factor awareness and concordance with clinically measured risk factor values could be an opportunity to advance public health knowledge and build effective interventions. The objective of this study was to determine if an Internet-based health risk assessment can highlight important aspects of agreement between respondents' self-reported and clinically measured CHD risk factors for community-dwelling adults who may be at risk for CHD. Data from an Internet-based cardiovascular health risk assessment (Heart Aware) administered to community-dwelling adults at 127 clinical sites were analyzed. Respondents were recruited through individual hospital marketing campaigns, such as media advertising and print media, found throughout inpatient and outpatient facilities. CHD risk factors from the Framingham Heart Study were examined. Weighted kappa statistics were calculated to measure interrater agreement between respondents' self-reported and clinically measured CHD risk factors. Weighted kappa statistics were then calculated for each sample by strata of overall 10-year CHD risk. Three samples were drawn based on strategies for treating missing data: a listwise deleted sample, a pairwise deleted sample, and a multiple imputation (MI) sample. The MI sample (n=16,879) was most appropriate for addressing missing data. No CHD risk factor had better than marginal interrater agreement (κ>.60). High-density lipoprotein cholesterol (HDL-C) exhibited suboptimal interrater agreement that deteriorated (eg, κ<.30) as overall CHD risk increased. Conversely, low-density lipoprotein cholesterol (LDL-C) interrater agreement improved (eg, up to κ=.25) as overall CHD risk increased. Overall CHD risk of the sample was lower than comparative population-based CHD risk (ie, no more than 15% risk of CHD for the sample vs up to a 30% chance of CHD for the population). Interventions are needed to improve knowledge of CHD risk factors. Specific interventions should address perceptions of HDL-C and LCL-C. Internet-based health risk assessments such as Heart Aware may contribute to public health surveillance, but they must address selection bias of Internet-based recruitment methods.

Mechanical circulatory support and heart transplantation in the Asia Pacific region.

PubMed

Sivathasan, Cumaraswamy; Lim, Choon Pin; Kerk, Ka Lee; Sim, David K L; Mehra, Mandeep R

2017-01-01

Globalization has resulted in epidemiologic transition in developing countries from infectious disease and nutritional deficiencies to non-communicable diseases. Epidemiologic data on heart failure (HF), particularly advanced HF therapy, in Asia are increasingly becoming available, although they remain sparse. Heart transplantation for advanced stage HF remains very low in Asia-approximately 0.075 heart transplants per 1 million population. North America, which comprises 7.5% of the world population, accounted for 55.8% of transplants recorded in the 2012 International Society for Heart and Lung Transplantation (ISHLT) Registry, whereas Asia, with 62.5% of the world population, accounted for 5.7% of transplants. There is also lack of reporting from heart transplant centers in Asia to the ISHLT Registry. Most transplant programs in Asia are in economically stable South East Asian countries, whereas in other parts of developing countries, the cost and health care infrastructures remain prohibitive for the development of these programs. Multi-cultural and racial factors, religious beliefs, and diverse traditions of many centuries have resulted in reluctance to organ donation. Mechanical circulatory support (MCS) is emerging as a viable alternative to transplantation, but despite technical capabilities, limitations in embracing MCS in Asia exist. Discrepant practices in the reimbursement of costly MCS therapy have led to differences in the availability of these devices to patients in the region. The HeartMate II (St. Jude Medical, Inc, St. Paul, MN) left ventricular assist device is currently the most widely used durable device in Asia, whereas the HeartWare HVAD (HeartWare, Inc, Framingham, MA) is used most often in Australia. By September 9, 2015, 341 HeartMate implants (293 as bridge to transplant and 48 as destination therapy) had been performed, of which 180 implants were in Japan. The overall 4-year survival is 88%. The longest duration of support is 6.5 years. By the end of 2015, 243 HeartWare HVADs had been implanted in Asia Pacific. There is a need for focused efforts at improving the reporting of data and intensifying health policy within the region to advocate organ transplantation. Individual governments need to take national responsibility to fulfill organ donation and transplantation needs of their populations. International collaboratives, coordinated by societies such as the ISHLT, will be essential in moving this field forward in Asia Pacific. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Association of urinary cadmium and myocardial infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Everett, Charles J.; Frithsen, Ivar L.

We conducted a cross-sectional analysis of individuals 45-79 years old in the National Health and Nutrition Examination Survey III (1988-1994) (NHANES III). Myocardial infarction was determined by electrocardiogram (ECG). Our sample included 4912 participants, which when weighted represented 52,234,055 Americans. We performed adjusted logistic regressions with the Framingham risk score, pack-years of smoking, race-ethnicity, and family history of heart attack, and diabetes as covariates. Urinary cadmium {>=}0.88 {mu}g/g creatinine had an odds ratio of 1.86 (95% CI 1.26-2.75) compared to urinary cadmium <0.43 {mu}g/g creatinine. This result supports the hypothesis that cadmium is associated with coronary heart disease. When logisticmore » regressions were done by gender, women, but not men, showed a significant association of urinary cadmium with myocardial infarction. Women with urinary cadmium {>=}0.88 {mu}g/g creatinine had an odds ratio of 1.80 (95% CI 1.06-3.04) compared to urinary cadmium <0.43 {mu}g/g creatinine. When the analysis was restricted to never smokers (N=2187) urinary cadmium {>=}0.88 {mu}g/g creatinine had an odds ratio of 1.85 (95% CI 1.10-3.14) compared to urinary cadmium <0.43 {mu}g/g creatinine.« less

EDUCATION AND CORONARY HEART DISEASE RISK: POTENTIAL MECHANISMS SUCH AS LITERACY, PERCEIVED CONSTRAINT AND DEPRESSIVE SYMPTOMS

PubMed Central

Loucks, Eric B.; Gilman, Stephen E.; Howe, Chanelle; Kawachi, Ichiro; Kubzansky, Laura D.; Rudd, Rima E.; Martin, Laurie T.; Nandi, Arijit; Wilhelm, Aude; Buka, Stephen L.

2015-01-01

OBJECTIVE Education is inversely associated with coronary heart disease (CHD) risk, however the mechanisms are poorly understood. The study objectives were to evaluate the extent to which rarely measured factors (literacy, time preference, sense of control) and more commonly measured factors (income, depressive symptomatology, body mass index) in the education-CHD literature explain the associations between education and CHD risk. METHOD The study sample included 346 participants, aged 38–47 years (59.5% women), of the New England Family Study birth cohort. Ten-year CHD risk was calculated using the validated Framingham risk algorithm that utilizes diabetes, smoking, blood pressure, total cholesterol, HDL cholesterol, age and gender. Multivariable regression and mediation analyses were performed. RESULTS Regression analyses adjusting for age, race/ethnicity and childhood confounders (e.g. parental socioeconomic status, intelligence) demonstrated that relative to those with ≥college education, men and women with

Assessment of cardiovascular risk profile based on measurement of tophus volume in patients with gout.

PubMed

Lee, Kyung-Ann; Ryu, Se-Ri; Park, Seong-Jun; Kim, Hae-Rim; Lee, Sang-Heon

2018-05-01

Hyperuricemia and gout are associated with increased risk of cardiovascular disease and metabolic syndrome. The aim of this study was to evaluate the correlation of total tophus volumes, measured using dual-energy computed tomography, with cardiovascular risk and the presence of metabolic syndrome. Dual-energy computed tomography datasets from 91 patients with a diagnosis of gout were analyzed retrospectively. Patients who received urate lowering therapy were excluded to avoid the effect on tophus volume. The total volumes of tophaceous deposition were quantified using automated volume assessment software. The 10-year cardiovascular risk using the Framingham Risk Score and metabolic syndrome based on the Third Adult Treatment Panel criteria were estimated. Fifty-five and 36 patients with positive and negative dual-energy computed tomography results, respectively, were assessed. Patients with positive dual-energy computed tomography results showed significantly higher systolic blood pressure, diastolic blood pressure, fasting glucose, and higher prevalence of chronic kidney disease, compared with those with negative dual-energy computed tomography results. The total tophus volumes were significantly correlated with the Framingham Risk Score, and the number of metabolic syndrome components (r = 0.22 and p = 0.036 and r = 0.373 and p < 0.001, respectively). The total tophus volume was one of the independent prognostic factors for the Framingham Risk Score in a multivariate analysis. This study showed the correlation of total tophus volumes with cardiovascular risk and metabolic syndrome-related comorbidities. A high urate burden could affect unfavorable cardiovascular profiles.

Association of hip pain with radiographic evidence of hip osteoarthritis: diagnostic test study

PubMed Central

Nevitt, Michael C; Niu, Jingbo; Clancy, Mary M; Lane, Nancy E; Link, Thomas M; Vlad, Steven; Tolstykh, Irina; Jungmann, Pia M.; Felson, David T; Guermazi, Ali

2015-01-01

Study question Is there concordance between hip pain and radiographic hip osteoarthritis? Methods In this diagnostic test study, pelvic radiographs were assessed for hip osteoarthritis in two cohorts: the Framingham Osteoarthritis Study (community of Framingham, Massachusetts) and the Osteoarthritis Initiative (a multicenter longitudinal cohort study of osteoarthritis in the United States). Using visual representation of the hip joint, participants reported whether they had hip pain on most days and the location of the pain: anterior, groin, lateral, buttocks, or low back. In the Framingham study, participants with hip pain were also examined for hip pain with internal rotation. The authors analysed the agreement between radiographic hip osteoarthritis and hip pain, and for those with hip pain suggestive of hip osteoarthritis they calculated the sensitivity, specificity, positive predictive value, and negative predictive value of radiographs as the diagnostic test. Study answer and limitations In the Framingham study (n=946), only 15.6% of hips in patients with frequent hip pain showed radiographic evidence of hip osteoarthritis, and 20.7% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of radiographic hip osteoarthritis for hip pain localised to the groin was 36.7%, specificity 90.5%, positive predictive value 6.0%, and negative predictive value 98.9%. Results did not differ much for hip pain at other locations or for painful internal rotation. In the Osteoarthritis Initiative study (n=4366), only 9.1% of hips in patients with frequent pain showed radiographic hip osteoarthritis, and 23.8% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of definite radiographic hip osteoarthritis for hip pain localised to the groin was 16.5%, specificity 94.0%, positive predictive value 7.1%, and negative predictive value 97.6%. Results also did not differ much for hip pain at other locations. What this study adds Hip pain was not present in many hips with radiographic osteoarthritis, and many hips with pain did not show radiographic hip osteoarthritis. Most older participants with a high suspicion for clinical hip osteoarthritis (groin or anterior pain and/or painful internal rotation) did not have radiographic hip osteoarthritis, suggesting that in many cases, hip osteoarthritis might be missed if diagnosticians relied solely on hip radiographs. Funding, competing interests, data sharing See the full paper on thebmj.com for funding. The authors have no competing interests. Additional data are available from bevochan@bu.edu. PMID:26631296

Predicting stroke through genetic risk functions: the CHARGE Risk Score Project.

PubMed

Ibrahim-Verbaas, Carla A; Fornage, Myriam; Bis, Joshua C; Choi, Seung Hoan; Psaty, Bruce M; Meigs, James B; Rao, Madhu; Nalls, Mike; Fontes, Joao D; O'Donnell, Christopher J; Kathiresan, Sekar; Ehret, Georg B; Fox, Caroline S; Malik, Rainer; Dichgans, Martin; Schmidt, Helena; Lahti, Jari; Heckbert, Susan R; Lumley, Thomas; Rice, Kenneth; Rotter, Jerome I; Taylor, Kent D; Folsom, Aaron R; Boerwinkle, Eric; Rosamond, Wayne D; Shahar, Eyal; Gottesman, Rebecca F; Koudstaal, Peter J; Amin, Najaf; Wieberdink, Renske G; Dehghan, Abbas; Hofman, Albert; Uitterlinden, André G; Destefano, Anita L; Debette, Stephanie; Xue, Luting; Beiser, Alexa; Wolf, Philip A; Decarli, Charles; Ikram, M Arfan; Seshadri, Sudha; Mosley, Thomas H; Longstreth, W T; van Duijn, Cornelia M; Launer, Lenore J

2014-02-01

Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke. In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P<10(-4)). The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.

Racial Discrimination & Cardiovascular Disease Risk: My Body My Story Study of 1005 US-Born Black and White Community Health Center Participants (US)

PubMed Central

Krieger, Nancy; Waterman, Pamela D.; Kosheleva, Anna; Chen, Jarvis T.; Smith, Kevin W.; Carney, Dana R.; Bennett, Gary G.; Williams, David R.; Thornhill, Gisele; Freeman, Elmer R.

2013-01-01

Objectives To date, limited and inconsistent evidence exists regarding racial discrimination and risk of cardiovascular disease (CVD). Methods Cross-sectional observational study of 1005 US-born non-Hispanic black (n = 504) and white (n = 501) participants age 35–64 randomly selected from community health centers in Boston, MA (2008–2010; 82.4% response rate), using 3 racial discrimination measures: explicit self-report; implicit association test (IAT, a time reaction test for self and group as target vs. perpetrator of discrimination); and structural (Jim Crow status of state of birth, i.e. legal racial discrimination prior 1964). Results Black and white participants both had adverse cardiovascular and socioeconomic profiles, with black participants most highly exposed to racial discrimination. Positive crude associations among black participants occurred for Jim Crow birthplace and hypertension (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.28, 2.89) and for explicit self-report and the Framingham 10 year CVD risk score (beta  = 0.04; 95% CI 0.01, 0.07); among white participants, only negative crude associations existed (for IAT for self, for lower systolic blood pressure (SBP; beta  = −4.86; 95% CI −9.08, −0.64) and lower Framingham CVD score (beta  = −0.36, 95% CI −0.63, −0.08)). All of these associations were attenuated and all but the white IAT-Framingham risk score association were rendered null in analyses that controlled for lifetime socioeconomic position and additional covariates. Controlling for racial discrimination, socioeconomic position, and other covariates did not attenuate the crude black excess risk for SBP and hypertension and left unaffected the null excess risk for the Framingham CVD score. Conclusion Despite worse exposures among the black participants, racial discrimination and socioeconomic position were not associated, in multivariable analyses, with risk of CVD. We interpret results in relation to constrained variability of exposures and outcomes and discuss implications for valid research on social determinants of health. PMID:24204765

Increased Arterial Stiffness in Systemic Lupus Erythematosus (SLE) Patients at Low Risk for Cardiovascular Disease: A Cross-Sectional Controlled Study

PubMed Central

Sacre, Karim; Escoubet, Brigitte; Pasquet, Blandine; Chauveheid, Marie-Paule; Zennaro, Maria-Christina; Tubach, Florence; Papo, Thomas

2014-01-01

Cardiovascular disease (CVD) is a major cause of death in systemic lupus erythematosus (SLE) patients. Although the risk for cardiovascular events in patients with SLE is significant, the absolute number of events per year in any given cohort remains small. Thus, CVD risks stratification in patients with SLE focuses on surrogate markers for atherosclerosis at an early stage, such as reduced elasticity of arteries. Our study was designed to determine whether arterial stiffness is increased in SLE patients at low risk for CVD and analyze the role for traditional and non-traditional CVD risk factors on arterial stiffness in SLE. Carotid-femoral pulse wave velocity (PWV) was prospectively assessed as a measure of arterial stiffness in 41 SLE patients and 35 controls (CTL). Adjustment on age or Framingham score was performed using a logistic regression model. Factors associated with PWV were identified separately in SLE patients and in controls using Pearson's correlation coefficient for univariate analysis and multiple linear regression for multivariate analysis. SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (1.8±3.6% in SLE vs 1.6±2.8% in CTL, p = 0.46). Pulse wave velocity was, however, higher in SLE patients (7.1±1.6 m/s) as compared to controls (6.3±0.8 m/s; p = 0.01, after Framingham score adjustment) and correlated with internal carotid wall thickness (p = 0.0017). In multivariable analysis, only systolic blood pressure (p = 0.0005) and cumulative dose of glucocorticoids (p = 0.01) were associated with PWV in SLE patients. Interestingly, the link between systolic blood pressure (SBP) and arterial stiffness was also confirmed in SLE patients with normal systolic blood pressure. In conclusion, arterial stiffness is increased in SLE patients despite a low risk for CVD according to Framingham score and is associated with systolic blood pressure and glucocorticoid therapy. PMID:24722263

Calcium intake is not associated with increased coronary artery calcification: The Framingham Study

USDA-ARS?s Scientific Manuscript database

Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern. We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification...

Dietary carbohydrates and cardiovascular disease risk factors in the Framingham Offspring Cohort

USDA-ARS?s Scientific Manuscript database

Evidence from observational studies has suggested that carbohydrate quality rather than absolute intake is associated with greater risk of chronic diseases. The aim of this study was to examine the relationship between carbohydrate intake and dietary glycemic index and several cardiovascular disease...

Gene expression analysis of whole blood, peripheral blood mononuclear cells, and lymphoblastoid cell lines from the Framingham Heart Study

PubMed Central

Joehanes, Roby; Johnson, Andrew D.; Barb, Jennifer J.; Raghavachari, Nalini; Liu, Poching; Woodhouse, Kimberly A.; O'Donnell, Christopher J.; Munson, Peter J.

2012-01-01

Despite a growing number of reports of gene expression analysis from blood-derived RNA sources, there have been few systematic comparisons of various RNA sources in transcriptomic analysis or for biomarker discovery in the context of cardiovascular disease (CVD). As a pilot study of the Systems Approach to Biomarker Research (SABRe) in CVD Initiative, this investigation used Affymetrix Exon arrays to characterize gene expression of three blood-derived RNA sources: lymphoblastoid cell lines (LCL), whole blood using PAXgene tubes (PAX), and peripheral blood mononuclear cells (PBMC). Their performance was compared in relation to identifying transcript associations with sex and CVD risk factors, such as age, high-density lipoprotein, and smoking status, and the differential blood cell count. We also identified a set of exons that vary substantially between participants, but consistently in each RNA source. Such exons are thus stable phenotypes of the participant and may potentially become useful fingerprinting biomarkers. In agreement with previous studies, we found that each of the RNA sources is distinct. Unlike PAX and PBMC, LCL gene expression showed little association with the differential blood count. LCL, however, was able to detect two genes related to smoking status. PAX and PBMC identified Y-chromosome probe sets similarly and slightly better than LCL. PMID:22045913

Individual and spousal unemployment as predictors of smoking and drinking behavior

PubMed Central

Arcaya, Mariana; Glymour, M. Maria; Christakis, Nicholas A; Kawachi, Ichiro; Subramanian, S V

2014-01-01

The effects of unemployment on health behaviors, and substance use in particular, is still unclear despite substantial existing research. This study aimed to assess the effects of individual and spousal unemployment on smoking and alcohol consumption. The study was based on eight waves of geocoded Framingham Heart Study Offspring Cohort data (US) from 1971-2008 that contained social network information. We fit three series of models to assess whether lagged 1) unemployment, and 2) spousal unemployment predicted odds of being a current smoker or drinks consumed per week, adjusting for a range of socioeconomic and demographic covariates. Compared with employment, unemployment was associated with nearly twice the subsequent odds of smoking, and with increased cigarette consumption among male, but not female, smokers. In contrast, unemployment predicted a one drink reduction in weekly alcohol consumption, though effects varied according to intensity of consumption, and appeared stronger among women. While spousal unemployment had no effect on substance use behaviors among men, wives responded to husbands' unemployment by reducing their alcohol consumption. We conclude that individual, and among women, spousal unemployment predicted changes in substance use behaviors, and that the direction of the change was substance-dependent. Complex interactions among employment status, sex, and intensity and type of consumption appear to be at play and should be investigated further. PMID:24727666

Self-rated stress is noncontributory to coronary artery disease in higher socioeconomic strata.

PubMed

Kermott, Cindy A; Cha, Stephen S; Hagen, Philip T; Behrenbeck, Thomas

2013-10-01

Stress and its attendant psychosocial and lifestyle variables have been associated with coronary artery disease (CAD), yet the contribution of socioeconomic status (SES) has not been addressed. The aim of this study is to determine if stress assessment is associated with CAD independent of SES, and is incremental to the Framingham Score. The study group consisted of 325 executive patients undergoing comprehensive health assessment. Stress was assessed utilizing the validated "Self-Rated Stress" (SRS) instrument. Coronary artery calcification (CAC) served to assess the degree of atherosclerosis, a CAD equivalent and risk assessment tool. The relationship between SRS and CAC was assessed, with adjustment by potential confounders. CAC was modeled by a variety of cut points (>0, ≥5, ≥100, ≥200) for the test of trend across stress levels per Mantel-Haenszel chi-square (1 df) with nonsignificant P values of 0.9960, 0.5242, 0.1692, 0.3233, respectively. A logistic regression model with SRS as a categorically ranked and continuous variable to predict binary outcome of calcification yielded P values of 0.2366 and 0.9644; this relationship, further adjusted by age, fruit and vegetable consumption, exercise, and education, yielded no statistically significant association. No improvement of fit was observed for the established Framingham Score to CAC relation utilizing SRS. The study concluded that SRS did not play a role in early CAD when focusing on a population in higher socioeconomic strata, and SRS did not add predictive value beyond patient age or calculated Framingham risk. Future studies should focus on additional validated instruments of stress to differentiate between subtypes of stress for varying SES strata.

Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: population based observational study (Framingham Osteoarthritis Study).

PubMed

Guermazi, Ali; Niu, Jingbo; Hayashi, Daichi; Roemer, Frank W; Englund, Martin; Neogi, Tuhina; Aliabadi, Piran; McLennan, Christine E; Felson, David T

2012-08-29

To examine use of magnetic resonance imaging (MRI) of knees with no radiographic evidence of osteoarthritis to determine the prevalence of structural lesions associated with osteoarthritis and their relation to age, sex, and obesity. Population based observational study. Community cohort in Framingham, MA, United States (Framingham osteoarthritis study). 710 people aged >50 who had no radiographic evidence of knee osteoarthritis (Kellgren-Lawrence grade 0) and who underwent MRI of the knee. Prevalence of MRI findings that are suggestive of knee osteoarthritis (osteophytes, cartilage damage, bone marrow lesions, subchondral cysts, meniscal lesions, synovitis, attrition, and ligamentous lesions) in all participants and after stratification by age, sex, body mass index (BMI), and the presence or absence of knee pain. Pain was assessed by three different questions and also by WOMAC questionnaire. Of the 710 participants, 393 (55%) were women, 660 (93%) were white, and 206 (29%) had knee pain in the past month. The mean age was 62.3 years and mean BMI was 27.9. Prevalence of "any abnormality" was 89% (631/710) overall. Osteophytes were the most common abnormality among all participants (74%, 524/710), followed by cartilage damage (69%, 492/710) and bone marrow lesions (52%, 371/710). The higher the age, the higher the prevalence of all types of abnormalities detectable by MRI. There were no significant differences in the prevalence of any of the features between BMI groups. The prevalence of at least one type of pathology ("any abnormality") was high in both painful (90-97%, depending on pain definition) and painless (86-88%) knees. MRI shows lesions in the tibiofemoral joint in most middle aged and elderly people in whom knee radiographs do not show any features of osteoarthritis, regardless of pain.

Foot Function, Foot Pain, and Falls in Older Adults: the Framingham Foot Study

PubMed Central

Awale, Arunima; Hagedorn, Thomas J.; Dufour, Alyssa B.; Menz, Hylton B.; Casey, Virginia A.; Hannan, Marian T.

2017-01-01

Background Although foot pain has been linked to fall risk, contributions of pain severity, foot posture or foot function are unclear. These factors were examined in a cohort of older adults. Objective The purpose of this study was to examine the associations of foot pain, severity of foot pain and measures of foot posture and dynamic foot function with reported falls in a large, well-described cohort of older adults from the Framingham Foot Study. Methods Foot pain, posture and function were collected from Framingham Foot Study participants who were queried about falls over the past year (0, 1, 2+ falls). Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the relation of falls with foot pain, pain severity, foot posture, and foot function adjusting for covariates. Results Of 1375 participants, mean age was 69y; 57% were female; 21% reported foot pain (40% mild pain, 47% moderate, 13% severe pain). One-third reported falls in past year (1 fall: n=263, 2+ falls: n=152). Foot pain was associated with a 62% increased odds of recurrent falls. Those with moderate and severe foot pain showed increased odds of 2+ falls (OR=1.78, CI 1.06–2.99, and OR = 3.25, CI 1.65–7.48, respectively) compared to no foot pain. Foot function was not associated with falls. Compared to normal foot posture, those with planus foot posture had 78% higher odds of 2+ falls. Conclusion Higher odds of recurrent falls were observed in individuals with foot pain, especially severe foot pain, as well as individuals with planus foot posture, indicating that both foot pain and foot posture may play a role in increasing the risk of falls among older adults. PMID:28482340

Coronary artery disease risk assessment from unstructured electronic health records using text mining.

PubMed

Jonnagaddala, Jitendra; Liaw, Siaw-Teng; Ray, Pradeep; Kumar, Manish; Chang, Nai-Wen; Dai, Hong-Jie

2015-12-01

Coronary artery disease (CAD) often leads to myocardial infarction, which may be fatal. Risk factors can be used to predict CAD, which may subsequently lead to prevention or early intervention. Patient data such as co-morbidities, medication history, social history and family history are required to determine the risk factors for a disease. However, risk factor data are usually embedded in unstructured clinical narratives if the data is not collected specifically for risk assessment purposes. Clinical text mining can be used to extract data related to risk factors from unstructured clinical notes. This study presents methods to extract Framingham risk factors from unstructured electronic health records using clinical text mining and to calculate 10-year coronary artery disease risk scores in a cohort of diabetic patients. We developed a rule-based system to extract risk factors: age, gender, total cholesterol, HDL-C, blood pressure, diabetes history and smoking history. The results showed that the output from the text mining system was reliable, but there was a significant amount of missing data to calculate the Framingham risk score. A systematic approach for understanding missing data was followed by implementation of imputation strategies. An analysis of the 10-year Framingham risk scores for coronary artery disease in this cohort has shown that the majority of the diabetic patients are at moderate risk of CAD. Copyright © 2015 Elsevier Inc. All rights reserved.

Critical factors in case management: practical lessons from a cardiac case management program.

PubMed

Stafford, Randall S; Berra, Kathy

2007-08-01

Case management (CM) is an important strategy for chronic disease care. By utilizing non-physician providers for conditions requiring ongoing care and follow-up, CM can facilitate guideline-concordant care, patient empowerment, and improvement in quality of life. We identify a series of critical factors required for successful CM implementation. Heart to Heart is a clinical trial evaluating CM for coronary heart disease (CHD) risk reduction in a multiethnic, low-income population. Patients at elevated cardiac risk were randomized to CM plus primary care (212 patients) or to primary care alone (207). Over a mean follow-up of 17 months, patients received face-to-face nurse and dietitian visits. Mean contact time was 14 hours provided at an estimated cost of $1250 per patient for the 341 (81%) patients completing follow-up. Visits emphasized behavior change, risk-factor monitoring, self-management skills, and guideline-based pharmacotherapy. A statistically significant reduction in mean Framingham risk probability occurred in CM plus primary care relative to primary care alone (1.6% decrease in 10-year CHD risk, p = 0.007). Favorable changes were noted across individual risk factors. Our findings suggest that successful CM implementation relies on choosing appropriate case managers and investing in training, integrating CM into existing care systems, delineating the scope and appropriate levels of clinical decision making, using information systems, and monitoring outcomes and costs. While our population, setting, and intervention model are unique, these insights are broadly relevant. If implemented with attention to critical factors, CM has great potential to improve the process and outcomes of chronic disease care.

Association between CT-evaluated lumbar lordosis and features of spinal degeneration, evaluated in supine position

PubMed Central

Kalichman, Leonid; Li, Ling; Hunter, David; Been, Ella

2013-01-01

Background Context Few studies have directly evaluated the association of lumbar lordosis and segmental wedging of the vertebral bodies and intervertebral disks with prevalence of spinal degenerative features. Purpose To evaluate the association of CT-evaluated lumbar lordosis, segmental wedging of the vertebral bodies and that of the intervertebral disks with various spinal degeneration features. Study design This cross-sectional study was a nested project to the Framingham Heart Study. Sample A random consecutive subset of 191 participants chosen from the 3590 participants enrolled in the Framingham Heart Study who underwent multi-detector CT to assess aortic calcification. Outcome Measures Physiologic Measures Dichotomous variables indicating the presence of intervertebral disc narrowing, facet joint osteoarthritis, spondylolysis, spondylolisthesis and spinal stenosis and density (in Hounsfield units) of multifidus and erector spinae muscles were evaluated on supine CT, as well as the lordosis angle (LA) and the wedging of the vertebral bodies and intervertebral disks. Sum of vertebral bodies wedging (ΣB) and sum of intervertebral discs wedging (ΣD) were used in analyses. Methods Mean values (±SD) of LA, ΣB and ΣD were calculated in males and females and compared using the t-test. Mean values (±SD) of LA, ΣB and ΣD in 4 age groups: <40, 40–49, 50–59 and 60+ years were calculated. We tested the linear relationship between LA, ΣB and ΣD and age groups. We evaluated the association between each spinal degeneration feature and LA, ΣB and ΣD using multiple logistic regression analysis where studied degeneration features were the dependent variable and all LA, ΣB and ΣD (separately) as well as age, sex, and BMI were independent predictors. Results LA was slightly lower than the normal range for standing individuals, and no difference was found between males and females (p=0.4107). However, the sex differences in sum of vertebral bodies wedging (ΣB) and sum of intervertebral discs wedging (ΣD) were statistically significant (0.0001 and 0.001, respectively). Females exhibit more dorsal wedging of the vertebral bodies and less dorsal wedging of the intervertebral discs than do males. All these parameters showed no association (p>0.05) with increasing age. LA showed statistically significant association with presence of spondylolysis (OR(95%CI): 1.08(1.02–1.14)) and with density of multifidus (1.06 (1.01–1.11). as well as a marginally significant association with isthmic spondylolisthesis (1.07(1.00–1.14). ΣB showed a positive association with degenerative spondylolisthesis and disc narrowing ((1.14(1.06–1.23) and 1.04 (1.00–1.08), correspondingly), whereas ΣD showed negative one (0.93(0.87–0.98) and (0.93(0.89–0.97), correspondingly). Conclusions Significant associations were found between lumbar lordosis evaluated in supine position and segmental wedging of the vertebral bodies and intervertebral disks and prevalence of spondylolysis and spondylolisthesis. Additional studies are needed, to evaluate the association between spondylolysis, isthmic and degenerative spondylolisthesis and vertebral and disc wedging at segmental level. PMID:21474082

Job strain and cognitive decline: a prospective study of the framingham offspring cohort.

PubMed

Agbenyikey, W; Karasek, R; Cifuentes, M; Wolf, P A; Seshadri, S; Taylor, J A; Beiser, A S; Au, R

2015-04-01

Workplace stress is known to be related with many behavioral and disease outcomes. However, little is known about its prospective relationship with measures of cognitive decline. To investigate the association of job strain, psychological demands and job control on cognitive decline. Participants from Framingham Offspring cohort (n=1429), were assessed on job strain, and received neuropsychological assessment approximately 15 years and 21 years afterwards. High job strain and low control were associated with decline in verbal learning and memory. Job strain was associated with decline in word recognition skills. Active job and passive job predicted decline in verbal learning and memory relative to low strain jobs in the younger subgroup. Active job and demands were positively associated with abstract reasoning skills. Job strain and job control may influence decline in cognitive performance.

Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the framingham offspring study

USDA-ARS?s Scientific Manuscript database

Several biomarkers have been individually associated with vascular brain injury, but no prior study has explored the simultaneous association of a biologically plausible panel of biomarkers with the incidence of stroke/transient ischemic attack and the prevalence of subclinical brain injury. In 3127...

Utility of the History and Physical Examination in the Detection of Acute Coronary Syndromes in Emergency Department Patients.

PubMed

Dezman, Zachary Dw; Mattu, Amal; Body, Richard

2017-06-01

Chest pain accounts for approximately 6% of all emergency department (ED) visits and is the most common reason for emergency hospital admission. One of the most serious diagnoses emergency physicians must consider is acute coronary syndrome (ACS). This is both common and serious, as ischemic heart disease remains the single biggest cause of death in the western world. The history and physical examination are cornerstones of our diagnostic approach in this patient group. Their importance is emphasized in guidelines, but there is little evidence to support their supposed association. The purpose of this article was to summarize the findings of recent investigations regarding the ability of various components of the history and physical examination to identify which patients presenting to the ED with chest pain require further investigation for possible ACS. Previous studies have consistently identified a number of factors that increase the probability of ACS. These include radiation of the pain, aggravation of the pain by exertion, vomiting, and diaphoresis. Traditional cardiac risk factors identified by the Framingham Heart Study are of limited diagnostic utility in the ED. Clinician gestalt has very low predictive ability, even in patients with a non-diagnostic electrocardiogram (ECG), and gestalt does not seem to be enhanced appreciably by clinical experience. The history and physical alone are unable to reduce a patient's risk of ACS to a generally acceptable level (<1%). Ultimately, our review of the evidence clearly demonstrates that "atypical" symptoms cannot rule out ACS, while "typical" symptoms cannot rule it in. Therefore, if a patient has symptoms that are compatible with ACS and an alternative cause cannot be identified, clinicians must strongly consider the need for further investigation with ECG and troponin measurement.

Self-Reported Stroke Risk Stratification: Reasons for Geographic and Racial Differences in Stroke Study.

PubMed

Howard, George; McClure, Leslie A; Moy, Claudia S; Howard, Virginia J; Judd, Suzanne E; Yuan, Ya; Long, D Leann; Muntner, Paul; Safford, Monika M; Kleindorfer, Dawn O

2017-07-01

The standard for stroke risk stratification is the Framingham Stroke Risk Function (FSRF), an equation requiring an examination for blood pressure assessment, venipuncture for glucose assessment, and ECG to determine atrial fibrillation and heart disease. We assess a self-reported stroke risk function (SRSRF) to stratify stroke risk in comparison to the FSRF. Participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) were evaluated at baseline and followed for incident stroke. The FSRF was calculated using directly assessed stroke risk factors. The SRSRF was calculated from 13 self-reported questions to exclude those with prevalent stroke and assess stroke risk. Proportional hazards analysis was used to assess incident stroke risk using the FSRF and SRSRF. Over an average 8.2-year follow-up, 939 of 23 983 participants had a stroke. The FSRF and SRSRF produced highly correlated risk scores ( r Spearman =0.852; 95% confidence interval, 0.849-0.856); however, the SRSRF had higher discrimination of stroke risk than the FSRF (c SRSRF =0.7266; 95% confidence interval, 0.7076-0.7457; c FSRF =0.7075; 95% confidence interval, 0.6877-0.7273; P =0.0038). The 10-year stroke risk in the highest decile of predicted risk was 11.1% for the FSRF and 13.4% for the SRSRF. A simple self-reported questionnaire can be used to identify those at high risk for stroke better than the gold standard FSRF. This instrument can be used clinically to easily identify individuals at high risk for stroke and also scientifically to identify a subpopulation enriched for stroke risk. © 2017 American Heart Association, Inc.

Microbiota-Dependent Marker TMAO Is Elevated in Silent Ischemia but Is Not Associated With First-Time Myocardial Infarction in HIV Infection.

PubMed

Haissman, Judith M; Knudsen, Andreas; Hoel, Hedda; Kjær, Andreas; Kristoffersen, Ulrik S; Berge, Rolf K; Katzenstein, Terese L; Svardal, Asbjørn; Ueland, Thor; Aukrust, Pål; Lebech, Anne-Mette; Nielsen, Susanne D; Trøseid, Marius

2016-02-01

HIV infection is associated with increased risk of coronary heart disease beyond that explained by traditional risk factors, and altered gut microbiota has been proposed as a potential trigger. Trimethylamine-N-oxide (TMAO) is a proatherogenic substance formed in the liver from trimethylamine, exclusively generated by gut microbiota from dietary phosphatidylcholine. We aimed to investigate whether TMAO is associated with subclinical and clinical coronary heart disease in HIV infection. Two previously described cohorts were examined as follows: (1) cross-sectional cohort of HIV-infected persons and uninfected controls with known atherosclerotic plaque burden as assessed by myocardial perfusion scintigraphy, coronary artery calcium score, and intima-media thickness and (2) nested case-control study of HIV-infected persons with first-time myocardial infarction (MI) compared with HIV-infected persons without MI, assessed at 4 time points from before initiation of antiretroviral therapy (ART) to last sample before the case's MI (median: 51, range: 0-239 days). There was no difference in plasma TMAO when comparing HIV-infected persons and uninfected controls. TMAO was elevated in HIV-infected persons with myocardial perfusion defects but was not associated with coronary artery calcium score, intima media thickness, or Framingham risk score. In the nested case control study, plasma TMAO was not associated with first-time MI. However, TMAO increased after ART introduction and was associated with the use of protease inhibitors in both cohorts. TMAO was elevated in HIV-infected persons with myocardial perfusion defects, but was not associated with first-time MI. Our data question TMAO as a useful biomarker of cardiovascular risk in HIV infection, at least in ART-treated individuals.

Prognosis of Adults with Borderline Left Ventricular Ejection Fraction

PubMed Central

Tsao, Connie W.; Lyass, Asya; Larson, Martin G.; Cheng, Susan; Lam, Carolyn S.P.; Aragam, Jayashri R.; Benjamin, Emelia J.; Vasan, Ramachandran S.

2016-01-01

Objectives To examine the association of borderline LVEF of 50-55% with cardiovascular morbidity and mortality in a community-based cohort. Background Guidelines stipulate left ventricular ejection fraction (LVEF) >55% as normal, but the optimal threshold, if any, remains uncertain. The prognosis of a “borderline” LVEF, 50-55%, is unknown. Methods We evaluated Framingham Heart Study participants who underwent echocardiography between 1979 and 2008 (n=10,270 person-observations, mean age 60 years, 57% women). Using pooled data with up to 12 years of follow-up and multivariable Cox regression, we evaluated the associations of borderline LVEF, and continuous LVEF to the risk of developing a composite outcome (heart failure [HF] or death; primary outcome) and incident HF (secondary outcome). Results During follow-up (median 7.9 years), 355 participants developed HF and 1070 died. Among participants with LVEF 50-55% (prevalence 3.5%), rates of the composite outcome and HF were 0.24 and 0.13 per 10 years follow-up, respectively, versus 0.16 and 0.05 in those having normal LVEF. In multivariable-adjusted analyses, LVEF 50-55% was associated with increased risk of the composite outcome (Hazards ratio [HR] 1.37, 95% CI 1.05-1.80) and HF (HR 2.15, 95% CI 1.41-3.28). There was a linear inverse relationship of continuous LVEF with the composite outcome (HR per 5 LVEF% decrement: 1.12, 95% CI 1.07-1.16) and HF (HR 1.23 per 5 LVEF% decrement, 95% CI 1.15-1.32). Conclusions Individuals with LVEF of 50-55% in the community have greater risk for morbidity and mortality relative to those with LVEF >55%. Additional studies are warranted to elucidate their optimal management. PMID:27256754

[New definition of metabolic syndrome: does it have the same cardiovascular risk?].

PubMed

Rodilla, E; González, C; Costa, J A; Pascual, J M

2007-02-01

The International Diabetes Federation (IDF) has recently published the new criteria for the diagnosis of metabolic syndrome. The aim of this study was to compare the clinical characteristics and cardiovascular risk of the new patients with MS compared to the previous National Cholesterol Education Program ATP III definition, its differential characteristics and cardiovascular risk. Cross sectional study in a hypertension clinic. Coronary risk was calculated (Framingham function NCEP-ATP III) and other cardiovascular markers, urinary albumin excretion (UAE in mg/24 hours) and high sensitivity C-reactive protein (CRP) were assessed. A total 2,404 patients were evaluated, 1,901 non-diabetic and 503 diabetic hypertensive subjects. The non-diabetics 726 (38.2%) had MS with the previous NCEP ATP-III definition, the number increasing sharply to 1,091 (57.4%) with the new IDF definition. The proportion did not increase in diabetics (93% vs. 92%). Concordance in the diagnosis was 78% in non-diabetics and 91% in diabetics. The new patients had a similar coronary risk (Framingham) but lower values of other cardiovascular markers: logUAE 1.00 (0.49) mg/24 hours vs. 1.06 (0.55) mg/24 hours (p = 0.003), and CRP 1.9 (2.7) mg/L vs. 2.5 (3.2) mg/L (median, interquartile range; p < 0.001). The new IDF definition of MS increases the number of patients with MS. The new patients have a similar coronary risk (Framingham) but the new parameters used to assess cardiovascular risk (UAE and CRP) were lower. The relationship of the new definition of MS and cardiovascular risk remains to be defined.

High plasma folate is negatively associated with leukocyte telomere length in Framingham Offspring cohort.

PubMed

Paul, Ligi; Jacques, Paul F; Aviv, Abraham; Vasan, Ramachandran S; D'Agostino, Ralph B; Levy, Daniel; Selhub, Jacob

2015-03-01

Shortening of telomeres, the protective structures at the ends of eukaryotic chromosomes, is associated with age-related pathologies. Telomere length is influenced by DNA integrity and DNA and histone methylation. Folate plays a role in providing precursors for nucleotides and methyl groups for methylation reactions and has the potential to influence telomere length. We determined the association between leukocyte telomere length and long-term plasma folate status (mean of 4 years) in Framingham Offspring Study (n = 1,044, females = 52.1 %, mean age 59 years) using data from samples collected before and after folic acid fortification. Leukocyte telomere length was determined by Southern analysis and fasting plasma folate concentration using microbiological assay. There was no significant positive association between long-term plasma folate and leukocyte telomere length among the Framingham Offspring Study participants perhaps due to their adequate folate status. While the leukocyte telomere length in the second quintile of plasma folate was longer than that in the first quintile, the difference was not statistically significant. The leukocyte telomere length of the individuals in the fifth quintile of plasma folate was shorter than that of those in the second quintile by 180 bp (P < 0.01). There was a linear decrease in leukocyte telomere length with higher plasma folate concentrations in the upper four quintiles of plasma folate (P for trend = 0.001). Multivitamin use was associated with shorter telomeres in this cohort (P = 0.015). High plasma folate status possibly resulting from high folic acid intake may interfere with the role of folate in maintaining telomere integrity.

Relationship between estimated cardiovascular disease risk and insulin resistance in a black African population living with HIV: a cross-sectional study from Cameroon.

PubMed

Noumegni, Steve Raoul; Bigna, Jean Joel; Ama Moor Epse Nkegoum, Vicky Jocelyne; Nansseu, Jobert Richie; Assah, Felix K; Jingi, Ahmadou Musa; Guewo-Fokeng, Magellan; Leumi, Steve; Katte, Jean-Claude; Dehayem, Mesmin Y; Mfeukeu Kuate, Liliane; Kengne, Andre Pascal; Sobngwi, Eugene

2017-08-11

Cardiovascular disease (CVD) and metabolic diseases are growing concerns among patients with HIV infection as a consequence of the improving survival of this population. We aimed to assess the relationship between CVD risk and insulin resistance in a group of black African individuals with HIV infection. This cross-sectional study involved patients with HIV infection aged 30-74 years and followed up at the Yaoundé Central Hospital, Cameroon. Absolute CVD risk was calculated using the Framingham and the DAD CVD risk equations while the HOMA-IR index was used to assess insulin resistance (index ≥2.1). A total of 452 patients (361 women; 80%) were screened. The mean age was 44.4 years and most of the respondents were on antiretroviral therapy (88.5%). The median 5-year cardiovascular risk was 0.7% (25th-75th percentiles: 0.2-2.0) and 0.6% (0.3-1.3) according to the Framingham and DAD equations respectively. Of all participants, 47.3% were insulin resistant. The Framingham equation derived absolute CVD risk was significantly associated with insulin resistance; while no linear association was found using the DAD equation. The relationship between cardiovascular risk and insulin resistance in black African patients with HIV infection seems to depend on the cardiovascular risk equation used. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sugary beverage intake and preclinical Alzheimer's disease in the community.

PubMed

Pase, Matthew P; Himali, Jayandra J; Jacques, Paul F; DeCarli, Charles; Satizabal, Claudia L; Aparicio, Hugo; Vasan, Ramachandran S; Beiser, Alexa S; Seshadri, Sudha

2017-09-01

Excess sugar consumption has been linked with Alzheimer's disease (AD) pathology in animal models. We examined the cross-sectional association of sugary beverage consumption with neuropsychological (N = 4276) and magnetic resonance imaging (N = 3846) markers of preclinical Alzheimer's disease and vascular brain injury (VBI) in the community-based Framingham Heart Study. Intake of sugary beverages was estimated using a food frequency questionnaire. Relative to consuming less than one sugary beverage per day, higher intake of sugary beverages was associated with lower total brain volume (1-2/day, β ± standard error [SE] = -0.55 ± 0.14 mean percent difference, P = .0002; >2/day, β ± SE = -0.68 ± 0.18, P < .0001), and poorer performance on tests of episodic memory (all P < .01). Daily fruit juice intake was associated with lower total brain volume, hippocampal volume, and poorer episodic memory (all P < .05). Sugary beverage intake was not associated with VBI in a consistent manner across outcomes. Higher intake of sugary beverages was associated cross-sectionally with markers of preclinical AD. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Mapping Quantitative Traits in Unselected Families: Algorithms and Examples

PubMed Central

Dupuis, Josée; Shi, Jianxin; Manning, Alisa K.; Benjamin, Emelia J.; Meigs, James B.; Cupples, L. Adrienne; Siegmund, David

2009-01-01

Linkage analysis has been widely used to identify from family data genetic variants influencing quantitative traits. Common approaches have both strengths and limitations. Likelihood ratio tests typically computed in variance component analysis can accommodate large families but are highly sensitive to departure from normality assumptions. Regression-based approaches are more robust but their use has primarily been restricted to nuclear families. In this paper, we develop methods for mapping quantitative traits in moderately large pedigrees. Our methods are based on the score statistic which in contrast to the likelihood ratio statistic, can use nonparametric estimators of variability to achieve robustness of the false positive rate against departures from the hypothesized phenotypic model. Because the score statistic is easier to calculate than the likelihood ratio statistic, our basic mapping methods utilize relatively simple computer code that performs statistical analysis on output from any program that computes estimates of identity-by-descent. This simplicity also permits development and evaluation of methods to deal with multivariate and ordinal phenotypes, and with gene-gene and gene-environment interaction. We demonstrate our methods on simulated data and on fasting insulin, a quantitative trait measured in the Framingham Heart Study. PMID:19278016

Cardiovascular disease risk in women with migraine

PubMed Central

2013-01-01

Background Studies suggest a higher prevalence of unfavourable cardiovascular risk factors amongst migraineurs, but results have been conflicting. The aim of this study was to investigate traditional and newly recognized risk factors as well as other surrogate markers of cardiovascular risk in obese and normal weight women with migraine. Methods Fifty-nine adult female probands participated in this case–control study. The sample was divided into normal weight and obese migraineurs and age- and body mass index-matched control groups. The following cardiovascular risk factors were analyzed: serum levels of lipids, fasting glucose, and insulin; insulin resistance; blood pressure; smoking (categorized as current, past or never); Framingham 10-year risk of general cardiovascular disease score; C-reactive protein; family history of cardiovascular disease; physical activity; sleep disturbances; depression; and bioelectrical impedance phase angle. The means of continuous variables were compared using Student’s t-test for independent samples or the Mann–Whitney U-test (for 2 groups) and ANOVA or the Kruskal-Wallis test (for 4 groups) depending on the distribution of data. Results All migraineurs were sedentary irrespective of nutritional status. Migraineurs had higher depression scores and shorter sleep duration, and obese migraineurs, in particular, had worse sleep quality scores. Insulin resistance and insulinaemia were associated with obesity, and obese migraineurs had lower HDL-c than normal weight controls and migraineurs. Also, the Framingham risk score was higher in obese migraineurs. Conclusion These findings suggest that female migraineurs experience marked inactivity, depression, and some sleep disturbance, that higher insulin resistance and insulinaemia are related to obesity, and that obesity and migraine probably exert overlapping effects on HDL-c levels and Framingham 10-year cardiovascular risk. PMID:24011175

Does present use of cardiovascular medication reflect elevated cardiovascular risk scores estimated ten years ago? A population based longitudinal observational study

PubMed Central

2011-01-01

Background It is desirable that those at highest risk of cardiovascular disease should have priority for preventive measures, eg. treatment with prescription drugs to modify their risk. We wanted to investigate to what extent present use of cardiovascular medication (CVM) correlates with cardiovascular risk estimated by three different risk scores (Framingham, SCORE and NORRISK) ten years ago. Methods Prospective logitudinal observational study of 20 252 participants in The Hordaland Health Study born 1950-57, not using CVM in 1997-99. Prescription data obtained from The Norwegian Prescription Database in 2008. Results 26% of men and 22% of women aged 51-58 years had started to use some CVM during the previous decade. As a group, persons using CVM scored significantly higher on the risk algorithms Framingham, SCORE and NORRISK compared to those not treated. 16-20% of men and 20-22% of women with risk scores below the high-risk thresholds for the three risk scores were treated with CVM, while 60-65% of men and 25-45% of women with scores above the high-risk thresholds received no treatment. Among women using CVM, only 2.2% (NORRISK), 4.4% (SCORE) and 14.5% (Framingham) had risk scores above the high-risk values. Low education, poor self-reported general health, muscular pains, mental distress (in females only) and a family history of premature cardiovascular disease correlated with use of CVM. Elevated blood pressure was the single factor most strongly predictive of CVM treatment. Conclusion Prescription of CVM to middle-aged individuals by large seems to occur independently of estimated total cardiovascular risk, and this applies especially to females. PMID:21366925

Cardiovascular risk according to educational status in India.

PubMed

Gupta, Rajeev; Kaul, Vijay; Agrawal, Aachu; Guptha, Soneil; Gupta, V P

2010-11-01

Influence of socioeconomic status on cardiovascular risk has not been well studied in low income countries. To determine risks in various educational status (ES) subjects we performed a study in India. Epidemiological study was performed in years 1999-2003 in Jaipur (India) for coronary risk factors among 1280 adults 20-59 years (men 619, women 661). ES was categorized into low (education ≤5 years); middle (6-12 years) and high (>12 years). Prevalence of risk factors and Framingham risk scores were determined. Low ES was in 306, middle in 436 and high in 538. In low, middle and high ES respectively age-adjusted prevalence (%) of smoking was 19.0, 19.3, and 11.7; obesity 9.5, 16.7, and 22.1, hypertension 15.3, 30.5, and 44.0; hypercholesterolemia ≥200mg/dl 46.0, 48.4, and 54.6; low HDL cholesterol <40mg/dl 46.4, 56.4, and 38.3; metabolic syndrome 20.9, 25.7, and 28.6; and diabetes 6.9, 5.5, and 26.4. Framingham risk score was 5.7±4.8, 6.3±5.7 and 4.7±5.1 and calculated cardiovascular risk probability 5.2±5.7, 6.8±7.8 and 5.2±6.0 (P(trend)<0.05). Framingham risk score was significantly greater in low and middle ES (6.1±5.3) compared to high (4.7±5.1) (p<0.001). Adjustment for smoking attenuated the risk. Low and middle educational status urban subjects in India have greater cardiovascular risk. Copyright © 2010 Elsevier Inc. All rights reserved.

Magnesium Intake Is Inversely Associated With Coronary Artery Calcification

PubMed Central

Hruby, Adela; O'Donnell, Christopher J.; Jacques, Paul F.; Meigs, James B.; Hoffmann, Udo; McKeown, Nicola M.

2014-01-01

OBJECTIVES The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying cardiovascular disease. Little is known about the association of magnesium intake and atherosclerotic calcification in humans. METHODS We examined cross-sectional associations of self-reported total (dietary and supplemental) magnesium intake estimated by food frequency questionnaire with CAC and AAC in participants of the Framingham Heart Study who were free of cardiovascular disease and underwent Multi-Detector Computed Tomography (MDCT) of the heart and abdomen (n = 2,695; age: 53 ± 11 years), using multivariate-adjusted Tobit regression. CAC and AAC were quantified using modified Agatston scores (AS). Models were adjusted for age, sex, body mass index, smoking status, systolic blood pressure, fasting insulin, total-to-high-density lipoprotein cholesterol ratio, use of hormone replacement therapy (women only), menopausal status (women only), treatment for hyperlipidemia, hypertension, cardiovascular disease prevention, or diabetes, as well as self-reported intake of calcium, vitamins D and K, saturated fat, fiber, alcohol, and energy. Secondary analyses included logistic regressions of CAC and AAC outcomes as cut-points (AS >0 and AS ≥90th percentile for age and sex), as well as sex-stratified analyses. RESULTS In fully adjusted models, a 50-mg/day increment in self-reported total magnesium intake was associated with 22% lower CAC (p < 0.001) and 12% lower AAC (p = 0.07). Consistent with these observations, the odds of having any CAC were 58% lower (p trend: <0.001) and any AAC were 34% lower (p trend: 0.01), in those with the highest compared to those with the lowest magnesium intake. Stronger inverse associations were observed in women than in men. CONCLUSIONS In community-dwelling participants free of cardiovascular disease, self-reported magnesium intake was inversely associated with arterial calcification, which may play a contributing role in magnesium's protective associations in stroke and fatal coronary heart disease. PMID:24290571

Statin underuse and low prevalence of LDL-C control among U.S. adults at high risk of coronary heart disease.

PubMed

Gamboa, Christopher M; Safford, Monika M; Levitan, Emily B; Mann, Devin M; Yun, Huifeng; Glasser, Stephen P; Woolley, J Michael; Rosenson, Robert; Farkouh, Michael; Muntner, Paul

2014-08-01

Statins reduce the risk of coronary heart disease (CHD) in individuals with a history of CHD or risk equivalents. A 10-year CHD risk >20% is considered a risk equivalent but is frequently not detected. Statin use and low-density lipoprotein cholesterol (LDL-C) control were examined among participants with CHD or risk equivalents in the nationwide Reasons for Geographic and Racial Differences in Stroke study (n = 8812). Participants were categorized into 4 mutually exclusive groups: (1) history of CHD (n = 4025); (2) no history of CHD but with a history of stroke and/or abdominal aortic aneurysm (AAA) (n = 946); (3) no history of CHD or stroke/AAA but with diabetes mellitus (n = 3134); or (4) no history of the conditions in (1) through (3) but with 10-year Framingham CHD risk score (FRS) >20% calculated using the third Adult Treatment Panel point scoring system (n = 707). Statins were used by 58.4% of those in the CHD group and 41.7%, 40.4% and 20.1% of those in the stroke/AAA, diabetes mellitus and FRS >20% groups, respectively. Among those taking statins, 65.1% had LDL-C <100 mg/dL, with no difference between the CHD, stroke/AAA, or diabetes mellitus groups. However, compared with those in the CHD group, LDL-C <100 mg/dL was less common among participants in the FRS >20% group (multivariable adjusted prevalence ratio: 0.72; 95% confidence interval: 0.62-0.85). Results were similar using the 2013 American College of Cardiology/American Heart Association cholesterol treatment guideline. These data suggest that many people with high CHD risk, especially those with an FRS >20%, do not receive guideline-concordant lipid-lowering therapy and do not achieve an LDL-C <100 mg/dL.

Right ventricular function in heart failure with preserved ejection fraction: a community-based study.

PubMed

Mohammed, Selma F; Hussain, Imad; AbouEzzeddine, Omar F; Abou Ezzeddine, Omar F; Takahama, Hiroyuki; Kwon, Susan H; Forfia, Paul; Roger, Véronique L; Redfield, Margaret M

2014-12-23

The prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved ejection fraction (HFpEF) are not well characterized. Consecutive, prospectively identified HFpEF (Framingham HF criteria, ejection fraction ≥50%) patients (n=562) from Olmsted County, Minnesota, underwent echocardiography at HF diagnosis and follow-up for cause-specific mortality and HF hospitalization. RV function was categorized by tertiles of tricuspid annular plane systolic excursion and by semiquantitative (normal, mild RVD, or moderate to severe RVD) 2-dimensional assessment. Whether RVD was defined by semiquantitative assessment or tricuspid annular plane systolic excursion ≤15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers, and chronic diuretic therapy. At echocardiography, patients with RVD had slightly lower left ventricular ejection fraction, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure, and more severe RV enlargement and tricuspid valve regurgitation. After adjustment for age, sex, pulmonary artery systolic pressure, and comorbidities, the presence of any RVD by semiquantitative assessment was associated with higher all-cause (hazard ratio=1.35; 95% confidence interval, 1.03-1.77; P=0.03) and cardiovascular (hazard ratio=1.85; 95% confidence interval, 1.20-2.80; P=0.006) mortality and higher first (hazard ratio=1.99; 95% confidence interval, 1.35-2.90; P=0.0006) and multiple (hazard ratio=1.81; 95% confidence interval, 1.18-2.78; P=0.007) HF hospitalization rates. RVD defined by tricuspid annular plane systolic excursion values showed similar but weaker associations with mortality and HF hospitalizations. In the community, RVD is common in HFpEF patients, is associated with clinical and echocardiographic evidence of more advanced HF, and is predictive of poorer outcomes. © 2014 American Heart Association, Inc.

Identification and Management of Pump Thrombus in the HeartWare Left Ventricular Assist Device System: A Novel Approach Using Log File Analysis.

PubMed

Jorde, Ulrich P; Aaronson, Keith D; Najjar, Samer S; Pagani, Francis D; Hayward, Christopher; Zimpfer, Daniel; Schlöglhofer, Thomas; Pham, Duc T; Goldstein, Daniel J; Leadley, Katrin; Chow, Ming-Jay; Brown, Michael C; Uriel, Nir

2015-11-01

The study sought to characterize patterns in the HeartWare (HeartWare Inc., Framingham, Massachusetts) ventricular assist device (HVAD) log files associated with successful medical treatment of device thrombosis. Device thrombosis is a serious adverse event for mechanical circulatory support devices and is often preceded by increased power consumption. Log files of the pump power are easily accessible on the bedside monitor of HVAD patients and may allow early diagnosis of device thrombosis. Furthermore, analysis of the log files may be able to predict the success rate of thrombolysis or the need for pump exchange. The log files of 15 ADVANCE trial patients (algorithm derivation cohort) with 16 pump thrombus events treated with tissue plasminogen activator (tPA) were assessed for changes in the absolute and rate of increase in power consumption. Successful thrombolysis was defined as a clinical resolution of pump thrombus including normalization of power consumption and improvement in biochemical markers of hemolysis. Significant differences in log file patterns between successful and unsuccessful thrombolysis treatments were verified in 43 patients with 53 pump thrombus events implanted outside of clinical trials (validation cohort). The overall success rate of tPA therapy was 57%. Successful treatments had significantly lower measures of percent of expected power (130.9% vs. 196.1%, p = 0.016) and rate of increase in power (0.61 vs. 2.87, p < 0.0001). Medical therapy was successful in 77.7% of the algorithm development cohort and 81.3% of the validation cohort when the rate of power increase and percent of expected power values were <1.25% and 200%, respectively. Log file parameters can potentially predict the likelihood of successful tPA treatments and if validated prospectively, could substantially alter the approach to thrombus management. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Early-Life Intelligence Predicts Midlife Biological Age

PubMed Central

Caspi, Avshalom; Belsky, Daniel W.; Harrington, Honalee; Houts, Renate; Israel, Salomon; Levine, Morgan E.; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Moffitt, Terrie E.

2016-01-01

Objectives: Early-life intelligence has been shown to predict multiple causes of death in populations around the world. This finding suggests that intelligence might influence mortality through its effects on a general process of physiological deterioration (i.e., individual variation in “biological age”). We examined whether intelligence could predict measures of aging at midlife before the onset of most age-related disease. Methods: We tested whether intelligence assessed in early childhood, middle childhood, and midlife predicted midlife biological age in members of the Dunedin Study, a population-representative birth cohort. Results: Lower intelligence predicted more advanced biological age at midlife as captured by perceived facial age, a 10-biomarker algorithm based on data from the National Health and Nutrition Examination Survey (NHANES), and Framingham heart age (r = 0.1–0.2). Correlations between intelligence and telomere length were less consistent. The associations between intelligence and biological age were not explained by differences in childhood health or parental socioeconomic status, and intelligence remained a significant predictor of biological age even when intelligence was assessed before Study members began their formal schooling. Discussion: These results suggest that accelerated aging may serve as one of the factors linking low early-life intelligence to increased rates of morbidity and mortality. PMID:26014827

Association between Epicondylitis and Cardiovascular Risk Factors in Pooled Occupational Cohorts.

PubMed

Hegmann, Kurt T; Thiese, Matthew S; Kapellusch, Jay; Merryweather, Andrew; Bao, Stephen; Silverstein, Barbara; Wood, Eric M; Kendall, Richard; Foster, James; Drury, David L; Garg, Arun

2017-05-30

The pathophysiology of lateral epicondylitis (LE) is unclear. Recent evidence suggests some common musculoskeletal disorders may have a basis in cardiovascular disease (CVD) risk factors. Thus, we examined CVD risks as potential LE risks. Workers (n = 1824) were enrolled in two large prospective studies and underwent structured interviews and physical examinations at baseline. Analysis of pooled baseline data assessed the relationships separately between a modified Framingham Heart Study CVD risk score and three prevalence outcomes of: 1) lateral elbow pain, 2) positive resisted wrist or middle finger extension, and 3) a combination of both symptoms and at least one resisted maneuver. Quantified job exposures, personal and psychosocial confounders were statistically controlled. Odds ratios (ORs) and 95% Confidence Intervals (CIs) were calculated. There was a strong relationship between CVD risk score and lateral elbow symptoms, resisted wrist or middle finger extension and LE after adjustment for confounders. The adjusted ORs for symptoms were as high as 3.81 (95% CI 2.11, 6.85), for positive examination with adjusted odds ratios as high as 2.85 (95% CI 1.59, 5.12) and for combined symptoms and physical examination 6.20 (95% CI 2.04, 18.82). Relationships trended higher with higher CVD risk scores. These data suggest a potentially modifiable disease mechanism for LE.

Job Strain and Cognitive Decline: A Prospective Study of the Framingham Offspring Cohort

PubMed Central

Agbenyikey, W; Karasek, R; Cifuentes, M; Wolf, PA; Seshadri, S; Taylor, JA; Beiser, AS; Au, R

2017-01-01

Background Workplace stress is known to be related with many behavioral and disease outcomes. However, little is known about its prospective relationship with measures of cognitive decline. Objective To investigate the association of job strain, psychological demands and job control on cognitive decline. Methods Participants from Framingham Offspring cohort (n=1429), were assessed on job strain, and received neuropsychological assessment approximately 15 years and 21 years afterwards. Results High job strain and low control were associated with decline in verbal learning and memory. Job strain was associated with decline in word recognition skills. Active job and passive job predicted decline in verbal learning and memory relative to low strain jobs in the younger subgroup. Active job and demands were positively associated with abstract reasoning skills. Conclusions Job strain and job control may infuence decline in cognitive performance. PMID:25890602

Dydrogesterone does not reverse the cardiovascular benefits of percutaneous estradiol.

PubMed

Kuba, V M; Teixeira, M A M; Meirelles, R M R; Assumpção, C R L; Costa, O S

2013-02-01

To evaluate the influence of dydrogesterone on estimated cardiovascular risk of users of hormone replacement therapy (HRT) (with percutaneous 17β-estradiol in monotherapy and in combination with dydrogesterone) and HRT non-users through the Framingham score tool for a period of 2 years. Framingham scores were calculated from the medical records of patients treated for at least 2 years with 17β-estradiol alone or in combination with dydrogesterone, along with HRT non-users, through the analysis of patient medical records, followed for at least 2 years at Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione. Improvements in lipid profile, glucose and blood pressure levels, which reduced the estimated cardiovascular risk, were observed in the 17β-estradiol group. Similar changes were observed in the users of 17β-estradiol + dydrogesterone, suggesting that this progestogen does not attenuate the effects caused by 17β-estradiol. Both HRT groups showed a reduction in their Framingham score. In contrast to data from other HRT investigations on cardiovascular risk, these formulations proved to be safe, even in the first year of use.

The Systolic Blood Pressure Difference Between Arms and Cardiovascular Disease in the Framingham Heart Study

PubMed Central

Weinberg, Ido; Gona, Philimon; O’Donnell, Christopher J.; Jaff, Michael R.; Murabito, Joanne M.

2014-01-01

Background An increased inter-arm systolic blood pressure difference is an easily determined physical examination finding. The relationship between inter-arm systolic blood pressure difference and risk of future cardiovascular disease is uncertain. We described the prevalence and risk factor correlates of inter-arm systolic blood pressure difference in the Framingham Heart Study (FHS) original and offspring cohorts and examined the association between inter-arm systolic blood pressure difference and incident cardiovascular disease and all-cause mortality. Methods An increased inter-arm systolic blood pressure difference was defined as ≥10mmHg using the average of initial and repeat blood pressure measurements obtained in both arms. Participants were followed through 2010 for incident cardiovascular disease events. Multivariable Cox proportional hazards regression analyses were performed to investigate the effect of inter-arm systolic blood pressure difference on incident cardiovascular disease. Results We examined 3,390 (56.3% female) participants aged 40 years and older, free of cardiovascular disease at baseline, mean age of 61.1 years, who attended a FHS examination between 1991 and 1994 (original cohort) and from 1995 to 1998 (offspring cohort). The mean absolute inter-arm systolic blood pressure difference was 4.6 mmHg (range 0 to 78). Increased inter-arm systolic blood pressure difference was present in 317 (9.4%) participants. The median follow-up time was 13.3 years, during which time 598 participants (17.6%) experienced a first cardiovascular event including 83 (26.2%) participants with inter-arm systolic blood pressure difference ≥10 mmHg. Compared to those with normal inter-arm systolic blood pressure difference, participants with an elevated inter-arm systolic blood pressure difference were older (63.0 years vs. 60.9 years), had a greater prevalence of diabetes mellitus (13.3% vs. 7.5%,), higher systolic blood pressure (136.3 mmHg vs. 129.3 mmHg), and a higher total cholesterol level (212.1 mg/dL vs. 206.5 mg/dL). Inter-arm systolic blood pressure difference was associated with a significantly increased hazard of incident cardiovascular events in the multivariable adjusted model (hazard ratio 1.38, 95% CI, 1.09 to 1.75). For each 1-standard deviation unit increase in absolute interarm systolic blood pressure difference, the hazard ratio for incident cardiovascular events was 1.07 (CI, 1.00 to 1.14) in the fully-adjusted model. There was no such association with mortality (hazard ratio 1.02, 95% CI 0.76 to 1.38). Conclusions In this community-based cohort, an inter-arm systolic blood pressure difference is common and associated with a significant increased risk for future cardiovascular events, even when the absolute difference in arm systolic blood pressure is modest. These findings support research to expand clinical use of this simple measurement. PMID:24287007

Prevalence of Heart Failure Signs and Symptoms in a Large Primary Care Population Identified Through the Use of Text and Data Mining of the Electronic Health Record

PubMed Central

Vijayakrishnan, Rajakrishnan; Steinhubl, Steven R.; Ng, Kenney; Sun, Jimeng; Byrd, Roy J.; Daar, Zahra; Williams, Brent A.; deFilippi, Christopher; Ebadollahi, Shahram; Stewart, Walter F.

2014-01-01

Background The electronic health record contains a tremendous amount of data that if appropriately detected can lead to earlier identification of disease states such as heart failure (HF). Using a novel text and data analytic tool we explored the longitudinal EHR of over 50,000 primary care patients to identify the documentation of the signs and symptoms of HF in the years preceding its diagnosis. Methods and Results Retrospective analysis consisting of 4,644 incident HF cases and 45,981 group-matched controls. Documentation of Framingham HF signs and symptoms within encounter notes were carried out using a previously validated natural language processing procedure. A total of 892,805 affirmed criteria were documented over an average observation period of 3.4 years. Among eventual HF cases, 85% had at least one criterion within a year prior to their HF diagnosis (as did 55% of controls). Substantial variability in the prevalence of individual signs and symptoms were found in both cases and controls. Conclusions HF signs and symptoms are frequently documented in a primary care population as identified through automated text and data mining of EHRs. Their frequent identification demonstrates the rich data available within EHRs that will allow for future work on automated criterion identification to help develop predictive models for HF. PMID:24709663

Advancing the Hypothesis that Geographic Variations in Risk Factors Contribute Relatively Little to Observed Geographic Variations in Heart Disease and Stroke Mortality

PubMed Central

Howard, George; Cushman, Mary; Prineas, Ronald J.; Howard, Virginia J.; Moy, Claudia S.; Sullivan, Lisa M.; D’Agostino, Ralph B.; McClure, Leslie A.; Pulley, Lea Vonne; Safford, Monika M.

2009-01-01

Purpose Geographic variation in risk factors may underlie geographic disparities in coronary heart disease (CHD) and stroke mortality. Methods Framingham CHD Risk Score (FCRS) and Stroke Risk Score (FSRS) were calculated for 25,770 stroke-free and 22,247 CHD-free participants from the REasons for Geographic And Racial Differences in Stroke cohort. Vital statistics provided age-adjusted CHD and stroke mortality rates. In an ecologic analysis, the age-adjusted, race-sex weighted, average state-level risk factor levels were compared to state-level mortality rates. Results There was no relationship between CHD and stroke mortality rates (r = 0.04; p = 0.78), but there was between CHD and stroke risk scores at the individual (r = 0.68; p < 0.0001) and state (r = 0.64, p < 0.0001) level. There was a stronger (p < 0.0001) association between state-level FCRS and state-level CHD mortality (r = 0.28, p = 0.18), than between FSRS and stroke mortality (r = 0.12, p = 0.56). Conclusions Weak associations between CHD and stroke mortality and strong associations between CHD and stroke risk scores suggest geographic variation in risk factors may not underlie geographic variations in stroke and CHD mortality. The relationship between risk factor scores and mortality was stronger for CHD than stroke. PMID:19285103

Framingham risk score for prediction of cardiovascular diseases: a population-based study from southern Europe.

PubMed

Artigao-Rodenas, Luis M; Carbayo-Herencia, Julio A; Divisón-Garrote, Juan A; Gil-Guillén, Vicente F; Massó-Orozco, Javier; Simarro-Rueda, Marta; Molina-Escribano, Francisca; Sanchis, Carlos; Carrión-Valero, Lucinio; López de Coca, Enrique; Caldevilla, David; López-Abril, Juan; Carratalá-Munuera, Concepción; Lopez-Pineda, Adriana

2013-01-01

The question about what risk function should be used in primary prevention remains unanswered. The Framingham Study proposed a new algorithm based on three key ideas: use of the four risk factors with the most weight (cholesterol, blood pressure, diabetes and smoking), prediction of overall cardiovascular diseases and incorporating the concept of vascular age. The objective of this study was to apply this new function in a cohort of the general non Anglo-Saxon population, with a 10-year follow-up to determine its validity. The cohort was studied in 1992-94 and again in 2004-06. The sample comprised 959 randomly-selected persons, aged 30-74 years, who were representative of the population of Albacete, Spain. At the first examination cycle, needed data for the new function were collected and at the second examination, data on all events were recorded during the follow-up period. Discrimination was studied with ROC curves. Comparisons of prediction models and reality in tertiles (Hosmer-Lemeshow) were performed, and the individual survival functions were calculated. The mean risks for women and men, respectively, were 11.3% and 19.7% and the areas under the ROC curve were 0.789 (95%CI, 0.716-0.863) and 0.780 (95%CI, 0.713-0.847) (P<0.001, both). Cardiovascular disease events occurred in the top risk tertiles. Of note were the negative predictive values in both sexes, and a good specificity in women (85.6%) and sensitivity in men (79.1%) when their risk for cardiovascular disease was high. This model overestimates the risk in older women and in middle-aged men. The cumulative probability of individual survival by tertiles was significant in both sexes (P<0.001). The results support the proposal for "reclassification" of Framingham. This study, with a few exceptions, passed the test of discrimination and calibration in a random sample of the general population from southern Europe.

Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations

PubMed Central

Chen, Brian H.; Hivert, Marie-France; Peters, Marjolein J.; Pilling, Luke C.; Hogan, John D.; Pham, Lisa M.; Harries, Lorna W.; Fox, Caroline S.; Bandinelli, Stefania; Dehghan, Abbas; Hernandez, Dena G.; Hofman, Albert; Hong, Jaeyoung; Joehanes, Roby; Johnson, Andrew D.; Munson, Peter J.; Rybin, Denis V.; Singleton, Andrew B.; Uitterlinden, André G.; Ying, Saixia; Melzer, David; Levy, Daniel; van Meurs, Joyce B.J.; Ferrucci, Luigi; Florez, Jose C.; Dupuis, Josée

2016-01-01

Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q <0.05, we identified three transcripts associated with fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes–imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis. PMID:27625022

The prevalence of cardiovascular disease risk factors and the Framingham Risk Score in patients undergoing percutaneous intervention over the last 17 years by gender: time-trend analysis from the Mayo Clinic PCI Registry.

PubMed

Lee, Moo-Sik; Flammer, Andreas J; Kim, Hyun-Soo; Hong, Jee-Young; Li, Jing; Lennon, Ryan J; Lerman, Amir

2014-07-01

This study aims to investigate trends of cardiovascular disease (CVD) risk factor profiles over 17 years in percutaneous coronary intervention (PCI) patients at the Mayo Clinic. We performed a time-trend analysis within the Mayo Clinic PCI Registry from 1994 to 2010. Results were the incidence and prevalence of CVD risk factors as estimate by the Framingham risk score. Between 1994 and 2010, 25 519 patients underwent a PCI. During the time assessed, the mean age at PCI became older, but the gender distribution did not change. A significant trend towards higher body mass index and more prevalent hypercholesterolemia, hypertension, and diabetes was found over time. The prevalence of current smokers remained unchanged. The prevalence of ever-smokers decreased among males, but increased among females. However, overall CVD risk according to the Framingham risk score (FRS) and 10-year CVD risk significantly decreased. The use of most of medications elevated from 1994 to 2010, except for β-blockers and angiotensin converting enzyme inhibitors decreased after 2007 and 2006 in both baseline and discharge, respectively. Most of the major risk factors improved and the FRS and 10-year CVD risk declined in this population of PCI patients. However, obesity, history of hypercholesterolemia, hypertension, diabetes, and medication use increased substantially. Improvements to blood pressure and lipid profile management because of medication use may have influenced the positive trends. This study aims to investigate trends of cardiovascular disease (CVD) risk factor profiles over 17 years in percutaneous coronary intervention (PCI) patients at the Mayo Clinic. We performed a time-trend analysis within the Mayo Clinic PCI Registry from 1994 to 2010. Results were the incidence and prevalence of CVD risk factors as estimate by the Framingham risk score. Between 1994 and 2010, 25 519 patients underwent a PCI. During the time assessed, the mean age at PCI became older, but the gender distribution did not change. A significant trend towards higher body mass index and more prevalent hypercholesterolemia, hypertension, and diabetes was found over time. The prevalence of current smokers remained unchanged. The prevalence of ever-smokers decreased among males, but increased among females. However, overall CVD risk according to the Framingham risk score (FRS) and 10-year CVD risk significantly decreased. The use of most of medications elevated from 1994 to 2010, except for β-blockers and angiotensin converting enzyme inhibitors decreased after 2007 and 2006 in both baseline and discharge, respectively. Most of the major risk factors improved and the FRS and 10-year CVD risk declined in this population of PCI patients. However, obesity, history of hypercholesterolemia, hypertension, diabetes, and medication use increased substantially. Improvements to blood pressure and lipid profile management because of medication use may have influenced the positive trends.

Heritability, linkage, and genetic associations of exercise treadmill test responses.

PubMed

Ingelsson, Erik; Larson, Martin G; Vasan, Ramachandran S; O'Donnell, Christopher J; Yin, Xiaoyan; Hirschhorn, Joel N; Newton-Cheh, Christopher; Drake, Jared A; Musone, Stacey L; Heard-Costa, Nancy L; Benjamin, Emelia J; Levy, Daniel; Atwood, Larry D; Wang, Thomas J; Kathiresan, Sekar

2007-06-12

The blood pressure (BP) and heart rate responses to exercise treadmill testing predict incidence of cardiovascular disease, but the genetic determinants of hemodynamic and chronotropic responses to exercise are largely unknown. We assessed systolic BP, diastolic BP, and heart rate during the second stage of the Bruce protocol and at the third minute of recovery in 2982 Framingham Offspring participants (mean age 43 years; 53% women). With use of residuals from multivariable models adjusted for clinical correlates of exercise treadmill testing responses, we estimated the heritability (variance-components methods), genetic linkage (multipoint quantitative trait analyses), and association with 235 single-nucleotide polymorphisms in 14 candidate genes selected a priori from neurohormonal pathways for their potential role in exercise treadmill testing responses. Heritability estimates for heart rate during exercise and during recovery were 0.32 and 0.34, respectively. Heritability estimates for BP variables during exercise were 0.25 and 0.26 (systolic and diastolic BP) and during recovery, 0.16 and 0.13 (systolic and diastolic BP), respectively. Suggestive linkage was found for systolic BP during recovery from exercise (locus 1q43-44, log-of-the-odds score 2.59) and diastolic BP during recovery from exercise (locus 4p15.3, log-of-the-odds score 2.37). Among 235 single-nucleotide polymorphisms tested for association with exercise treadmill testing responses, the minimum nominal probability value was 0.003, which was nonsignificant after adjustment for multiple testing. Hemodynamic and chronotropic responses to exercise are heritable and demonstrate suggestive linkage to select loci. Genetic mapping with newer approaches such as genome-wide association may yield novel insights into the physiological responses to exercise.

[Clinical examination and the Valsalva maneuver in heart failure].

PubMed

Liniado, Guillermo E; Beck, Martín A; Gimeno, Graciela M; González, Ana L; Cianciulli, Tomás F; Castiello, Gustavo G; Gagliardi, Juan A

2018-01-01

Congestion in heart failure patients with reduced ejection fraction (HFrEF) is relevant and closely linked to the clinical course. Bedside blood pressure measurement during the Valsalva maneuver (Val) added to clinical examination may improve the assessment of congestion when compared to NT-proBNP levels and left atrial pressure (LAP) estimation by Doppler echocardiography, as surrogate markers of congestion in HFrEF. A clinical examination, LAP and blood tests were performed in 69 HFrEF ambulatory patients with left ventricular ejection fraction ≤ 40% and sinus rhythm. Framingham Heart Failure Score (HFS) was used to evaluate clinical congestion; Val was classified as normal or abnormal, NT-proBNP was classified as low (< 1000 pg/ml) or high (≥ 1000 pg/ml) and the ratio between Doppler early mitral inflow and tissue diastolic velocity was used to estimate LAP and was classified as low (E/e'< 15) or high (E/e' ≥ 15). A total of 69 patients with HFrEF were included; 27 had a HFS ≥ 2 and 13 of them had high NT-proBNP. HFS ≥ 2 had a 62% sensitivity, 70% specificity and a positive likelihood ratio of 2.08 (p=0.01) to detect congestion. When Val was added to clinical examination, the presence of a HFS ≥ 2 and abnormal Val showed a 100% sensitivity, 64% specificity and a positive likelihood ratio of 2.8 (p = 0.0004). Compared with LAP, the presence of HFS = 2 and abnormal Val had 86% sensitivity, 54% specificity and a positive likelihood ratio of 1.86 (p = 0.03). In conclusion, an integrated clinical examination with the addition Valsalva maneuver may improve the assessment of congestion in patients with HFrEF.

Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population.

PubMed

Gómez, Miquel; Vila, Joan; Elosua, Roberto; Molina, Lluís; Bruguera, Jordi; Sala, Joan; Masià, Rafel; Covas, Maria Isabel; Marrugat, Jaume; Fitó, Montserrat

2014-01-01

To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population. Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants. End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index <0.9 were considered indicators of subclinical atherosclerosis. Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02-2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles). OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Phylloquinone and vitamin D status: associations with incident chronic kidney disease in the Framingham Offspring Cohort

USDA-ARS?s Scientific Manuscript database

Cardiovascular risk factors are associated with the development of chronic kidney disease (CKD), and CKD and vascular disease are etiologically linked. Evidence suggests deficiencies of vitamins D and K may adversely affect the cardiovascular system, but data from longitudinal studies are lacking. W...

Sex specific differences in the predictive value of cholesterol homeostasis markers and 10-Year CVD event rate in Framingham Offspring Study participants

USDA-ARS?s Scientific Manuscript database

Available data are inconsistent on factors influencing plasma cholesterol homeostasis marker concentrations and their value in predicting subsequent cardiovascular disease (CVD) events. To address this issue the relationship between markers of cholesterol absorption (campesterol, sitosterol, cholest...

Carbohydrate nutrition and risk of adiposity-related cancers: results from the Framingham Offspring cohort (1991-2013)

USDA-ARS?s Scientific Manuscript database

High carbohydrate intake, glycemic index (GI), and glycemic load (GL) are hypothesized to increase cancer risk through metabolic dysregulation of the glucose-insulin axis and adiposity-related mechanisms, but epidemiologic evidence is inconsistent. This prospective cohort study investigates the impa...

Dietary flavonoid intakes and cardiovascular disease incidence in the Framingham Offspring Cohort

USDA-ARS?s Scientific Manuscript database

This study examines the relationship between long-term intake of six flavonoid classes and incidence of CVD and CHD, using a comprehensive flavonoid database and repeated measures of intake, while accounting for possible confounding by components of a healthy dietary pattern. Flavonoid intakes were ...

Left ventricular hypertrophy by ECG versus cardiac MRI as a predictor for heart failure.

PubMed

Oseni, Abdullahi O; Qureshi, Waqas T; Almahmoud, Mohamed F; Bertoni, Alain G; Bluemke, David A; Hundley, William G; Lima, Joao A C; Herrington, David M; Soliman, Elsayed Z

2017-01-01

To determine if there is a significant difference in the predictive abilities of left ventricular hypertrophy (LVH) detected by ECG-LVH versus LVH ascertained by cardiac MRI-LVH in a model similar to the Framingham Heart Failure Risk Score (FHFRS). This study included 4745 (mean age 61±10 years, 53.5% women, 61.7% non-whites) participants in the Multi-Ethnic Study of Atherosclerosis. ECG-LVH was defined using Cornell voltage product while MRI-LVH was derived from left ventricular mass. Cox proportional hazard regression was used to examine the association between ECG-LVH and MRI-LVH with incident heart failure (HF). Harrell's concordance C-index was used to estimate the predictive ability of the model when either ECG-LVH or MRI-LVH was included as one of its components. ECG-LVH was present in 291 (6.1%), while MRI-LVH was present in 499 (10.5%) of the participants. Both ECG-LVH (HR 2.25, 95% CI 1.38 to 3.69) and MRI-LVH (HR 3.80, 95% CI 1.56 to 5.63) were predictive of HF. The absolute risk of developing HF was 8.81% for MRI-LVH versus 2.26% for absence of MRI-LVH with a relative risk of 3.9. With ECG-LVH, the absolute risk of developing HF 6.87% compared with 2.69% for absence of ECG-LVH with a relative risk of 2.55. The ability of the model to predict HF was better with MRI-LVH (C-index 0.871, 95% CI 0.842 to 0.899) than with ECG-LVH (C-index 0.860, 95% CI 0.833 to 0.888) (p<0.0001). ECG-LVH and MRI-LVH are predictive of HF. Substituting MRI-LVH for ECG-LVH improves the predictive ability of a model similar to the FHFRS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effect of ziprasidone on metabolic syndrome risk factors in subjects with schizophrenia: a 1 year, open-label, prospective study.

PubMed

Chue, Pierre; Mandel, Francine S; Therrien, François

2014-06-01

Metabolic syndrome (MetS) is prevalent in subjects with schizophrenia-related psychotic disorders and contributes to increased rates of premature death due to cardiovascular disease. This study examined the impact of switching from another antipsychotic to ziprasidone on the distribution of the number of risk factors for MetS in subjects with schizophrenia or related psychotic disorders. In this 1 year, open-label, prospective study, all subjects received ziprasidone 40-160 mg/day. Standard exclusion criteria included treatment resistance, physical health disorders, and substance abuse. The primary end point was the percentage of subjects achieving a reduction from baseline of at least one risk factor for MetS at end point (week 52 or premature discontinuation) in the per-protocol population (treated for at least 16 weeks). Secondary end points included the mean change from baseline in number of MetS risk factors, the prevalence of MetS, individual MetS risk factors (waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and glucose), and 10 year coronary heart disease (Framingham score) risk. www.clinicaltrials.gov: NCT00748566. Of 114 evaluable subjects, 58.77% demonstrated one less MetS risk factor at week 52 (last observation carried forward) compared with baseline. Secondary end points also improved, with reductions in other metabolic parameters (fasting low-density lipoprotein cholesterol, total cholesterol and serum insulin, weight, body mass index and glycosylated hemoglobin [HbA1c]). The 10 year coronary heart disease risk decreased continually over time. The open-label and uncontrolled design is a limitation of the study. Ziprasidone treatment reduced both the rate of MetS and its individual risk factors in subjects with schizophrenia and related psychotic disorders. The results have implications for the selection of first-line treatments in schizophrenia and related psychotic disorders, and provide treatment options for subjects who have developed MetS as a result of other antipsychotics.

TSLP Polymorphisms are Associated with Asthma in a Sex-Specific Fashion

PubMed Central

Hunninghake, Gary M.; Soto-Quirós, Manuel E.; Avila, Lydiana; Kim, Hong P.; Lasky-Su, Jessica; Rafaels, Nicholas; Ruczinski, Ingo; Beaty, Terry H.; Mathias, Rasika A.; Barnes, Kathleen C.; Wilk, Jemma B.; O’Connor, George T.; Gauderman, W. James; Vora, Hita; Baurley, James W.; Gilliland, Frank; Liang, Catherine; Sylvia, Jody S.; Klanderman, Barbara J.; Sharma, Sunita S.; Himes, Blanca E.; Bossley, Cara J.; Israel, Elliot; Raby, Benjamin A.; Bush, Andrew; Choi, Augustine M.; Weiss, Scott T.; Celedón, Juan C.

2010-01-01

Background Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. Methods We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of asthmatic children in Costa Rica. Significant findings were replicated in white and African-American participants in the Childhood Asthma Management Program, in African Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children’s Health Study, and in whites in the Framingham Heart Study (FHS). Main Results Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (p values of 2×10−5 and 1×10−5, respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (p= 3×10−6). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (p= 2×10−4). Findings for rs2289276 were consistent in all cohorts except the FHS. Conclusions TSLP variants are associated with asthma in a sex-specific fashion. PMID:20560908

2-Aminoadipic acid is a biomarker for diabetes risk

PubMed Central

Wang, Thomas J.; Ngo, Debby; Psychogios, Nikolaos; Dejam, Andre; Larson, Martin G.; Vasan, Ramachandran S.; Ghorbani, Anahita; O’Sullivan, John; Cheng, Susan; Rhee, Eugene P.; Sinha, Sumita; McCabe, Elizabeth; Fox, Caroline S.; O’Donnell, Christopher J.; Ho, Jennifer E.; Florez, Jose C.; Magnusson, Martin; Pierce, Kerry A.; Souza, Amanda L.; Yu, Yi; Carter, Christian; Light, Peter E.; Melander, Olle; Clish, Clary B.; Gerszten, Robert E.

2013-01-01

Improvements in metabolite-profiling techniques are providing increased breadth of coverage of the human metabolome and may highlight biomarkers and pathways in common diseases such as diabetes. Using a metabolomics platform that analyzes intermediary organic acids, purines, pyrimidines, and other compounds, we performed a nested case-control study of 188 individuals who developed diabetes and 188 propensity-matched controls from 2,422 normoglycemic participants followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic acid (2-AAA) was most strongly associated with the risk of developing diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a 4-fold risk of developing diabetes. Levels of 2-AAA were not well correlated with other metabolite biomarkers of diabetes, such as branched chain amino acids and aromatic amino acids, suggesting they report on a distinct pathophysiological pathway. In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic β cell line as well as murine and human islets. These data highlight a metabolite not previously associated with diabetes risk that is increased up to 12 years before the onset of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk and a potential modulator of glucose homeostasis in humans. PMID:24091325

TSLP polymorphisms are associated with asthma in a sex-specific fashion.

PubMed

Hunninghake, G M; Soto-Quirós, M E; Avila, L; Kim, H P; Lasky-Su, J; Rafaels, N; Ruczinski, I; Beaty, T H; Mathias, R A; Barnes, K C; Wilk, J B; O'Connor, G T; Gauderman, W James; Vora, H; Baurley, J W; Gilliland, F; Liang, C; Sylvia, J S; Klanderman, B J; Sharma, S S; Himes, B E; Bossley, C J; Israel, E; Raby, B A; Bush, A; Choi, A M; Weiss, S T; Celedón, J C

2010-12-01

Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African-American participants in the Childhood Asthma Management Program, in African-Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS). Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 × 10(-5) and 1 × 10(-5) , respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 × 10(-6) ). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 × 10(-4) ). Findings for rs2289276 were consistent in all cohorts except the FHS. TSLP variants are associated with asthma in a sex-specific fashion. © 2010 John Wiley & Sons A/S.

2-Aminoadipic acid is a biomarker for diabetes risk.

PubMed

Wang, Thomas J; Ngo, Debby; Psychogios, Nikolaos; Dejam, Andre; Larson, Martin G; Vasan, Ramachandran S; Ghorbani, Anahita; O'Sullivan, John; Cheng, Susan; Rhee, Eugene P; Sinha, Sumita; McCabe, Elizabeth; Fox, Caroline S; O'Donnell, Christopher J; Ho, Jennifer E; Florez, Jose C; Magnusson, Martin; Pierce, Kerry A; Souza, Amanda L; Yu, Yi; Carter, Christian; Light, Peter E; Melander, Olle; Clish, Clary B; Gerszten, Robert E

2013-10-01

Improvements in metabolite-profiling techniques are providing increased breadth of coverage of the human metabolome and may highlight biomarkers and pathways in common diseases such as diabetes. Using a metabolomics platform that analyzes intermediary organic acids, purines, pyrimidines, and other compounds, we performed a nested case-control study of 188 individuals who developed diabetes and 188 propensity-matched controls from 2,422 normoglycemic participants followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic acid (2-AAA) was most strongly associated with the risk of developing diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a 4-fold risk of developing diabetes. Levels of 2-AAA were not well correlated with other metabolite biomarkers of diabetes, such as branched chain amino acids and aromatic amino acids, suggesting they report on a distinct pathophysiological pathway. In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic β cell line as well as murine and human islets. These data highlight a metabolite not previously associated with diabetes risk that is increased up to 12 years before the onset of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk and a potential modulator of glucose homeostasis in humans.

Individual and spousal unemployment as predictors of smoking and drinking behavior.

PubMed

Arcaya, Mariana; Glymour, M Maria; Christakis, Nicholas A; Kawachi, Ichiro; Subramanian, S V

2014-06-01

The effects of unemployment on health behaviors, and substance use in particular, is still unclear despite substantial existing research. This study aimed to assess the effects of individual and spousal unemployment on smoking and alcohol consumption. The study was based on eight waves of geocoded Framingham Heart Study Offspring Cohort data (US) from 1971 to 2008 that contained social network information. We fit three series of models to assess whether lagged 1) unemployment, and 2) spousal unemployment predicted odds of being a current smoker or drinks consumed per week, adjusting for a range of socioeconomic and demographic covariates. Compared with employment, unemployment was associated with nearly twice the subsequent odds of smoking, and with increased cigarette consumption among male, but not female, smokers. In contrast, unemployment predicted a one drink reduction in weekly alcohol consumption, though effects varied according to intensity of consumption, and appeared stronger among women. While spousal unemployment had no effect on substance use behaviors among men, wives responded to husbands' unemployment by reducing their alcohol consumption. We conclude that individual, and among women, spousal unemployment predicted changes in substance use behaviors, and that the direction of the change was substance-dependent. Complex interactions among employment status, sex, and intensity and type of consumption appear to be at play and should be investigated further. Copyright © 2014 Elsevier Ltd. All rights reserved.

Study of Health Outcomes in School Children: Key Challenges and Lessons Learned from the Framingham Schools' Natural History of Nevi Study

ERIC Educational Resources Information Center

Geller, Alan C.; Oliveria, Susan A.; Bishop, Marilyn; Buckminster, Marcia; Brooks, Katie R.; Halpern, Allan C.

2007-01-01

Background: We describe the planning, recruitment, key challenges, and lessons learned in the development of a study of the evolution of nevi (moles) among children in a school setting. Methods: This population-based study of digital photography and dermoscopy of the child's back (overview, close-up, and dermoscopic images) and genetic specimens…

The factor-of-risk biomechanical approach predicts hip fracture in men and women: the Framingham Study.

PubMed

Dufour, A B; Roberts, B; Broe, K E; Kiel, D P; Bouxsein, M L; Hannan, M T

2012-02-01

We examined the relation between a biomechanical measure, factor-of-risk, and hip fracture risk in 1,100 men and women from the Framingham Study and found that it predicted hip fracture (men, ORs of 1.8; women, 1.2-1.4). Alternative methods of predicting hip fracture are needed since 50% of adults who fracture do not have osteoporosis by bone mineral density (BMD) measurements. One method, factor-of-risk (Φ), computes the ratio of force on the hip in a fall to femoral strength. We examined the relation between Φ and hip fracture in 1,100 subjects from the Framingham Study with measured hip BMD, along with weight, height, and age, collected in 1988-1989. We estimated both peak and attenuated force applied to the hip in a sideways fall from standing height, where attenuated force incorporated cushioning effects of trochanteric soft tissue. Femoral strength was estimated from femoral neck BMD, using cadaveric femoral strength data. Sex-specific, age-adjusted survival models were used to calculate hazard ratios (HR) and 95% confidence intervals for the relation between Φ (peak), Φ (attenuated), and their components with hip fracture. In 425 men and 675 women (mean age, 76 years), 136 hip fractures occurred over median follow-up of 11.3 years. Factor-of-risk, Φ, was associated with increased age-adjusted risk for hip fracture. One standard deviation increase in Φ (peak) and Φ (attenuated) was associated with HR of 1.88 and 1.78 in men and 1.23 and 1.41 in women, respectively. Examining components of Φ, in women, we found fall force and soft tissue thickness were predictive of hip fracture independent of femoral strength (was estimated from BMD). Thus, both Φ (peak) and Φ (attenuated) predict hip fracture in men and women. These findings suggest additional studies of Φ predicting hip fracture using direct measurements of trochanteric soft tissue.

Foot Function, Foot Pain, and Falls in Older Adults: The Framingham Foot Study.

PubMed

Awale, Arunima; Hagedorn, Thomas J; Dufour, Alyssa B; Menz, Hylton B; Casey, Virginia A; Hannan, Marian T

2017-01-01

Although foot pain has been linked to fall risk, contributions of pain severity, foot posture, or foot function are unclear. These factors were examined in a cohort of older adults. The purpose of this study was to examine the associations of foot pain, severity of foot pain, and measures of foot posture and dynamic foot function with reported falls in a large, well-described cohort of older adults from the Framingham Foot Study. Foot pain, posture, and function were collected from Framingham Foot Study participants who were queried about falls over the past year (0, 1, and ≥2 falls). Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of falls with foot pain, pain severity, foot posture, and foot function adjusting for covariates. The mean age of the 1,375 participants was 69 years; 57% were female, and 21% reported foot pain (40% mild pain, 47% moderate pain, and 13% severe pain). One-third reported falls in the past year (1 fall: n = 263, ≥2 falls: n = 152). Foot pain was associated with a 62% increased odds of recurrent falls. Those with moderate and severe foot pain showed increased odds of ≥2 falls (OR 1.78, CI 1.06-2.99, and OR 3.25, CI 1.65-7.48, respectively) compared to those with no foot pain. Foot function was not associated with falls. Compared to normal foot posture, those with planus foot posture had 78% higher odds of ≥2 falls. Higher odds of recurrent falls were observed in individuals with foot pain, especially severe foot pain, as well as in individuals with planus foot posture, indicating that both foot pain and foot posture may play a role in increasing the risk of falls among older adults. © 2017 S. Karger AG, Basel.

Graphical assessment of incremental value of novel markers in prediction models: From statistical to decision analytical perspectives.

PubMed

Steyerberg, Ewout W; Vedder, Moniek M; Leening, Maarten J G; Postmus, Douwe; D'Agostino, Ralph B; Van Calster, Ben; Pencina, Michael J

2015-07-01

New markers may improve prediction of diagnostic and prognostic outcomes. We aimed to review options for graphical display and summary measures to assess the predictive value of markers over standard, readily available predictors. We illustrated various approaches using previously published data on 3264 participants from the Framingham Heart Study, where 183 developed coronary heart disease (10-year risk 5.6%). We considered performance measures for the incremental value of adding HDL cholesterol to a prediction model. An initial assessment may consider statistical significance (HR = 0.65, 95% confidence interval 0.53 to 0.80; likelihood ratio p < 0.001), and distributions of predicted risks (densities or box plots) with various summary measures. A range of decision thresholds is considered in predictiveness and receiver operating characteristic curves, where the area under the curve (AUC) increased from 0.762 to 0.774 by adding HDL. We can furthermore focus on reclassification of participants with and without an event in a reclassification graph, with the continuous net reclassification improvement (NRI) as a summary measure. When we focus on one particular decision threshold, the changes in sensitivity and specificity are central. We propose a net reclassification risk graph, which allows us to focus on the number of reclassified persons and their event rates. Summary measures include the binary AUC, the two-category NRI, and decision analytic variants such as the net benefit (NB). Various graphs and summary measures can be used to assess the incremental predictive value of a marker. Important insights for impact on decision making are provided by a simple graph for the net reclassification risk. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cost-effectiveness of optimizing prevention in patients with coronary heart disease: the EUROASPIRE III health economics project.

PubMed

De Smedt, Delphine; Kotseva, Kornelia; De Bacquer, Dirk; Wood, David; De Backer, Guy; Dallongeville, Jean; Seppo, Lehto; Pajak, Andrzej; Reiner, Zeljko; Vanuzzo, Diego; Georgiev, Borislav; Gotcheva, Nina; Annemans, Lieven

2012-11-01

The EUROASPIRE III survey indicated that the guidelines on cardiovascular disease prevention are poorly implemented in patients with established coronary heart disease (CHD). The purpose of this health economic project was to assess the potential clinical effectiveness and cost-effectiveness of optimizing cardiovascular prevention in eight EUROASPIRE III countries (Belgium, Bulgaria, Croatia, Finland, France, Italy, Poland, and the U.K.). METHODS AND RESULTS The individual risk for subsequent cardiovascular events was estimated, based on published Framingham equations. Based on the EUROASPIRE III data, the type of suboptimal prevention, if any, was identified for each individual, and the effects of optimized tailored prevention (smoking cessation, diet and exercise, better management of elevated blood pressure and/or LDL-cholesterol) were estimated. Costs of prevention and savings of avoided events were based on country-specific data. A willingness to pay threshold of €30,000/quality-adjusted life year (QALY) was used. The robustness of the results was validated by sensitivity analyses. Overall, the cost-effectiveness analyses for the eight countries showed mainly favourable results with an average incremental cost-effectiveness ratio (ICER) of €12,484 per QALY. Only in the minority of patients at the lowest risk for recurrent events, intensifying preventive therapy seems not cost-effective. Also, the single impact of intensified cholesterol control seems less cost-effective, possibly because their initial 2-year risk was already fairly low, hence the room for improvement is rather limited. These results underscore the societal value of optimizing prevention in most patients with established CHD, but also highlight the need for setting priorities towards patients more at risk and the need for more studies comparing intensified prevention with usual care in these patients.

Economic analysis of Heart and Stroke Foundation of Ontario's Hypertension Management Initiative.

PubMed

de Oliveira, Claire; Wijeysundera, Harindra C; Tobe, Sheldon W; Lum-Kwong, Margaret Moy; Von Sychowski, Shirley; Wang, Xuesong; Tu, Jack V; Krahn, Murray D

2012-01-01

Hypertension is suboptimally treated in primary care settings. We evaluated the cost-effectiveness of the Heart and Stroke Foundation of Ontario's Hypertension Management Initiative (HMI), an interdisciplinary, evidence-informed chronic disease management model for primary care that focuses on improving blood pressure management and control by primary care providers and patients according to clinical best practice guidelines. The perspective of our analysis was that of the Ontario Ministry of Health and Long-Term Care with a lifetime horizon and 5% annual discount rate. Using data from a prospective cohort study from the HMI, we created two matched groups: pre-HMI (standard care), and post-HMI (n = 1720). For each patient, we estimated the 10-year risk of cardiovascular disease (CVD) using the Framingham risk equation and life expectancy from life tables. Long-term health care costs incurred with physician visits, acute and chronic care hospitalizations, emergency department visits, same-day surgeries, and medication use were determined through linkage to administrative databases, using a bottom-up approach. The HMI intervention was associated with significant reductions in systolic blood pressure (126 mmHg vs 134 mmHg with standard care; P-value < 0.001). These improvements were associated with a reduction in the 10-year risk of CVD (9.5% risk vs 10.7% in standard care; P-value < 0.001) and a statistically significant improvement in discounted life expectancy (9.536 years vs 9.516 in standard care; P-value < 0.001). The HMI cohort had a discounted mean lifetime cost of $22,884 CAD vs $22,786 CAD for standard care, with an incremental cost-effectiveness ratio of $4939 CAD per life-year gained. We found that the HMI is a cost-effective means of providing evidence-informed, chronic disease management in primary care to patients with hypertension.

The discipline of epidemiology: engaging in the full breadth of population health science.

PubMed

Feldman, Harold I

2018-06-01

This address was delivered by Harold I. Feldman, MD, MSCE, at the Annual Meeting of the American College of Epidemiology in New Orleans, Louisiana, on September 26, 2017. Dr. Feldman is George S. Pepper Professor of Public Health and Preventive Medicine, Professor of Epidemiology and Medicine, and Chair, Department of Biostatistics, Epidemiology, and Informatics at the Perelman School of Medicine at the University of Pennsylvania. He is recognized nationally and internationally for his expertise in kidney disease epidemiology. Dr. Feldman pioneered the integration of epidemiology and renal medicine with his first studies of dialyzer reuse and hemodialysis vascular access morbidity. He is internationally renowned in nephrology and clinical epidemiology and an architect of one of the largest and most successful epidemiological research programs in chronic kidney disease. For over 15 years, he has led NIH's Chronic Renal Insufficiency Cohort Study, placing him at the helm of the "Framingham Study of Renal Disease". It has elucidated the chronic kidney disease-specific relationships of mineral dysmetabolism and cardiovascular complications; dietary sodium and heart failure; novel vascular stiffness metrics and renal disease progression; cardiovascular biomarkers and heart failure; and cognitive decline and renal dysfunction, among others. He has also led the nation's largest trials targeting hemodialysis vascular access morbidity, discovered the benefits of transplantation before dialysis dependence, elucidated racial disparities and the role of genetics in kidney failure, and shaped our understanding of the toxicity from unregulated reuse of medical devices. He is the past President of the American College of Epidemiology and directs one of the nation's largest clinical epidemiology and biostatistics programs. Dr. Feldman has an MD from Boston University and an MSCE from the University of Pennsylvania. He is an elected member of the American Society of Clinical Investigation, the Association of American Physicians, and the American Epidemiological Society. Copyright © 2018 Elsevier Inc. All rights reserved.

Stress, Job Satisfaction and the Community College Faculty.

ERIC Educational Resources Information Center

Happ, Albert C.; Yoder, Edgar P.

In 1991, a study was undertaken to determine the relationship between stress and job satisfaction among community college faculty in Pennsylvania. All full-time faculty at the state's 14 two-year community colleges were surveyed using the Faculty Stress Index, the Minnesota Job Satisfaction Questionnaire, and the Framingham Type A Scale. Selected…

Yogurt consumption is associated with longitudinal changes of body weight and waist circumference: the framingham study

USDA-ARS?s Scientific Manuscript database

Yogurt, as a low-fat, nutrient-dense dairy product, may be beneficial in preventing weight gain. We aimed to examine the longitudinal association between yogurt consumption and annualized change in weight and waist circumference (WC) among adults. We included 3,285 adults (11,169 observations) parti...

Plasma 25-Hydroxyvitamin D is Associated with Markers of the Insulin Resistance Phenotype in Non-diabetic Adults

USDA-ARS?s Scientific Manuscript database

We examined the cross-sectional association between plasma 25-hydroxyvitamin D [25(OH)D] and markers of the insulin resistance phenotype. Plasma 25(OH)D concentrations were measured in 808 non-diabetic participants of the Framingham Offspring Study. Outcome measures included fasting and 2-hour pos...

Keys to the Future of American Business. Proceedings of the Creativity, Innovation and Entrepreneurship Symposium (3rd, Framingham, Massachusetts, May 29-30, 1986).

ERIC Educational Resources Information Center

Solomon, George T., Ed.; Whiting, Bruce G.

The following papers are included: "The Visionary Entrepreneur" (Sidney J. Parnes); "Creative Discipline: Entrepreneurial Objective or Oxymoron" (Arthur Lipper III); "Wowing Your Customers" (Stew Leonard); "Results of Recent Studies Examining the Effect of Need for Achievement and Other Variables upon…

Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy.

PubMed

Hadigan, C; Meigs, J B; Corcoran, C; Rietschel, P; Piecuch, S; Basgoz, N; Davis, B; Sax, P; Stanley, T; Wilson, P W; D'Agostino, R B; Grinspoon, S

2001-01-01

We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution.

Cardiovascular risk scores for coronary atherosclerosis.

PubMed

Yalcin, Murat; Kardesoglu, Ejder; Aparci, Mustafa; Isilak, Zafer; Uz, Omer; Yiginer, Omer; Ozmen, Namik; Cingozbay, Bekir Yilmaz; Uzun, Mehmet; Cebeci, Bekir Sitki

2012-10-01

The objective of this study was to compare frequently used cardiovascular risk scores in predicting the presence of coronary artery disease (CAD) and 3-vessel disease. In 350 consecutive patients (218 men and 132 women) who underwent coronary angiography, the cardiovascular risk level was determined using the Framingham Risk Score (FRS), the Modified Framingham Risk Score (MFRS), the Prospective Cardiovascular Münster (PROCAM) score, and the Systematic Coronary Risk Evaluation (SCORE). The area under the curve for receiver operating characteristic curves showed that FRS had more predictive value than the other scores for CAD (area under curve, 0.76, P < or = 0.001), but all scores had good specificity and positive predictive value. For 3-vessel disease, the FRS had better predictive value than the other scores (area under curve, 0.74, P < or = 0.001), but all scores had good specificity and negative predictive value. The risk scores (FRS, MFRS, PROCAM, and SCORE) may predict the presence and severity of coronary atherosclerosis.The FRS had better predictive value than the other scores.

Cardiovascular risks in firefighters: implications for occupational health nurse practice.

PubMed

Byczek, Lance; Walton, Surrey M; Conrad, Karen M; Reichelt, Paul A; Samo, Daniel G

2004-02-01

Limited cardiovascular risk data are available for firefighters. This cross sectional study of data collected during annual physical examinations described the prevalence of cardiovascular risk factors among firefighters (N = 200) and examined relationships between body mass index (BMI) and other cardiovascular risk factors. Evidence based guidelines were used to determine prevalence of cardiovascular risk factors and Framingham risk scoring was used to estimate probability of coronary heart disease (CHD). Firefighters ranged in age from 22 to 64 with a mean of 41. The prevalence of obesity, elevated total cholesterol, and elevated blood pressure in firefighters exceeded Healthy People 2010 targets. In addition, their prevalence of obesity, low high density lipoprotein (HDL), high low density lipoprotein (LDL), and high total cholesterol levels was higher relative to the general population. Elevated body mass index (BMI) values had positive significant (p < or = .01) associations with elevated blood pressures, triglycerides, and glucose levels, and a negative significant (p < .05) association with lower HDL cholesterol levels. Fire department worksite health and fitness policies and programs should proactively target firefighters' cardiovascular risks. Future firefighter related intervention research will benefit from considering not only the individual determinants of cardiovascular disease, but also the ecological framework that includes the influences of workplace and external environmental factors.

Short-Term Exposure to Air Pollution and Digital Vascular Function

PubMed Central

Ljungman, Petter L.; Wilker, Elissa H.; Rice, Mary B.; Schwartz, Joel; Gold, Diane R.; Koutrakis, Petros; Vita, Joseph A.; Mitchell, Gary F.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Mittleman, Murray A.; Hamburg, Naomi M.

2014-01-01

We investigated associations between ambient air pollution and microvessel function measured by peripheral arterial tonometry between 2003 and 2008 in the Framingham Heart Study Offspring and Third Generation Cohorts. We measured particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), black carbon, sulfates, particle number, nitrogen oxides, and ozone by using fixed monitors, and we determined moving averages for 1–7 days preceding vascular testing. We examined associations between these exposures and hyperemic response to ischemia and baseline pulse amplitude, a measure of arterial tone (n = 2,369). Higher short-term exposure to air pollutants, including PM2.5, black carbon, and particle number was associated with higher baseline pulse amplitude. For example, higher 3-day average PM2.5 exposure was associated with 6.3% higher baseline pulse amplitude (95% confidence interval: 2.0, 10.9). However, there were no consistent associations between the air pollution exposures assessed and hyperemic response. Our findings in a community-based sample exposed to relatively low pollution levels suggest that short-term exposure to ambient particulate pollution is not associated with vasodilator response, but that particulate air pollution is associated with baseline pulse amplitude, suggesting potentially adverse alterations in baseline vascular tone or compliance. PMID:25100647

Data mining and computationally intensive methods: summary of Group 7 contributions to Genetic Analysis Workshop 13.

PubMed

Costello, Tracy J; Falk, Catherine T; Ye, Kenny Q

2003-01-01

The Framingham Heart Study data, as well as a related simulated data set, were generously provided to the participants of the Genetic Analysis Workshop 13 in order that newly developed and emerging statistical methodologies could be tested on that well-characterized data set. The impetus driving the development of novel methods is to elucidate the contributions of genes, environment, and interactions between and among them, as well as to allow comparison between and validation of methods. The seven papers that comprise this group used data-mining methodologies (tree-based methods, neural networks, discriminant analysis, and Bayesian variable selection) in an attempt to identify the underlying genetics of cardiovascular disease and related traits in the presence of environmental and genetic covariates. Data-mining strategies are gaining popularity because they are extremely flexible and may have greater efficiency and potential in identifying the factors involved in complex disorders. While the methods grouped together here constitute a diverse collection, some papers asked similar questions with very different methods, while others used the same underlying methodology to ask very different questions. This paper briefly describes the data-mining methodologies applied to the Genetic Analysis Workshop 13 data sets and the results of those investigations. Copyright 2003 Wiley-Liss, Inc.

Triglycerides and small dense low density lipoprotein in the discrimination of coronary heart disease risk in South Asian populations.

PubMed

Patel, J V; Caslake, M J; Vyas, A; Cruickshank, J K; Prabhakaran, D; Bhatnagar, D; Reddy, K S; Lip, G Y H; Mackness, M I; Hughes, E A; Durrington, P N

2010-04-01

Coronary heart disease (CHD) is exceptionally prevalent amongst globally dispersed migrant groups originating from the Indian subcontinent, but the contribution of dyslipidaemia to their increased risk remains poorly defined. Fasting lipids and lipoproteins, apolipoproteins (Apo), low density lipoprotein (LDL) diameter and oxidised LDL were measured amongst rural Indians in India (n=294) and their migrant contemporaries in the UK (n=242). The performance of qualitative and quantitative measures of lipid metabolism were compared in the discrimination of WHO defined metabolic risk and raised Framingham CHD risk scores (>15%) using Receiver Operating Characteristic (ROC) curves. LDL diameter was correlated with triglycerides (R(2)=0.12, P<0.001) and with high density lipoprotein (HDL) cholesterol levels (R(2)=0.15, P<0.001) in both groups. Migrants had less small dense LDL (95% CI: 12.5-14.2%) vs. rural Indians (15.7-17.2, P<0.05). On ROC analysis, triglycerides were the only consistent discriminators of metabolic and CHD risk scores (all P< or =0.001). Apo B was also a strong indicator of raised CHD risk scores. Irrespective of site, individuals with raised triglycerides also had higher total cholesterol and Apo B, denser LDL, lower HDL and more oxidised LDL (all P< or =0.01). Fasting triglycerides reflect both qualitative and quantitative aspects of lipid metabolism, and are a comprehensive discriminator of CHD risk in this South Asian population. Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.

Comparing two correlated C indices with right-censored survival outcome: a one-shot nonparametric approach

PubMed Central

Kang, Le; Chen, Weijie; Petrick, Nicholas A.; Gallas, Brandon D.

2014-01-01

The area under the receiver operating characteristic (ROC) curve (AUC) is often used as a summary index of the diagnostic ability in evaluating biomarkers when the clinical outcome (truth) is binary. When the clinical outcome is right-censored survival time, the C index, motivated as an extension of AUC, has been proposed by Harrell as a measure of concordance between a predictive biomarker and the right-censored survival outcome. In this work, we investigate methods for statistical comparison of two diagnostic or predictive systems, of which they could either be two biomarkers or two fixed algorithms, in terms of their C indices. We adopt a U-statistics based C estimator that is asymptotically normal and develop a nonparametric analytical approach to estimate the variance of the C estimator and the covariance of two C estimators. A z-score test is then constructed to compare the two C indices. We validate our one-shot nonparametric method via simulation studies in terms of the type I error rate and power. We also compare our one-shot method with resampling methods including the jackknife and the bootstrap. Simulation results show that the proposed one-shot method provides almost unbiased variance estimations and has satisfactory type I error control and power. Finally, we illustrate the use of the proposed method with an example from the Framingham Heart Study. PMID:25399736

Emotions as infectious diseases in a large social network: the SISa model

PubMed Central

Hill, Alison L.; Rand, David G.; Nowak, Martin A.; Christakis, Nicholas A.

2010-01-01

Human populations are arranged in social networks that determine interactions and influence the spread of diseases, behaviours and ideas. We evaluate the spread of long-term emotional states across a social network. We introduce a novel form of the classical susceptible–infected–susceptible disease model which includes the possibility for ‘spontaneous’ (or ‘automatic’) infection, in addition to disease transmission (the SISa model). Using this framework and data from the Framingham Heart Study, we provide formal evidence that positive and negative emotional states behave like infectious diseases spreading across social networks over long periods of time. The probability of becoming content is increased by 0.02 per year for each content contact, and the probability of becoming discontent is increased by 0.04 per year per discontent contact. Our mathematical formalism allows us to derive various quantities from the data, such as the average lifetime of a contentment ‘infection’ (10 years) or discontentment ‘infection’ (5 years). Our results give insight into the transmissive nature of positive and negative emotional states. Determining to what extent particular emotions or behaviours are infectious is a promising direction for further research with important implications for social science, epidemiology and health policy. Our model provides a theoretical framework for studying the interpersonal spread of any state that may also arise spontaneously, such as emotions, behaviours, health states, ideas or diseases with reservoirs. PMID:20610424

Early-Life Intelligence Predicts Midlife Biological Age.

PubMed

Schaefer, Jonathan D; Caspi, Avshalom; Belsky, Daniel W; Harrington, Honalee; Houts, Renate; Israel, Salomon; Levine, Morgan E; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Moffitt, Terrie E

2016-11-01

Early-life intelligence has been shown to predict multiple causes of death in populations around the world. This finding suggests that intelligence might influence mortality through its effects on a general process of physiological deterioration (i.e., individual variation in "biological age"). We examined whether intelligence could predict measures of aging at midlife before the onset of most age-related disease. We tested whether intelligence assessed in early childhood, middle childhood, and midlife predicted midlife biological age in members of the Dunedin Study, a population-representative birth cohort. Lower intelligence predicted more advanced biological age at midlife as captured by perceived facial age, a 10-biomarker algorithm based on data from the National Health and Nutrition Examination Survey (NHANES), and Framingham heart age (r = 0.1-0.2). Correlations between intelligence and telomere length were less consistent. The associations between intelligence and biological age were not explained by differences in childhood health or parental socioeconomic status, and intelligence remained a significant predictor of biological age even when intelligence was assessed before Study members began their formal schooling. These results suggest that accelerated aging may serve as one of the factors linking low early-life intelligence to increased rates of morbidity and mortality. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.

PubMed

Hughes, Kim; Flynn, Tanya; de Zoysa, Janak; Dalbeth, Nicola; Merriman, Tony R

2014-02-01

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors.

Emotions as infectious diseases in a large social network: the SISa model.

PubMed

Hill, Alison L; Rand, David G; Nowak, Martin A; Christakis, Nicholas A

2010-12-22

Human populations are arranged in social networks that determine interactions and influence the spread of diseases, behaviours and ideas. We evaluate the spread of long-term emotional states across a social network. We introduce a novel form of the classical susceptible-infected-susceptible disease model which includes the possibility for 'spontaneous' (or 'automatic') infection, in addition to disease transmission (the SISa model). Using this framework and data from the Framingham Heart Study, we provide formal evidence that positive and negative emotional states behave like infectious diseases spreading across social networks over long periods of time. The probability of becoming content is increased by 0.02 per year for each content contact, and the probability of becoming discontent is increased by 0.04 per year per discontent contact. Our mathematical formalism allows us to derive various quantities from the data, such as the average lifetime of a contentment 'infection' (10 years) or discontentment 'infection' (5 years). Our results give insight into the transmissive nature of positive and negative emotional states. Determining to what extent particular emotions or behaviours are infectious is a promising direction for further research with important implications for social science, epidemiology and health policy. Our model provides a theoretical framework for studying the interpersonal spread of any state that may also arise spontaneously, such as emotions, behaviours, health states, ideas or diseases with reservoirs.

Bone Strength Estimated by Micro-Finite Element Analysis (µFEA) Is Heritable and Shares Genetic Predisposition With Areal BMD: The Framingham Study.

PubMed

Karasik, David; Demissie, Serkalem; Lu, Darlene; Broe, Kerry E; Boyd, Steven K; Liu, Ching-Ti; Hsu, Yi-Hsiang; Bouxsein, Mary L; Kiel, Douglas P

2017-11-01

Genetic factors contribute to the risk of bone fractures, partly because of effects on bone strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) estimates bone strength using micro-finite element analysis (µFEA). The goal of this study was to investigate if the bone failure load estimated by HR-pQCT-based µFEA is heritable and to what extent it shares genetic regulation with areal bone mineral density (aBMD). Bone microarchitecture was measured by HR-pQCT at the ultradistal tibia and ultradistal radius in adults from the Framingham Heart Study (n = 1087, mean age 72 years; 57% women). Radial and tibial failure load in compression were estimated by µFEA. Femoral neck (FN) and ultradistal forearm (UD) aBMD were measured by dual-energy X-ray absorptiometry (DXA). Heritability (h 2 ) of failure load and aBMD and genetic correlations between them was estimated adjusting for covariates (age and sex). Failure load values at the non-weight-bearing ultradistal radius and at the weight-bearing ultradistal tibia were highly correlated (r = 0.906; p < 0.001). Estimates of h 2 adjusted for covariates were 0.522 for the radius and 0.497 for the tibia. Additional adjustment for height did not impact on the h 2 results, but adjustment for aBMD at the UD and FN somewhat decreased h 2 point estimates: 0.222 and 0.380 for radius and tibia, respectively. In bivariate analysis, there was a high phenotypic and genetic correlation between covariate-adjusted failure load at the radius and UD aBMD (ρ P  = 0.826, ρ G  = 0.954, respectively), whereas environmental correlations were lower (ρ E  = 0.696), all highly significant (p < 0.001). Similar correlations were observed between tibial failure load and femoral neck aBMD (ρ P  = 0.577, ρ G  = 0.703, both p < 0.001; ρ E  = 0.432, p < 0.05). These data from adult members of families from a population-based cohort suggest that bone strength of distal extremities estimated by micro-finite element analysis is heritable and shares some genetic composition with areal BMD, regardless of the skeletal site. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Foot Disorders, Foot Posture, and Foot Function: The Framingham Foot Study

PubMed Central

Hagedorn, Thomas J.; Dufour, Alyssa B.; Riskowski, Jody L.; Hillstrom, Howard J.; Menz, Hylton B.; Casey, Virginia A.; Hannan, Marian T.

2013-01-01

Introduction Foot disorders are common among older adults and may lead to outcomes such as falls and functional limitation. However, the associations of foot posture and foot function to specific foot disorders at the population level remain poorly understood. The purpose of this study was to assess the relation between specific foot disorders, foot posture, and foot function. Methods Participants were from the population-based Framingham Foot Study. Quintiles of the modified arch index and center of pressure excursion index from plantar pressure scans were used to create foot posture and function subgroups. Adjusted odds ratios of having each specific disorder were calculated for foot posture and function subgroups relative to a referent 3 quintiles. Results Pes planus foot posture was associated with increased odds of hammer toes and overlapping toes. Cavus foot posture was not associated with the foot disorders evaluated. Odds of having hallux valgus and overlapping toes were significantly increased in those with pronated foot function, while odds of hallux valgus and hallux rigidus were significantly decreased in those with supinated function. Conclusions Foot posture and foot function were associated with the presence of specific foot disorders. PMID:24040231

Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations.

PubMed

Chen, Brian H; Hivert, Marie-France; Peters, Marjolein J; Pilling, Luke C; Hogan, John D; Pham, Lisa M; Harries, Lorna W; Fox, Caroline S; Bandinelli, Stefania; Dehghan, Abbas; Hernandez, Dena G; Hofman, Albert; Hong, Jaeyoung; Joehanes, Roby; Johnson, Andrew D; Munson, Peter J; Rybin, Denis V; Singleton, Andrew B; Uitterlinden, André G; Ying, Saixia; Melzer, David; Levy, Daniel; van Meurs, Joyce B J; Ferrucci, Luigi; Florez, Jose C; Dupuis, Josée; Meigs, James B; Kolaczyk, Eric D

2016-12-01

Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q <0.05, we identified three transcripts associated with fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes-imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis. © 2016 by the American Diabetes Association.

The QT Interval and Risk of Incident Atrial Fibrillation

PubMed Central

Mandyam, Mala C.; Soliman, Elsayed Z.; Alonso, Alvaro; Dewland, Thomas A.; Heckbert, Susan R.; Vittinghoff, Eric; Cummings, Steven R.; Ellinor, Patrick T.; Chaitman, Bernard R.; Stocke, Karen; Applegate, William B.; Arking, Dan E.; Butler, Javed; Loehr, Laura R.; Magnani, Jared W.; Murphy, Rachel A.; Satterfield, Suzanne; Newman, Anne B.; Marcus, Gregory M.

2013-01-01

BACKGROUND Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine. OBJECTIVE To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF. METHODS We examined a prolonged QT corrected by the Framingham formula (QTFram) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (Health ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by other formulae. RESULTS Among 14,538 ARIC participants, a prolonged QTFram predicted a roughly two-fold increased risk of AF (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.42–2.96, p<0.001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in CHS and Health ABC and were similar across various QT correction methods. Also in ARIC, each 10-ms increase in QTFram was associated with an increased unadjusted (HR 1.14, 95%CI 1.10–1.17, p<0.001) and adjusted (HR 1.11, 95%CI 1.07–1.14, p<0.001) risk of AF. Findings regarding a short QT were inconsistent across cohorts. CONCLUSIONS A prolonged QT interval is associated with an increased risk of incident AF. PMID:23872693

Association of pulse pressure with new-onset atrial fibrillation in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study.

PubMed

Larstorp, Anne Cecilie K; Ariansen, Inger; Gjesdal, Knut; Olsen, Michael H; Ibsen, Hans; Devereux, Richard B; Okin, Peter M; Dahlöf, Björn; Kjeldsen, Sverre E; Wachtell, Kristian

2012-08-01

Previous studies have found pulse pressure (PP), a marker of arterial stiffness, to be an independent predictor of atrial fibrillation (AF) in general and hypertensive populations. We examined whether PP predicted new-onset AF in comparison with other blood pressure components in the Losartan Intervention For Endpoint reduction in hypertension study, a double-blind, randomized (losartan versus atenolol), parallel-group study, including 9193 patients with hypertension and electrocardiographic left ventricular hypertrophy. In 8810 patients with neither a history of AF nor AF at baseline, Minnesota coding of electrocardiograms confirmed new-onset AF in 353 patients (4.0%) during mean 4.9 years of follow-up. In multivariate Cox regression analyses, baseline and in-treatment PP and baseline and in-treatment systolic blood pressure predicted new-onset AF, independent of baseline age, height, weight, and Framingham Risk Score; sex, race, and treatment allocation; and in-treatment heart rate and Cornell product. PP was the strongest single blood pressure predictor of new-onset AF determined by the decrease in the -2 Log likelihood statistic, in comparison with systolic blood pressure, diastolic blood pressure, and mean arterial pressure. When evaluated in the same model, the predictive effect of systolic and diastolic blood pressures together was similar to that of PP. In this population of patients with hypertension and left ventricular hypertrophy, PP was the strongest single blood pressure predictor of new-onset AF, independent of other risk factors.

Genome-wide gene–gene interaction analysis for next-generation sequencing

PubMed Central

Zhao, Jinying; Zhu, Yun; Xiong, Momiao

2016-01-01

The critical barrier in interaction analysis for next-generation sequencing (NGS) data is that the traditional pairwise interaction analysis that is suitable for common variants is difficult to apply to rare variants because of their prohibitive computational time, large number of tests and low power. The great challenges for successful detection of interactions with NGS data are (1) the demands in the paradigm of changes in interaction analysis; (2) severe multiple testing; and (3) heavy computations. To meet these challenges, we shift the paradigm of interaction analysis between two SNPs to interaction analysis between two genomic regions. In other words, we take a gene as a unit of analysis and use functional data analysis techniques as dimensional reduction tools to develop a novel statistic to collectively test interaction between all possible pairs of SNPs within two genome regions. By intensive simulations, we demonstrate that the functional logistic regression for interaction analysis has the correct type 1 error rates and higher power to detect interaction than the currently used methods. The proposed method was applied to a coronary artery disease dataset from the Wellcome Trust Case Control Consortium (WTCCC) study and the Framingham Heart Study (FHS) dataset, and the early-onset myocardial infarction (EOMI) exome sequence datasets with European origin from the NHLBI's Exome Sequencing Project. We discovered that 6 of 27 pairs of significantly interacted genes in the FHS were replicated in the independent WTCCC study and 24 pairs of significantly interacted genes after applying Bonferroni correction in the EOMI study. PMID:26173972

Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians12

PubMed Central

Fretts, Amanda M; Follis, Jack L; Nettleton, Jennifer A; Lemaitre, Rozenn N; Ngwa, Julius S; Wojczynski, Mary K; Kalafati, Ioanna Panagiota; Varga, Tibor V; Frazier-Wood, Alexis C; Houston, Denise K; Lahti, Jari; Ericson, Ulrika; van den Hooven, Edith H; Mikkilä, Vera; Kiefte-de Jong, Jessica C; Mozaffarian, Dariush; Rice, Kenneth; Renström, Frida; North, Kari E; McKeown, Nicola M; Feitosa, Mary F; Kanoni, Stavroula; Smith, Caren E; Garcia, Melissa E; Tiainen, Anna-Maija; Sonestedt, Emily; Manichaikul, Ani; van Rooij, Frank JA; Dimitriou, Maria; Raitakari, Olli; Pankow, James S; Djoussé, Luc; Province, Michael A; Hu, Frank B; Lai, Chao-Qiang; Keller, Margaux F; Perälä, Mia-Maria; Rotter, Jerome I; Hofman, Albert; Graff, Misa; Kähönen, Mika; Mukamal, Kenneth; Johansson, Ingegerd; Ordovas, Jose M; Liu, Yongmei; Männistö, Satu; Uitterlinden, André G; Deloukas, Panos; Seppälä, Ilkka; Psaty, Bruce M; Cupples, L Adrienne; Borecki, Ingrid B; Franks, Paul W; Arnett, Donna K; Nalls, Mike A; Eriksson, Johan G; Orho-Melander, Marju; Franco, Oscar H; Lehtimäki, Terho; Dedoussis, George V; Meigs, James B; Siscovick, David S

2015-01-01

Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. Design: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. Results: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049–ln-pmol/L (95% CI: 0.035, 0.063–ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance. Conclusion: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. Six of the participating studies are registered at clinicaltrials.gov as NCT0000513 (Atherosclerosis Risk in Communities), NCT00149435 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetics of Lipid Lowering Drugs and Diet Network), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis). PMID:26354543

Associations of whole and refined grain intakes with adiposity-related cancer risk in the Framingham Offspring Cohort (1991-2013)

USDA-ARS?s Scientific Manuscript database

Objective: The objective of this prospective cohort study is to evaluate associations between whole and refined grains and their food sources in relation to risk of adiposity-related cancers combined and three of the most commonly diagnosed site-specific cancers in the US: breast, prostate, and colo...

Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake.

PubMed

Tanaka, Toshiko; Ngwa, Julius S; van Rooij, Frank J A; Zillikens, M Carola; Wojczynski, Mary K; Frazier-Wood, Alexis C; Houston, Denise K; Kanoni, Stavroula; Lemaitre, Rozenn N; Luan, Jian'an; Mikkilä, Vera; Renstrom, Frida; Sonestedt, Emily; Zhao, Jing Hua; Chu, Audrey Y; Qi, Lu; Chasman, Daniel I; de Oliveira Otto, Marcia C; Dhurandhar, Emily J; Feitosa, Mary F; Johansson, Ingegerd; Khaw, Kay-Tee; Lohman, Kurt K; Manichaikul, Ani; McKeown, Nicola M; Mozaffarian, Dariush; Singleton, Andrew; Stirrups, Kathleen; Viikari, Jorma; Ye, Zheng; Bandinelli, Stefania; Barroso, Inês; Deloukas, Panos; Forouhi, Nita G; Hofman, Albert; Liu, Yongmei; Lyytikäinen, Leo-Pekka; North, Kari E; Dimitriou, Maria; Hallmans, Goran; Kähönen, Mika; Langenberg, Claudia; Ordovas, Jose M; Uitterlinden, André G; Hu, Frank B; Kalafati, Ioanna-Panagiota; Raitakari, Olli; Franco, Oscar H; Johnson, Andrew; Emilsson, Valur; Schrack, Jennifer A; Semba, Richard D; Siscovick, David S; Arnett, Donna K; Borecki, Ingrid B; Franks, Paul W; Kritchevsky, Stephen B; Lehtimäki, Terho; Loos, Ruth J F; Orho-Melander, Marju; Rotter, Jerome I; Wareham, Nicholas J; Witteman, Jacqueline C M; Ferrucci, Luigi; Dedoussis, George; Cupples, L Adrienne; Nettleton, Jennifer A

2013-06-01

Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. The objective of the study was to identify common genetic variants that are associated with macronutrient intake. We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 × 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data. A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (β ± SE: 0.25 ± 0.04%; P = 1.68 × 10(-8)) and lower fat (β ± SE: -0.21 ± 0.04%; P = 1.57 × 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)-increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (β ± SE: 0.10 ± 0.02%; P = 9.96 × 10(-10)), independent of BMI (after adjustment for BMI, β ± SE: 0.08 ± 0.02%; P = 3.15 × 10(-7)). Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

Worksite-based cardiovascular risk screening and management: a feasibility study.

PubMed

Padwal, Raj; Rashead, Mohammad; Snider, Jonathan; Morrin, Louise; Lehman, Agnes; Campbell, Norm Rc

2017-01-01

Established cardiovascular risk factors are highly prevalent and contribute substantially to cardiovascular morbidity and mortality because they remain uncontrolled in many Canadians. Worksite-based cardiovascular risk factor screening and management represent a largely untapped strategy for optimizing risk factor control. In a 2-phase collaborative demonstration project between Alberta Health Services (AHS) and the Alberta Newsprint Company (ANC), ANC employees were offered cardiovascular risk factor screening and management. Screening was performed at the worksite by AHS nurses, who collected baseline history, performed automated blood pressure measurement and point-of-care testing for lipids and A1c, and calculated 10-year Framingham risk. Employees with a Framingham risk score of ≥10% and uncontrolled blood pressure, dyslipidemia, or smoking were offered 6 months of pharmacist case management to optimize their risk factor control. In total, 87 of 190 (46%) employees volunteered to undergo cardiovascular risk factor screening. Mean age was 44.5±11.9 years, 73 (83.9%) were male, 14 (16.1%) had hypertension, 4 (4.6%) had diabetes, 12 (13.8%) were current smokers, and 9 (10%) had dyslipidemia. Of 36 employees with an estimated Framingham risk score of ≥10%, 21 (58%) agreed to receive case management and 15 (42%) attended baseline and 6-month follow-up case management visits. Statistically significant reductions in left arm systolic blood pressure (-8.0±12.4 mmHg; p =0.03) and triglyceride levels (-0.8±1.4 mmol/L; p =0.04) occurred following case management. These findings demonstrate the feasibility and usefulness of collaborative, worksite-based cardiovascular risk factor screening and management. Expansion of this type of partnership in a cost-effective manner is warranted.

The preferred magnetic resonance imaging planes in quantifying visceral adipose tissue and evaluating cardiovascular risk.

PubMed

Liu, K H; Chan, Y L; Chan, J C N; Chan, W B; Kong, M O; Poon, M Y

2005-09-01

Magnetic Resonance Imaging (MRI) is a well-accepted non-invasive method in the quantification of visceral adipose tissue. However, a standard method of measurement has not yet been universally agreed. The objectives of the present study were 2-fold, firstly, to identify the imaging plane in the Chinese population which gives the best correlation with total visceral adipose tissue volume and cardiovascular risk factors; and secondly to compare the correlations between single-slice and multiple-slice approach with cardiovascular risk factors. Thirty-seven Chinese subjects with no known medical history underwent MRI examination for quantifying total visceral adipose tissue volume. The visceral adipose tissue area at five axial imaging levels within abdomen and pelvis were determined. All subjects had blood pressure measured and fasting blood taken for analysis of cardiovascular risk factors. Framingham risk score for each subject was calculated. The imaging plane at the level of 'lower costal margin' (LCM) in both men and women had the highest correlation with total visceral adipose tissue volume (r = 0.97 and 0.99 respectively). The visceral adipose tissue area at specific imaging levels showed higher correlations with various cardiovascular risk factors and Framingham risk score than total visceral adipose tissue volume. The visceral adipose tissue area at 'umbilicus' (UMB) level in men (r = 0.88) and LCM level in women (r = 0.70) showed the best correlation with Framingham risk score. The imaging plane at the level of LCM is preferred for reflecting total visceral adipose tissue volume in Chinese subjects. For investigating the association of cardiovascular risk with visceral adipose tissue in MRI-obesity research, the single-slice approach is superior to the multiple-slice approach, with the level of UMB in men and LCM in women as the preferred imaging planes.

[Screening of asymptomatic left ventricular systolic dysfunction in a population sample at high cardiovascular risk in Lombardy (Italy): the DAVID-Berg study].

PubMed

Gavazzi, Antonello; De Maria, Renata; Grosu, Aurelia; Iacovoni, Attilio; Fontana, Alessandra; Gori, Mauro; Ferrari, Paola; Canova, Paolo; Calabrese, Alice; Filippi, Alessandro; Rutili, Maria Rosaria; Donzelli, Luigi; Parolini, Marina; Senni, Michele

2014-05-01

Prevalence of asymptomatic left ventricular systolic dysfunction (ALVSD) increases with age and cardiovascular (CV) risk exposure. Early diagnosis and treatment allow reducing heart failure and fatal and non-fatal event rates. Data on ALVSD prevalence in Italy are still scarce and ALVSD remains commonly under-diagnosed in primary care, where diagnostic facilities are limited. Among subjects at high CV risk in primary care, we assessed the prevalence of ALVSD and the relative predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the Framingham Heart Failure Risk Score (FHFRS). Records of 4047 subjects aged 55-80 years, without history, symptoms or signs of heart failure, registered at three primary care practices in Lombardy, Northern Italy, were reviewed; 623 subjects at high CV risk underwent visit, ECG, echocardiography, NT-proBNP and FHFRS calculation. ALVSD, defined as left ventricular ejection fraction <50%, was detected in 33 subjects (5.3%) who showed higher NT-proBNP (p<0.001) and FHFRS (p=0.013) than those without ALVSD. NT-proBNP levels beyond normal age and gender-specific 95th percentile had a 97.7% negative predictive value for ALVSD and were associated with a 6-fold increase in ALVSD risk. Adding NT-proBNP to FHFRS significantly improved prediction (C-statistic 0.76, 95% confidence interval [CI] 0.67-0.84 vs 0.63, 95% CI 0.53-0.73, p=0.04; net reclassification improvement 38.4%). The combination of FHFRS and major ECG abnormalities was not superior to stand alone NT-proBNP (C-statistic 0.71, 95% CI 0.63-0.80 vs 0.74, 95% CI 0.64-0.83, p=0.61). In subjects at high CV risk in primary care, prevalence of ALVSD is 5.3%; for diagnosis NT-proBNP adds predictive value to the FHFRS and is equivalent to the combination of FHFRS and ECG. Because of its practical advantages, NT-proBNP might be routinely used for ALVSD screening in primary care.

Analysis of Minimally Invasive Left Thoracotomy HVAD Implantation - A Single-Center Experience.

PubMed

Reichart, D; Brand, C F; Bernhardt, A M; Schmidt, S; Schaefer, A; Blankenberg, S; Reichenspurner, H; Wagner, F M; Deuse, T; Barten, M J

2018-05-27

 Minimally invasive left ventricular assist device (LVAD) implantation may reduce peri-/postoperative complications and risks associated with resternotomies. In this study, we describe our first results using a minimally invasive LVAD implantation technique (lateral thoracotomy [LT] group). These results were compared with LVAD implantations done via full median sternotomy (STX group).  HVAD (HeartWare, Framingham, Massachusetts, United States) implantations in 70 patients (LT group n  = 22, 52 ± 15 years old; STX group n  = 48, 59 ± 11 years old) were retrospectively analyzed. Minimally invasive access via left thoracotomy was feasible in 22 patients. Peri- and postoperative analyses of survival and adverse events were performed.  No survival differences were observed between the LT and STX group ( p  = 0.43). LT patients without temporary right ventricular assist device (tRVAD) showed a significantly better survival rate compared to LT patients with concomitant tRVAD implantation ( p  = 0.02), which could not be demonstrated in the STX group ( p  = 0.11). Two LT and four STX patients were successfully bridged to heart transplantation and three STX patients were successfully weaned with subsequent LVAD explantations. LVAD-related infections ( n  = 4 LT group vs n  = 20 STX group, p  = 0.04) were less likely in the LT group. No wound dehiscence occurred in the LT group, whereas five were observed in the STX group ( p  = 0.17). The amount of perioperative blood transfusions (within the first 7 postoperative days) did not differ in both study groups ( p  = 0.48).  The minimally invasive approach is a viable alternative with the possibility to reduce complications and should be particularly considered for bridge-to-transplant patients. Georg Thieme Verlag KG Stuttgart · New York.

Anthropometric measurements of general and central obesity and the prediction of cardiovascular disease risk in women: a cross-sectional study

PubMed Central

Goh, Louise G H; Dhaliwal, Satvinder S; Welborn, Timothy A; Lee, Andy H; Della, Phillip R

2014-01-01

Objectives It is important to ascertain which anthropometric measurements of obesity, general or central, are better predictors of cardiovascular disease (CVD) risk in women. 10-year CVD risk was calculated from the Framingham risk score model, SCORE risk chart for high-risk regions, general CVD and simplified general CVD risk score models. Increase in CVD risk associated with 1 SD increment in each anthropometric measurement above the mean was calculated, and the diagnostic utility of obesity measures in identifying participants with increased likelihood of being above the treatment threshold was assessed. Design Cross-sectional data from the National Heart Foundation Risk Factor Prevalence Study. Setting Population-based survey in Australia. Participants 4487 women aged 20–69 years without heart disease, diabetes or stroke. Outcome measures Anthropometric obesity measures that demonstrated the greatest increase in CVD risk as a result of incremental change, 1 SD above the mean, and obesity measures that had the greatest diagnostic utility in identifying participants above the respective treatment thresholds of various risk score models. Results Waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-stature ratio had larger effects on increased CVD risk compared with body mass index (BMI). These central obesity measures also had higher sensitivity and specificity in identifying women above and below the 20% treatment threshold than BMI. Central obesity measures also recorded better correlations with CVD risk compared with general obesity measures. WC and WHR were found to be significant and independent predictors of CVD risk, as indicated by the high area under the receiver operating characteristic curves (>0.76), after controlling for BMI in the simplified general CVD risk score model. Conclusions Central obesity measures are better predictors of CVD risk compared with general obesity measures in women. It is equally important to maintain a healthy weight and to prevent central obesity concurrently. PMID:24503301

Anthropometric measurements of general and central obesity and the prediction of cardiovascular disease risk in women: a cross-sectional study.

PubMed

Goh, Louise G H; Dhaliwal, Satvinder S; Welborn, Timothy A; Lee, Andy H; Della, Phillip R

2014-02-06

It is important to ascertain which anthropometric measurements of obesity, general or central, are better predictors of cardiovascular disease (CVD) risk in women. 10-year CVD risk was calculated from the Framingham risk score model, SCORE risk chart for high-risk regions, general CVD and simplified general CVD risk score models. Increase in CVD risk associated with 1 SD increment in each anthropometric measurement above the mean was calculated, and the diagnostic utility of obesity measures in identifying participants with increased likelihood of being above the treatment threshold was assessed. Cross-sectional data from the National Heart Foundation Risk Factor Prevalence Study. Population-based survey in Australia. 4487 women aged 20-69 years without heart disease, diabetes or stroke. Anthropometric obesity measures that demonstrated the greatest increase in CVD risk as a result of incremental change, 1 SD above the mean, and obesity measures that had the greatest diagnostic utility in identifying participants above the respective treatment thresholds of various risk score models. Waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-stature ratio had larger effects on increased CVD risk compared with body mass index (BMI). These central obesity measures also had higher sensitivity and specificity in identifying women above and below the 20% treatment threshold than BMI. Central obesity measures also recorded better correlations with CVD risk compared with general obesity measures. WC and WHR were found to be significant and independent predictors of CVD risk, as indicated by the high area under the receiver operating characteristic curves (>0.76), after controlling for BMI in the simplified general CVD risk score model. Central obesity measures are better predictors of CVD risk compared with general obesity measures in women. It is equally important to maintain a healthy weight and to prevent central obesity concurrently.

Cross-sectional relations of arterial stiffness, pressure pulsatility, wave reflection, and arterial calcification.

PubMed

Tsao, Connie W; Pencina, Karol M; Massaro, Joseph M; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Hoffmann, Udo; O'Donnell, Christopher J; Mitchell, Gary F

2014-11-01

Arterial hemodynamics and vascular calcification are associated with increased risk for cardiovascular disease, but their inter-relations remain unclear. We sought to examine the associations of arterial stiffness, pressure pulsatility, and wave reflection with arterial calcification in individuals free of prevalent cardiovascular disease. Framingham Heart Study Third Generation and Offspring Cohort participants free of cardiovascular disease underwent applanation tonometry to measure arterial stiffness, pressure pulsatility, and wave reflection, including carotid-femoral pulse wave velocity, central pulse pressure, forward wave amplitude, and augmentation index. Participants in each cohort (n=1905, 45±6 years and n=1015, 65±9 years, respectively) underwent multidetector computed tomography to assess the presence and quantity of thoracic aortic calcification, abdominal aortic calcification, and coronary artery calcification. In multivariable-adjusted models, both higher carotid-femoral pulse wave velocity and central pulse pressure were associated with greater thoracic aortic calcification and abdominal aortic calcification, whereas higher augmentation index was associated with abdominal aortic calcification. Among the tonometry measures, carotid-femoral pulse wave velocity was the strongest correlate of all calcification measures in multivariable-adjusted models (odds ratio per SD for thoracic aortic calcification, 2.69 [95% confidence interval, 2.17-3.35]; abdominal aortic calcification, 1.47 [95% confidence interval, 1.26-1.73]; and coronary artery calcification, 1.48 [95% confidence interval, 1.28-1.72]; all P<0.001, respectively). We observed stronger relations of carotid-femoral pulse wave velocity, central pulse pressure, and forward wave amplitude with nearly all continuous calcification measures in the younger Third Generation Cohort as compared with the Offspring Cohort. In community-dwelling individuals without prevalent cardiovascular disease, abnormal central arterial hemodynamics were positively associated with vascular calcification and were observed at younger ages than previously recognized. The mechanisms of these associations may be bidirectional and deserve further study. © 2014 American Heart Association, Inc.

Inter-Relations of Orthostatic Blood Pressure Change, Aortic Stiffness, and Brain Structure and Function in Young Adults.

PubMed

Cooper, Leroy L; Himali, Jayandra J; Torjesen, Alyssa; Tsao, Connie W; Beiser, Alexa; Hamburg, Naomi M; DeCarli, Charles; Vasan, Ramachandran S; Seshadri, Sudha; Pase, Matthew P; Mitchell, Gary F

2017-08-17

Relations of orthostatic change in blood pressure with brain structure and function have not been studied thoroughly, particularly in younger, healthier individuals. Elucidation of factors that contribute to early changes in brain integrity may lead to development of interventions that delay or prevent cognitive impairment. In a sample of the Framingham Heart Study Third Generation (N=2119; 53% women; mean age±SD, 47±8 years), we assessed orthostatic change in mean arterial pressure (MAP), aortic stiffness (carotid-femoral pulse wave velocity), neuropsychological function, and markers of subclinical brain injury on magnetic resonance imaging. Multivariable regression analyses were used to assess relations between orthostatic change in MAP and brain structural and neuropsychological outcomes. Greater orthostatic increase in MAP on standing was related to better Trails B-A performance among participants aged <49 years (β±SE, 0.062±0.029; P =0.031) and among participants with carotid-femoral pulse wave velocity <6.9 m/s (β±SE, 0.063±0.026; P =0.016). This relation was not significant among participants who were older or had stiffer aortas. Conversely, greater orthostatic increase in MAP was related to larger total brain volume among older participants (β±SE, 0.065±0.029; P =0.023) and among participants with carotid-femoral pulse wave velocity ≥6.9 m/s (β±SE, 0.078±0.031; P =0.011). Blunted orthostatic increase in MAP was associated with smaller brain volume among participants who were older or had stiffer aortas and with poorer executive function among persons who were younger or who had more-elastic aortas. Our findings suggest that the brain is sensitive to orthostatic change in MAP, with results dependent on age and aortic stiffness. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Primary prevention of cardiovascular disease: a web‐based risk score for seven British black and minority ethnic groups

PubMed Central

Brindle, P; May, M; Gill, P; Cappuccio, F; D'Agostino, R; Fischbacher, C; Ebrahim, S

2006-01-01

Objective To recalibrate an existing Framingham risk score to produce a web‐based tool for estimating the 10‐year risk of coronary heart disease (CHD) and cardiovascular disease (CVD) in seven British black and minority ethnic groups. Design Risk prediction models were recalibrated against survey data on ethnic group risk factors and disease prevalence compared with the general population. Ethnic‐ and sex‐specific 10‐year risks of CHD and CVD, at the means of the risk factors for each ethnic group, were calculated from the product of the incidence rate in the general population and the prevalence ratios for each ethnic group. Setting Two community‐based surveys. Participants 3778 men and 4544 women, aged 35–54, from the Health Surveys for England 1998 and 1999 and the Wandsworth Heart and Stroke Study. Main outcome measures 10‐year risk of CHD and CVD. Results 10‐year risk of CHD and CVD for non‐smoking people aged 50 years with a systolic blood pressure of 130 mm Hg and a total cholesterol to high density lipoprotein cholesterol ratio of 4.2 was highest in men for those of Pakistani and Bangladeshi origin (CVD risk 12.6% and 12.8%, respectively). CHD risk in men with the same risk factor values was lowest in Caribbeans (2.8%) and CVD risk was lowest in Chinese (5.4%). Women of Pakistani origin were at highest risk and Chinese women at lowest risk for both outcomes with CVD risks of 6.6% and 1.2%, respectively. A web‐based risk calculator (ETHRISK) allows 10‐year risks to be estimated in routine primary care settings for relevant risk factor and ethnic group combinations. Conclusions In the absence of cohort studies in the UK that include significant numbers of black and minority ethnic groups, this risk score provides a pragmatic solution to including people from diverse ethnic backgrounds in the primary prevention of CVD. PMID:16762981

Association of HSP70 and its co-chaperones with Alzheimer’s Disease

PubMed Central

Broer, Linda; Ikram, Mohammad Arfan; Schuur, Maaike; DeStefano, Anita L.; Bis, Joshua C.; Liu, Fan; Rivadeneira, Fernando; Uitterlinden, Andre G.; Beiser, Alexa S.; Longstreth, William T.; Hofman, Albert; Aulchenko, Yurii; Seshadri, Sudha; Fitzpatrick, Annette L.; Oostra, Ben A.; Breteler, Monique M.B.; van Duijn, Cornelia M.

2012-01-01

The heat shock protein (HSP) 70 family has been implicated in the pathology of Alzheimer’s disease (AD). In this study, we examined common genetic variations in the 80 genes encoding HSP70 and its co-chaperones. We conducted a study in a series of 462 patients and 5238 unaffected participants derived from the Rotterdam Study, a population-based study including 7983 persons aged 55 years and older. We genotyped a total of 12,053 Single Nucleotide Polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. Replication was performed in two independent cohort studies, the Framingham Heart study (FHS; N=806) and Cardiovascular Health Study (CHS; N=2150). When adjusting for multiple testing, we found a small but consistent, though not significant effect of rs12118313 located 32kb from PFDN2, with an OR of 1.19 (p-value from meta-analysis =0.003). However this SNP was in the intron of another gene, suggesting it is unlikely this SNP reflects the effect of PFDN2. In a formal pathway analysis we found nominally significant evidence for an association of BAG, DNAJA and prefoldin with AD. These findings corroborate with those of a study of 2032 AD patients and 5328 controls, in which several members of the prefoldin family showed evidence for association to AD. Our study did not reveal evidence for a genetic variant if the HSP70 family with a major effect on AD. However, our findings of the single SNP analysis and pathway analysis suggest that multiple genetic variants in prefoldin are associated with AD. PMID:21403392

Operationalizing diagnostic criteria for Alzheimer’s disease and other age-related cognitive impairment—Part 2*

PubMed Central

Seshadri, Sudha; Beiser, Alexa; Au, Rhoda; Wolf, Philip A.; Evans, Denis A.; Wilson, Robert S.; Petersen, Ronald C.; Knopman, David S.; Rocca, Walter A.; Kawas, Claudia H.; Corrada, Maria M.; Plassman, Brenda L.; Langa, Kenneth M.; Chui, Helena C.

2011-01-01

This article focuses on the effects of operational differences in case ascertainment on estimates of prevalence and incidence of cognitive impairment/dementia of the Alzheimer type. Experience and insights are discussed by investigators from the Framingham Heart Study, the East Boston Senior Health Project, the Chicago Health and Aging Project, the Mayo Clinic Study of Aging, the Baltimore Longitudinal Study of Aging, and the Aging, Demographics, and Memory Study. There is a general consensus that the single most important factor regulating prevalence estimates of Alzheimer’s disease (AD) is the severity of cognitive impairment used for case ascertainment. Studies that require a level of cognitive impairment in which persons are unable to provide self-care will have much lower estimates than studies aimed at identifying persons in the earliest stages of AD. There is limited autopsy data from the above-mentioned epidemiologic studies to address accuracy in the diagnosis of etiologic subtype, namely the specification of AD alone or in combination with other types of pathology. However, other community-based cohort studies show that many persons with mild cognitive impairment (MCI) meet pathologic criteria for AD, and a large minority of persons without dementia or MCI also meets pathologic criteria for AD, thereby suggesting that the number of persons who would benefit from an effective secondary prevention intervention is probably higher than the highest published prevalence estimates. Improved accuracy in the clinical diagnosis of AD is anticipated with the addition of molecular and structural biomarkers in the next generation of epidemiologic studies. PMID:21255742

Normal limits of the electrocardiogram derived from a large database of Brazilian primary care patients.

PubMed

Palhares, Daniel M F; Marcolino, Milena S; Santos, Thales M M; da Silva, José L P; Gomes, Paulo R; Ribeiro, Leonardo B; Macfarlane, Peter W; Ribeiro, Antonio L P

2017-06-13

Knowledge of the normal limits of the electrocardiogram (ECG) is mandatory for establishing which patients have abnormal ECGs. No studies have assessed the reference standards for a Latin American population. Our aim was to establish the normal ranges of the ECG for pediatric and adult Brazilian primary care patients. This retrospective observational study assessed all the consecutive 12-lead digital electrocardiograms of primary care patients at least 1 year old in Minas Gerais state, Brazil, recorded between 2010 and 2015. ECGs were excluded if there were technical problems, selected abnormalities were present or patients with selected self-declared comorbidities or on drug therapy. Only the first ECG from patients with multiple ECGs was accepted. The University of Glasgow ECG analysis program was used to automatically interpret the ECGs. For each variable, the 1st, 2nd, 50th, 98th and 99th percentiles were determined and results were compared to selected studies. A total of 1,493,905 ECGs were recorded. 1,007,891 were excluded and 486.014 were analyzed. This large study provided normal values for heart rate, P, QRS and T frontal axis, P and QRS overall duration, PR and QT overall intervals and QTc corrected by Hodges, Bazett, Fridericia and Framingham formulae. Overall, the results were similar to those from other studies performed in different populations but there were differences in extreme ages and specific measurements. This study has provided reference values for Latinos of both sexes older than 1 year. Our results are comparable to studies performed in different populations.

A polymorphism in a gene encoding Perilipin 4 is associated with height but not with bone measures in individuals from the Framingham Osteoporosis Study

USDA-ARS?s Scientific Manuscript database

There is increasing interest in identifying new pathways and candidate genes that confer susceptibility to osteoporosis. There is evidence that adipogenesis and osteogenesis may be related, including a common bone marrow progenitor cell for both adipocytes and osteoblasts. Perilipin 1 (PLIN1) and Pe...

The effect of giving global coronary risk information to adults: a systematic review.

PubMed

Sheridan, Stacey L; Viera, Anthony J; Krantz, Mori J; Ice, Christa L; Steinman, Lesley E; Peters, Karen E; Kopin, Laurie A; Lungelow, Danielle

2010-02-08

Global coronary heart disease (CHD) risk estimation (ie, a quantitative estimate of a patient's chances of CHD calculated by combining risk factors in an empirical equation) is recommended as a starting point for primary prevention efforts in all US adults. Whether it improves outcomes is currently unknown. To assess the effect of providing global CHD risk information to adults, we performed a systematic evidence review. We searched MEDLINE for the years 1980 to 2008, Psych Info, CINAHL, and the Cochrane Database and included English-language articles that met prespecified inclusion criteria. Two reviewers independently reviewed titles, abstracts, and articles for inclusion and assessed study quality. We identified 20 articles, reporting on 18 unique fair or good quality studies (including 14 randomized controlled studies). These showed that global CHD risk information alone or with accompanying education increased the accuracy of perceived risk and probably increased intent to start therapy. Studies with repeated risk information or risk information and repeated doses of counseling showed small significant reductions in predicted CHD risk (absolute differences, -0.2% to -2% over 10 years in studies using risk estimates derived from Framingham equations). Studies providing global risk information at only 1 point in time seemed ineffective. Global CHD risk information seems to improve the accuracy of risk perception and may increase intent to initiate CHD prevention among individuals at moderate to high risk. The effect of global risk presentation on more distal outcomes is less clear and seems to be related to the intensity of accompanying interventions.

Rheumatoid arthritis-specific cardiovascular risk scores are not superior to general risk scores: a validation analysis of patients from seven countries.

PubMed

Crowson, Cynthia S; Gabriel, Sherine E; Semb, Anne Grete; van Riel, Piet L C M; Karpouzas, George; Dessein, Patrick H; Hitchon, Carol; Pascual-Ramos, Virginia; Kitas, George D

2017-07-01

Cardiovascular disease (CVD) risk calculators developed for the general population do not accurately predict CVD events in patients with RA. We sought to externally validate risk calculators recommended for use in patients with RA including the EULAR 1.5 multiplier, the Expanded Cardiovascular Risk Prediction Score for RA (ERS-RA) and QRISK2. Seven RA cohorts from UK, Norway, Netherlands, USA, South Africa, Canada and Mexico were combined. Data on baseline CVD risk factors, RA characteristics and CVD outcomes (including myocardial infarction, ischaemic stroke and cardiovascular death) were collected using standardized definitions. Performance of QRISK2, EULAR multiplier and ERS-RA was compared with other risk calculators [American College of Cardiology/American Heart Association (ACC/AHA), Framingham Adult Treatment Panel III Framingham risk score-Adult Treatment Panel (FRS-ATP) and Reynolds Risk Score] using c-statistics and net reclassification index. Among 1796 RA patients without prior CVD [mean ( s . d .) age: 54.0 (14.0) years, 74% female], 100 developed CVD events during a mean follow-up of 6.9 years (12430 person-years). Estimated CVD risk by ERS-RA [mean ( s . d .) 8.8% (9.8%)] was comparable to FRS-ATP [mean ( s . d .) 9.1% (8.3%)] and Reynolds [mean ( s . d .) 9.2% (12.2%)], but lower than ACC/AHA [mean ( s . d .) 9.8% (12.1%)]. QRISK2 substantially overestimated risk [mean ( s . d .) 15.5% (13.9%)]. Discrimination was not improved for ERS-RA (c-statistic = 0.69), QRISK2 or EULAR multiplier applied to ACC/AHA compared with ACC/AHA (c-statistic = 0.72 for all) or for FRS-ATP (c-statistic = 0.75). The net reclassification index for ERS-RA was low (-0.8% vs ACC/AHA and 2.3% vs FRS-ATP). The QRISK2, EULAR multiplier and ERS-RA algorithms did not predict CVD risk more accurately in patients with RA than CVD risk calculators developed for the general population. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke.

PubMed

Andersson, Charlotte; Preis, Sarah R; Beiser, Alexa; DeCarli, Charles; Wollert, Kai C; Wang, Thomas J; Januzzi, James L; Vasan, Ramachandran S; Seshadri, Sudha

2015-09-01

Growth differentiation factor-15 (GDF-15) and soluble (s)ST2 are markers of cardiac and vascular stress. We investigated the associations between circulating concentrations of these biomarkers and incident stroke and subclinical vascular brain injury in a sample from the Framingham Offspring cohort. We followed 3374 stroke- and dementia-free individuals (mean age, 59.0±9.7 years; 53% women) attending the Framingham Offspring sixth examination cycle 11.8±3.0 years for incident stroke. A subsample of 2463 individuals underwent brain magnetic resonance imaging and neuropsychological testing ≈4.0±1.7 years after the sixth examination. After adjustment for traditional cardiovascular risk factors, B-type natriuretic peptide, high-sensitivity C-reactive protein, and urine albumin levels, higher stress biomarker levels were associated cross-sectionally with lower brain volumes (β coefficients for intracranial volume comparing fourth [Q4] versus first biomarker [Q1] quartiles: -0.71% for GDF-15; P=0.002 and 0.47% for sST2; P=0.02) and worse performance on the visual reproduction test (β coefficients for Q4 versus Q1: -0.62 for GDF-15; P=0.009 and -0.40 for sST2; P=0.04). Higher GDF-15 concentrations were also associated with greater log-transformed white-matter hyperintensity volumes (β for Q4 versus Q1=0.19; P=0.01). Prospectively, a total of 203 (6%) individuals developed incident stroke/transient ischemic attack during follow-up. After multivariable adjustment, sST2 remained significantly associated with stroke/transient ischemic attack, hazard ratio for Q4 versus Q1 of 1.76, 95% confidence interval of 1.06 to 2.92, and P=0.03. Circulating GDF-15 and sST2 are associated with subclinical brain injury and cognitive impairment. Higher sST2 concentrations are also associated with incident stroke, suggesting potential links between cardiac stress biomarkers and brain injury. © 2015 American Heart Association, Inc.

Effects of an evidence-based computerized virtual clinician on low-density lipoprotein and non-high-density lipoprotein cholesterol in adults without cardiovascular disease: The Interactive Cholesterol Advisory Tool.

PubMed

Block, Robert C; Abdolahi, Amir; Niemiec, Christopher P; Rigby, C Scott; Williams, Geoffrey C

2016-12-01

There is a lack of research on the use of electronic tools that guide patients toward reducing their cardiovascular disease risk. We conducted a 9-month clinical trial in which participants who were at low (n = 100) and moderate (n = 23) cardiovascular disease risk-based on the National Cholesterol Education Program III's 10-year risk estimator-were randomized to usual care or to usual care plus use of an Interactive Cholesterol Advisory Tool during the first 8 weeks of the study. In the moderate-risk category, an interaction between treatment condition and Framingham risk estimate on low-density lipoprotein and non-high-density lipoprotein cholesterol was observed, such that participants in the virtual clinician treatment condition had a larger reduction in low-density lipoprotein and non-high-density lipoprotein cholesterol as their Framingham risk estimate increased. Perceptions of the Interactive Cholesterol Advisory Tool were positive. Evidence-based information about cardiovascular disease risk and its management was accessible to participants without major technical challenges. © The Author(s) 2015.

Prognosis of stable angina pectoris: why we need larger population studies with higher endpoint resolution

PubMed Central

Timmis, Adam D; Feder, Gene; Hemingway, Harry

2007-01-01

The prognosis of angina was described as “"unhappy” by the Framingham investigators and as little different from that of 1‐year survivors of acute myocardial infarction. Yet recent clinical trials now report that angina has a good prognosis with adverse outcomes reduced to “normal levels”. These disparate prognostic assessments may not be incompatible, applying as they do to population cohorts (Framingham) and selected participants in clinical trials. Comparisons between studies are further complicated by the absence of agreed case definitions for stable angina (contrast this with acute coronary syndromes). Our recent data show that for patients with recent onset symptoms attending chest pain clinics, angina remains a high‐risk diagnosis and although many patients receive symptomatic benefit from revascularisation, prognosis is usually unaffected. This leaves little room for complacency and, with angina the commonest initial manifestation of coronary artery disease, there is the opportunity for early detection, risk stratification and treatment to modify outcomes. Meanwhile, larger population‐based studies are needed to define the patient journey from earliest presentation through the various syndrome transitions to coronary or noncardiac death in order to increase understanding of the aetiological and prognostic differences between the different coronary disease phenotypes. PMID:16952966

Alimentary habits, physical activity, and Framingham global risk score in metabolic syndrome.

PubMed

Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo

2014-04-01

Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p < 0.001). We obtained a reduction for intermediate risk in 25.7% of subjects. After intervention, there was a significant reduction (p < 0.01) on cardiovascular age, this being more significant in groups DIP (5.2%) and DIPE (5.3%). Proposed interventions produced beneficial effects for reducing cardiovascular risk score. This study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases.

Effects of Ramadan fasting on cardiovascular risk factors: a prospective observational study.

PubMed

Nematy, Mohsen; Alinezhad-Namaghi, Maryam; Rashed, Masoud Mahdavi; Mozhdehifard, Mostafa; Sajjadi, Seyedeh Sania; Akhlaghi, Saeed; Sabery, Maryam; Mohajeri, Seyed Amir R; Shalaey, Neda; Moohebati, Mohsen; Norouzy, Abdolreza

2012-09-10

Previous research has shown that Ramadan fasting has beneficial effects on cardiovascular risk factors, however there are controversies. In the present study, the effect of Ramadan fasting on cardiovascular risk factors has been investigated. This is a prospective observational study that was carried out in a group of patients with at least one cardiovascular risk factor (including history of documented previous history of either coronary artery disease (CAD), metabolic syndrome or cerebro-vascular disease in past 10 y). Eighty two volunteers including 38 male and 44 female, aged 29-70 y, mean 54.0 ± 10 y, with a previous history of either coronary artery disease, metabolic syndrome or cerebro-vascular disease were recruited. Subjects attended the metabolic unit after at least 10 h fasting, before and after Ramadan who were been fasting for at least 10 days. A fasting blood sample was obtained, blood pressure was measured and body mass index (BMI) was calculated. Lipids profile, fasting blood sugar (FBS) and insulin, homocysteine (hcy), high-sensitivity C-reactive protein (hs-CRP) and complete blood count (CBC) were analyzed on all blood samples. A significant improvement in 10 years coronary heart disease risk (based on Framingham risk score) was found (13.0 ± 8 before Ramadan and 10.8 ±7 after Ramadan, P <0.001, t test).There was a significant higher HDL-c, WBC, RBC and platelet count (PLT), and lower plasma cholesterol, triglycerides, LDL-c, VLDL-c, systolic blood pressure, body mass index and waist circumference after Ramadan (P <0.05, t test). The changes in FBS, insulin, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), hcy, hs-CRP and diastolic blood pressure before and after Ramadan were not significant (P >0.05, t test). This study shows a significant improvement in 10 years coronary heart disease risk score and other cardiovascular risk factors such as lipids profile, systolic blood pressure, weight, BMI and waist circumference in subjects with a previous history of cardiovascular disease.

Plasma phosphatidylcholine concentrations of polyunsaturated fatty acids are differentially associated with hop bone mineral density and hip fracture in older adults: The Framingham Osteoporosis Study

USDA-ARS?s Scientific Manuscript database

Polyunsaturated fatty acids (PUFA) may influence bone health. Our objective was to examine associations between plasma phosphatidylcholine (PC) PUFA concentrations and hip measures: 1) femoral neck bone mineral density (FN-BMD) (n=765); 2) 4-y change in FN-BMD (n=556); and 3) hip fracture risk (n=76...

Short-term exposure to air pollution and digital vascular function.

PubMed

Ljungman, Petter L; Wilker, Elissa H; Rice, Mary B; Schwartz, Joel; Gold, Diane R; Koutrakis, Petros; Vita, Joseph A; Mitchell, Gary F; Vasan, Ramachandran S; Benjamin, Emelia J; Mittleman, Murray A; Hamburg, Naomi M

2014-09-01

We investigated associations between ambient air pollution and microvessel function measured by peripheral arterial tonometry between 2003 and 2008 in the Framingham Heart Study Offspring and Third Generation Cohorts. We measured particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), black carbon, sulfates, particle number, nitrogen oxides, and ozone by using fixed monitors, and we determined moving averages for 1-7 days preceding vascular testing. We examined associations between these exposures and hyperemic response to ischemia and baseline pulse amplitude, a measure of arterial tone (n = 2,369). Higher short-term exposure to air pollutants, including PM2.5, black carbon, and particle number was associated with higher baseline pulse amplitude. For example, higher 3-day average PM2.5 exposure was associated with 6.3% higher baseline pulse amplitude (95% confidence interval: 2.0, 10.9). However, there were no consistent associations between the air pollution exposures assessed and hyperemic response. Our findings in a community-based sample exposed to relatively low pollution levels suggest that short-term exposure to ambient particulate pollution is not associated with vasodilator response, but that particulate air pollution is associated with baseline pulse amplitude, suggesting potentially adverse alterations in baseline vascular tone or compliance. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cost-effectiveness of treating resistant hypertension with an implantable carotid body stimulator

PubMed Central

Young, KC; Teeters, JC; Benesch, CG; Bisognano, JD; Illig, KA

2013-01-01

Introduction The purposes of this study are to investigate the cost-effectiveness of an implantable carotid body stimulator (Rheos®) for treating resistant hypertension and determine the range of starting systolic blood pressure (SBP) values where the device remains cost-effective. Methods A Markov model compared a 20 mmHg drop in SBP from an initial level of 180 with Rheos® to failed medical management in a hypothetical 50-year old cohort. Direct costs (2007$), utilities and event rates for future myocardial infarction, stroke, heart failure and end-stage renal disease were modeled. Sensitivity analyses tested the assumptions in the model. Results The incremental cost-effectiveness ratio (ICER) for Rheos® was $64,400 per quality-adjusted life-year (QALY) using Framingham-derived event probabilities. The ICER was <$100,000/QALY for SBPs ≥142. A probability of device removal of <1% per year or SBP reductions of ≥24 mmHg were variables that decreased the ICER below $50,000/QALY. For cohort characteristics similar to ASCOT-BPLA trial participants, the ICER became $26,700/QALY. Two-way sensitivity analyses demonstrated that lowering SBP 12 mmHg from 220 or 21 mmHg from 140 were required. Conclusions Rheos® may be cost-effective, with an ICER between $50,000-$100,000/QALY. Cohort characteristics and efficacy are key to the cost-effectiveness of new therapies for resistant hypertension. PMID:19817936

The Mt. Hood challenge: cross-testing two diabetes simulation models.

PubMed

Brown, J B; Palmer, A J; Bisgaard, P; Chan, W; Pedula, K; Russell, A

2000-11-01

Starting from identical patients with type 2 diabetes, we compared the 20-year predictions of two computer simulation models, a 1998 version of the IMIB model and version 2.17 of the Global Diabetes Model (GDM). Primary measures of outcome were 20-year cumulative rates of: survival, first (incident) acute myocardial infarction (AMI), first stroke, proliferative diabetic retinopathy (PDR), macro-albuminuria (gross proteinuria, or GPR), and amputation. Standardized test patients were newly diagnosed males aged 45 or 75, with high and low levels of glycated hemoglobin (HbA(1c)), systolic blood pressure (SBP), and serum lipids. Both models generated realistic results and appropriate responses to changes in risk factors. Compared with the GDM, the IMIB model predicted much higher rates of mortality and AMI, and fewer strokes. These differences can be explained by differences in model architecture (Markov vs. microsimulation), different evidence bases for cardiovascular prediction (Framingham Heart Study cohort vs. Kaiser Permanente patients), and isolated versus interdependent prediction of cardiovascular events. Compared with IMIB, GDM predicted much higher lifetime costs, because of lower mortality and the use of a different costing method. It is feasible to cross-validate and explicate dissimilar diabetes simulation models using standardized patients. The wide differences in the model results that we observed demonstrate the need for cross-validation. We propose to hold a second 'Mt Hood Challenge' in 2001 and invite all diabetes modelers to attend.

[Brain Perfusion, Cognitive Functions, and Vascular Age in Middle Aged Patients With Essential Arterial Hypertension].

PubMed

Parfenov, V A; Ostroumova, T M; Pеrepelova, E M; Perepelov, V A; Kochetkov, A I; Ostroumova, O D

2018-05-01

This study aimed to assess the cognitive functions and cerebral blood flow measured with arterial spin labeling (ASL) and their possible correlations with vascular age in untreated middle-aged patients with grade 1-2 essential arterial hypertension (EAH). We examined 73 subjects aged 40-59 years (33 with EAH and 40 healthy volunteers [controls]). Neuropsychological assessment included Montreal Cognitive Assessment (MoCA), Trail Making test (part A and part B), Stroop Color and Word Test, verbal fluency test (phonemic verbal fluency and semantic verbal fluency), 10‑item word list learning task. All subjects underwent brain MRI. MRI protocol included ASL. Vascular age was calculated by two techniques - using Framingham Heart Study risk tables and SCORE project scales. Patients with EAH had lower performance on phonemic verbal fluency test and lower mean MoCA score (29.2±1.4 vs. 28.1±1.7 points) compared to controls (13.4±3.2, р=0.002; 29.2±1.4, p=0.001, respectively). White matter hyperintensities (WMH) were present in 7.5 % controls and in 51.5 % EAH patients (р=0.0002). Cerebral blood flow (CBF) in EAH patients was lower in both right (39.1±5.6 vs. 45.8±3.2 ml / 100 g / min) and left frontal lobes of the brain (39.2±6.2 и 45.2±3.6 ml / 100 g / min, respectively) compared to controls (р.

Comparing two correlated C indices with right-censored survival outcome: a one-shot nonparametric approach.

PubMed

Kang, Le; Chen, Weijie; Petrick, Nicholas A; Gallas, Brandon D

2015-02-20

The area under the receiver operating characteristic curve is often used as a summary index of the diagnostic ability in evaluating biomarkers when the clinical outcome (truth) is binary. When the clinical outcome is right-censored survival time, the C index, motivated as an extension of area under the receiver operating characteristic curve, has been proposed by Harrell as a measure of concordance between a predictive biomarker and the right-censored survival outcome. In this work, we investigate methods for statistical comparison of two diagnostic or predictive systems, of which they could either be two biomarkers or two fixed algorithms, in terms of their C indices. We adopt a U-statistics-based C estimator that is asymptotically normal and develop a nonparametric analytical approach to estimate the variance of the C estimator and the covariance of two C estimators. A z-score test is then constructed to compare the two C indices. We validate our one-shot nonparametric method via simulation studies in terms of the type I error rate and power. We also compare our one-shot method with resampling methods including the jackknife and the bootstrap. Simulation results show that the proposed one-shot method provides almost unbiased variance estimations and has satisfactory type I error control and power. Finally, we illustrate the use of the proposed method with an example from the Framingham Heart Study. Copyright © 2014 John Wiley & Sons, Ltd.

The utility of observational studies in clinical decision making: lessons learned from statin trials.

PubMed

Foody, JoAnne M; Mendys, Phillip M; Liu, Larry Z; Simpson, Ross J

2010-05-01

Contemporary clinical decision making is well supported by a wide variety of information sources, including clinical practice guidelines, position papers, and insights from randomized controlled trials (RCTs). Much of our fundamental understanding of cardiovascular risk factors is based on multiple observations from major epidemiologic studies, such as The Seven Country Studies and the US-based Framingham Heart Study. These studies provided the framework for the development of clinical practice guidelines, including the National Cholesterol Education Program Adult Treatment Panel series. The objective of this article is to highlight the value of observational studies as a complement to clinical trial data for clinical decision making in real-world practice. Although RCTs are still the benchmark for assessing clinical efficacy and safety of a specific therapeutic approach, they may be of limited utility to practitioners who must then adapt the lessons learned from the trial into the patient care environment. The use of well-structured observational studies can improve our understanding of the translation of clinical trials into clinical practice, as demonstrated here with the example of statins. Although such studies have their own limitations, improved techniques for design and analysis have reduced the impact of bias and confounders. The introduction of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines has provided more uniformity for such studies. When used together with RCTs, observational studies can enhance our understanding of effectiveness and utility in real-world clinical practice. In the examples of statin observational studies, the results suggest that relative effectiveness of different statins and potential impact of switching statins should be carefully considered in treating individual patients by practicing physicians.

Obesity, hypertension and aldosterone: is leptin the link?

PubMed

Xie, Ding; Bollag, Wendy B

2016-07-01

Obesity is a serious health hazard with rapidly increasing prevalence in the United States. In 2014, the World Health Organization estimated that nearly 2 billion people worldwide were overweight with an estimated 600 million of these obese. Obesity is associated with many chronic diseases, including cardiovascular disease and hypertension. Data from the Framingham Heart study suggest that approximately 78% of the risk for hypertension in men and 65% in women is related to excess body weight, a relationship that is further supported by studies showing increases in blood pressure with weight gain and decreases with weight loss. However, the exact mechanism by which excess body fat induces hypertension remains poorly understood. Several clinical studies have demonstrated elevated plasma aldosterone levels in obese individuals, especially those with visceral adiposity, with decreased aldosterone levels measured in concert with reduced blood pressure following weight loss. Since aldosterone is a mineralocorticoid hormone that regulates blood volume and pressure, serum aldosterone levels may link obesity and hypertension. Nevertheless, the mechanism by which obesity induces aldosterone production is unclear. A recent study by Belin de Chantemele and coworkers suggests that one adipose-released factor, leptin, is a direct agonist for aldosterone secretion; other adipose-related factors may also contribute to elevated aldosterone levels in obesity, such as very low-density lipoprotein (VLDL), the levels of which are elevated in obesity and which also directly stimulates aldosterone biosynthesis. This focused review explores the possible roles of leptin and VLDL in modulating aldosterone secretion to underlie obesity-associated hypertension. © 2016 Society for Endocrinology.

Effect of Current Dietary Recommendations on Weight Loss and Cardiovascular Risk Factors.

PubMed

Jenkins, David J A; Boucher, Beatrice A; Ashbury, Fredrick D; Sloan, Margaret; Brown, Patrick; El-Sohemy, Ahmed; Hanley, Anthony J; Willett, Walter; Paquette, Melanie; de Souza, Russell J; Ireland, Christopher; Kwan, Natalie; Jenkins, Amy; Pichika, Sathish C; Kreiger, Nancy

2017-03-07

Dietary recommendations emphasize increased consumption of fruit, vegetables, and whole grain cereals for prevention of chronic disease. This study assessed the effect of dietary advice and/or food provision on body weight and cardiovascular disease risk factors. Healthy overweight men (n = 209) and women (n = 710), mean age 44.7 years, body mass index [BMI] 32.4 kg/m 2 , were randomized between November 2005 and August 2009 to receive Health Canada's food guide (control, n = 486) or 1 of 3 interventions: dietary advice consistent with both Dietary Approaches to Stop Hypertension (DASH) and dietary portfolio principles (n = 145); weekly food provision reflecting this advice (n = 148); or food delivery plus advice (n = 140). Interventions lasted 6 months with 12-month follow-up. Semiquantitative food frequency questionnaires and fasting blood, anthropometric and blood pressure measurements were obtained at baseline, 6 months, and 18 months. Participant retention at 6 and 18 months was 91% and 81%, respectively, after food provision compared to 67% and 57% when no food was provided (p < 0.0001). Test and control treatments showed small reductions in body weight (-0.8 to -1.2 kg), waist circumference (-1.1 to -1.9 cm), and mean arterial pressure (0.0 to -1.1 mm Hg) at 6 months and Framingham coronary heart disease risk score at 18 months (-0.19 to -0.42%), which were significant overall. Outcomes did not differ among test and control groups. Provision of foods increased retention but only modestly increased intake of recommended foods. Current dietary recommendations showed small overall benefits in coronary heart disease risk factors. Additional dietary strategies to maximize these benefits are required. (Fruits, Vegetables, and Whole Grains: A Community-based Intervention; NCT00516620). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Prevalence and prognostic implications of anaemia and iron deficiency in Tanzanian patients with heart failure.

PubMed

Makubi, Abel; Hage, Camilla; Lwakatare, Johnson; Mmbando, Bruno; Kisenge, Peter; Lund, Lars H; Rydén, Lars; Makani, Julie

2015-04-01

To determine the prevalence, correlates and prognostic implications of anaemia and iron deficiency (ID) in patients with heart failure (HF) in Tanzania. This was a cross-sectional and prospective observational study conducted at Muhimbili National Hospital in Dar es Salaam, Tanzania. Patients were ≥ 18 years of age, with HF defined according to the Framingham criteria. The primary outcome was anaemia and the secondary outcome was a composite of hospitalisation for HF or all-cause mortality. A total of 401 HF patients (median age 56 years, IQR 41-67 years; women 51%) were included. The prevalence of anaemia was 57%. The overall prevalence of ID was 49% distributed as 69% versus 21% in subjects with and without anaemia (p < 0.001). Normocytic anaemia was seen in 18% of the patients while none had macrocytic anaemia. The risk of having anaemia was positively associated with residency outside Dar es Salaam (OR 1.72 (95% CI 1.02 to 2.89); p = 0.038), atrial fibrillation (4.12 (1.60 to 10.61); p=0.003), LVEF < 45% (2.70 (1.57 to 4.67); p < 0.001) and negatively (ORs per unit decrease) with creatinine clearance (0.98 (0.97 to 0.99); p = 0.012) and total cholesterol (0.78 (0.63 to 0.98); p = 0.029). One-year survival free from a composite endpoint was 70%. The presence of ID anaemia increased the likelihood for an event (HR 2.67; 95% CI 1.39 to 5.07; p = 0.003), while anaemia without ID did not influence the risk. ID anaemia was common in Tanzanian patients with HF and was independently associated with the risk for hospitalisation or death. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Physical activity measured by accelerometry and its associations with cardiac structure and vascular function in young and middle-aged adults.

PubMed

Andersson, Charlotte; Lyass, Asya; Larson, Martin G; Spartano, Nicole L; Vita, Joseph A; Benjamin, Emelia J; Murabito, Joanne M; Esliger, Dale W; Blease, Susan J; Hamburg, Naomi M; Mitchell, Gary F; Vasan, Ramachandran S

2015-03-19

Physical activity is associated with several health benefits, including lower cardiovascular disease risk. The independent influence of physical activity on cardiac and vascular function in the community, however, has been sparsely investigated. We related objective measures of moderate- to vigorous-intensity physical activity (MVPA, assessed by accelerometry) to cardiac and vascular indices in 2376 participants of the Framingham Heart Study third generation cohort (54% women, mean age 47 years). Using multivariable regression models, we related MVPA to the following echocardiographic and vascular measures: left ventricular mass, left atrial and aortic root sizes, carotid-femoral pulse wave velocity, augmentation index, and forward pressure wave. Men and women engaged in MVPA 29.9±21.4 and 25.5±19.4 min/day, respectively. Higher values of MVPA (per 10-minute increment) were associated with lower carotid-femoral pulse wave velocity (estimate -0.53 ms/m; P=0.006) and lower forward pressure wave (estimate -0.23 mm Hg; P=0.03) but were not associated with augmentation index (estimate 0.13%; P=0.25). MVPA was associated positively with log(e) left ventricular mass (estimate 0.006 log(e) [g/m(2)]; P=0.0003), left ventricular wall thickness (estimate 0.07 mm; P=0.0001), and left atrial dimension (estimate 0.10 mm; P=0.01). MVPA also tended to be positively associated with aortic root dimension (estimate 0.05 mm; P=0.052). Associations of MVPA with cardiovascular measures were similar, in general, for bouts lasting <10 versus ≥10 minutes. In our community-based sample, greater physical activity was associated with lower vascular stiffness but with higher echocardiographic left ventricular mass and left atrial size. These findings suggest complex relations of usual levels of physical activity and cardiovascular remodeling. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Assessment of vitamin D and its association with cardiovascular disease risk factors in an adult migrant population: an audit of patient records at a Community Health Centre in Kensington, Melbourne, Australia.

PubMed

Ruwanpathirana, Thilanga; Reid, Christopher M; Owen, Alice J; Fong, David P S; Gowda, Usha; Renzaho, Andre M N

2014-11-11

Vitamin D deficiency is a global public health problem associated with increased risk of cardio-metabolic diseases and osteoarthritis. Migrants with dark skin settled in temperate climates are at greater risk of both vitamin D deficiency and cardiovascular diseases. This study aims to identify the risk of vitamin D deficiency and associations with cardiovascular disease in a migrant population in Australia. An audit was carried out at a Community Health Service in Kensington, Melbourne which, services a large migrant population. Data from the clinical records of all adults who visited the medical centre at least once during the period from 1st January 2010 to 31st December 2012 was extracted. The future (10 year) coronary heart disease risk was estimated using Framingham Risk Score. The centre has given higher priority to vitamin D testing in migrants, those middle-aged, females and those with diabetes and osteoarthritis. Migrants from countries located in lower latitude regions (Latitude N230 to S230) were 1.48 (95% C.I. 1.32-1.65) times more likely to develop vitamin D deficiency post migration and 0.44 (95% C.I. 0.31-0.62) times less likely to have a >15% 10-year risk of coronary heart disease when compared to their Australian-born counterparts. Adherence to a high risk strategy for vitamin D testing was observed in the centre. Pre-migration latitude is an important factor for vitamin D deficiency (lower the latitude higher the risk) and in predicting future risk of cardiovascular disease in migrants. These findings suggest that a targeted approach for vitamin D testing, including zone of origin might better identify individuals at higher risk of both vitamin D deficiency and cardiovascular disease.

Economic analysis of Heart and Stroke Foundation of Ontario’s Hypertension Management Initiative

PubMed Central

de Oliveira, Claire; Wijeysundera, Harindra C; Tobe, Sheldon W; Lum-Kwong, Margaret Moy; Von Sychowski, Shirley; Wang, Xuesong; Tu, Jack V; Krahn, Murray D

2012-01-01

Objectives Hypertension is suboptimally treated in primary care settings. We evaluated the cost-effectiveness of the Heart and Stroke Foundation of Ontario’s Hypertension Management Initiative (HMI), an interdisciplinary, evidence-informed chronic disease management model for primary care that focuses on improving blood pressure management and control by primary care providers and patients according to clinical best practice guidelines. Methods The perspective of our analysis was that of the Ontario Ministry of Health and Long-Term Care with a lifetime horizon and 5% annual discount rate. Using data from a prospective cohort study from the HMI, we created two matched groups: pre-HMI (standard care), and post-HMI (n = 1720). For each patient, we estimated the 10-year risk of cardiovascular disease (CVD) using the Framingham risk equation and life expectancy from life tables. Long-term health care costs incurred with physician visits, acute and chronic care hospitalizations, emergency department visits, same-day surgeries, and medication use were determined through linkage to administrative databases, using a bottom-up approach. Results The HMI intervention was associated with significant reductions in systolic blood pressure (126 mmHg vs 134 mmHg with standard care; P-value < 0.001). These improvements were associated with a reduction in the 10-year risk of CVD (9.5% risk vs 10.7% in standard care; P-value < 0.001) and a statistically significant improvement in discounted life expectancy (9.536 years vs 9.516 in standard care; P-value < 0.001). The HMI cohort had a discounted mean lifetime cost of $22,884 CAD vs $22,786 CAD for standard care, with an incremental cost-effectiveness ratio of $4939 CAD per life-year gained. Conclusion We found that the HMI is a cost-effective means of providing evidence-informed, chronic disease management in primary care to patients with hypertension. PMID:23180969

Circulating brain-derived neurotrophic factor concentrations and the risk of cardiovascular disease in the community.

PubMed

Kaess, Bernhard M; Preis, Sarah R; Lieb, Wolfgang; Beiser, Alexa S; Yang, Qiong; Chen, Tai C; Hengstenberg, Christian; Erdmann, Jeanette; Schunkert, Heribert; Seshadri, Sudha; Vasan, Ramachandran S; Assimes, Themistocles L; Deloukas, Panos; Holm, Hilma; Kathiresan, Sekar; König, Inke R; McPherson, Ruth; Reilly, Muredach P; Roberts, Robert; Samani, Nilesh J; Stewart, Alexandre F R

2015-03-11

Brain-derived neurotrophic factor (BDNF) is a pleiotropic peptide involved in maintaining endothelial integrity. It is unknown if circulating BDNF levels are associated with risk of cardiovascular disease (CVD). We prospectively investigated the association of circulating BDNF levels with cardiovascular events and mortality in 3687 participants (mean age 65 years, 2068 women) from the Framingham Heart Study (FHS). Using a common nonsynonomous single nucleotide polymorphism (SNP) in the BDNF gene (rs6265), we then performed a Mendelian randomization experiment in the CARDIoGRAM (Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis) consortium (>22,000 coronary artery disease [CAD] cases, >60,000 controls) to investigate whether SNP rs6265 was associated with CAD in CARDIoGRAM and, if so, whether the effect estimate differed from that predicted based on FHS data. On follow-up (median 8.9 years), 467 individuals (261 women) in FHS experienced a CVD event, and 835 (430 women) died. In multivariable-adjusted Cox regression, serum BDNF was associated inversely with CVD risk (hazard ratio [HR] per 1-SD increase 0.88, 95% CI 0.80 to 0.97, P=0.01) and with mortality (HR 0.87, 95% CI 0.80 to 0.93, P=0.0002). SNP rs6265 was associated with BDNF concentrations (0.772 ng/mL increase per minor allele copy) in FHS. In CARDIoGRAM, SNP rs6265 was associated with CAD (odds ratio 0.957, 95% CI 0.923 to 0.992), a magnitude consistent with the predicted effect (HR per minor allele copy 0.99, 95% CI 0.98 to 1.0; P=0.06 for difference between predicted and observed effect). Higher serum BDNF is associated with a decreased risk of CVD and mortality. Mendelian randomization suggests a causal protective role of BDNF in the pathogenesis of CVD. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Association between liver fibrosis and coronary heart disease risk in patients with nonalcoholic fatty liver disease.

PubMed

Dogan, Serkan; Celikbilek, Mehmet; Yilmaz, Yunus K; Sarikaya, Savas; Zararsiz, Gokmen; Serin, Halil I; Borekci, Elif; Akyol, Lütfi; Pirti, Ilyas; Davarci, Sena E

2015-03-01

Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as the most common cause of chronic liver disease worldwide. It has been shown that NAFLD in adults is associated with increased risk of coronary heart disease (CHD). Because of the limitations of liver biopsy, noninvasive scoring indexes such as the NAFLD fibrosis score (NFS) were developed. The Framingham risk score (FRS) provides an estimate of CHD risk. In our study we aimed to investigate whether the severity of liver fibrosis estimated with the NFS is associated with a higher risk of CHD among individuals with ultrasonography-diagnosed NAFLD. A total of 155 patients and controls (81 patients with NAFLD and 74 controls) with ages ranging from 18 to 70 years were enrolled in this cross-sectional prospective study. Demographic, anthropometric, clinical, and laboratory data were obtained from each individual. The NAFLD patients were divided into subgroups on the basis of the severity of fatty liver. The FRS and NFS were adopted to predict the risk of CHD and the severity of hepatic fibrosis. In our study, we found that the FRS was higher in NAFLD patients than in controls (P<0.05). According to the FRS category, NFSs were higher in the intermediate/high probability CHD risk group in NAFLD (P<0.05). In multiple models, only age, sex, cholesterol, and HDL were independently associated with intermediate/high CHD risk (P<0.05). We also found a positive correlation between the NFS and the FRS (r=0.373, P<0.001). The optimum NFS cutoff point for identifying intermediate/high CHD risk in NAFLD patients was -2.1284, with a sensitivity and specificity of 95.20 and 48.30%, respectively. The predictive performance of the NFS in the determination of intermediate/high CHD risk in NAFLD patients was found to be 72% based on the area under the curve value. The FRS is associated with the NFS in NAFLD. The assessment of liver fibrosis may be useful for the risk stratification of CHD in the absence of liver biopsy in clinical practice.

Use of Chronic Kidney Disease to Enhance Prediction of Cardiovascular Risk in Those at Medium Risk.

PubMed

Chia, Yook Chin; Lim, Hooi Min; Ching, Siew Mooi

2015-01-01

Based on global cardiovascular (CV) risk assessment for example using the Framingham risk score, it is recommended that those with high risk should be treated and those with low risk should not be treated. The recommendation for those of medium risk is less clear and uncertain. We aimed to determine whether factoring in chronic kidney disease (CKD) will improve CV risk prediction in those with medium risk. This is a 10-year retrospective cohort study of 905 subjects in a primary care clinic setting. Baseline CV risk profile and serum creatinine in 1998 were captured from patients record. Framingham general cardiovascular disease risk score (FRS) for each patient was computed. All cardiovascular disease (CVD) events from 1998-2007 were captured. Overall, patients with CKD had higher FRS risk score (25.9% vs 20%, p = 0.001) and more CVD events (22.3% vs 11.9%, p = 0.002) over a 10-year period compared to patients without CKD. In patients with medium CV risk, there was no significant difference in the FRS score among those with and without CKD (14.4% vs 14.6%, p = 0.84) However, in this same medium risk group, patients with CKD had more CV events compared to those without CKD (26.7% vs 6.6%, p = 0.005). This is in contrast to patients in the low and high risk group where there was no difference in CVD events whether these patients had or did not have CKD. There were more CV events in the Framingham medium risk group when they also had CKD compared those in the same risk group without CKD. Hence factoring in CKD for those with medium risk helps to further stratify and identify those who are actually at greater risk, when treatment may be more likely to be indicated.

Use of Chronic Kidney Disease to Enhance Prediction of Cardiovascular Risk in Those at Medium Risk

PubMed Central

Chia, Yook Chin; Lim, Hooi Min; Ching, Siew Mooi

2015-01-01

Based on global cardiovascular (CV) risk assessment for example using the Framingham risk score, it is recommended that those with high risk should be treated and those with low risk should not be treated. The recommendation for those of medium risk is less clear and uncertain. We aimed to determine whether factoring in chronic kidney disease (CKD) will improve CV risk prediction in those with medium risk. This is a 10-year retrospective cohort study of 905 subjects in a primary care clinic setting. Baseline CV risk profile and serum creatinine in 1998 were captured from patients record. Framingham general cardiovascular disease risk score (FRS) for each patient was computed. All cardiovascular disease (CVD) events from 1998–2007 were captured. Overall, patients with CKD had higher FRS risk score (25.9% vs 20%, p = 0.001) and more CVD events (22.3% vs 11.9%, p = 0.002) over a 10-year period compared to patients without CKD. In patients with medium CV risk, there was no significant difference in the FRS score among those with and without CKD (14.4% vs 14.6%, p = 0.84) However, in this same medium risk group, patients with CKD had more CV events compared to those without CKD (26.7% vs 6.6%, p = 0.005). This is in contrast to patients in the low and high risk group where there was no difference in CVD events whether these patients had or did not have CKD. There were more CV events in the Framingham medium risk group when they also had CKD compared those in the same risk group without CKD. Hence factoring in CKD for those with medium risk helps to further stratify and identify those who are actually at greater risk, when treatment may be more likely to be indicated. PMID:26496190

CVD-predictive performances of "a body shape index" versus simple anthropometric measures: Tehran lipid and glucose study.

PubMed

Bozorgmanesh, Mohammadreza; Sardarinia, Mahsa; Hajsheikholeslami, Farhad; Azizi, Fereidoun; Hadaegh, Farzad

2016-02-01

To examine whether a body shape index (ABSI) calculated by using waist circumference (WC) adjusted for height and weight could improve the predictive performances for cardiovascular disease (CVD) of the Framingham's general CVD algorithm and to compare its predictive performances with other anthropometric measures. We analyzed data on a 10-year population-based follow-up of 8,248 (4,471 women) individuals aged ≥30 years, free of CVD at baseline. CVD risk was estimated for a 1 SD increment in ABSI, body mass index (BMI), waist-to-hip ratio (WHpR) and waist-to-height ratio (WHtR), by incorporating them, one at a time, into multivariate accelerated failure time models. ABSI was associated with multivariate-adjusted increased risk of incident CVD among both men (1.26, 95% CI 1.09-1.46) and women (1.17, 1.03-1.32). Among men, for a one-SD increment, ABSI conferred a greater increase in the hazard of CVD [1.26 (1.09-1.46)] than did BMI [1.06 (0.94-1.20)], WC [1.15(1.03-1.28)], WHpR [1.02 (1.01-1.03)] and WHtR [1.16 (1.02-1.31)], and the corresponding figures among women were 1.17 (1.03-1.32), 1.02 (0.90-1.16), 1.11 (0.98-1.27), 1.03 (1.01-1.05) and 1.14 (0.99-1.03), respectively. ABSI as well as other anthropometric measures failed to add to the predictive ability of the Framingham general CVD algorithm either. Although ABSI could not improve the predictability of the Framingham algorithm, it provides more information than other traditional anthropometric measures in settings where information on traditional CVD risk factors are not available, and it can be used as a practical criterion to predict adiposity-related health risks in clinical assessments.

Mendelian randomization analysis of a time-varying exposure for binary disease outcomes using functional data analysis methods.

PubMed

Cao, Ying; Rajan, Suja S; Wei, Peng

2016-12-01

A Mendelian randomization (MR) analysis is performed to analyze the causal effect of an exposure variable on a disease outcome in observational studies, by using genetic variants that affect the disease outcome only through the exposure variable. This method has recently gained popularity among epidemiologists given the success of genetic association studies. Many exposure variables of interest in epidemiological studies are time varying, for example, body mass index (BMI). Although longitudinal data have been collected in many cohort studies, current MR studies only use one measurement of a time-varying exposure variable, which cannot adequately capture the long-term time-varying information. We propose using the functional principal component analysis method to recover the underlying individual trajectory of the time-varying exposure from the sparsely and irregularly observed longitudinal data, and then conduct MR analysis using the recovered curves. We further propose two MR analysis methods. The first assumes a cumulative effect of the time-varying exposure variable on the disease risk, while the second assumes a time-varying genetic effect and employs functional regression models. We focus on statistical testing for a causal effect. Our simulation studies mimicking the real data show that the proposed functional data analysis based methods incorporating longitudinal data have substantial power gains compared to standard MR analysis using only one measurement. We used the Framingham Heart Study data to demonstrate the promising performance of the new methods as well as inconsistent results produced by the standard MR analysis that relies on a single measurement of the exposure at some arbitrary time point. © 2016 WILEY PERIODICALS, INC.

Use of Longitudinal Data in Genetic Studies in the Genome-wide Association Studies Era: Summary of Group 14

PubMed Central

Kerner, Berit; North, Kari E; Fallin, M Daniele

2010-01-01

Participants analyzed actual and simulated longitudinal data from the Framingham Heart Study for various metabolic and cardiovascular traits. The genetic information incorporated into these investigations ranged from selected single-nucleotide polymorphisms to genome-wide association arrays. Genotypes were incorporated using a broad range of methodological approaches including conditional logistic regression, linear mixed models, generalized estimating equations, linear growth curve estimation, growth modeling, growth mixture modeling, population attributable risk fraction based on survival functions under the proportional hazards models, and multivariate adaptive splines for the analysis of longitudinal data. The specific scientific questions addressed by these different approaches also varied, ranging from a more precise definition of the phenotype, bias reduction in control selection, estimation of effect sizes and genotype associated risk, to direct incorporation of genetic data into longitudinal modeling approaches and the exploration of population heterogeneity with regard to longitudinal trajectories. The group reached several overall conclusions: 1) The additional information provided by longitudinal data may be useful in genetic analyses. 2) The precision of the phenotype definition as well as control selection in nested designs may be improved, especially if traits demonstrate a trend over time or have strong age-of-onset effects. 3) Analyzing genetic data stratified for high-risk subgroups defined by a unique development over time could be useful for the detection of rare mutations in common multi-factorial diseases. 4) Estimation of the population impact of genomic risk variants could be more precise. The challenges and computational complexity demanded by genome-wide single-nucleotide polymorphism data were also discussed. PMID:19924713

The inter-arm difference in systolic blood pressure is a novel risk marker for subclinical atherosclerosis in patients with type 2 diabetes.

PubMed

Tanaka, Yoshimitsu; Fukui, Michiaki; Tanaka, Muhei; Fukuda, Yukiko; Mitsuhashi, Kazuteru; Okada, Hiroshi; Yamazaki, Masahiro; Hasegawa, Goji; Yoshioka, Keiji; Nakamura, Naoto

2014-06-01

Recent studies have suggested that the inter-arm blood pressure difference (IAD) is associated with cardiovascular events and mortality. The aim of this study was to assess whether the IAD could be a marker for subclinical atherosclerosis in patients with type 2 diabetes who are at high risk of cardiovascular disease (CVD). In a cross-sectional retrospective study of 206 Japanese patients with type 2 diabetes aged 49-76 years, we examined the correlation of the IAD with the carotid intima-media thickness (IMT), ankle-brachial index (ABI) or cardio ankle vascular index (CAVI). The IAD was positively correlated with the maximum IMT (r=0.266, P<0.0001), mean IMT (r=0.209, P=0.00726) or CAVI (r=0.240, P=0.0005). The IAD was higher in patients with CVD than in those without (P=0.0020). A multiple linear regression analysis demonstrated that the IAD was an independent determinant of maximum IMT (β=0.169, P=0.0167), mean IMT (β=0.178, P=0.0153), ABI (β=-0.222, P=0.0033) or CAVI (β=0.213, P=0.0011) after adjusting for known risk factors. The area under the receiver operating characteristic curve (AUC) of the IAD as a predictor of subclinical atherosclerosis was similar to the AUC of the Framingham 10-year coronary heart disease risk score. In conclusion, the IAD could be a novel risk marker for subclinical atherosclerosis in patients with type 2 diabetes.

Black women with polycystic ovary syndrome (PCOS) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with PCOS [corrected].

PubMed

Hillman, Jennifer K; Johnson, Lauren N C; Limaye, Meghana; Feldman, Rebecca A; Sammel, Mary; Dokras, Anuja

2014-02-01

To determine the prevalence of metabolic syndrome (MetSyn) and Framingham cardiovascular disease (CVD) risk in white and black adolescents and adult women with polycystic ovary syndrome (PCOS) compared with controls. Retrospective cohort study. Center for PCOS. Subjects with PCOS with data on race and cardiometabolic risk (n = 519). Controls were age and race matched from the National Health and Nutrition Examination Survey (NHANES) population (1999-2006). None. MetSyn, coronary heart disease risk, and general CVD risk. Black adolescents and young adults with PCOS had an increased prevalence of MetSyn compared with their white counterparts (adolescents relative risk 2.65 [95% confidence interval 1.29-5.4], adults relative risk 1.44 [95% confidence interval 1.21-2.6]). In contrast, there was no difference in risk of MetSyn between black and white adolescents and adult women in the NHANES dataset. After controlling for age and body mass index, black women with PCOS had a significantly increased prevalence of low high-density lipoprotein and high glucose. The general CVD risk was significantly increased in black adults with PCOS. This is the first study to comprehensively demonstrate increased risk of MetSyn in both black adolescents and adult women with PCOS compared with white subjects with PCOS. This racial disparity was not present in the NHANES controls. Longitudinal studies are needed to assess the independent impact of PCOS and race on CVD risk in women. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.