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...

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 ...

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...

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.

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...

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...

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.

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.

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...

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.

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.

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

Dietary intake of fiber and risk of knee osteoarthritis in two U.S. prospective cohorts

USDA-ARS?s Scientific Manuscript database

Objectives: Dietary fiber reduces body weight and inflammation both of which are linked with knee osteoarthritis (OA). We examined the association between fiber intake and risk of knee OA. Methods: We used data from the Osteoarthritis Initiative (OAI) of 4796 participants and Framingham Offspring Os...

Carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults in the Framingham Offspring Cohort

USDA-ARS?s Scientific Manuscript database

Diet may influence circulating adiponectin levels by improving insulin sensitivity. We examined the associations between carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults aged 26–81 y (n= 979 men and 1227 women). Dietary intakes were assessed using a FFQ. Fasting...

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.

The development of the Mediterranean-Style Dietary Pattern Score and its application to the American diet in the Framingham Offspring Cohort

USDA-ARS?s Scientific Manuscript database

Previous Mediterranean diet scores were simple to apply but may not be appropriate for non-Mediterranean populations. We developed a Mediterranean-Style Dietary Pattern Score (MSDPS) to assess the conformity of an individual’s diet to a traditional Mediterranean-style diet. The MSDPS is based on the...

Left ventricular mass, blood pressure, and lowered cognitive performance in the Framingham offspring.

PubMed

Elias, Merrill F; Sullivan, Lisa M; Elias, Penelope K; D'Agostino, Ralph B; Wolf, Philip A; Seshadri, Sudha; Au, Rhoda; Benjamin, Emelia J; Vasan, Ramachandran S

2007-03-01

The purpose of this study was to determine whether echocardiographic left ventricular mass is related to cognitive performance beyond casual blood pressure adjusting for the influence of other vascular risk factors. We used multivariable regression analyses to relate left ventricular mass assessed at a routine examination (1995-1998) to measures of cognitive ability obtained routinely (1998-2001) in 1673 Framingham Offspring Study participants (56% women; mean age: 57 years) free from stroke, transient ischemic attack, and dementia. We adjusted for the following covariates hierarchically: (1) age, education, sex, body weight, height, interval between left ventricular mass measurement and neuropsychological testing (basic model); (2) basic model+blood pressure+treatment for hypertension; and (3) basic model+blood pressure+treatment for hypertension+vascular risk factors and prevalent cardiovascular disease. For the basic model, left ventricular mass was inversely associated with abstract reasoning (similarities), visual-spatial memory and organization, and verbal memory. For the basic model+blood pressure+treatment for hypertension, left ventricular mass was inversely associated with similarities and visual-spatial memory and organization. For the basic+blood pressure+treatment for hypertension+risk factors+cardiovascular disease model, no significant associations were observed. Echocardiographic left ventricular mass is associated with cognitive performance beyond casual and time-averaged systolic blood pressure, but this association is attenuated and rendered nonsignificant with additional adjustment for cardiovascular risk factors and cardiovascular disease, thus suggesting that these variables play an important role in mediating the association between left ventricular mass and cognition.

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.

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.

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

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

Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study.

PubMed

Talmud, Philippa J; Hingorani, Aroon D; Cooper, Jackie A; Marmot, Michael G; Brunner, Eric J; Kumari, Meena; Kivimäki, Mika; Humphries, Steve E

2010-01-14

To assess the performance of a panel of common single nucleotide polymorphisms (genotypes) associated with type 2 diabetes in distinguishing incident cases of future type 2 diabetes (discrimination), and to examine the effect of adding genetic information to previously validated non-genetic (phenotype based) models developed to estimate the absolute risk of type 2 diabetes. Workplace based prospective cohort study with three 5 yearly medical screenings. 5535 initially healthy people (mean age 49 years; 33% women), of whom 302 developed new onset type 2 diabetes over 10 years. Non-genetic variables included in two established risk models-the Cambridge type 2 diabetes risk score (age, sex, drug treatment, family history of type 2 diabetes, body mass index, smoking status) and the Framingham offspring study type 2 diabetes risk score (age, sex, parental history of type 2 diabetes, body mass index, high density lipoprotein cholesterol, triglycerides, fasting glucose)-and 20 single nucleotide polymorphisms associated with susceptibility to type 2 diabetes. Cases of incident type 2 diabetes were defined on the basis of a standard oral glucose tolerance test, self report of a doctor's diagnosis, or the use of anti-diabetic drugs. A genetic score based on the number of risk alleles carried (range 0-40; area under receiver operating characteristics curve 0.54, 95% confidence interval 0.50 to 0.58) and a genetic risk function in which carriage of risk alleles was weighted according to the summary odds ratios of their effect from meta-analyses of genetic studies (area under receiver operating characteristics curve 0.55, 0.51 to 0.59) did not effectively discriminate cases of diabetes. The Cambridge risk score (area under curve 0.72, 0.69 to 0.76) and the Framingham offspring risk score (area under curve 0.78, 0.75 to 0.82) led to better discrimination of cases than did genotype based tests. Adding genetic information to phenotype based risk models did not improve discrimination and provided only a small improvement in model calibration and a modest net reclassification improvement of about 5% when added to the Cambridge risk score but not when added to the Framingham offspring risk score. The phenotype based risk models provided greater discrimination for type 2 diabetes than did models based on 20 common independently inherited diabetes risk alleles. The addition of genotypes to phenotype based risk models produced only minimal improvement in accuracy of risk estimation assessed by recalibration and, at best, a minor net reclassification improvement. The major translational application of the currently known common, small effect genetic variants influencing susceptibility to type 2 diabetes is likely to come from the insight they provide on causes of disease and potential therapeutic targets.

Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study2

PubMed Central

Cho, Eunyoung; Zeisel, Steven H; Jacques, Paul; Selhub, Jacob; Dougherty, Lauren; Colditz, Graham A; Willett, Walter C

2008-01-01

Background: Epidemiologic studies of choline and betaine intakes have been sparse because a food-composition database was not available until recently. The physiologic relevance of a variation in dietary choline and betaine in the general population and the validity of intake assessed by food-frequency questionnaire (FFQ) have not been evaluated. Objective: This study was conducted to examine the physiologic relevance and validity of choline and betaine intakes measured by an FFQ. Design: We examined the relations between choline and betaine intakes measured by FFQ and plasma total homocysteine (tHcy) concentrations in 1960 participants from the Framingham Offspring Study. Results: Higher intakes of dietary choline and betaine were related to lower tHcy concentrations independent of other determinants, including folate and other B vitamins. For the lowest and highest quintiles of dietary choline plus betaine, the multivariate geometric means for tHcy were 10.9 and 9.9 μmol/L (P for trend < 0.0001). The inverse association was manifested primarily in participants with low folate intakes (P for interaction < 0.0001). Among participants with folate intakes ≤250 μg/d, the geometric mean tHcy concentrations in the lowest and highest quintiles of choline plus betaine intakes were 12.4 and 10.2 μmol/L (P for trend < 0.0001). Except for choline from phosphatidylcholine, individual forms of choline were inversely associated with tHcy concentrations. Conclusions: Our findings provide support for a physiologically important variation in choline and betaine intakes in the general population and for the validity of intake measured by FFQ. PMID:16600945

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.

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.

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

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).

PubMed

Makarem, Nour; Lin, Yong; Bandera, Elisa V; Jacques, Paul F; Parekh, Niyati

2015-02-01

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. The study sample consisted of adults from the Framingham Offspring cohort (n = 2,983). From 1991 to 2008, 480 incident doctor-diagnosed obesity-related cancers were identified. Data on diet, measured by a food frequency questionnaire, anthropometric measures, and self-reported physical activity, collected in 1991 was used to construct a 7-component score based on recommendations for body fatness, physical activity, foods that promote weight gain, plant foods, animal foods, alcohol, and food preservation, processing, and preparation. Multivariable Cox regression models were used to estimate associations between the computed score, its components, and subcomponents in relation to obesity-related cancer risk. The overall score was not associated with obesity-related cancer risk after adjusting for age, sex, smoking, energy, and preexisting conditions (HR 0.94, 95 % CI 0.86-1.02). When score components were evaluated separately, for every unit increment in the alcohol score, there was 29 % lower risk of obesity-related cancers (HR 0.71, 95 % CI 0.51-0.99) and 49-71 % reduced risk of breast, prostate, and colorectal cancers. Every unit increment in the subcomponent score for non-starchy plant foods (fruits, vegetables, and legumes) among participants who consume starchy vegetables was associated with 66 % reduced risk of colorectal cancer (HR 0.44, 95 % CI 0.22-0.88). Lower alcohol consumption and a plant-based diet consistent with the cancer prevention guidelines were associated with reduced risk of obesity-related cancers in this population.

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.

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.

Carbohydrate nutrition and risk of adiposity-related cancers: results from the Framingham Offspring cohort (1991-2013).

PubMed

Makarem, Nour; Bandera, Elisa V; Lin, Yong; Jacques, Paul F; Hayes, Richard B; Parekh, Niyati

2017-06-01

Higher carbohydrate intake, glycaemic index (GI), and glycaemic load (GL) are hypothesised to increase cancer risk through metabolic dysregulation of the glucose-insulin axis and adiposity-related mechanisms, but epidemiological evidence is inconsistent. This prospective cohort study investigates carbohydrate quantity and quality in relation to risk of adiposity-related cancers, which represent the most commonly diagnosed preventable cancers in the USA. In exploratory analyses, associations with three site-specific cancers: breast, prostate and colorectal cancers were also examined. The study sample consisted of 3184 adults from the Framingham Offspring cohort. Dietary data were collected in 1991-1995 using a FFQ along with lifestyle and medical information. From 1991 to 2013, 565 incident adiposity-related cancers, including 124 breast, 157 prostate and sixty-eight colorectal cancers, were identified. Cox proportional hazards models were used to evaluate the role of carbohydrate nutrition in cancer risk. GI and GL were not associated with risk of adiposity-related cancers or any of the site-specific cancers. Total carbohydrate intake was not associated with risk of adiposity-related cancers combined or prostate and colorectal cancers. However, carbohydrate consumption in the highest v. lowest quintile was associated with 41 % lower breast cancer risk (hazard ratio (HR) 0·59; 95 % CI 0·36, 0·97). High-, medium- and low-GI foods were not associated with risk of adiposity-related cancers or prostate and colorectal cancers. In exploratory analyses, low-GI foods, were associated with 49 % lower breast cancer risk (HR 0·51; 95 % CI 0·32, 0·83). In this cohort of Caucasian American adults, associations between carbohydrate nutrition and cancer varied by cancer site. Healthier low-GI carbohydrate foods may prevent adiposity-related cancers among women, but these findings require confirmation in a larger sample.

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.

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.

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.

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.

PubMed

Sayols-Baixeras, S; Subirana, I; Lluis-Ganella, C; Civeira, F; Roquer, J; Do, A N; Absher, D; Cenarro, A; Muñoz, D; Soriano-Tárraga, C; Jiménez-Conde, J; Ordovas, J M; Senti, M; Aslibekyan, S; Marrugat, J; Arnett, D K; Elosua, R

2016-10-15

Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is not only an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina Human Methylation 450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n = 645) and validation in the Framingham Offspring Study (n = 2,542). Fourteen CpG sites located in nine genes (SREBF1, SREBF2, PHOSPHO1, SYNGAP1, ABCG1, CPT1A, MYLIP, TXNIP and SLC7A11) and 2 intergenic regions showed differential methylation in association with lipid traits. Six of these genes and 1 intergenic region were new discoveries showing differential methylation related to total cholesterol (SREBF2), HDL-cholesterol (PHOSPHO1, SYNGAP1 and an intergenic region in chromosome 2) and triglycerides (MYLIP, TXNIP and SLC7A11). These CpGs explained 0.7%, 9.5% and 18.9% of the variability of total cholesterol, HDL cholesterol and triglycerides in the Framingham Offspring Study, respectively. The expression of the genes SREBF2 and SREBF1 was inversely associated with methylation of their corresponding CpGs (P-value = 0.0042 and 0.0045, respectively) in participants of the GOLDN study (n = 98). In turn, SREBF1 expression was directly associated with HDL cholesterol (P-value = 0.0429). Genetic variants in SREBF1, PHOSPHO1, ABCG1 and CPT1A were also associated with lipid profile. Further research is warranted to functionally validate these new loci and assess the causality of new and established associations between these differentially methylated loci and lipid metabolism.

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.

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.

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.

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.

Parental Age of Onset of Cardiovascular Disease as a Predictor for Offspring Age of Onset of Cardiovascular Disease.

PubMed

Allport, Shannon Anjelica; Kikah, Ngum; Abu Saif, Nessim; Ekokobe, Fonkem; Atem, Folefac D

2016-01-01

The risk for cardiovascular disease (CVD) is higher for individuals with a first-degree relative who developed premature CVD (with a threshold at age 55 years for a male or 65 years for a female). However, little is known about the effect that each unit increase or decrease of maternal or paternal age of onset of CVD has on offspring age of onset of CVD. We hypothesized that there is an association between maternal and paternal age of onset of CVD and offspring age of onset of CVD. We used the Framingham Heart Study database and performed conditional imputation for CVD-censored parental age (i.e. parents that didn't experience onset of CVD) and Cox proportional regression analysis, with offspring's age of onset of CVD as the dependent variable and parental age of onset of CVD as the primary predictor. Modifiable risk factors in offspring, such as cigarette smoking, body mass index (BMI), diabetes mellitus, systolic blood pressure (SBP), high-density lipoprotein (HDL) level, and low-density lipoprotein (LDL) level, were controlled for. Separate analyses were performed for the association between maternal age of onset of CVD and offspring age of onset of CVD and the association between paternal age of onset of CVD and offspring age of onset of CVD. Parental age of onset of CVD was predictive of offspring age of onset of CVD for maternal age of onset of CVD (P < .0001; N = 1401) and for paternal age of onset of CVD (P = 0.0134; N = 1221). A negative estimate of the coefficient of interest signifies that late onset of cardiovascular events in parents is protective of onset of CVD in offspring. Cigarette smoking and HDL level were important associated confounders. Offspring age of onset of cardiovascular disease is significantly associated with both maternal and paternal age of onset CVD. The incorporation of the parameters, maternal or paternal age of onset of CVD, into risk estimate calculators may improve accuracy of identification of high-risk patients in clinical settings.

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.

Milk and yogurt consumption are linked with higher bone mineral density but not with hip fracture: the Framingham Offspring Study

PubMed Central

Sahni, Shivani; Tucker, Katherine L.; Kiel, Douglas P.; Quach, Lien; Casey, Virginia A.; Hannan, Marian T.

2013-01-01

Purpose To examine associations of milk, yogurt, cheese, cream, most dairy (total dairy without cream) and fluid dairy (milk+yogurt) with bone density (BMD) at femoral neck (FN), trochanter (TR) and spine, and with incident hip fracture over 12-y follow-up in the Framingham Offspring Study. Methods 3,212 participants completed a food frequency questionnaire (1991–1995 or 1995–1998) and were followed for hip fracture until 2007. 2,506 participants had DXA BMD (1996–2001). Linear regression was used to estimate adjusted mean BMD while Cox-proportional hazards regression was used to estimate adjusted hazard ratios (HR) for hip fracture risk. Final models simultaneously included dairy foods adjusting for each other. Results Mean baseline age was 55 (±1.6)y, range: 26–85). Most dairy intake was positively associated with hip and spine BMD. Intake of fluid dairy and milk were related with hip but not spine BMD. Yogurt intake was associated with TR-BMD alone. Cheese and cream intakes were not associated with BMD. In final models, yogurt intake remained positively associated with TR-BMD, while cream tended to be negatively associated with FN-BMD. Yogurt intake showed a weak protective trend for hip fracture [HR(95%CI): ≤4 serv/wk: 0.46 (0.21–1.03) vs. >4 serv/wk: 0.43 (0.06–3.27)]. No other dairy groups showed a significant association (HRs range: 0.53–1.47) with limited power (n, fractures=43). Conclusion Milk and yogurt intakes were associated with hip but not spine BMD, while cream may adversely influence BMD. Thus, not all dairy products are equally beneficial for the skeleton. Suggestive fracture results for milk and yogurt intakes need further confirmation. PMID:23371478

Association of oxidative stress, insulin resistance, and diabetes risk phenotypes: the Framingham Offspring Study.

PubMed

Meigs, James B; Larson, Martin G; Fox, Caroline S; Keaney, John F; Vasan, Ramachandran S; Benjamin, Emelia J

2007-10-01

Systemic oxidative stress causes insulin resistance in rodents. We tested the hypothesis that oxidative stress and insulin resistance are associated in humans. We used cross-sectional data from 2,002 nondiabetic subjects of the community-based Framingham Offspring Study. We measured insulin resistance with the homeostasis model and defined categorical insulin resistance as homeostasis model assessment of insulin resistance (HOMA-IR) > 75th percentile. We measured oxidative stress using the ratio of urine 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) to creatinine and used age- and sex-adjusted regression models to test the association of oxidative stress with insulin resistance in individuals without diabetes and among subgroups at elevated risk of diabetes. Across 8-epi-PGF2alpha/creatinine tertiles, the prevalence of insulin resistance increased (18.0, 27.5, and 29.4% for the first, second, and third tertiles, respectively; P < 0.0001), as did mean levels of HOMA-IR (3.28, 3.83, and 4.06 units; P < 0.0001). The insulin resistance-oxidative stress association was attenuated by additional adjustment for BMI (P = 0.06 across tertiles for insulin resistance prevalence; P = 0.004 for mean HOMA-IR). Twenty-six percent of participants were obese (BMI > or = 30 kg/m2), 39% had metabolic syndrome (according to the Adult Treatment Panel III definition), and 37% had impaired fasting glucose (IFG) (fasting glucose 5.6-6.9 mmol/l). Among 528 obese participants, respectively, insulin resistance prevalence was 41.3, 60.6, and 54.2% across 8-epi-PGF2alpha/creatinine tertiles (P = 0.005); among 781 subjects with metabolic syndrome, insulin resistance prevalence was 41.3, 56.7, and 51.7% (P = 0.0025); and among 749 subjects with IFG, insulin resistance prevalence was 39.6, 47.2, and 51.6% (P = 0.04). Systemic oxidative stress is associated with insulin resistance in individuals at average or elevated risk of diabetes even after accounting for BMI.

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.

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

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.

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

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.

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.

Milk and yogurt consumption are linked with higher bone mineral density but not with hip fracture: the Framingham Offspring Study.

PubMed

Sahni, Shivani; Tucker, Katherine L; Kiel, Douglas P; Quach, Lien; Casey, Virginia A; Hannan, Marian T

2013-01-01

Dairy foods are a complex source of essential nutrients. In this study, fluid dairy intake, specifically milk, and yogurt intakes were associated with hip but not spine bone mineral density (BMD), while cream may adversely influence BMD, suggesting that not all dairy products are equally beneficial for the skeleton. This study seeks to examine associations of milk, yogurt, cheese, cream, most dairy (total dairy without cream), and fluid dairy (milk + yogurt) with BMD at femoral neck (FN), trochanter (TR), and spine, and with incident hip fracture over 12-year follow-up in the Framingham Offspring Study. Three thousand two hundred twelve participants completed a food frequency questionnaire (1991–1995 or 1995–1998) and were followed for hip fracture until 2007 [corrected]. Two thousand five hundred and six participants had DXA BMD (1996-2001). Linear regression was used to estimate adjusted mean BMD while Cox-proportional hazards regression was used to estimate adjusted hazard ratios (HR) for hip fracture risk. Final models simultaneously included dairy foods adjusting for each other. Mean baseline age was 55 (±1.6) years, range 26-85. Most dairy intake was positively associated with hip and spine BMD. Intake of fluid dairy and milk was related with hip but not spine BMD. Yogurt intake was associated with TR-BMD alone. Cheese and cream intakes were not associated with BMD. In final models, yogurt intake remained positively associated with TR-BMD, while cream tended to be negatively associated with FN-BMD. Yogurt intake showed a weak protective trend for hip fracture [HR(95%CI), ≤4 serv/week, 0.46 (0.21-1.03) vs. >4 serv/week, 0.43 (0.06-3.27)]. No other dairy groups showed a significant association (HRs range, 0.53-1.47) with limited power (n, fractures = 43). Milk and yogurt intakes were associated with hip but not spine BMD, while cream may adversely influence BMD. Thus, not all dairy products are equally beneficial for the skeleton. Suggestive fracture results for milk and yogurt intakes need further confirmation.

‘A delicate diplomatic situation’: Tobacco industry efforts to gain control of the Framingham study

PubMed Central

Cataldo, J. K.; Bero, L. A.; Malone, R. E.

2010-01-01

The Framingham Heart Study (henceforth Framingham) is among the gold standards for epidemiological research. A prospective cohort study of 5,000+ men and women, it provided early findings about causes of coronary heart disease (CHD), following a cohort over 24 years. After US government funding ended, the tobacco industry-funded Council for Tobacco Research (CTR) provided continued funding for analyses related to smoking. Objective This study sought to understand the tobacco industry's motivation and activities in funding Framingham. Study Design We analyzed previously undisclosed tobacco industry documents, conducting iterative searches of the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu/), and assembled an historical case study. Results CTR funded Framingham to obtain full access to Framingham data. CTR planned for longtime industry consultant Carl Seltzer to reanalyze them to suggest that tobacco-related morbidity and mortality primarily resulted from “constitutional” factors such as age/ethnicity. Once data were obtained, CTR terminated funding for the Framingham principal investigator, who disagreed with Seltzer. Seltzer's critical analyses of subsequently-published work by the Framingham team created confusion about the association between coronary heart disease and cigarette smoking. Conclusion Researchers accepting tobacco industry funding risk losing control of data, analysis, and publication. PMID:20630333

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.

Dietary Protein Intake Is Protective Against Loss of Grip Strength Among Older Adults in the Framingham Offspring Cohort

PubMed Central

McLean, Robert R.; Mangano, Kelsey M.; Hannan, Marian T.; Kiel, Douglas P.

2016-01-01

Abstract Background: Age-related decline in muscle strength is an important public health issue for older adults. Dietary protein has been associated with maintenance of muscle mass, yet its relation to muscle strength remains unclear. Methods: We determined the association of dietary protein (total, animal, and plant) intake, measured by food frequency questionnaire, with change in grip strength over 6 years in 1,746 men and women from the Framingham Offspring cohort. Results: Mean age at baseline was 58.7 years (range: 29–85), and mean total, animal, and plant protein intakes were 79, 57, and 22g/d, respectively. Adjusted baseline mean grip strength did not differ across quartiles of energy-adjusted total, animal or protein intake. Greater protein intake, regardless of source, was associated with less decrease in grip strength (all p for trend ≤.05): participants in the lowest quartiles lost 0.17% to 0.27% per year while those in the highest quartiles gained 0.52% to 0.60% per year. In analyses stratified by age, participants aged 60 years or older ( n = 646) had similar linear trends on loss of grip strength for total and animal (all p for trend <.03) but not plant protein, while the trends in participants younger than 60 years ( n = 896) were not statistically significant. Conclusions: Higher dietary intakes of total and animal protein were protective against loss of grip strength in community-dwelling adults aged 60 years and older. Increasing intake of protein from these sources may help maintain muscle strength and support prevention of mobility impairment in older adults. PMID:26525088

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.

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.

Protective Effect of High Protein and Calcium Intake on the Risk of Hip Fracture in the Framingham Offspring Cohort

PubMed Central

Sahni, Shivani; Cupples, L Adrienne; Mclean, Robert R; Tucker, Katherine L; Broe, Kerry E; Kiel, Douglas P; Hannan, Marian T

2010-01-01

The effect of protein on bone is controversial, and calcium intake may modify protein's effect on bone. We evaluated associations of energy-adjusted tertiles of protein intake (ie, total, animal, plant, animal/plant ratio) with incident hip fracture and whether total calcium intake modified these associations in the Framingham Offspring Study. A total of 1752 men and 1972 women completed a baseline food frequency questionnaire (1991–1995 or 1995–1998) and were followed for hip fracture until 2005. Hazard ratios (HRs) were estimated using Cox proportional hazards regression adjusting for confounders. Baseline mean age was 55 years (SD 9.9 years, range 26 to 86 years). Forty-four hip fractures occurred over 12 years of follow-up. Owing to significant interaction between protein (total, animal, animal/plant ratio) and calcium intake (p interaction range = .03 to .04), stratified results are presented. Among those with calcium intakes less than 800 mg/day, the highest tertile (T3) of animal protein intake had 2.8 times the risk of hip fracture [HR = 2.84, 95% confidence interval (CI) 1.20–6.74, p = .02] versus the lowest tertile (T1, p trend = .02). In the 800 mg/day or more group, T3 of animal protein had an 85% reduced hip fracture risk (HR = 0.15, 95% CI 0.02–0.92, p = .04) versus T1 (p trend = .04). Total protein intake and the animal/plant ratio were not significantly associated with hip fracture (p range = .12 to .65). Our results from middle-aged men and women show that higher animal protein intake coupled with calcium intake of 800 mg/day or more may protect against hip fracture, whereas the effect appears reversed for those with lower calcium intake. Calcium intake modifies the association of protein intake and the risk of hip fracture in this cohort and may explain the lack of concordance seen in previous studies. © 2010 American Society for Bone and Mineral Research. PMID:20662074

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

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

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.

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.

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

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.

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

The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort1234

PubMed Central

Poly, Coreyann; Massaro, Joseph M; Seshadri, Sudha; Wolf, Philip A; Cho, Eunyoung; Krall, Elizabeth; Jacques, Paul F; Au, Rhoda

2011-01-01

Background: Choline is the precursor to the neurotransmitter acetylcholine. Loss of cholinergic neurons is associated with impaired cognitive function, particularly memory loss and Alzheimer disease (AD). Brain atrophy and white-matter hyperintensity (WMH) are also associated with impaired cognitive function and AD. Objective: The objective was to determine whether a relation exists between dietary choline intake, cognitive function, and brain morphology in a large, nondemented community-based cohort. Design: A dementia-free cohort of 1391 subjects (744 women, 647 men; age range: 36–83 y; mean ± SD age: 60.9 ± 9.29 y) from the Framingham Offspring population completed a food-frequency questionnaire administered from 1991 to 1995 (exam 5; remote intake) and from 1998 to 2001 (exam 7; concurrent intake). Participants underwent neuropsychological evaluation and brain MRI at exam 7. Four neuropsychological factors were constructed: verbal memory (VM), visual memory (VsM), verbal learning, and executive function. MRI measures included WMH volume (WMHV). Results: Performance on the VM and VsM factors was better with higher concurrent choline intake in multivariable-adjusted models for VM (average change in neuropsychological factor per 1-unit change in choline = 0.60; 95% CI: 0.29, 0.91; P < 0.01) and VsM (0.66; 95% CI: 0.19, 1.13; P < 0.01). Remote choline intake was inversely related to log-transformed WMHV (average change in log WMHV per 1-unit change in choline = −0.05; 95% CI: −0.10, −0.01; P = 0.02). Furthermore, an inverse association was observed between remote higher choline intake and presence of large WMVH (OR: 0.56; 95% CI: 0.34, 0.92; P = 0.01). Conclusion: In this community-based population of nondemented individuals, higher concurrent choline intake was related to better cognitive performance, whereas higher remote choline intake was associated with little to no WMHV. PMID:22071706

Excess free fructose, high-fructose corn syrup and adult asthma: the Framingham Offspring Cohort.

PubMed

DeChristopher, Luanne R; Tucker, Katherine L

2018-05-01

There is growing evidence that intakes of high-fructose corn syrup (HFCS), HFCS-sweetened soda, fruit drinks and apple juice - a high-fructose 100 % juice - are associated with asthma, possibly because of the high fructose:glucose ratios and underlying fructose malabsorption, which may contribute to enteral formation of pro-inflammatory advanced glycation end products, which bind receptors that are mediators of asthma. Cox proportional hazards models were used to assess associations between intakes of these beverages and asthma risk, with data from the Framingham Offspring Cohort. Diet soda and orange juice - a 100 % juice with a 1:1 fructose:glucose ratio - were included for comparison. Increasing intake of any combination of HFCS-sweetened soda, fruit drinks and apple juice was significantly associated with progressively higher asthma risk, plateauing at 5-7 times/week v. never/seldom, independent of potential confounders (hazard ratio 1·91, P<0·001). About once a day consumers of HFCS-sweetened soda had a 49 % higher risk (P<0·011), moderate apple juice consumers (2-4 times/week) had a 61 % higher risk (P<0·007) and moderate fruit drink consumers had a 58 % higher risk (P<0·009), as compared with never/seldom consumers. There were no associations with diet soda/orange juice. These associations are possibly because of the high fructose:glucose ratios, and fructose malabsorption. Recommendations to reduce consumption may be inadequate to address asthma risk, as associations are evident even with moderate intake of these beverages, including apple juice - a 100 % juice. The juice reductions in the US Special Supplemental Nutrition Program for Women, Infants, and Children in 2009, and the plateauing/decreasing asthma prevalence (2010-2013), particularly among non-Hispanic black children, may be related. Further research regarding the consequences of fructose malabsorption is needed.

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

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

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.

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.

Lower Lean Mass Measured by Dual-Energy X-ray Absorptiometry (DXA) is Not Associated with Increased Risk of Hip Fracture in Women: The Framingham Osteoporosis Study.

PubMed

McLean, Robert R; Kiel, Douglas P; Berry, Sarah D; Broe, Kerry E; Zhang, Xiaochun; Cupples, L Adrienne; Hannan, Marian T

2018-01-05

Although muscle mass influences strength in older adults, it is unclear whether low lean mass measured by dual-energy X-ray absorptiometry (DXA) is an independent risk factor for hip fracture. Our objective was to determine the association between DXA lean mass and incident hip fracture risk among 1978 women aged 50 years and older participating in the Framingham Study Original and Offspring cohorts. Leg and total body lean mass (kg) were assessed from whole-body DXA scans collected in 1992-2001. Hip fracture follow-up extended from DXA assessment to the occurrence of fracture, death, drop-out, or end of follow-up in 2007. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) estimating the relative risk of hip fracture associated with a 1-kg increase in baseline lean mass. Mean age was 66 years (range 50-93). Over a median of 8 years of follow-up, 99 hip fractures occurred. In models adjusted for age, height, study cohort, and percent total body fat, neither leg (HR 1.11; 95% CI 0.94, 1.31) nor total body (HR 1.06; 95% CI 0.99, 1.13) lean mass were associated with hip fracture. After further adjustment for femoral neck bone mineral density, leg lean mass results were similar (HR 1.10; 95% CI 0.93, 1.30). In contrast, 1 kg greater total body lean mass was associated with 9% higher hip fracture risk (HR 1.09; 95% CI 1.02, 1.18). Our findings suggest that in women, lower lean mass measured by DXA is not associated with increased risk of hip fracture.

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

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.

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.

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

Association Between Dietary Fiber Intake and Bone Loss in the Framingham Offspring Study.

PubMed

Dai, Zhaoli; Zhang, Yuqing; Lu, Na; Felson, David T; Kiel, Douglas P; Sahni, Shivani

2018-02-01

Dietary fiber may increase calcium absorption, but its role in bone mineralization is unclear. Furthermore, the health effect of dietary fiber may be different between sexes. We examined the association between dietary fiber (total fiber and fiber from cereal, fruits, vegetables, nuts, and legumes) and bone loss at the femoral neck, trochanter, and lumbar spine (L 2 to L 4 ) in older men and women. In the Framingham Offspring Study, at baseline (1996-2001), diet was assessed using the Willett food-frequency questionnaire, and bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Follow-up BMD was measured in 2001-2005 and 2005-2008 among 792 men (mean age 58.1 years; BMI 28.6 kg/m 2 ) and 1065 women (mean age 57.3 years; BMI 27.2 kg/m 2 ). We used sex-specific generalized estimating equations in multivariable regressions to estimate the difference (β) of annualized BMD change in percent (%ΔBMD) at each skeletal site per 5 g/d increase in dietary fiber. We further estimated the adjusted mean for bone loss (annualized %ΔBMD) among participants in each higher quartile (Q2, Q3, or Q4) compared with those in the lowest quartile (Q1) of fiber intake. Higher dietary total fiber (β = 0.06, p = 0.003) and fruit fiber (β = 0.10, p = 0.008) was protective against bone loss at the femoral neck in men but not in women. When examined in quartiles, men in Q2-Q4 of total fiber had significantly less bone loss at the femoral neck versus those in Q1 (all p < 0.04). For women, we did not observe associations with hip bone loss, although fiber from vegetables appeared to be protective against spine bone loss in women but not men. There were no associations with cereal fiber or nut and legume fiber and bone loss in men or women. Our findings suggest that higher dietary fiber may modestly reduce bone loss in men at the hip. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Comparison between the Framingham and prospective cardiovascular of Münster scores for risk assessment of coronary heart disease in human immunodeficiency virus-positive patients in Pernambuco, Brazil.

PubMed

Barros, Zoraya Medeiros; de Alencar Ximenes, Ricardo Arraes; Miranda-Filho, Demócrito Barros; de Albuquerque, Maria de Fátima Pessoa Militão; Melo, Heloísa Ramos Lacerda; Carvalho, Erico Higino; Gelenske, Thais; Diniz, George; Bandeira, Francisco

2010-12-01

The Framingham score is used in most studies on human immunodeficiency virus (HIV)-positive patients to estimate the risk for coronary heart disease; however, it may have some limitations for detecting risk among these individuals. The aim of this study was to evaluate the agreement between the Framingham and Prospective Cardiovascular of Münster (PROCAM) scores among HIV-positive individuals and to investigate the factors associated with disagreement between the two scores. A cross-sectional study was conducted in a population of HIV/acquired immunodeficiency syndrome (AIDS) patients attending the outpatient's clinics of two reference centers for HIV/AIDS in Pernambuco, Brazil. Agreement between the Framingham and PROCAM scores was evaluated using the kappa index. From this analysis, a variable called "disagreement between scores" was created, and univariate and multivariate analysis were performed to investigate the factors associated with this variable. The prevalence of low, moderate, and high risk were, respectively, 78.7%, 13.5%, and 7.8% by Framingham score and 88.5%, 4.3%, and 7.2% by PROCAM (kappa = 0.64, P ≤ 0.0001). Agreement in the subgroup with metabolic syndrome by the International Diabetes Federation (IDF) (kappa = 0.51, P ≤ 0.0001) and the National Cholesterol Education Program (NCEP) (kappa = 0.59, P ≤ 0.0001) criteria was moderate. The Framingham score identified greater proportion of women with moderate risk. Factors independently associated with disagreement were: smoking, sex, age, low-density lipoprotein cholesterol, diastolic blood pressure, and metabolic syndrome. There was a good agreement between the Framingham and PROCAM scores in HIV-positive patients, but a higher proportion of moderate-high risk was identified by the Framingham score. This disagreement should be evaluated in cohort studies to observe clinical outcomes over the course of time.

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.

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.

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

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.

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

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.

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.

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.

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

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

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.

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.

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.

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

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

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.

Methods and management: NIH administrators, federal oversight, and the Framingham Heart Study.

PubMed

Patel, Sejal S

2012-01-01

This article explores the 1965 controversy over the Framingham Heart Study in the midst of growing oversight into the management of science at the National Institutes of Health (NIH). It describes how, beginning in the early 1960s, federal overseers demanded that NIH administrators adopt particular management styles in administering programs and how these growing pressures led administrators to favor investigative pursuits that allowed for easy prospective accounting of program payoffs, especially those based on experimental methods designed to examine discrete interventions or outcomes of interest. In light of this changing managerial culture within the NIH, the Framingham study and other population laboratories-with their bases in observation and in open-ended study designs-became harder for NIH administrators to justify and defend.

[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.

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…

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.

Methods and Management: NIH Administrators, Federal Oversight, and the Framingham Heart Study

PubMed Central

Patel, Sejal S.

2012-01-01

Summary This article explores the 1965 controversy over the Framingham Heart Study in the midst of growing oversight into the management of science at the National Institutes of Health (NIH). It describes how, beginning in the early 1960s, federal overseers demanded that NIH administrators adopt particular management styles in administering programs and how these growing pressures led administrators to favor investigative pursuits that allowed for easy prospective accounting of program payoffs, especially those based on experimental methods designed to examine discrete interventions or outcomes of interest. In light of this changing managerial culture within the NIH, the Framingham study and other population laboratories—with their bases in observation and in open-ended study designs—became harder for NIH administrators to justify and defend. PMID:22643985

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.

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.

Sixty-five common genetic variants and prediction of type 2 diabetes.

PubMed

Talmud, Philippa J; Cooper, Jackie A; Morris, Richard W; Dudbridge, Frank; Shah, Tina; Engmann, Jorgen; Dale, Caroline; White, Jon; McLachlan, Stela; Zabaneh, Delilah; Wong, Andrew; Ong, Ken K; Gaunt, Tom; Holmes, Michael V; Lawlor, Debbie A; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Langenberg, Claudia; Ben-Shlomo, Yoav; Wannamethee, S Goya; Strachan, Mark W J; Kumari, Meena; Whittaker, John C; Drenos, Fotios; Kivimaki, Mika; Hingorani, Aroon D; Price, Jacqueline F; Humphries, Steve E

2015-05-01

We developed a 65 type 2 diabetes (T2D) variant-weighted gene score to examine the impact on T2D risk assessment in a U.K.-based consortium of prospective studies, with subjects initially free from T2D (N = 13,294; 37.3% women; mean age 58.5 [38-99] years). We compared the performance of the gene score with the phenotypically derived Framingham Offspring Study T2D risk model and then the two in combination. Over the median 10 years of follow-up, 804 participants developed T2D. The odds ratio for T2D (top vs. bottom quintiles of gene score) was 2.70 (95% CI 2.12-3.43). With a 10% false-positive rate, the genetic score alone detected 19.9% incident cases, the Framingham risk model 30.7%, and together 37.3%. The respective area under the receiver operator characteristic curves were 0.60 (95% CI 0.58-0.62), 0.75 (95% CI 0.73 to 0.77), and 0.76 (95% CI 0.75 to 0.78). The combined risk score net reclassification improvement (NRI) was 8.1% (5.0 to 11.2; P = 3.31 × 10(-7)). While BMI stratification into tertiles influenced the NRI (BMI ≤24.5 kg/m(2), 27.6% [95% CI 17.7-37.5], P = 4.82 × 10(-8); 24.5-27.5 kg/m(2), 11.6% [95% CI 5.8-17.4], P = 9.88 × 10(-5); >27.5 kg/m(2), 2.6% [95% CI -1.4 to 6.6], P = 0.20), age categories did not. The addition of the gene score to a phenotypic risk model leads to a potentially clinically important improvement in discrimination of incident T2D. © 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.

[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.

Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study.

PubMed

Hoffmann, Udo; Massaro, Joseph M; D'Agostino, Ralph B; Kathiresan, Sekar; Fox, Caroline S; O'Donnell, Christopher J

2016-02-22

We determined whether vascular and valvular calcification predicted incident major coronary heart disease, cardiovascular disease (CVD), and all-cause mortality independent of Framingham risk factors in the community-based Framingham Heart Study. Coronary artery calcium (CAC), thoracic and abdominal aortic calcium, and mitral or aortic valve calcium were measured by cardiac computed tomography in participants free of CVD. Participants were followed for a median of 8 years. Multivariate Cox proportional hazards models were used to determine association of CAC, thoracic and abdominal aortic calcium, and mitral and aortic valve calcium with end points. Improvement in discrimination beyond risk factors was tested via the C-statistic and net reclassification index. In this cohort of 3486 participants (mean age 50±10 years; 51% female), CAC was most strongly associated with major coronary heart disease, followed by major CVD, and all-cause mortality independent of Framingham risk factors. Among noncoronary calcifications, mitral valve calcium was associated with major CVD and all-cause mortality independent of Framingham risk factors and CAC. CAC significantly improved discriminatory value beyond risk factors for coronary heart disease (area under the curve 0.78-0.82; net reclassification index 32%, 95% CI 11-53) but not for CVD. CAC accurately reclassified 85% of the 261 patients who were at intermediate (5-10%) 10-year risk for coronary heart disease based on Framingham risk factors to either low risk (n=172; no events observed) or high risk (n=53; observed event rate 8%). CAC improves discrimination and risk reclassification for major coronary heart disease and CVD beyond risk factors in asymptomatic community-dwelling persons and accurately reclassifies two-thirds of the intermediate-risk population. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

Family-oriented cardiac risk estimator: a Java web-based applet.

PubMed

Crouch, Michael A; Jadhav, Ashwin

2003-01-01

We developed a Java applet that calculates four different estimates of a person's 10-year risk for heart attack: (1) Estimate based on Framingham equation (2) Framingham equation estimate modified by C-reactive protein (CRP) level (3) Framingham estimate modified by family history of heart disease in parents or siblings (4) Framingham estimate modified by both CRP and family heart disease history. This web-based, family-oriented cardiac risk estimator uniquely considers family history and CRP while estimating risk.

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.

Common Clinical Practice versus new PRIM Score in Predicting Coronary Heart Disease Risk

PubMed Central

Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne; Schnohr, Peter; Jensen, Gorm B.; Nordestgaard, Børge G.

2011-01-01

Objectives To compare the new Patient Rule Induction Method(PRIM) Score and common clinical practice with the Framingham Point Score for classification of individuals with respect to coronary heart disease(CHD) risk. Methods and Results PRIM Score and the Framingham Point Score were estimated for 11,444 participants from the Copenhagen City Heart Study. Gender specific cumulative incidences and 10 year absolute CHD risks were estimated for subsets defined by age, total cholesterol, high-density lipoprotein(HDL) cholesterol, blood pressure, diabetes and smoking categories. PRIM defined seven mutually exclusive subsets in women and men, with cumulative incidences of CHD from 0.01 to 0.22 in women, and from 0.03 to 0.26 in men. PRIM versus Framingham Point Score found 11% versus 4% of all women, and 31% versus 35% of all men to have 10 year CHD risks >20%. Among women ≥65 years with hypertension and/or with diabetes, 10 year CHD risk >20% was found for 100% with PRIM scoring but for only 18% with the Framingham Point Score. Conclusion Compared to the PRIM Score, common clinical practice with the Framingham Point Score underestimates CHD risk in women, especially in women ≥65 years with hypertension and/or with diabetes. PMID:20728887

Correlation of trabeculae and papillary muscles with clinical and cardiac characteristics and impact on CMR measures of LV anatomy and function.

PubMed

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

2012-11-01

The goal of this study was to assess the relationship of left ventricular (LV) trabeculae and papillary muscles (TPM) with clinical characteristics in a community-based, free-living adult cohort and to determine the effect of TPM on quantitative measures of LV volume, mass, and ejection fraction (EF). Hypertrabeculation has been associated with adverse cardiovascular events, but the distribution and clinical correlates of the volume and mass of the TPM in a normal left ventricle have not been well characterized. Short-axis cine cardiac magnetic resonance images, obtained using a steady-state free precession sequence from 1,494 members of the Framingham Heart Study Offspring cohort, were analyzed with software that automatically segments TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV) (TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring and in a referent group of offspring free of clinical cardiovascular disease and hypertension. In the referent group (mean age 61 ± 9 years; 262 men and 423 women), mean TPM was 23 ± 3% of LV EDV in both sexes (p = 0.9). TPM/EDV decreased with age (p < 0.02) but was not associated with body mass index. TPM mass as a fraction of LV mass was inversely correlated with age (p < 0.0001), body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all 1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%, and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial mass rather than part of the LV blood pool. Global cardiac magnetic resonance LV parameters were significantly affected by whether TPM was considered as part of the LV blood pool or as part of LV mass. Our cross-sectional data from a healthy referent group of adults free of clinical cardiovascular disease demonstrated that TPM/EDV decreases with increasing age in both sexes but is not related to hypertension or obesity. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

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

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.

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.

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.

Diet quality, physical activity, smoking status, and weight fluctuation are associated with weight change in women and men.

PubMed

Kimokoti, Ruth W; Newby, P K; Gona, Philimon; Zhu, Lei; Jasuja, Guneet K; Pencina, Michael J; McKeon-O'Malley, Catherine; Fox, Caroline S; D'Agostino, Ralph B; Millen, Barbara E

2010-07-01

The effect of diet quality on weight change, relative to other body weight determinants, is insufficiently understood. Furthermore, research on long-term weight change in U.S. adults is limited. We evaluated prospectively patterns and predictors of weight change in Framingham Offspring/Spouse (FOS) women and men (n = 1515) aged > or =30 y with BMI > or = 18.5 kg/m2 and without cardiovascular disease, diabetes, and cancer at baseline over a 16-y period. Diet quality was assessed using the validated Framingham Nutritional Risk Score. In women, older age (P < 0.0001) and physical activity (P < 0.05) were associated with lower weight gain. Diet quality interacted with former smoking status (P-interaction = 0.02); former smokers with lower diet quality gained an additional 5.2 kg compared with those with higher diet quality (multivariable-adjusted P-trend = 0.06). Among men, older age (P < 0.0001) and current smoking (P < 0.01) were associated with lower weight gain, and weight fluctuation (P < 0.01) and former smoking status (P < 0.0001) were associated with greater weight gain. Age was the strongest predictor of weight change in both women (partial R(2) = 11%) and men (partial R(2) = 8.6%). Normal- and overweight women gained more than obese women (P < 0.05) and younger adults gained more weight than older adults (P < 0.0001). Patterns and predictors of weight change differ by sex. Age in both sexes and physical activity among women as well as weight fluctuation and smoking status in men were stronger predictors of weight change than diet quality among FOS adults. Women who stopped smoking over follow-up and had poor diet quality gained the most weight. Preventive interventions need to be sex-specific and consider lifestyle factors.

A risk score for predicting near-term incidence of hypertension: the Framingham Heart Study.

PubMed

Parikh, Nisha I; Pencina, Michael J; Wang, Thomas J; Benjamin, Emelia J; Lanier, Katherine J; Levy, Daniel; D'Agostino, Ralph B; Kannel, William B; Vasan, Ramachandran S

2008-01-15

Studies suggest that targeting high-risk, nonhypertensive individuals for treatment may delay hypertension onset, thereby possibly mitigating vascular complications. Risk stratification may facilitate cost-effective approaches to management. To develop a simple risk score for predicting hypertension incidence by using measures readily obtained in the physician's office. Longitudinal cohort study. Framingham Heart Study, Framingham, Massachusetts. 1717 nonhypertensive white individuals 20 to 69 years of age (mean age, 42 years; 54% women), without diabetes and with both parents in the original cohort of the Framingham Heart Study, contributed 5814 person-examinations. Scores were developed for predicting the 1-, 2-, and 4-year risk for new-onset hypertension, and performance characteristics of the prediction algorithm were assessed by using calibration and discrimination measures. Parental hypertension was ascertained from examinations of the original cohort of the Framingham Heart Study. During follow-up (median time over all person-examinations, 3.8 years), 796 persons (52% women) developed new-onset hypertension. In multivariable analyses, age, sex, systolic and diastolic blood pressure, body mass index, parental hypertension, and cigarette smoking were significant predictors of hypertension. According to the risk score based on these factors, the 4-year risk for incident hypertension was classified as low (<5%) in 34% of participants, medium (5% to 10%) in 19%, and high (>10%) in 47%. The c-statistic for the prediction model was 0.788, and calibration was very good. The risk score findings may not be generalizable to persons of nonwhite race or ethnicity or to persons with diabetes. The risk score algorithm has not been validated in an independent cohort and is based on single measurements of risk factors and blood pressure. The hypertension risk prediction score can be used to estimate an individual's absolute risk for hypertension on short-term follow-up, and it represents a simple, office-based tool that may facilitate management of high-risk individuals with prehypertension.

Heritability of Thoracic Spine Curvature and Genetic Correlations With Other Spine Traits: The Framingham Study

PubMed Central

Yau, Michelle S; Demissie, Serkalem; Zhou, Yanhua; Anderson, Dennis E; Lorbergs, Amanda L; Kiel, Douglas P; Allaire, Brett T; Yang, Laiji; Cupples, L Adrienne; Travison, Thomas G; Bouxsein, Mary L; Karasik, David; Samelson, Elizabeth J

2017-01-01

Hyperkyphosis is a common spinal disorder in older adults, characterized by excessive forward curvature of the thoracic spine and adverse health outcomes. The etiology of hyperkyphosis has not been firmly established, but may be related to changes that occur with aging in the vertebrae, discs, joints, and muscles, which function as a unit to support the spine. Determining the contribution of genetics to thoracic spine curvature and the degree of genetic sharing among co-occurring measures of spine health may provide insight into the etiology of hyperkyphosis. The purpose of our study was to estimate heritability of thoracic spine curvature using T4–T12 kyphosis (Cobb) angle and genetic correlations between thoracic spine curvature and vertebral fracture, intervertebral disc height narrowing, facet joint osteoarthritis (OA), lumbar spine volumetric bone mineral density (vBMD), and paraspinal muscle area and density, which were all assessed from computed tomography (CT) images. Participants included 2063 women and men in the second and third generation offspring of the original cohort of the Framingham Study. Heritability of kyphosis angle, adjusted for age, sex, and weight, was 54% (95% confidence interval [CI], 43% to 64%). We found moderate genetic correlations between kyphosis angle and paraspinal muscle area ( ρ^G, −0.46; 95% CI, −0.67 to −0.26), vertebral fracture ( ρ^G, 0.39; 95% CI, 0.18 to 0.61), vBMD ( ρ^G,−0.23; 95% CI, −0.41 to −0.04), and paraspinal muscle density ( ρ^G,−0.22; 95% CI, −0.48 to 0.03). Genetic correlations between kyphosis angle and disc height narrowing ( ρ^G, 0.17; 95% CI, −0.05 to 0.38) and facet joint OA ( ρ^G, 0.05; 95% CI, −0.15 to 0.24) were low. Thoracic spine curvature may be heritable and share genetic factors with other age-related spine traits including trunk muscle size, vertebral fracture, and bone mineral density. PMID:27455046

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.

Quantifying cardiometabolic risk using modifiable non-self-reported risk factors.

PubMed

Marino, Miguel; Li, Yi; Pencina, Michael J; D'Agostino, Ralph B; Berkman, Lisa F; Buxton, Orfeu M

2014-08-01

Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. To develop and validate a cumulative general cardiometabolic risk score that focuses on non-self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut-off points for risk categories. We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14-year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender-specific Cox proportional hazards models were considered to evaluate the effects of non-self-reported modifiable risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10-year general cardiometabolic risk score functions and evaluated its predictive performance in 2012-2013. HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit chi-square=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk on the basis of modifiable risk factors that can motivate an individual's commitment to prevention and intervention. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Quantifying Cardiometabolic Risk Using Modifiable Non–Self-Reported Risk Factors

PubMed Central

Marino, Miguel; Li, Yi; Pencina, Michael J.; D’Agostino, Ralph B.; Berkman, Lisa F.; Buxton, Orfeu M.

2014-01-01

Background Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. Purpose To develop and validate a cumulative general cardiometabolic risk score that focuses on non–self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut off points for risk categories. Methods We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14–year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender–specific Cox proportional hazards models were considered to evaluate the effects of non–self-reported modifiable risk factors (blood pressure, total cholesterol, high–density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10–year general cardiometabolic risk score functions and evaluated its predictive performance in 2012–2013. Results HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit χ2=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). Conclusions This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk based on modifiable risk factors that can motivate an individual’s commitment to prevention and intervention. PMID:24951039

Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

PubMed

Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Krumerman, Andrew; Ferrick, Kevin J

2016-01-01

A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and <95 years, had <10-year follow-up, if their initial electrocardiogram was without AF, had ≥ 2 electrocardiograms, and declared a race and/or ethnicity as non-Hispanic white, African-American, or Hispanic. For the Framingham Heart Study, 49,599 patients met inclusion criteria, of which 4,860 developed AF. Discrimination analysis using area under the curve (AUC) for original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts. Copyright © 2016 Elsevier Inc. All rights reserved.

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

[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.

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

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.

Structured mating: Patterns and implications

PubMed Central

Sebro, Ronnie; Peloso, Gina M.; Risch, Neil J.

2017-01-01

Genetic similarity of spouses can reflect factors influencing mate choice, such as physical/behavioral characteristics, and patterns of social endogamy. Spouse correlations for both genetic ancestry and measured traits may impact genotype distributions (Hardy Weinberg and linkage equilibrium), and therefore genetic association studies. Here we evaluate white spouse-pairs from the Framingham Heart Study (FHS) original and offspring cohorts (N = 124 and 755, respectively) to explore spousal genetic similarity and its consequences. Two principal components (PCs) of the genome-wide association (GWA) data were identified, with the first (PC1) delineating clines of Northern/Western to Southern European ancestry and the second (PC2) delineating clines of Ashkenazi Jewish ancestry. In the original (older) cohort, there was a striking positive correlation between the spouses in PC1 (r = 0.73, P = 3x10-22) and also for PC2 (r = 0.80, P = 7x10-29). In the offspring cohort, the spouse correlations were lower but still highly significant for PC1 (r = 0.38, P = 7x10-28) and for PC2 (r = 0.45, P = 2x10-39). We observed significant Hardy-Weinberg disequilibrium for single nucleotide polymorphisms (SNPs) loading heavily on PC1 and PC2 across 3 generations, and also significant linkage disequilibrium between unlinked SNPs; both decreased with time, consistent with reduced ancestral endogamy over generations and congruent with theoretical calculations. Ignoring ancestry, estimates of spouse kinship have a mean significantly greater than 0, and more so in the earlier generations. Adjusting kinship estimates for genetic ancestry through the use of PCs led to a mean spouse kinship not different from 0, demonstrating that spouse genetic similarity could be fully attributed to ancestral assortative mating. These findings also have significance for studies of heritability that are based on distantly related individuals (kinship less than 0.05), as we also demonstrate the poor correlation of kinship estimates in that range when ancestry is or is not taken into account. PMID:28384154

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.

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

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.

Using additional information on working hours to predict coronary heart disease: a cohort study

PubMed Central

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

2011-01-01

Background Long hours are associated with increased risk of coronary heart disease. Adding information on long hours to traditional risk factors could potentially help improve risk prediction. Objective To examine whether information on long working hours improves the ability of the Framingham risk model to predict coronary heart disease in a low-risk employed population. Design Prospective cohort study; baseline medical examination (1991-1993) and coronary heart disease follow-up to 2004. Settings Civil service departments in London (the Whitehall II study). Participants 7095 adults (2109 women) aged 39 to 62, working full time, and free of coronary heart disease at baseline. Measurements Working hours and the Framingham risk score were measured at baseline. Coronary death and non-fatal myocardial infarction were ascertained from three sources: medical screenings every 5 years, hospital data and register linkage. Results 192 persons had incident coronary heart disease during a median 12.3 year follow-up. After adjustment for the Framingham score, participants working ≥11 hours per day had a 1.67-fold (95% CI: 1.10-2.55) increased risk of coronary heart disease relative to those working 7-8 hours. The addition of working hours to the Framingham score led to a net reclassification improvement of 4.7% (p=0.034), resulting from a better identification of individuals who later developed coronary heart disease (sensitivity gain). Limitations The findings may not be generalizable to populations with a larger proportion of high-risk individuals. Furthermore, the predictive utility of working hours was not validated in an independent cohort. Conclusion Information on working hours may improve prediction of coronary heart disease risk based on the Framingham risk score in low-risk working populations. Primary Funding Source Medical Research Council, British Heart Foundation, BUPA Foundation, UK; National Heart, Lung and Blood Institute and National Institute on Aging, NIH, US. PMID:21464347

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.

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.

If the Framingham Heart Study Did Not Invent the Risk Factor, Who Did?

PubMed

Jones, David Shumway; Oppenheimer, Gerald M

2017-01-01

Most historians, epidemiologists, and physicians credit the Framing-ham Heart Study for introducing the term "risk factor" to public health and medicine. Many add that the term came from life insurance companies. This familiar history is incorrect. Taking advantage of the expanding availability of digitized and full-text searchable journals, textbooks, newspapers, and other sources, we have uncovered a deeper and broader history. Antecedent concepts (such as risk, factor, predisposition) have ancient roots. "Risk factor" began to appear in the late 19th and early 20th centuries in many industries, not just in insurance but also in finance, agriculture, and manufacturing. The term appeared in the occupational health literature in 1922. It reappeared in the 1950s in many different areas of medicine including psychiatry, surgery, cardiology, epidemiology, and aerospace medicine. Furthermore, despite the influential appearance of "risk factor" in a 1961 Framingham Heart Study publication, the term did not gain momentum in medicine and public health until the mid-1970s. While our analysis is not exhaustive, our findings are extensive enough to require a substantial revision to the history of the risk factor.

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.

Becoming the Framingham Study 1947–1950

PubMed Central

Oppenheimer, Gerald M.

2005-01-01

In the epidemiological imagination, the Framingham Heart Study has attained iconic status, both as the prototype of the cohort study and as a result of its scientific success. When the Public Health Service launched the study in 1947, epidemiological knowledge of coronary heart disease was poor, and epidemiology primarily involved the study of infectious disease. In constructing their investigation, Framingham’s initiators had to invent new approaches to epidemiological research. These scientific goals were heavily influenced by the contending institutional and personal interests buffeting the study. The study passed through vicissitudes and stages during its earliest years as its organizers grappled to define its relationship to medicine, epidemiology, and the local community. PMID:15798116

Normative Data for the Cognitively Intact Oldest-Old: The Framingham Heart Study.

PubMed

Miller, Ivy N; Himali, Jayandra J; Beiser, Alexa S; Murabito, Joanne M; Seshadri, Sudha; Wolf, Philip A; Au, Rhoda

2015-01-01

BACKGROUND/STUDY CONTEXT: The number of individuals who reach extreme age is quickly increasing. Much of the current literature focuses on impaired cognition in extreme age, and debate continues regarding what constitutes "normal" cognition in extreme age. This study aimed to provide oldest-old normative data and to compare cognitive performances of cognitively intact elderly individuals from the Framingham Heart Study. A total of 1302 individuals aged 65+ years from the Framingham Heart Study were separated into 5-year age bands and compared on cognitive tests. Multivariate linear regression analyses were conducted, adjusting for gender, the Wide Range Achievement Test-Third Edition (WRAT-III) Reading score, and cohort. Analyses also included comparisons between 418 individuals aged 80+ and 884 individuals aged 65-79, and comparisons within oldest-old age bands. Normative data for all participants are presented. Significant differences were found on most tests between age groups in the overall analysis between young-old and oldest-old, and analysis of oldest-old age bands also revealed select significant differences (all ps <.05). As aging increases, significant cognitive differences and increased variability in performances are evident. These results support the use of age-appropriate normative data for oldest-old individuals.

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

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.

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.

Normative Data for the Cognitively-Intact Oldest-Old: The Framingham Heart Study

PubMed Central

Miller, Ivy N.; Himali, Jayandra J.; Beiser, Alexa S.; Murabito, Joanne M.; Seshadri, Sudha; Wolf, Philip A.; Au, Rhoda

2017-01-01

Background The number of individuals who reach extreme age is quickly increasing. Much of the current literature focuses on impaired cognition in extreme age, and debate continues regarding what constitutes “normal” cognition in extreme age. This study aimed to provide oldest-old normative data and to compare cognitive performances of cognitively-intact elderly individuals from the Framingham Heart Study. Methods 1302 individuals ages 65+ years old from the Framingham Heart Study were separated into five-year age bands and compared on cognitive tests. Multivariate linear regression analyses were conducted, adjusting for gender, the WRAT-III Reading score, and cohort. Analyses also included comparisons between 418 individuals ages 80+ and 884 individuals ages 65–79, and comparisons within oldest-old age bands. Results Normative data for all participants are presented. Significant differences were found on most tests between age groups in the overall analysis between young-old and oldest-old, and analysis of oldest-old age bands also revealed select significant differences (all p’s <.05). Conclusion As aging increases, significant cognitive differences and increased variability in performances are evident. These results support the use of age appropriate normative data for oldest-old individuals. PMID:26214098

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.

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

Plasma asymmetric dimethylarginine, L-arginine and left ventricular structure and function in a community-based sample.

PubMed

Lieb, Wolfgang; Benndorf, Ralf A; Benjamin, Emelia J; Sullivan, Lisa M; Maas, Renke; Xanthakis, Vanessa; Schwedhelm, Edzard; Aragam, Jayashri; Schulze, Friedrich; Böger, Rainer H; Vasan, Ramachandran S

2009-05-01

Increasing evidence indicates that cardiac structure and function are modulated by the nitric oxide (NO) system. Elevated plasma concentrations of asymmetric dimethylarginine (ADMA; a competitive inhibitor of NO synthase) have been reported in patients with end-stage renal disease. It is unclear if circulating ADMA and L-arginine levels are related to cardiac structure and function in the general population. We related plasma ADMA and L-arginine (the amino acid precursor of NO) to echocardiographic left ventricular (LV) mass, left atrial (LA) size and fractional shortening (FS) using multivariable linear regression analyses in 1919 Framingham Offspring Study participants (mean age 57 years, 58% women). Overall, neither ADMA or L-arginine, nor their ratio was associated with LV mass, LA size and FS in multivariable models (p>0.10 for all). However, we observed effect modification by obesity of the relations of ADMA and LA size (p for interaction p=0.04): ADMA was positively related to LA size in obese individuals (adjusted-p=0.0004 for trend across ADMA quartiles) but not in non-obese people. In our large community-based sample, plasma ADMA and l-arginine concentrations were not related to cardiac structure or function. The observation of positive relations of LA size and ADMA in obese individuals warrants confirmation.

Diet Quality, Physical Activity, Smoking Status, and Weight Fluctuation Are Associated with Weight Change in Women and Men1–3

PubMed Central

Kimokoti, Ruth W.; Newby, P. K.; Gona, Philimon; Zhu, Lei; Jasuja, Guneet K.; Pencina, Michael J.; McKeon-O'Malley, Catherine; Fox, Caroline S.; D'Agostino, Ralph B.; Millen, Barbara E.

2010-01-01

The effect of diet quality on weight change, relative to other body weight determinants, is insufficiently understood. Furthermore, research on long-term weight change in U.S. adults is limited. We evaluated prospectively patterns and predictors of weight change in Framingham Offspring/Spouse (FOS) women and men (n = 1515) aged ≥30 y with BMI ≥ 18.5 kg/m2 and without cardiovascular disease, diabetes, and cancer at baseline over a 16-y period. Diet quality was assessed using the validated Framingham Nutritional Risk Score. In women, older age (P < 0.0001) and physical activity (P < 0.05) were associated with lower weight gain. Diet quality interacted with former smoking status (P-interaction = 0.02); former smokers with lower diet quality gained an additional 5.2 kg compared with those with higher diet quality (multivariable-adjusted P-trend = 0.06). Among men, older age (P < 0.0001) and current smoking (P < 0.01) were associated with lower weight gain, and weight fluctuation (P < 0.01) and former smoking status (P < 0.0001) were associated with greater weight gain. Age was the strongest predictor of weight change in both women (partial R2 = 11%) and men (partial R2 = 8.6%). Normal- and overweight women gained more than obese women (P < 0.05) and younger adults gained more weight than older adults (P < 0.0001). Patterns and predictors of weight change differ by sex. Age in both sexes and physical activity among women as well as weight fluctuation and smoking status in men were stronger predictors of weight change than diet quality among FOS adults. Women who stopped smoking over follow-up and had poor diet quality gained the most weight. Preventive interventions need to be sex-specific and consider lifestyle factors. PMID:20484553

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

Confounding by dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk.

PubMed

Imamura, Fumiaki; Lichtenstein, Alice H; Dallal, Gerard E; Meigs, James B; Jacques, Paul F

2009-07-01

The ability to interpret epidemiologic observations is limited because of potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as standard risk factors and selected nutrients, the authors modeled the longitudinal association between alcohol consumption and 7-year risk of type 2 diabetes mellitus in 2,879 healthy adults enrolled in the Framingham Offspring Study (1991-2001) by Cox proportional hazard models. After adjustment for standard risk factors, consumers of > or =9.0 drinks/week had a significantly lower risk of type 2 diabetes mellitus compared with abstainers (hazard ratio = 0.47, 95% confidence interval (CI): 0.27, 0.81). Adjustment for selected nutrients had little effect on the hazard ratio, whereas adjustment for dietary pattern variables by factor analysis significantly shifted the hazard ratio away from null (hazard ratio = 0.33, 95% CI: 0.17, 0.64) by 40.0% (95% CI: 16.8, 57.0; P = 0.002). Dietary pattern variables by partial least squares showed similar results. Therefore, the observed inverse association, consistent with past studies, was confounded by dietary patterns, and this confounding was not captured by individual nutrient adjustment. The data suggest that alcohol intake, not dietary patterns associated with alcohol intake, is responsible for the observed inverse association with type 2 diabetes mellitus risk.

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.

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.

Genetics of the Framingham Heart Study Population

PubMed Central

Govindaraju, Diddahally R.; Cupples, L. Adrienne; Kannel, William B.; O’Donnell, Christopher J.; Atwood, Larry D.; D’Agostino, Ralph B.; Fox, Caroline S.; Larson, Marty; Levy, Daniel; Morabito, Joanne; Vasan, Ramachandran S.; Splansky, Greta Lee; Wolf, Philip A.; Benjamin, Emelia J.

2010-01-01

This article provides an introduction to the Framingham Heart Study (FHS) and the genetic research related to cardiovascular diseases conducted in this unique population1. It briefly describes the origins of the study, the risk factors that contribute to heart disease and the approaches taken to discover the genetic basis of some of these risk factors. The genetic architecture of several biological risk factors has been explained using family studies, segregation analysis, heritability, phenotypic and genetic correlations. Many quantitative trait loci underlying cardiovascular diseases have been discovered using different molecular markers. Additionally, results from genome-wide association studies using 100,000 markers, and the prospects of using 550,000 markers for association studies are presented. Finally, the use of this unique sample in genotype and environment interaction is described. PMID:19010253

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.

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

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.

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.

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.

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.

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.

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.

Plasma asymmetric dimethylarginine, L-arginine and Left Ventricular Structure and Function in a Community-based Sample

PubMed Central

Lieb, Wolfgang; Benndorf, Ralf A.; Benjamin, Emelia J.; Sullivan, Lisa M.; Maas, Renke; Xanthakis, Vanessa; Schwedhelm, Edzard; Aragam, Jayashri; Schulze, Friedrich; Böger, Rainer H.; Vasan, Ramachandran S.

2009-01-01

Objective Increasing evidence indicates that cardiac structure and function are modulated by the nitric oxide (NO) system. Elevated plasma concentrations of asymmetric dimethylarginine (ADMA; a competitive inhibitor of NO synthase) have been reported in patients with end-stage renal disease. It is unclear if circulating ADMA and L-arginine levels are related to cardiac structure and function in the general population. Methods We related plasma ADMA and L-Arginine (the amino acid precursor of NO) to echocardiographic left ventricular (LV) mass, left atrial (LA) size and fractional shortening (FS) using multivariable linear regression analyses in 1,919 Framingham Offspring Study participants (mean age 57 years, 58 % women). Results Overall, neither ADMA or L-arginine, nor their ratio was associated with LV mass, LA size and FS in multivariable models (p>0.10 for all). However, we observed effect modification by obesity of the relations of ADMA and LA size (p for interaction p=0.04): ADMA was positively related to LA size in obese individuals (adjusted-p=0.0004 for trend across ADMA quartiles) but not in non-obese people. Conclusion In our large community-based sample, plasma ADMA and L-arginine concentrations were not related to cardiac structure or function. The observation of positive relations of LA size and ADMA in obese individuals warrants confirmation. PMID:18829028

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.

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.

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...

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...

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...

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.

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.

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...

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.

Genetic and non-genetic correlates of vitamins K and D.

PubMed

Shea, M K; Benjamin, E J; Dupuis, J; Massaro, J M; Jacques, P F; D'Agostino, R B; Ordovas, J M; O'Donnell, C J; Dawson-Hughes, B; Vasan, R S; Booth, S L

2009-04-01

To assess the genetic and nongenetic correlates of circulating measures of vitamins K and D status in a community-based sample of men and women. A cross-sectional study of 1762 participants of the Framingham Offspring Study (919 women; mean age 59 years). Vitamin K status was measured as plasma phylloquinone and serum percent undercarboxylated osteocalcin (ucOC), and vitamin D was measured using plasma 25-hydroxyvitamin D (25(OH)D). Associations between vitamin K status and vitamin D status with biologically plausible nongenetic factors were assessed using stepwise regression. Heritability and linkage were determined using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Nongenetic factors accounted for 20.1 and 12.3% of the variability in plasma phylloquinone in men and women respectively, with triglycerides and phylloquinone intake being the primary correlates. In men 12.2% and in women 14.6% of the variability in %ucOC was explained by nongenetic factors in our models. Heritability estimates for these vitamin K status biomarkers were nonsignificant. Season, vitamin D intake, high-density lipoprotein (HDL) cholesterol and waist circumference explained 24.7% (men) and 24.2% (women) of the variability in plasma 25(OH)D. Of the three vitamins examined, only 25(OH)D was significantly heritable (heritability estimate=28.8%, P<0.01), but linkage analysis of 25(OH)D did not achieve genome-wide significance. Variability in biomarkers of vitamin K status was attributed to nongenetic factors, whereas plasma 25(OH)D was found to be significantly heritable. Further studies are warranted to investigate genetic loci influencing vitamin D status.

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.

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.

Effectiveness of the Heart Age tool for improving modifiable cardiovascular risk factors in a Southern European population: a randomized trial.

PubMed

Lopez-Gonzalez, Angel A; Aguilo, Antoni; Frontera, Margalida; Bennasar-Veny, Miquel; Campos, Irene; Vicente-Herrero, Teofila; Tomas-Salva, Matias; De Pedro-Gomez, Joan; Tauler, Pedro

2015-03-01

To test whether communicating cardiovascular diseases (CVD) risk using a novel risk assessment tool (Heart Age) will be able to motivate a population to adopt healthier lifestyles and improve CVD risk profile over the use of a traditional percentage-based tool. A single-blind randomized intervention study was carried out in a Caucasian population. A total of 3153 subjects were randomly allocated to one of three study groups: control (conventional medical advice was given to the subjects), Framingham REGICOR (10-year percentage risk score, calibrated to Spanish population was given to the subjects), or Heart Age group (Heart Age tool was administered to the subjects). Anthropometrical and metabolic parameters were measured and lifestyle habits were recorded at recruitment and 12-months post intervention. Both the Framingham REGICOR and the Heart Age intervention groups demonstrated significant decreases in their risk scores at post intervention compared to the control group, with the improvement being of a greater magnitude in the Heart Age group. No differences per gender were observed in the Heart Age group. Informing patients about their CVD risk expressed as the new Heart Age tool results in a reduction in their CVD risk higher than the one observed when the Framingham REGICOR risk score was used. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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.

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.

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...

Sugar-Sweetened Beverage Consumption Is Associated with Abdominal Fat Partitioning in Healthy Adults123

PubMed Central

Ma, Jiantao; Sloan, Matthew; Fox, Caroline S.; Hoffmann, Udo; Smith, Caren E.; Saltzman, Edward; Rogers, Gail T.; Jacques, Paul F.; McKeown, Nicola M.

2014-01-01

Abdominal adiposity, particularly visceral adipose tissue (VAT), is independently linked to the pathogenesis of diabetes and cardiovascular diseases. Emerging evidence suggests that greater intake of sugar-sweetened beverages (SSBs) may be associated with abnormal fat accumulation in VAT. We examined whether habitual SSB consumption and diet soda intakes are differentially associated with deposition of body fat. We conducted a cross-sectional analysis using previously collected data in 2596 middle-aged adults (1306 men and 1290 women) from the Framingham Heart Study Offspring and Third Generation cohorts. VAT and abdominal subcutaneous adipose tissue (SAT) were measured using multidetector computed tomography. Habitual intake of SSBs and diet soda was assessed by a validated food frequency questionnaire. We observed that SSB consumption was positively associated with VAT after adjustment for SAT and other potential confounders (P-trend < 0.001). We observed an inverse association between SSB consumption and SAT (P-trend = 0.04) that persisted after additional adjustment for VAT (P-trend < 0.001). Higher SSB consumption was positively associated with the VAT-to-SAT ratio (P-trend < 0.001). No significant association was found between diet soda consumption and either VAT or the VAT-to-SAT ratio, but diet soda was positively associated with SAT (P-trend < 0.001). Daily consumers of SSBs had a 10% higher absolute VAT volume and a 15% greater VAT-to-SAT ratio compared with nonconsumers, whereas consumption of diet soda was not associated with either volume or distribution of VAT. PMID:24944282

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

Bimodal Aldosterone Distribution in Low-Renin Hypertension

PubMed Central

2013-01-01

BACKGROUND In low-renin hypertension (LRH), serum aldosterone levels are higher in those subjects with primary aldosteronism and may be lower in those with non-aldosterone mineralocorticoid excess or primary renal sodium retention. We investigated the hypothesis that the frequency distribution of aldosterone in LRH is bimodal. METHODS Of the 3,532 attendees at the sixth examination cycle of the Framingham Offspring Study, 1,831 were included in this cross-sectional analysis after we excluded those with conditions or taking medications such as antihypertensive drugs that might affect renin or aldosterone. RESULTS Three hundred three subjects (17%) had untreated hypertension (SBP ≥140mm Hg or DBP ≥90mm Hg). LRH, defined as plasma renin ≤5 mU/L, was present in 93 of those 303 hypertensive subjects (31%). Aldosterone values were adjusted statistically for age, sex, and the urinary sodium/creatinine ratio. In the subjects with LRH, the adjusted aldosterone distribution was bimodal (dip test for unimodality, P = 0.008). The adjusted aldosterone distribution was unimodal in the normal subjects (P = 0.98) and in the hypertensive subjects with normal plasma renin (P = 0.94). CONCLUSIONS In this community-based sample of white subjects, those with low-renin hypertension had a bimodal adjusted aldosterone distribution. Subjects with normal-renin hypertension and subjects with normal blood pressure had unimodal adjusted aldosterone distributions. These findings suggest 2 pathophysiological variants of LRH, one that is aldosterone-dependent and one that is non-aldosterone-dependent. PMID:23757402

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.

Yogurt consumption is associated with better diet quality and metabolic profile in American men and women

PubMed Central

Wang, Huifen; Livingston, Kara A.; Fox, Caroline S.; Meigs, James B.; Jacques, Paul F.

2013-01-01

The evidence-based Dietary Guidelines for Americans recommends increasing the intake of fat-free or low-fat milk and milk products. However, yogurt, a nutrient-dense milk product, has been understudied. This cross-sectional study examined whether yogurt consumption was associated with better diet quality and metabolic profile among adults (n = 6526) participating in the Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-2005) cohorts. A validated food frequency questionnaire was used to assess dietary intake, and the Dietary Guidelines Adherence Index (DGAI) was used to measure overall diet quality. Standardized clinical examinations and laboratory tests were conducted. Generalized estimating equations examined the associations of yogurt consumption with diet quality and levels of metabolic factors. Approximately 64% of women (vs 41% of men) were yogurt consumers (ie, consumed >0 servings/week). Yogurt consumers had a higher DGAI score (ie, better diet quality) than nonconsumers. Adjusted for demographic and lifestyle factors and DGAI, yogurt consumers, compared with nonconsumers, had higher potassium intakes (difference, 0.12 g/d) and were 47%, 55%, 48%, 38%, and 34% less likely to have inadequate intakes (based on Dietary Reference Intake) of vitamins B2 and B12, calcium, magnesium, and zinc, respectively (all P ≤ .001). In addition, yogurt consumption was associated with lower levels of circulating triglycerides, glucose, and lower systolic blood pressure and insulin resistance (all P < .05). Yogurt is a good source of several micronutrients and may help to improve diet quality and maintain metabolic well-being as part of a healthy, energy-balanced dietary pattern. PMID:23351406

Smoking, alcohol consumption, and Raynaud's phenomenon in middle age.

PubMed

Suter, Lisa G; Murabito, Joanne M; Felson, David T; Fraenkel, Liana

2007-03-01

Data suggest Raynaud's phenomenon shares risk factors with cardiovascular disease. Studies of smoking, alcohol consumption, and Raynaud's have produced conflicting results and were limited by small sample size and failure to adjust for confounders. Our objective was to determine whether smoking and alcohol are independently associated with Raynaud's in a large, community-based cohort. By using a validated survey to classify Raynaud's in the Framingham Heart Study Offspring Cohort, we performed sex-specific analyses of Raynaud's status by smoking and alcohol consumption in 1840 women and 1602 men. Multivariable logistic regression analyses were used to examine the relationship of Raynaud's to smoking and alcohol consumption. Current smoking was not associated with Raynaud's in women but was associated with increased risk in men (adjusted odds ratio [OR] 2.59, 95% confidence interval [CI], 1.11-6.04). Heavy alcohol consumption in women was associated with increased risk of Raynaud's (adjusted OR 1.69, 95% CI, 1.02-2.82), whereas moderate alcohol consumption in men was associated with reduced risk (adjusted OR 0.51, 95% CI, 0.29-0.89). In both genders, red wine consumption was associated with a reduced risk of Raynaud's (adjusted OR 0.59, 95% CI, 0.36-0.96 in women and adjusted OR 0.30, 95% CI, 0.15-0.62 in men). Our data suggest that middle-aged women and men may have distinct physiologic mechanisms underlying their Raynaud's, and thus sex-specific therapeutic approaches may be appropriate. Our data also support the possibility that moderate red wine consumption may protect against Raynaud's.

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.

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.

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.

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...

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

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.

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

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...

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...

Sugar- and artificially-sweetened beverages and the risks of incident stroke and dementia: A prospective cohort study

PubMed Central

Pase, Matthew P.; Himali, Jayandra J.; Beiser, Alexa S.; Aparicio, Hugo J.; Satizabal, Claudia L.; Vasan, Ramachandran S.; Seshadri, Sudha; Jacques, Paul F.

2017-01-01

Background and purpose Sugar- and artificially-sweetened beverage intake have been linked to cardiometabolic risk factors, which increase the risk of cerebrovascular disease and dementia. We examined whether sugar- or artificially-sweetened beverage consumption were associated with the prospective risks of incident stroke or dementia in the community-based Framingham Heart Study Offspring cohort. Methods We studied 2888 participants aged over 45 for incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged over 60 for incident dementia (mean age 69 [SD, 6] years; 46% men). Beverage intake was quantified using a food frequency questionnaire at cohort examinations 5 (1991–1995), 6 (1995–1998) and 7 (1998–2001). We quantified recent consumption at examination 7 and cumulative consumption by averaging across examinations. Surveillance for incident events commenced at examination 7 and continued for 10-years. We observed 97 cases of incident stroke (82 ischemic) and 81 cases of incident dementia (63 consistent with Alzheimer’s disease [AD]). Results After adjustments for age, sex, education (for analysis of dementia), caloric intake, diet quality, physical activity and smoking, higher recent and higher cumulative intake of artificially-sweetened soft drinks were associated with an increased risk of ischemic stroke, all-cause dementia, and AD dementia. When comparing daily cumulative intake to <1 per week (reference), the hazard ratios were 2.96 (95% CI, 1.26–6.97) for ischemic stroke and 2.89 (95% CI, 1.18–7.07) for AD. Sugar-sweetened beverages were not associated with stroke or dementia. Conclusions Artificially-sweetened soft drink consumption was associated with a higher risk of stroke and dementia. PMID:28428346

Evaluation of a new approach to compute intervertebral disc height measurements from lateral radiographic views of the spine.

PubMed

Allaire, Brett T; DePaolis Kaluza, M Clara; Bruno, Alexander G; Samelson, Elizabeth J; Kiel, Douglas P; Anderson, Dennis E; Bouxsein, Mary L

2017-01-01

Current standard methods to quantify disc height, namely distortion compensated Roentgen analysis (DCRA), have been mostly utilized in the lumbar and cervical spine and have strict exclusion criteria. Specifically, discs adjacent to a vertebral fracture are excluded from measurement, thus limiting the use of DCRA in studies that include older populations with a high prevalence of vertebral fractures. Thus, we developed and tested a modified DCRA algorithm that does not depend on vertebral shape. Participants included 1186 men and women from the Framingham Heart Study Offspring and Third Generation Multidetector CT Study. Lateral CT scout images were used to place 6 morphometry points around each vertebra at 13 vertebral levels in each participant. Disc heights were calculated utilizing these morphometry points using DCRA methodology and our modified version of DCRA, which requires information from fewer morphometry points than the standard DCRA. Modified DCRA and standard DCRA measures of disc height are highly correlated, with concordance correlation coefficients above 0.999. Both measures demonstrate good inter- and intra-operator reproducibility. 13.9 % of available disc heights were not evaluable or excluded using the standard DCRA algorithm, while only 3.3 % of disc heights were not evaluable using our modified DCRA algorithm. Using our modified DCRA algorithm, it is not necessary to exclude vertebrae with fracture or other deformity from disc height measurements as in the standard DCRA. Modified DCRA also yields identical measurements to the standard DCRA. Thus, the use of modified DCRA for quantitative assessment of disc height will lead to less missing data without any loss of accuracy, making it a preferred alternative to the current standard methodology.

Psychiatric disorders in child and adolescent offspring of patients with schizophrenia and bipolar disorder: A controlled study.

PubMed

Sanchez-Gistau, Vanessa; Romero, Soledad; Moreno, Dolores; de la Serna, Elena; Baeza, Inmaculada; Sugranyes, Gisela; Moreno, Carmen; Sanchez-Gutierrez, Teresa; Rodriguez-Toscano, Elisa; Castro-Fornieles, Josefina

2015-10-01

Early clinical manifestations predating schizophrenia (SZ) and bipolar disorder (BP) have not been fully characterized. Child offspring studies are a valuable opportunity to study the natural history of the illness from its earliest stages. However, there is limited evidence assessing young offspring of SZ and BP simultaneously. We set out to assess rates of psychiatric disorders in child and adolescent offspring of SZ and BP, relative to offspring of community controls, so as to characterize the early phenotype of the disorders comparatively. SZ and BP parents with offspring aged 7-17years were recruited through adult mental health services of two tertiary hospitals. Community control (CC) parents were recruited from the same geographical area. Ninety BP-offspring, 41 SZ-offspring and 107 CC-offspring were assessed using the K-SADS-PL by child psychiatrists blinded to parental status. Differences in prevalence of psychiatric disorders between groups were adjusted for confounders and for sibling correlation using generalised estimating equations. We found a gradient of clinical severity and social disadvantage between SZ, BP and CC-offspring. After adjusting for socio-demographic confounders, SZ and BP-offspring presented higher rates of attention deficit hyperactivity disorder (ADHD) than CC-offspring. ADHD was more prevalent in SZ-offspring than BP-offspring, and BP-offspring presented a higher prevalence of depression than CC-offspring. The higher rates of ADHD in SZ-offspring suggest that abnormal neurodevelopmental processes may exert a stronger influence in SZ than BP. Follow-up of these children will help elucidate the role of ADHD and depression phenotypes in predicting future transition to SZ or BP. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Why does offspring size affect performance? Integrating metabolic scaling with life-history theory

PubMed Central

Pettersen, Amanda K.; White, Craig R.; Marshall, Dustin J.

2015-01-01

Within species, larger offspring typically outperform smaller offspring. While the relationship between offspring size and performance is ubiquitous, the cause of this relationship remains elusive. By linking metabolic and life-history theory, we provide a general explanation for why larger offspring perform better than smaller offspring. Using high-throughput respirometry arrays, we link metabolic rate to offspring size in two species of marine bryozoan. We found that metabolism scales allometrically with offspring size in both species: while larger offspring use absolutely more energy than smaller offspring, larger offspring use proportionally less of their maternally derived energy throughout the dependent, non-feeding phase. The increased metabolic efficiency of larger offspring while dependent on maternal investment may explain offspring size effects—larger offspring reach nutritional independence (feed for themselves) with a higher proportion of energy relative to structure than smaller offspring. These findings offer a potentially universal explanation for why larger offspring tend to perform better than smaller offspring but studies on other taxa are needed. PMID:26559952

Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal, family study

PubMed Central

MacGregor, Erica K.; Grunebaum, Michael F.; Galfalvy, Hanga C.; Melhem, Nadine; Burke, Ainsley K.; Brent, David A.; Oquendo, Maria A.; Mann, J. John

2015-01-01

Objective To investigate relationships of depressed parents' attachment style to offspring suicidal behavior. Method 244 parents diagnosed with a DSM-IV depressive episode completed the Adult Attachment Questionnaire at study entry. Baseline and yearly follow-up interviews of their 488 offspring tracked suicidal behavior and psychopathology. Survival analysis and marginal regression models with correlated errors for siblings investigated the relationship between parent insecure attachment traits and offspring characteristics. Data analyzed were collected 1992–2008 during a longitudinal family study completed January 31, 2014. Results Parent avoidant attachment predicted offspring suicide attempts at a trend level (p=0.083). Parent anxious attachment did not predict offspring attempts (p=0.961). In secondary analyses, anxious attachment in parents was associated with offspring impulsivity (p=0.034), and in offspring suicide attempters, was associated with greater intent (p=0.045) and lethality of attempts (p=0.003). Avoidant attachment in parents was associated with offspring impulsivity (p=0.025) and major depressive disorder (p=0.012). Parent avoidant attachment predicted a greater number of suicide attempts (p=0.048) and greater intent in offspring attempters (p=0.003). Results were comparable after adjusting for parent diagnosis of borderline personality disorder. Conclusion Insecure avoidant, but not anxious, attachment in depressed parents may predict offspring suicide attempt. Insecure parent attachment traits were associated with impulsivity and major depressive disorder in all offspring, and with more severe suicidal behavior in offspring attempters. Insecure parental attachment merits further study as a potential target to reduce risk of offspring psychopathology and more severe suicidal behavior. PMID:25098943

Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal family study.

PubMed

MacGregor, Erica K; Grunebaum, Michael F; Galfalvy, Hanga C; Melhem, Nadine; Burke, Ainsley K; Brent, David A; Oquendo, Maria A; Mann, J John

2014-08-01

To investigate relationships of depressed parents' attachment style to offspring suicidal behavior. 244 parents diagnosed with a DSM-IV depressive episode completed the Adult Attachment Questionnaire at study entry. Baseline and yearly follow-up interviews of their 488 offspring tracked suicidal behavior and psychopathology. Survival analysis and marginal regression models with correlated errors for siblings investigated the relationship between parent insecure attachment traits and offspring characteristics. Data analyzed were collected 1992-2008 during a longitudinal family study completed January 31, 2014. Parental avoidant attachment predicted offspring suicide attempts at a trend level (P = .083). Parental anxious attachment did not predict offspring attempts (P = .961). In secondary analyses, anxious attachment in parents was associated with offspring impulsivity (P = .034) and, in offspring suicide attempters, was associated with greater intent (P = .045) and lethality of attempts (P = .003). Avoidant attachment in parents was associated with offspring impulsivity (P = .025) and major depressive disorder (P = .012). Parental avoidant attachment predicted a greater number of suicide attempts (P = .048) and greater intent in offspring attempters (P = .003). Results were comparable after adjusting for parent diagnosis of borderline personality disorder. Insecure avoidant, but not anxious, attachment in depressed parents may predict offspring suicide attempt. Insecure parental attachment traits were associated with impulsivity and major depressive disorder in all offspring and with more severe suicidal behavior in offspring attempters. Insecure parental attachment merits further study as a potential target to reduce risk of offspring psychopathology and more severe suicidal behavior. © Copyright 2014 Physicians Postgraduate Press, Inc.

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.

Maternal depression during pregnancy and offspring depression in adulthood: role of child maltreatment

PubMed Central

Plant, Dominic T.; Pariante, Carmine M.; Sharp, Deborah; Pawlby, Susan

2015-01-01

Background Studies have shown that maternal depression during pregnancy predicts offspring depression in adolescence. Child maltreatment is also a risk factor for depression. Aims To investigate (a) whether there is an association between offspring exposure to maternal depression in pregnancy and depression in early adulthood, and (b) whether offspring child maltreatment mediates this association. Method Prospectively collected data on maternal clinical depression in pregnancy, offspring child maltreatment and offspring adulthood (18–25 years) DSM-IV depression were analysed in 103 mother–offspring dyads of the South London Child Development Study. Results Adult offspring exposed to maternal depression in pregnancy were 3.4 times more likely to have a DSM-IV depressive disorder, and 2.4 times more likely to have experienced child maltreatment, compared with non-exposed offspring. Path analysis revealed that offspring experience of child maltreatment mediated the association between exposure to maternal depression in pregnancy and depression in adulthood. Conclusions Maternal depression in pregnancy is a key vulnerability factor for offspring depression in early adulthood. PMID:26045352

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...

[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.

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.

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

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.

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.

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

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.

Academic Achievement in Primary School in Offspring Born to Mothers With Type 1 Diabetes (the EPICOM Study): A Register-Based Prospective Cohort Study.

PubMed

Knorr, Sine; Clausen, Tine D; Vlachová, Zuzana; Bytoft, Birgitte; Damm, Peter; Beck-Nielsen, Henning; Jensen, Dorte M; Juul, Svend; Gravholt, Claus Højbjerg

2015-07-01

This study examined the effect of maternal pregestational type 1 diabetes on offspring primary school performance. We performed a prospective combined clinical and register-based cohort study comparing primary school performance in offspring (n = 707) of women with pregestational type 1 diabetes with matched control offspring (n = 60,341). We also examined the association between HbA1c levels during pregnancy and later school performance among offspring born to women with pregestational type 1 diabetes. Offspring of mothers with pregestational type 1 diabetes obtained similar school grades as control offspring when finishing primary school (regression coefficient [β] = -0.13; 95% CI = -0.30 to 0.03; P = 0.12). Adjusting for parental education also resulted in an insignificant difference between the two groups (β = -0.07; 95% CI = -0.23 to 0.09; P = 0.37). Among offspring of women with type 1 diabetes, increasing maternal HbA1c pregestationally and throughout the pregnancy was associated with lower average school grades. Offspring born to mothers with good glycemic control in the third trimester obtained higher average school grades compared with control offspring. The opposite applied to offspring born to mothers with inadequate glycemic control, who obtained significantly lower average school grades compared with control offspring. Offspring of mothers with pregestational type 1 diabetes obtained similar average grades when finishing primary school compared with matched control offspring. Among offspring of women with type 1 diabetes, we found a consistent negative association between maternal HbA1c in pregnancy and primary school grades. However, whether this association reflects a direct causal influence of intrauterine hyperglycemia is uncertain. © 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.

The Relationship Between Stressful Life Events and Axis I Diagnoses Among Adolescent Offspring of Probands With Bipolar and Non-Bipolar Psychiatric Disorders and Healthy Controls: The Pittsburgh Bipolar Offspring Study (BIOS).

PubMed

Pan, Lisa A; Goldstein, Tina R; Rooks, Brian T; Hickey, Mary; Fan, Jie Yu; Merranko, John; Monk, Kelly; Diler, Rasim S; Sakolsky, Dara J; Hafeman, Danella; Iyengar, Satish; Goldstein, Benjamin; Kupfer, David J; Axelson, David A; Brent, David A; Birmaher, Boris

2017-03-01

Previous studies have explored the role of stressful life events in the development of mood disorders. We examined the frequency and nature of stressful life events as measured by the Stressful Life Events Schedule (SLES) among 3 groups of adolescent offspring of probands with bipolar (BD), with non-BD psychiatric disorders, and healthy controls. Furthermore, we examined the relationship between stressful life events and the presence of DSM-IV Axis I disorders in these offspring. Stressful life events were characterized as dependent, independent, or uncertain (neither dependent nor independent) and positive, negative, or neutral (neither positive nor negative). Offspring of probands with BD aged 13-18 years (n = 269), demographically matched offspring of probands with non-BD Axis I disorders (n = 88), and offspring of healthy controls (n = 81) from the Pittsburgh Bipolar Offspring Study were assessed from 2002 to 2007 with standardized instruments at intake. Probands completed the SLES for their offspring for life events within the prior year. Life events were evaluated with regard to current Axis I diagnoses in offspring after adjusting for confounds. After adjusting for demographic and clinical between-group differences (in probands and offspring), offspring of probands with BD had greater independent (χ² = 11.96, P < .04) and neutral (χ² = 17.99, P < .003) life events compared with offspring of healthy controls and greater number of more severe stressful life events than offspring of healthy controls, but not offspring of probands with non-BD. Offspring of BD probands with comorbid substance use disorder reported more independent stressful life events compared to those without comorbid substance use disorder (P = .024). Greater frequency and severity of stressful life events were associated with current Axis I disorder in offspring of both probands with BD and probands with other Axis I disorders regardless of dependency or valence. Greater frequency and severity of stressful life events were associated with greater current Axis I disorder in all offspring. Offspring of probands with BD have greater exposure to independent and neutral life events than offspring of healthy controls. Greater frequency and severity of stressful life events were associated with Axis I disorder in offspring of both BD and non-BD affected probands. © Copyright 2017 Physicians Postgraduate Press, Inc.

The Role of Depression in the Differential Effect of Childhood Parental Divorce on Male and Female Adult Offspring Suicide Attempt Risk

PubMed Central

Lizardi, Dana; Thompson, Ronald G.; Keyes, Katherine; Hasin, Deborah

2013-01-01

In previous studies by our group, we found that female offspring of parental divorce and parental remarriage are more susceptible to suicide attempt than male offspring. In this study, we examine whether these findings remain even after controlling for offspring depression. The sample consists of respondents from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Multivariable regressions controlled for offspring depression, parental depression, age, race/ethnicity, income, and marital status. Our previous findings that female offspring of parental divorce and parental remarriage are more likely to report a lifetime suicide attempt than male offspring remained even after controlling for offspring depression. Findings suggest that focusing on engaging female offspring who demonstrate symptoms of depression is not sufficient to reduce suicide attempt risk in this group as many at risk individuals will remain unrecognized. PMID:20823733

The role of depression in the differential effect of childhood parental divorce on male and female adult offspring suicide attempt risk.

PubMed

Lizardi, Dana; Thompson, Ronald G; Keyes, Katherine; Hasin, Deborah

2010-09-01

In previous studies by our group, we found that female offspring of parental divorce and parental remarriage are more susceptible to suicide attempt than male offspring. In this study, we examine whether these findings remain even after controlling for offspring depression. The sample consists of respondents from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Multivariable regressions controlled for offspring depression, parental depression, age, race/ethnicity, income, and marital status. Our previous findings that female offspring of parental divorce and parental remarriage are more likely to report a lifetime suicide attempt than male offspring remained even after controlling for offspring depression. Findings suggest that focusing on engaging female offspring who demonstrate symptoms of depression is not sufficient to reduce suicide attempt risk in this group as many at risk individuals will remain unrecognized.

Parental Legacy in Insects: Variation of Transgenerational Immune Priming during Offspring Development

PubMed Central

Trauer, Ute; Hilker, Monika

2013-01-01

In insects, a parental immune challenge can prepare and enhance offspring immune activity. Previous studies of such transgenerational immune priming (TGIP) mainly focused on a single offspring life stage. However, different developmental stages may be exposed to different risks and show different susceptibility to parental immune priming. Here we addressed the question (i) whether TGIP effects on the immunity of Manduca sexta offspring vary among the different developmental offspring stages. We differentiated between unchallenged and immunochallenged offspring; for the latter type of offspring, we further investigated (ii) whether TGIP has an impact on the time that enhanced immune levels persist after offspring immune challenge. Finally, we determined (iii) whether TGIP effects on offspring performance depend on the offspring stage. Our results show that TGIP effects on phenoloxidase (PO) activity, but not on antibacterial activity, vary among unchallenged offspring stages. In contrast, TGIP effects on PO and antibacterial activity did not vary among immunochallenged offspring stages. The persistence of enhanced immune levels in immunochallenged offspring was dependent on the parental immune state. Antibacterial (but not PO) activity in offspring of immunochallenged parents decreased over five days after pupal immune challenge, whereas no significant change over time was detectable in offspring of control parents. Finally, TGIP effects on the developmental time of unchallenged offspring varied among stages; young larvae of immunochallenged parents developed faster and gained more weight than larvae of control parents. However, offspring females of immunochallenged parents laid fewer eggs than females derived from control parents. These findings suggest that the benefits which the offspring gains from TGIP during juvenile development are paid by the adults with reduced reproductive power. Our study shows that TGIP effects vary among offspring stages and depend on the type of immunity (PO or antibacterial activity) as well as the time past offspring immune challenge. PMID:23700423

Choline and betaine food sources and intakes in Taiwanese.

PubMed

Chu, Da-Ming; Wahlqvist, Mark L; Chang, Hsing-Yi; Yeh, Nai-Hua; Lee, Meei-Shyuan

2012-01-01

Choline and betaine are involved in several similar health-relevant metabolic pathways, but the foods sources are different. We have assessed their intakes (individual, sums and ratios) from a dominantly Chinese food cultural point of view. A representative free-living Taiwanese population aged 13-64 years was drawn from the Nutrition and Health Survey in Taiwan (NAHSIT) 1993-1996. Food intake was derived from interviews as 24-hour recalls. The USDA database, with adaptations for Taiwan, provided choline and betaine food compositions. Major food contributors of these nutrients were identified and compared with data from the US Framingham offspring study. Mean and variance reduced median nutrient intakes were calculated. Top ten major food contributors of choline in Taiwan were eggs, pork, chicken, fish, soybean and its products, dark leafy vegetables, dairy, fruit, wheat products and light leafy vegetables in sequence. For betaine, the top ten were dark leafy vegetables, wheat products, fish, pork, bread, chicken, cake/cookies, grain-based alcoholic beverages, rice and its products and sauces. The main contributors of choline in Taiwan and the USA were, respectively, eggs and red meat; and for betaine, greens were similarly best contributor. The rankings of the main food contributors of choline and betaine differed substantially between Taiwan and the USA. The total daily intakes (mean±SE, mg) in Taiwan for choline were 372±19 (median=348) in men and 265±9 (median 261) for women; for betaine, values were 101±3 (median 93) in men and 78±8 (median 76) for women. These allow for health outcome considerations.

Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis.

PubMed

Lowry, Kathryn P; Gazelle, G Scott; Gilmore, Michael E; Johanson, Colden; Munshi, Vidit; Choi, Sung Eun; Tramontano, Angela C; Kong, Chung Yin; McMahon, Pamela M

2015-05-15

Lung cancer screening with annual chest computed tomography (CT) is recommended for current and former smokers with a ≥30-pack-year smoking history. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and may benefit from screening at lower pack-year thresholds. We used a previously validated simulation model to compare the health benefits of lung cancer screening in current and former smokers ages 55-80 with ≥30 pack-years with hypothetical programs using lower pack-year thresholds for individuals with COPD (≥20, ≥10, and ≥1 pack-years). Calibration targets for COPD prevalence and associated lung cancer risk were derived using the Framingham Offspring Study limited data set. We performed sensitivity analyses to evaluate the stability of results across different rates of adherence to screening, increased competing mortality risk from COPD, and increased surgical ineligibility in individuals with COPD. The primary outcome was projected life expectancy. Programs using lower pack-year thresholds for individuals with COPD yielded the highest life expectancy gains for a given number of screens. Highest life expectancy was achieved when lowering the pack-year threshold to ≥1 pack-year for individuals with COPD, which dominated all other screening strategies. These results were stable across different adherence rates to screening and increases in competing mortality risk for COPD and surgical ineligibility. Current and former smokers with COPD may disproportionately benefit from lung cancer screening. A lower pack-year threshold for screening eligibility may benefit this high-risk patient population. © 2015 American Cancer Society.

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.

Protein Biomarkers for Insulin Resistance and Type 2 Diabetes Risk in Two Large Community Cohorts

PubMed Central

Nowak, Christoph; Sundström, Johan; Gustafsson, Stefan; Giedraitis, Vilmantas; Lind, Lars; Ingelsson, Erik; Fall, Tove

2016-01-01

Insulin resistance (IR) is a precursor of type 2 diabetes (T2D), and improved risk prediction and understanding of the pathogenesis are needed. We used a novel high-throughput 92-protein assay to identify circulating biomarkers for HOMA of IR in two cohorts of community residents without diabetes (n = 1,367) (mean age 73 ± 3.6 years). Adjusted linear regression identified cathepsin D and confirmed six proteins (leptin, renin, interleukin-1 receptor antagonist [IL-1ra], hepatocyte growth factor, fatty acid–binding protein 4, and tissue plasminogen activator [t-PA]) as IR biomarkers. Mendelian randomization analysis indicated a positive causal effect of IR on t-PA concentrations. Two biomarkers, IL-1ra (hazard ratio [HR] 1.28, 95% CI 1.03–1.59) and t-PA (HR 1.30, 1.02–1.65) were associated with incident T2D, and t-PA predicted 5-year transition to hyperglycemia (odds ratio 1.30, 95% CI 1.02–1.65). Additional adjustment for fasting glucose rendered both coefficients insignificant and revealed an association between renin and T2D (HR 0.79, 0.62–0.99). LASSO regression suggested a risk model including IL-1ra, t-PA, and the Framingham Offspring Study T2D score, but prediction improvement was nonsignificant (difference in C-index 0.02, 95% CI −0.08 to 0.12) over the T2D score only. In conclusion, proteomic blood profiling indicated cathepsin D as a new IR biomarker and suggested a causal effect of IR on t-PA. PMID:26420861

PPARG by Dietary Fat Interaction Influences Bone Mass in Mice and Humans

PubMed Central

Ackert-Bicknell, Cheryl L; Demissie, Serkalem; Marín de Evsikova, Caralina; Hsu, Yi-Hsiang; DeMambro, Victoria E; Karasik, David; Cupples, L Adrienne; Ordovas, Jose M; Tucker, Katherine L; Cho, Kelly; Canalis, Ernesto; Paigen, Beverly; Churchill, Gary A; Forejt, Jiri; Beamer, Wesley G; Ferrari, Serge; Bouxsein, Mary L; Kiel, Douglas P; Rosen, Clifford J

2008-01-01

Adult BMD, an important risk factor for fracture, is the result of genetic and environmental interactions. A quantitative trait locus (QTL) for the phenotype of volumetric BMD (vBMD), named Bmd8, was found on mid-distal chromosome (Chr) 6 in mice. This region is homologous to human Chr 3p25. The B6.C3H-6T (6T) congenic mouse was previously created to study this QTL. Using block haplotyping of the 6T congenic region, expression analysis in the mouse, and examination of nonsynonymous SNPs, peroxisome proliferator activated receptor γ (Pparg) was determined to be the most likely candidate gene for the Bmd8 QTL of the 630 genes located in the congenic region. Furthermore, in the C3H/HeJ (C3H) strain, which is the donor strain for the 6T congenic, several polymorphisms were found in the Pparg gene. On challenge with a high-fat diet, we found that the 6T mouse has a lower areal BMD (aBMD) and volume fraction of trabecular bone (BV/TV%) of the distal femur compared with B6 mice. Interactions between SNPs in the PPARG gene and dietary fat for the phenotype of BMD were examined in the Framingham Offspring Cohort. This analysis showed that there was a similar interaction of the PPARG gene and diet (fat intake) on aBMD in both men and women. These findings suggest that dietary fat has a significant influence on BMD that is dependent on the alleles present for the PPARG gene. PMID:18707223

Fruit and Juice Epigenetic Signatures Are Associated with Independent Immunoregulatory Pathways.

PubMed

Nicodemus-Johnson, Jessie; Sinnott, Robert A

2017-07-14

Epidemiological evidence strongly suggests that fruit consumption promotes many health benefits. Despite the general consensus that fruit and juice are nutritionally similar, epidemiological results for juice consumption are conflicting. Our objective was to use DNA methylation marks to characterize fruit and juice epigenetic signatures within PBMCs and identify shared and independent signatures associated with these groups. Genome-wide DNA methylation marks (Illumina Human Methylation 450k chip) for 2,148 individuals that participated in the Framingham Offspring exam 8 were analyzed for correlations between fruit or juice consumption using standard linear regression. CpG sites with low P -values ( P < 0.01) were characterized using Gene Set Enrichment Analysis (GSEA), Ingenuity Pathway Analysis (IPA), and epigenetic Functional element Overlap analysis of the Results of Genome Wide Association Study Experiments (eFORGE). Fruit and juice-specific low P -value epigenetic signatures were largely independent. Genes near the fruit-specific epigenetic signature were enriched among pathways associated with antigen presentation and chromosome or telomere maintenance, while the juice-specific epigenetic signature was enriched for proinflammatory pathways. IPA and eFORGE analyses implicate fruit and juice-specific epigenetic signatures in the modulation of macrophage (fruit) and B or T cell (juice) activities. These data suggest a role for epigenetic regulation in fruit and juice-specific health benefits and demonstrate independent associations with distinct immune functions and cell types, suggesting that these groups may not confer the same health benefits. Identification of such differences between foods is the first step toward personalized nutrition and ultimately the improvement of human health and longevity.

Fruit and Juice Epigenetic Signatures Are Associated with Independent Immunoregulatory Pathways

PubMed Central

Nicodemus-Johnson, Jessie; Sinnott, Robert A.

2017-01-01

Epidemiological evidence strongly suggests that fruit consumption promotes many health benefits. Despite the general consensus that fruit and juice are nutritionally similar, epidemiological results for juice consumption are conflicting. Our objective was to use DNA methylation marks to characterize fruit and juice epigenetic signatures within PBMCs and identify shared and independent signatures associated with these groups. Genome-wide DNA methylation marks (Illumina Human Methylation 450k chip) for 2,148 individuals that participated in the Framingham Offspring exam 8 were analyzed for correlations between fruit or juice consumption using standard linear regression. CpG sites with low P-values (P < 0.01) were characterized using Gene Set Enrichment Analysis (GSEA), Ingenuity Pathway Analysis (IPA), and epigenetic Functional element Overlap analysis of the Results of Genome Wide Association Study Experiments (eFORGE). Fruit and juice-specific low P-value epigenetic signatures were largely independent. Genes near the fruit-specific epigenetic signature were enriched among pathways associated with antigen presentation and chromosome or telomere maintenance, while the juice-specific epigenetic signature was enriched for proinflammatory pathways. IPA and eFORGE analyses implicate fruit and juice-specific epigenetic signatures in the modulation of macrophage (fruit) and B or T cell (juice) activities. These data suggest a role for epigenetic regulation in fruit and juice-specific health benefits and demonstrate independent associations with distinct immune functions and cell types, suggesting that these groups may not confer the same health benefits. Identification of such differences between foods is the first step toward personalized nutrition and ultimately the improvement of human health and longevity. PMID:28708104

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 ...

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

Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample.

PubMed

Fox, Caroline S; Pencina, Michael J; D'Agostino, Ralph B; Murabito, Joanne M; Seely, Ellen W; Pearce, Elizabeth N; Vasan, Ramachandran S

2008-03-24

Overt hypothyroidism and hyperthyroidism may be associated with weight gain and loss. We assessed whether variations in thyroid function within the reference (physiologic) range are associated with body weight. Framingham Offspring Study participants (n=2407) who attended 2 consecutive routine examinations, were not receiving thyroid hormone therapy, and had baseline serum thyrotropin (TSH) concentrations of 0.5 to 5.0 mIU/L and follow-up concentrations of 0.5 to 10.0 mIU/L were included in this study. Baseline TSH concentrations were related to body weight and body weight change during 3.5 years of follow-up. At baseline, adjusted mean weight increased progressively from 64.5 to 70.2 kg in the lowest to highest TSH concentration quartiles in women (P< .001 for trend), and from 82.8 (lowest quartile) to 85.6 kg (highest quartile) in men (P= .007 for trend). During 3.5 years of follow-up, mean (SD) body weight increased by 1.5 (5.6) kg in women and 1.0 (5.0) kg in men. Baseline TSH concentrations were not associated with weight change during follow-up. However, an increase in TSH concentration at follow-up was positively associated with weight gain in women (0.5-2.3 kg across increasing quartiles of TSH concentration change; P< .001 for trend) and men (0.4-1.3 kg across quartiles of TSH concentration change; P= .007 for trend). Thyroid function (as assessed by serum TSH concentration) within the reference range is associated with body weight in both sexes. Our findings raise the possibility that modest increases in serum TSH concentrations within the reference range may be associated with weight gain.

Sex-dependent Association of a Common Low Density Lipoprotein Receptor Polymorphism with RNA Splicing Efficiency in the Brain and Alzheimers Disease

PubMed Central

Zou, Fanggeng; Gopalraj, Rangaraj K.; Lok, Johann; Zhu, Haiyan; Ling, I-Fang; Simpson, James F.; Tucker, H. Michael; Kelly, Jeremiah F.; Younkin, Samuel G.; Dickson, Dennis W.; Petersen, Ronald C; Graff-Radford, Neill R.; Bennett, David A.; Crook, Julia E.; G.Younkin, Steven; Estus, Steven

2008-01-01

Since apoE allele status is the predominant Alzheimers disease (AD) genetic risk factor, functional single nucleotide polymorphisms (SNP)s in brain apoE receptors represent excellent candidates for association with AD. Recently, we identified a SNP, rs688, as modulating the splicing efficiency of low-density lipoprotein receptor (LDLR) exon 12 in the female human liver and in minigene transfected HepG2 cells. Moreover, the rs688T minor allele associated with significantly higher LDL and total cholesterol in women in the Framingham Offspring Study. Since LDLR is a major apoE receptor in the brain, we hypothesized that rs688 modulates LDLR splicing in neural tissues and associates with AD. To evaluate this hypothesis, we first transfected LDLR minigenes into SH-SY5Y neuroblastoma cells and found that rs688T reduces exon 12 inclusion in this neural model. We then evaluated rs688 association with exon 12 splicing efficiency in vivo by quantifying LDLR splicing in human anterior cingulate tissue obtained at autopsy; the rs688T allele associated with decreased LDLR exon 12 splicing efficiency in aged men but not women. Lastly, we evaluated whether rs688 associates with AD by genotyping DNA from 1,457 men and 2,055 women drawn from three case-control series. The rs688T/T genotype was associated with increased AD odds in males (recessive model, odds ratio (OR) of 1.49, 95% confidence interval (CI) of 1.13−1.97, uncorrected p=0.005), but not in females. In summary, these studies identify a functional apoE receptor SNP that is associated with AD in a sex-dependent fashion. PMID:18065781

Relations of arterial stiffness and endothelial function to brain aging in the community.

PubMed

Tsao, Connie W; Seshadri, Sudha; Beiser, Alexa S; Westwood, Andrew J; Decarli, Charles; Au, Rhoda; Himali, Jayandra J; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Larson, Martin G; Benjamin, Emelia J; Wolf, Philip A; Vasan, Ramachandran S; Mitchell, Gary F

2013-09-10

To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging. Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively). Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05). Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.

Functional polymorphisms affecting the clinically important arginine-137 residue of AVPR2 do not influence serum sodium concentration at the population level

PubMed Central

Fu, Yi; Cheetham, Tim; Bourn, David; Orwoll, Eric

2013-01-01

The protein product of the AVPR2 gene, coding for the arginine vasopressin receptor type 2, is essential for vasopressin-dependent concentration of the urine. The arginine residue at position 137 in the protein product of this gene is uniquely pivotal for function. The R137H mutant inactivates the receptor conferring congenital nephrogenic diabetes insipidus, whereas activating mutations at this same residue (i.e., R137C and R137L) confer pathological water retention in the nephrogenic syndrome of inappropriate antidiuresis. These mutations were discovered in human subjects with conspicuous phenotypes in clinical water balance. Prevalence of these polymorphisms among asymptomatic individuals has not been assessed, nor has their contribution to broad interindividual variation in serum sodium concentration; no data addressing minor allele frequency are available. We genotyped two large cohorts using a validated high-throughput Pyrosequencing-based assay that we designed to capture the totality of pathological variation at this important residue. In the Osteoporotic Fractures in Men (MrOS) Study, all participants were male (i.e., hemizygous for AVPR2 gene on the X-chromosome), and participants were oversampled at the extremes of the population distribution for serum sodium concentration. In the Offspring Cohort of the Framingham Heart Study, male and female participants were genotyped. No pathological variants affecting R137 were detected among the 5,142 AVPR2 alleles successfully genotyped. Even at the population extremes of serum sodium distribution, we estimate minor allele frequency < 0.06%. We conclude that these disease-associated variants are exceedingly uncommon and do not contribute broadly to interindividual variability in serum sodium concentration or to its heritability. PMID:23362144

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.

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...

Pathways to suicide-related behavior in offspring of mothers with depression: the role of offspring psychopathology.

PubMed

Hammerton, Gemma; Zammit, Stanley; Mahedy, Liam; Pearson, Rebecca M; Sellers, Ruth; Thapar, Anita; Collishaw, Stephan

2015-05-01

Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers' first 11 years of their child's life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Pathways to Suicide-Related Behavior in Offspring of Mothers With Depression: The Role of Offspring Psychopathology

PubMed Central

Hammerton, Gemma; Zammit, Stanley; Mahedy, Liam; Pearson, Rebecca M.; Sellers, Ruth; Thapar, Anita; Collishaw, Stephan

2015-01-01

Objective Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Method Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers’ first 11 years of their child’s life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. Results There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Conclusion Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology. PMID:25901775

Parental Post-traumatic Stress Disorder Symptoms Are Related to Successful Aging in Offspring of Holocaust Survivors

PubMed Central

Shrira, Amit; Ayalon, Liat; Bensimon, Moshe; Bodner, Ehud; Rosenbloom, Tova; Yadid, Gal

2017-01-01

A fascinating, yet underexplored, question is whether traumatic events experienced by previous generations affect the aging process of subsequent generations. This question is especially relevant for offspring of Holocaust survivors (OHS), who begin to face the aging process. Some preliminary findings point to greater physical dysfunction among middle-aged OHS, yet the mechanisms behind this dysfunction need further clarification. Therefore, the current studies assess aging OHS using the broad-scoped conceptualization of successful aging, while examining whether offspring successful aging relates to parental post-traumatic stress disorder (PTSD) symptoms and offspring’s secondary traumatization symptoms. In Study 1, 101 adult offspring (mean age = 62.31) completed measures of parental PTSD, secondary traumatization, as well as successful aging indices – objective (medical conditions, disability and somatic symptoms) and subjective (perceptions of one’s aging). Relative to comparisons and OHS who reported that none of their parents suffered from probable PTSD, OHS who reported that their parents suffered from probable PTSD had lower scores in objective and subjective measures of successful aging. Mediation analyses showed that higher level of secondary traumatization mediated the relationship between parental PTSD and less successful aging in the offspring. Study 2 included 154 dyads of parents (mean age = 81.86) and their adult offspring (mean age = 54.48). Parents reported PTSD symptoms and offspring reported secondary traumatization and completed measures of objective successful aging. Relative to comparisons, OHS whose parent had probable PTSD have aged less successfully. Once again, offspring secondary traumatization mediated the effect. The findings suggest that parental post-traumatic reactions assessed both by offspring (Study 1) and by parents themselves (Study 2) take part in shaping the aging of the subsequent generation via reactions of secondary traumatization in the offspring. The studies also provide initial evidence that these processes can transpire even when offspring do not have probable PTSD or when controlling offspring anxiety symptoms. Our findings allude to additional behavioral and epigenetic processes that are potentially involved in the effect of parental PTSD on offspring aging, and further imply the need to develop interdisciplinary interventions aiming at promoting successful aging among offspring of traumatized parents. PMID:28706503

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.

Parental obesity and risk factors for cardiovascular disease among their offspring in mid-life: findings from the 1958 British Birth Cohort Study.

PubMed

Cooper, R; Pinto Pereira, S M; Power, C; Hyppönen, E

2013-12-01

Few studies have investigated whether parental adiposity is associated with offspring cardiovascular health or the underlying pathways. Studying these associations may help to illuminate the paradox of increasing prevalence of obesity and declining trends in cardiovascular disease (CVD) mortality, which may be partially explained by beneficial adaptations to an obesogenic environment among people exposed to such environments from younger ages. To investigate associations between parental body mass index (BMI) and risk factors for CVD among their offspring in mid-life and to test whether associations of offspring BMI with CVD risk factors were modified by parental BMI. Data from parents and offspring in the 1958 British birth cohort were used (N=9328). Parental BMI was assessed when offspring were aged 11 years; offspring BMI, waist circumference and CVD risk factors (lipid levels, blood pressure, glycosylated haemoglobin (HbA1c) and inflammatory and haemostatic markers) were measured at 44-45 years. Higher parental BMI was associated with less favourable levels of offspring risk factors for CVD. Most associations were maintained after adjustment for offspring lifestyle and socioeconomic factors but were largely abolished or reversed after adjustment for offspring adiposity. For some CVD risk factors, there was evidence of effect modification; the association between higher BMI and an adverse lipid profile among offspring was weaker if maternal BMI had been higher. Conversely, offspring BMI was more strongly associated with HbA1c if parental BMI had been higher. Intergenerational influences may be important in conferring the effect of high BMI on CVD risk among offspring.

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.

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.

Psychosocial functioning in offspring of parents with bipolar disorder.

PubMed

Bella, Tolulope; Goldstein, Tina; Axelson, David; Obreja, Mihaela; Monk, Kelly; Hickey, Mary Beth; Goldstein, Benjamin; Brent, David; Diler, Rasim Somer; Kupfer, David; Sakolsky, Dara; Birmaher, Boris

2011-09-01

Offspring of parents with bipolar disorder are at increased risk for a range of psychopathology, including bipolar disorder. It is not clear if they also have impairments in their psychosocial functioning. We compared the psychosocial functioning of three groups of children enrolled in the Pittsburgh Bipolar Offspring Study (BIOS): offspring of probands with bipolar disorder (n=388), offspring of probands with other types of psychopathology (n=132), and offspring of healthy probands (n=118). Psychosocial functioning was assessed at study intake using the schedule of the Adolescent Longitudinal Interval Follow-Up Evaluation (A-LIFE), the Child Behavior Check List (CBCL) and the Children's Global Assessment Scale (CGAS). Offspring of probands with bipolar disorder exhibited impairments in various aspects of psychosocial functioning. On all measures, they had worse functioning in comparison with offspring of healthy probands. Offspring of probands with bipolar disorder generally exhibited more impairment than offspring of probands with nonbipolar psychopathology. After adjusting for proband parent functioning and the child's Axis I psychopathology, functioning of offspring of probands with bipolar disorder was similar to that of offspring of healthy probands. Data are cross-sectional and therefore do not allow for causal conclusions about the association between parental psychopathology, child psychopathology and offspring psychosocial functioning. Offspring of parents with bipolar disorder exhibit impairments in psychosocial functioning which appear largely attributable to proband parent functional impairment and the child's own psychopathology. As such, interventions to improve parental functioning, as well as early interventions to treat the child's psychopathology may help reduce the risk for long-term functional impairment in offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

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...

Adrenocortical responses to offspring-directed threats in two open-nesting birds.

PubMed

Butler, Luke K; Bisson, Isabelle-Anne; Hayden, Timothy J; Wikelski, Martin; Romero, L Michael

2009-07-01

Dependent young are often easy targets for predators, so for many parent vertebrates, responding to offspring-directed threats is a fundamental part of reproduction. We tested the parental adrenocortical response of the endangered black-capped vireo (Vireo atricapilla) and the common white-eyed vireo (V. griseus) to acute and chronic threats to their offspring. Like many open-nesting birds, our study species experience high offspring mortality. Parents responded behaviorally to a predator decoy or human 1-2m from their nests, but, in contrast to similar studies of cavity-nesting birds, neither these acute threats nor chronic offspring-directed threats altered plasma corticosterone concentrations of parents. Although parents in this study showed no corticosterone response to offspring-directed threats, they always increased corticosterone concentrations in response to capture. To explain these results, we propose that parents perceive their risk of nest-associated death differently depending on nest type, with cavity-nesting adults perceiving greater risk to themselves than open-nesters that can readily detect and escape from offspring-directed threats. Our results agree with previous studies suggesting that the hypothalamic-pituitary-adrenal axis, a major physiological mechanism for coping with threats to survival, probably plays no role in coping with threats to offspring when risks to parents and offspring are not correlated. We extend that paradigm by demonstrating that nest style may influence how adults perceive the correlation between offspring-directed and self-directed threats.

A mouse model of pre-pregnancy maternal obesity combined with offspring exposure to a high-fat diet resulted in cognitive impairment in male offspring.

PubMed

Zhu, Chen; Han, Ting-Li; Zhao, Yalan; Zhou, Xiaobo; Mao, Xun; Qi, Hongbo; Baker, Philip N; Zhang, Hua

2018-04-23

Cognitive impairment is a brain dysfunction characterized by neuropsychological deficits in attention, working memory, and executive function. Maternal obesity and consumption of a high-fat diet (HFD) in the offspring has been suggested to have detrimental consequences for offspring cognitive function through its effect on the hippocampus and prefrontal cortex. Therefore, our study aimed to investigate the effects of maternal obesity and offspring HFD exposure on the brain metabolome of the offspring. In our pilot study, a LepRdb/+ mouse model was used to model pre-pregnancy maternal obesity and the c57bl/6 wildtype was used as a control group. Offspring were fed either a HFD or a low-fat control diet (LFD) after weaning (between 8 and 10 weeks). The Mirrors water maze was performed between 28 and 30 weeks to measure cognitive function. Fatty acid metabolomic profiles of the prefrontal cortex and hippocampus from the offspring at 30-32 weeks were analyzed using gas chromatography-mass spectrometry. The memory of male offspring from obese maternal mice, consuming a HFD post-weaning, was significantly impaired when compared to the control offspring mice. No significant differences were observed in female offspring. In male mice, the fatty acid metabolites in the prefrontal cortex were most affected by maternal obesity, whereas, the fatty acid metabolites in the hippocampus were most affected by the offspring's diet. Hexadecanoic acid and octadecanoic acid were significantly affected in both the hippocampus and pre-frontal cortex, as a result of maternal obesity and a HFD in the offspring. Our findings suggest that the combination of maternal obesity and HFD in the offspring can result in spatial cognitive deficiency in the male offspring, by influencing the fatty acid metabolite profiles in the prefrontal cortex and hippocampus. Further research is needed to validate the results of our pilot study. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Functional impairment due to bereavement after the death of adolescent or young adult offspring in a national population study of 1,051,515 parents.

PubMed

Wilcox, Holly C; Mittendorfer-Rutz, Ellenor; Kjeldgård, Linnea; Alexanderson, Kristina; Runeson, Bo

2015-08-01

This study addresses the burden of grief after the death of an adolescent or young adult offspring. Parental bereavement following the death of an adolescent or young adult offspring is associated with considerable psychiatric and somatic impairment. Our aim is to fill a research gap by examining offspring death due to suicide, accidents, or natural causes in relation to risk of parental sickness absence with psychiatric or somatic disorders. This whole population-based prospective study included mothers and fathers of all offspring aged 16-24 years in Sweden on December 31, 2004 (n = 1,051,515). This study had no loss to follow-up and exposure, confounders, and the outcome were recorded independently of each other. Cox survival analysis was used to model time to sickness absence exceeding 30 days, adjusting for parental demographic characteristics, previous parental sickness absence and disability pension, and inpatient and outpatient psychiatric and somatic healthcare prior to offspring death in 2001-2004. This large study population provided satisfactory statistical power for stratification by parents' sex and adolescent and young adults' cause of death. Mothers and fathers of offspring suicide and accident decedents both had over tenfold higher risk for psychiatric sickness absence exceeding 30 days as compared to parents of live offspring. Fathers of suicide decedents were at 40 % higher risk for somatic sickness absence. This is the largest study to date of parents who survived their offspring's death and the first study of work-related outcomes in bereaved parents. This study uses a broad metric of work-related functional impairment, sickness absence, for capturing the burden of sudden offspring death.

The Effects of Parental Mood on Reports of Their Children's Psychopathology

PubMed Central

Maoz, Hagai; Goldstein, Tina; Goldstein, Benjamin I.; Axelson, David A.; Fan, Jieyu; Hickey, Mary Beth; Monk, Kelly; Sakolsky, Dara; Diler, Rasim S.; Brent, David; Kupfer, David J.; Birmaher, Boris

2014-01-01

Objective In this study, we aim to assess whether current mood state (depressed or manic/hypomanic) among parents with a mood disorder affects their reports of their offspring's psychopathology. Method Sixty-five parents with current depression, 42 with current mania/hypomania, 181 with mood disorder in remission, and their offspring (n=479, ages 6-18) completed assessments of offspring IP psychopathology as part of the Pittsburgh Bipolar Offspring Study (BIOS). We compared rates of offspring psychopathology assessed using the following: a clinician-administered semi-structured interview with parent and child using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS); parent-reported Child Behavior Checklist (CBCL); offspring self-reported Youth Self Reports (YSR) for those 11 years and older (n=250); and teachers’ reports when available (n= 209). Results There were no between-group differences in rates of psychopathology yielded from the K-SADS, except for more depressive disorders in offspring of parents with current mania/hypomania compared to offspring of parents in remission. Conversely, using the CBCL and comparing with parents who were in remission, parents with current depression reported significantly more externalizing psychopathology in offspring, whereas parents with current mania/hypomania reported more externalizing and internalizing psychopathology in their offspring. On the YSR, offspring of parents with current mania/hypomania had more internalizing psychopathology compared to offspring of parents in remission. Teacher's reports showed no between-group differences in rates of any psychopathology. Conclusion Parental active mood symptomatology, especially during a manic/hypomanic episode, significantly affects their reports of their offspring's psychopathology. Trained interviewers reduce potential report bias. Clinicians and studies assessing children's psychopathology should take into account parental current mood state. PMID:25245355

Risk of mental illness in offspring of parents with schizophrenia, bipolar disorder, and major depressive disorder: a meta-analysis of family high-risk studies.

PubMed

Rasic, Daniel; Hajek, Tomas; Alda, Martin; Uher, Rudolf

2014-01-01

Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) are at an increased risk of developing mental illness. We aimed to quantify the risk of mental disorders in offspring and determine whether increased risk extends beyond the disorder present in the parent. Meta-analyses of absolute and relative rates of mental disorders in offspring of parents with schizophrenia, bipolar disorder, or depression in family high-risk studies published by December 2012. We included 33 studies with 3863 offspring of parents with SMI and 3158 control offspring. Offspring of parents with SMI had a 32% probability of developing SMI (95% CI: 24%-42%) by adulthood (age >20). This risk was more than twice that of control offspring (risk ratio [RR] 2.52; 95% CI 2.08-3.06, P < .001). High-risk offspring had a significantly increased rate of the disorder present in the parent (RR = 3.59; 95% CI: 2.57-5.02, P < .001) and of other types of SMI (RR = 1.92; 95% CI: 1.48-2.49, P < .001). The risk of mood disorders was significantly increased among offspring of parents with schizophrenia (RR = 1.62; 95% CI: 1.02-2.58; P = .042). The risk of schizophrenia was significantly increased in offspring of parents with bipolar disorder (RR = 6.42; 95% CI: 2.20-18.78, P < .001) but not among offspring of parents with depression (RR = 1.71; 95% CI: 0.19-15.16, P = .631). Offspring of parents with SMI are at increased risk for a range of psychiatric disorders and one third of them may develop a SMI by early adulthood.

Parental obesity and risk factors for cardiovascular disease among their offspring in mid-life: findings from the 1958 British Birth Cohort Study

PubMed Central

Cooper, R; Pinto Pereira, S M; Power, C; Hyppönen, E

2013-01-01

Background: Few studies have investigated whether parental adiposity is associated with offspring cardiovascular health or the underlying pathways. Studying these associations may help to illuminate the paradox of increasing prevalence of obesity and declining trends in cardiovascular disease (CVD) mortality, which may be partially explained by beneficial adaptations to an obesogenic environment among people exposed to such environments from younger ages. Objective: To investigate associations between parental body mass index (BMI) and risk factors for CVD among their offspring in mid-life and to test whether associations of offspring BMI with CVD risk factors were modified by parental BMI. Methods: Data from parents and offspring in the 1958 British birth cohort were used (N=9328). Parental BMI was assessed when offspring were aged 11 years; offspring BMI, waist circumference and CVD risk factors (lipid levels, blood pressure, glycosylated haemoglobin (HbA1c) and inflammatory and haemostatic markers) were measured at 44–45 years. Results: Higher parental BMI was associated with less favourable levels of offspring risk factors for CVD. Most associations were maintained after adjustment for offspring lifestyle and socioeconomic factors but were largely abolished or reversed after adjustment for offspring adiposity. For some CVD risk factors, there was evidence of effect modification; the association between higher BMI and an adverse lipid profile among offspring was weaker if maternal BMI had been higher. Conversely, offspring BMI was more strongly associated with HbA1c if parental BMI had been higher. Conclusions: Intergenerational influences may be important in conferring the effect of high BMI on CVD risk among offspring. PMID:23567929

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.

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.

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.

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...

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...

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...

Intergenerational Transmission of Stress in Humans

PubMed Central

Bowers, Mallory E; Yehuda, Rachel

2016-01-01

The hypothesis that offspring are affected by parental trauma or stress exposure, first noted anecdotally, is now supported empirically by data from Holocaust survivor offspring cohorts and other populations. These findings have been extended to less extreme forms of stress, where differential physical, behavioral, and cognitive outcomes are observed in affected offspring. Parental stress-mediated effects in offspring could be explained by genetics or social learning theory. Alternatively, biological variations stemming from stress exposure in parents could more directly have an impact on offspring, a concept we refer to here as ‘intergenerational transmission', via changes to gametes and the gestational uterine environment. We further extend this definition to include the transmission of stress to offspring via early postnatal care, as animal studies demonstrate the importance of early maternal care of pups in affecting offsprings' long-term behavioral changes. Here, we review clinical observations in offspring, noting that offspring of stress- or trauma-exposed parents may be at greater risk for physical, behavioral, and cognitive problems, as well as psychopathology. Furthermore, we review findings concerning offspring biological correlates of parental stress, in particular, offspring neuroendocrine, epigenetic, and neuroanatomical changes, in an attempt to determine the extent of parental stress effects. Although understanding the etiology of effects in offspring is currently impeded by methodological constraints, and limitations in our knowledge, we summarize current information and conclude by presenting hypotheses that have been prompted by recent studies in the field. PMID:26279078

The relationship between stressful life events and Axis I diagnoses among adolescent offspring of probands with bipolar and non-bipolar psychiatric disorders and healthy controls

PubMed Central

Pan, Lisa A.; Goldstein, Tina R.; Rooks, Brian T.; Hickey, Mary; Fan, Jie Yu; Merranko, John; Monk, Kelly; Diler, Rasim S.; Sakolsky, Dara J.; Hafeman, Daniella; Iyengar, Satish; Goldstein, Benjamin; Kupfer, David J.; Axelson, David; Brent, David A.; Birmaher, Boris

2018-01-01

Background Previous studies have explored the role of stressful life events in the development of mood disorders. We examined the frequency and nature of stressful life events as measured by the Stressful Life Events Scale(SLES) among three groups of adolescent offspring of probands: with bipolar(BD), with non-BD psychiatric disorders, and healthy control(HC). Furthermore, we examined the relationship between stressful life events and presence of DSM-IV Axis I disorders in these offspring. Stressful life events were characterized as dependent, independent, or uncertain (neither dependent or independent), and positive, negative, and neutral (neither positive or negative). Method Offspring of probands with BD aged 13–18 years(N=269), demographically-matched offspring of probands with non-BD Axis I disorders(N=88), and HC probands(N=81) from the Pittsburgh Bipolar Offspring Study were assessed from 2002–2007 with standardized instruments at intake. Probands completed the SLES for their offspring for life events within the prior year. Life events were evaluated with regard to current offspring Axis I diagnoses after adjusting for confounds. Results After adjusting for demographic and clinical between-group differences(in probands and offspring), offspring of BD probands had greater independent and neutral life events compared with HC offspring and greater number of more severe stressful life events than HC offspring, but not non-BD offspring. Offspring of BD probands with comorbid substance use disorder reported more independent stressful life events. Greater frequency and severity of stressful life events were associated with current Axis I disorder in offspring of both BD and non-BD affected probands regardless of dependency or valence. Greater frequency and severity of stressful life events were associated with greater current Axis I disorder in all offspring. Conclusions Offspring of BD probands have greater exposure to independent and neutral life events than HC offspring. Greater frequency and severity of stressful life events was associated with Axis I disorder in offspring of both BD and non-BD affected probands. PMID:28199068

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.

Clinical, Demographic, and Familial Correlates of Bipolar Spectrum Disorders among Offspring of Parents with Bipolar Disorder

ERIC Educational Resources Information Center

Goldstein, Benjamin I.; Shamseddeen, Wael; Axelson, David A.; Kalas, Cathy; Monk, Kelly; Brent, David A.; Kupfer, David J.; Birmaher, Boris

2010-01-01

Objective: Despite increased risk, most offspring of parents with bipolar disorder (BP) do not manifest BP. The identification of risk factors for BP among offspring could improve preventive and treatment strategies. We examined this topic in the Pittsburgh Bipolar Offspring Study (BIOS). Method: Subjects included 388 offspring, ages 7-17 years,…

Maternal early pregnancy lipid profile and offspring's lipids and glycaemic control at age 5-6 years: The ABCD study.

PubMed

van Lieshout, Noekie; Oostvogels, Adriëtte J J M; Gademan, Maaike G J; Vrijkotte, Tanja G M

2017-12-01

Maternal early pregnancy lipid profile might influence offspring's lipids and glycaemic control, through an increased offspring's fat percentage. This explorative study investigates whether maternal early pregnancy lipid profile is associated with offspring's lipids and glycaemic control independently of offspring's fat percentage and if these associations are mediated by offspring's fat percentage. Possible sex differences in these associations are also examined. 1133 mother-child pairs of the prospective ABCD-study were included. Maternal non-fasting lipids were collected in early pregnancy: triglycerides, total cholesterol (TC), Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and free fatty acids (FFA). Fasting triglycerides, TC, high density lipoprotein (HDL), low density lipoprotein (LDL), glucose and C-peptide were assessed in offspring aged 5-6 years and HOMA2-IR was calculated. After adjustment for covariates, strongest associations were found between maternal TC and offspring's TC (boys β(95%CI) = 0.141 (0.074-0.207); girls β(95%CI) = 0.268 (0.200; 0.336)) and LDL (boys β(95%CI) = 0.114 (0.052; 0.176); girls β(95%CI) = 0.247 (0.181-0.312)), maternal ApoB and offspring's TC (boys β(95%CI) = 0.638 (0.311-0.965); girls β(95%CI) = 1.121 (0.766-1.475)) and LDL (boys β(95%CI) = 0.699 (0.393-1.005); girls β(95%CI) = 1.198 (0.868-1.529)), and maternal ApoA1 and offspring's HDL (only boys β(95%CI) = 0.221 (0.101-0.341)). No significant association was found between maternal lipids and offspring's glycaemic control, and offspring's fat percentage played no mediating role. Maternal early pregnancy lipid profile is associated with offspring's lipid profile in childhood, with overall stronger associations in girls. This study provides further evidence that lowering lipid levels during pregnancy might be beneficial for the long term health of the offspring. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Metabolite Profiling and Cardiovascular Event Risk: A Prospective Study of Three Population-Based Cohorts

PubMed Central

Würtz, Peter; Havulinna, Aki S; Soininen, Pasi; Tynkkynen, Tuulia; Prieto-Merino, David; Tillin, Therese; Ghorbani, Anahita; Artati, Anna; Wang, Qin; Tiainen, Mika; Kangas, Antti J; Kettunen, Johannes; Kaikkonen, Jari; Mikkilä, Vera; Jula, Antti; Kähönen, Mika; Lehtimäki, Terho; Lawlor, Debbie A; Gaunt, Tom R; Hughes, Alun D; Sattar, Naveed; Illig, Thomas; Adamski, Jerzy; Wang, Thomas J; Perola, Markus; Ripatti, Samuli; Vasan, Ramachandran S; Raitakari, Olli T; Gerszten, Robert E; Casas, Juan-Pablo; Chaturvedi, Nish; Ala-Korpela, Mika; Salomaa, Veikko

2015-01-01

Background High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors. Methods and Results We applied quantitative NMR metabolomics to identify biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the FINRISK study (n=7256; 800 events). Replication and incremental risk prediction was assessed in the SABRE study (n=2622; 573 events) and British Women’s Health and Heart Study (n=3563; 368 events). In targeted analyses of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events at P<0.0007 after adjusting for age, sex, blood pressure, smoking, diabetes and medication. When further adjusting for routine lipids, four metabolites were associated with future cardiovascular events in meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation: 1.18 [95%CI 1.12–1.24]; P=4×10−10) and monounsaturated fatty acid levels (1.17 [1.11–1.24]; P=1×10−8) were associated with increased cardiovascular risk, while higher omega-6 fatty acids (0.89 [0.84–0.94]; P=6×10−5) and docosahexaenoic acid levels (0.90 [0.86–0.95]; P=5×10−5) were associated with lower risk. A risk score incorporating these four biomarkers was derived in FINRISK. Risk prediction estimates were more accurate in the two validation cohorts (relative integrated discrimination improvement 8.8% and 4.3%), albeit discrimination was not enhanced. Risk classification was particularly improved for persons in the 5–10% risk range (net reclassification 27.1% and 15.5%). Biomarker associations were further corroborated with mass spectrometry in FINRISK (n=671) and the Framingham Offspring Study (n=2289). Conclusions Metabolite profiling in large prospective cohorts identified phenylalanine, monounsaturated and polyunsaturated fatty acids as biomarkers for cardiovascular risk. This study substantiates the value of high-throughput metabolomics for biomarker discovery and improved risk assessment. PMID:25573147

Temperament and major depression: How does difficult temperament affect frequency, severity, and duration of major depressive episodes among offspring of parents with or without depression?

PubMed Central

Sherman, Brian J.; Vousoura, Eleni; Wickramaratne, Priya; Warner, Virginia; Verdeli, Helen

2016-01-01

Introduction The current study examined the relationships between parental depression, offspring depression, and offspring temperament among 203 offspring of parents with or without depression. The specific aim was to investigate how offspring difficult temperament affects frequency, severity, and duration of offspring major depressive episodes (MDEs). Methods As part of an ongoing multigenerational study assessing familial transmission of depression, offspring were assessed over a 20-year study period. Offspring temperament was assessed at baseline using the Dimensions of Temperament Survey and diagnostic interviews were conducted at each of the four waves using best estimate procedures. Results Difficult temperament predicted greater frequency of lifetime MDEs. Parental depression moderated the relationship between offspring difficult temperament and severity of MDEs, such that difficult temperament was associated with increased severity ratings among high-risk, but not low-risk offspring. Dimensional analysis revealed that lower rhythmicity and adaptability were associated with greater number of lifetime MDEs, while higher inattention/distractibility was associated with shorter duration of MDEs. Discussion Certain limitations must be noted, namely the self-report nature of temperament data and the relatively small sample size drawn from a clinical and predominantly Caucasian and Christian sample. Notwithstanding these limitations, our results suggest that the clinical presentation of major depression may reflect temperamental profiles and should be considered in diagnostic and treatment settings. PMID:27130957

The psychological, social, and behavioural impact of a parent's cancer on adolescent and young adult offspring aged 10-24 at time of diagnosis: A systematic review.

PubMed

Morris, Julia; Turnbull, Deborah; Preen, David; Zajac, Ian; Martini, Angelita

2018-06-01

This study reviewed the literature regarding the psychological, social, and behavioural impact of parental cancer on offspring aged 10-24 years, at the time of the parent's first diagnosis. A systematic literature review was conducted following 2015 PRISMA guidelines. Seven studies met inclusion criteria. Offspring were impacted by their parent's cancer and experienced psychological and behavioural problems. Daughters and offspring who experienced more problems at their parent's diagnosis appeared to be most impacted. Offspring refrained from communicating their disease-related concerns, but expected their parents to communicate openly. Turning to oneself and peer-support were coping strategies used by offspring. The majority of offspring were significantly impacted by their parent's cancer. The paucity of literature focusing on offspring aged 10-24 years at the time of their parent's incident cancer diagnosis indicates that research has overlooked offspring age at their parent's cancer onset as a factor that may influence their future outcomes. Copyright © 2018. Published by Elsevier Ltd.

Psychopathology in the adolescent and young adult offspring of parents with dysthymic disorder and major depressive disorder.

PubMed

Lizardi, Humberto; Klein, Daniel N; Shankman, Stewart A

2004-03-01

This study addressed the following question: are the adolescent and young adult offspring of parents with early-onset dysthymic disorder (DD) at increased risk for psychopathology? Participants included 41 offspring of 21 outpatients with early-onset DD, 19 offspring of nine outpatients with episodic major depressive disorder (MDD), and 32 offspring of 11 normal controls (NCs). Lifetime best-estimate diagnoses were determined for each offspring using a team consensus method. Diagnoses were derived blind to all information about the index parents. The offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of a broad range of psychiatric disorders than the offspring of NCs. In addition, the offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of DD, anxiety disorders, and phobia than the offspring of outpatients with episodic MDD. These results support the importance of early-onset DD in parents as a risk factor for psychopathology in their offspring.

Risk/protective factors among addicted mothers' offspring: a replication study.

PubMed

Weissman, M M; McAvay, G; Goldstein, R B; Nunes, E V; Verdeli, H; Wickramaratne, P J

1999-11-01

There are few systematic studies of the school-aged offspring of drug-dependent patients, although this information is useful for planning evidence-based prevention programs. We have completed such a study, which we compare to a similar study independently conducted in 1998. In both studies, both the parent and offspring were assessed blindly and independently by direct diagnostic interviews, and parental assessment of offspring was also obtained. The similarity in design and methods between studies provided an opportunity for replication by reanalysis of data. The major findings are a replication in two independently conducted studies of school-aged offspring of opiate- and/or cocaine-addicted mothers of the high rates of any psychiatric disorder (60% in both studies), major depression (20%, 26%), oppositional defiant disorder (ODD) (18%, 23%), conduct disorder (17%, 9%), attention-deficit/hyperactivity disorder (ADHD) (13%, 8%), and substance abuse (5%, 10%) among offspring. Both studies also found high rates of comorbid alcohol abuse, depression, and multiple drugs of abuse in the mothers. We conclude that efforts to replicate findings by analyses of independently conducted studies are an inexpensive way to test the sturdiness of findings that can provide the empirical basis for preventive efforts. Clinically, the data in both studies suggest that both drug dependence and associated psychopathology should be assessed and treated in opiate addicts with young offspring, and the offspring should be monitored for the development of conduct and mood disorders and substance use.

Does relationship satisfaction and financial aid from offspring influence the quality of life of older parents?: a longitudinal study based on findings from the Korean longitudinal study of aging, 2006-2012.

PubMed

Ju, Yeong Jun; Han, Kyu-Tae; Lee, Tae-Hoon; Kim, Woorim; Kim, Juyeong; Park, Eun-Cheol

2016-07-26

Quality of life (QoL) in old age is of major importance because the global population is aging rapidly. Offspring support, including financial and emotional support, is important in later life and directly affects the wellbeing of elderly individuals. The aim of this study was to examine the relationship between QoL in older parents and offspring support. We used baseline data from the 2006-2012 Korean Longitudinal Study of Aging, from 3,274 individuals aged 65 years or older. We measured the individual's QoL using a visual analog scale and included both relationship satisfaction and regular economic support as variables. A generalized estimating equation (GEE) model was used to perform longitudinal regression analysis on the data. Regarding the QoL of older parents, those with an unsatisfying relationship with their offspring had a QoL of -21.93 (SE = 0.55; P < 0.0001) compared to those with satisfying offspring relationships. Those receiving no regular financial aid from their offspring had a QoL of -0.92 (SE = 0.38; P = 0.0171) compared to those who received such economic support. Combination effects were observed, with cases living alone - and having poor offspring relationships and no regular financial support from their offspring - showing the most drastic decrease in QoL (-23.46; SE = 1.03; P < 0.0001). Offspring support influences the QoL of elderly individuals, and Korean children appear to play a crucial role in the QoL of their (older) parents. Considering that the role of offspring is rapidly diminishing due to industrialization policies, initiatives are required to revitalize offspring support for elderly parents.

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 role of the mother-child relationship for anxiety disorders and depression: results from a prospective-longitudinal study in adolescents and their mothers.

PubMed

Asselmann, Eva; Wittchen, Hans-Ulrich; Lieb, Roselind; Beesdo-Baum, Katja

2015-04-01

This study aims to examine whether (a) low child valence (emotional connectedness) within the mother-child relationship increases the risk for offspring depression, (b) low child potency (individual autonomy) increases the risk for offspring anxiety, and (c) maternal psychopathology pronounces these associations. We used data from a prospective-longitudinal study of adolescents (aged 14-17 at baseline) and their mothers (N = 1,015 mother-child dyads). Anxiety disorders and depression were assessed repeatedly over 10 years in adolescents (T0, T1, T2, T3) and their mothers (T1, T3) using the DSM-IV/M-CIDI. Valence and potency were assessed in mothers (T1) with the Subjective Family Image Questionnaire. Odds ratios (OR) from logistic regression were used to estimate associations between low child valence/potency and offspring psychopathology (cumulated lifetime incidences; adjusted for sex and age). In separate models (low valence or low potency as predictor), low child valence predicted offspring depression only (OR = 1.26 per SD), while low child potency predicted offspring anxiety (OR = 1.24) and depression (OR = 1.24). In multiple models (low valence and low potency as predictors), low child valence predicted offspring depression only (OR = 1.19), while low child potency predicted offspring anxiety only (OR = 1.22). Low child potency interacted with maternal anxiety on predicting offspring depression (OR = 1.49), i.e. low child potency predicted offspring depression only in the presence of maternal anxiety (OR = 1.33). These findings suggest that low child valence increases the risk for offspring depression, while low child potency increases the risk for offspring anxiety and depression and interacts with maternal psychopathology on predicting offspring depression.

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.

Using Response Surface Analysis to Interpret the Impact of Parent–Offspring Personality Similarity on Adolescent Externalizing Problems

PubMed Central

Laceulle, Odillia M.; Van Aken, Marcel A.G.; Ormel, Johan

2017-01-01

Abstract Personality similarity between parent and offspring has been suggested to play an important role in offspring's development of externalizing problems. Nonetheless, much remains unknown regarding the nature of this association. This study aimed to investigate the effects of parent–offspring similarity at different levels of personality traits, comparing expectations based on evolutionary and goodness‐of‐fit perspectives. Two waves of data from the TRAILS study (N = 1587, 53% girls) were used to study parent–offspring similarity at different levels of personality traits at age 16 predicting externalizing problems at age 19. Polynomial regression analyses and Response Surface Analyses were used to disentangle effects of different levels and combinations of parents and offspring personality similarity. Although several facets of the offspring's personality had an impact on offspring's externalizing problems, few similarity effects were found. Therefore, there is little support for assumptions based on either an evolutionary or a goodness‐of‐fit perspective. Instead, our findings point in the direction that offspring personality, and at similar levels also parent personality might impact the development of externalizing problems during late adolescence. © 2017 The Authors. European Journal of Personality published by John Wiley & Sons Ltd on behalf of European Association of Personality Psychology PMID:28303077

Family functioning in the context of parental bipolar disorder: associations with offspring age, sex, and psychopathology.

PubMed

Freed, Rachel D; Tompson, Martha C; Wang, Christine H; Otto, Michael W; Hirshfeld-Becker, Dina R; Nierenberg, Andrew A; Henin, Aude

2015-02-01

Previous research has shown that families with a parent who has bipolar disorder (BD) may experience family functioning difficulties. However, the association between family functioning and psychopathology among offspring of parents with BD, and offspring characteristics that may moderate this association, remains poorly understood. This study examined the cross-sectional associations between family functioning (cohesion, expressiveness, and conflict) and psychopathology in 117 offspring (ages 5-18) of 75 parents with BD. We also examined whether age and sex differences moderated these associations. We measured offspring psychopathology by examining current dimensional symptoms and DSM-IV emotional and behavioral disorders. Correlational analyses indicated that higher family conflict and lower cohesion were associated with higher internalizing and externalizing symptoms in offspring. Lower family cohesion was also associated with current offspring mood disorders. Moderation analyses indicated, first, that the link between lower family cohesion and internalizing symptoms was stronger for younger offspring compared to older offspring. Second, higher family conflict and current mood disorder were associated in younger males but not in older males or in females. Results remained the same after controlling for parental anxiety or substance use disorder comorbidity. Our study highlights the importance of accounting for family functioning when working with offspring at risk for BD, while also recognizing that the connections between family functioning and offspring outcomes are complex and differ based on offspring sex and developmental stage. PsycINFO Database Record (c) 2015 APA, all rights reserved.

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

Cross-generational environmental effects and the evolution of offspring size in the Trinidadian guppy Poecilia reticulata.

PubMed

Bashey, Farrah

2006-02-01

The existence of adaptive phenotypic plasticity demands that we study the evolution of reaction norms, rather than just the evolution of fixed traits. This approach requires the examination of functional relationships among traits not only in a single environment but across environments and between traits and plasticity itself. In this study, I examined the interplay of plasticity and local adaptation of offspring size in the Trinidadian guppy, Poecilia reticulata. Guppies respond to food restriction by growing and reproducing less but also by producing larger offspring. This plastic difference in offspring size is of the same order of magnitude as evolved genetic differences among populations. Larger offspring sizes are thought to have evolved as an adaptation to the competitive environment faced by newborn guppies in some environments. If plastic responses to maternal food limitation can achieve the same fitness benefit, then why has guppy offspring size evolved at all? To explore this question, I examined the plastic response to food level of females from two natural populations that experience different selective environments. My goals were to examine whether the plastic responses to food level varied between populations, test the consequences of maternal manipulation of offspring size for offspring fitness, and assess whether costs of plasticity exist that could account for the evolution of mean offspring size across populations. In each population, full-sib sisters were exposed to either a low- or high-food treatment. Females from both populations produced larger, leaner offspring in response to food limitation. However, the population that was thought to have a history of selection for larger offspring was less plastic in its investment per offspring in response to maternal mass, maternal food level, and fecundity than the population under selection for small offspring size. To test the consequences of maternal manipulation of offspring size for offspring fitness, I raised the offspring of low- and high-food mothers in either low- or high-food environments. No maternal effects were detected at high food levels, supporting the prediction that mothers should increase fecundity rather than offspring size in noncompetitive environments. For offspring raised under low food levels, maternal effects on juvenile size and male size at maturity varied significantly between populations, reflecting their initial differences in maternal manipulation of offspring size; nevertheless, in both populations, increased investment per offspring increased offspring fitness. Several correlates of plasticity in investment per offspring that could affect the evolution of offspring size in guppies were identified. Under low-food conditions, mothers from more plastic families invested more in future reproduction and less in their own soma. Similarly, offspring from more plastic families were smaller as juveniles and female offspring reproduced earlier. These correlations suggest that a fixed, high level of investment per offspring might be favored over a plastic response in a chronically low-resource environment or in an environment that selects for lower reproductive effort.

Familial association of anxiety sensitivity and psychopathology.

PubMed

East, Allison J; Berman, Mitchell E; Stoppelbein, Laura

2007-01-01

The purpose of this study was to examine the association between parental (biological mother and father) and adult-offspring anxiety sensitivity (AS), and to determine whether parental AS is related to psychopathology in offspring. We obtained offspring (N=174) self-ratings of anxiety, mood, and stress symptoms, and assigned psychiatric diagnoses using a semistructured clinical interview. Biological mothers, fathers, and offspring independently completed a self-report measure of AS. We hypothesized that (1) there would be a positive relation between parental and offspring AS, and (2) AS in parents would be positively associated with psychopathology in offspring. Results indicated that paternal (but not maternal) AS was associated with offspring AS and psychopathology.

Sugared water consumption by adult offspring of mothers fed a protein-restricted diet during pregnancy results in increased offspring adiposity: the second hit effect.

PubMed

Cervantes-Rodríguez, M; Martínez-Gómez, M; Cuevas, E; Nicolás, L; Castelán, F; Nathanielsz, P W; Zambrano, E; Rodríguez-Antolín, J

2014-02-01

Poor maternal nutrition predisposes offspring to metabolic disease. This predisposition is modified by various postnatal factors. We hypothesised that coupled to the initial effects of developmental programming due to a maternal low-protein diet, a second hit resulting from increased offspring postnatal sugar consumption would lead to additional changes in metabolism and adipose tissue function. The objective of the present study was to determine the effects of sugared water consumption (5% sucrose in the drinking-water) on adult offspring adiposity as a 'second hit' following exposure to maternal protein restriction during pregnancy. We studied four offspring groups: (1) offspring of mothers fed the control diet (C); (2) offspring of mothers fed the restricted protein diet (R); (3) offspring of control mothers that drank sugared water (C-S); (4) offspring of restricted mothers that drank sugared water (R-S). Maternal diet in pregnancy was considered the first factor and sugared water consumption as the second factor - the second hit. Body weight and total energy consumption, before and after sugared water consumption, were similar in all the groups. Sugared water consumption increased TAG, insulin and cholesterol concentrations in both the sexes of the C-S and R-S offspring. Sugared water consumption increased leptin concentrations in the R-S females and males but not in the R offspring. There was also an interaction between sugared water and maternal diet in males. Sugared water consumption increased adipocyte size and adiposity index in both females and males, but the interaction with maternal diet was observed only in females. Adiposity index and plasma leptin concentrations were positively correlated in both the sexes. The present study shows that a second hit during adulthood can amplify the effects of higher adiposity arising due to poor maternal pregnancy diet in an offspring sex dependent fashion.

Deficits in social behavior and reversal learning are more prevalent in male offspring of VIP deficient female mice

PubMed Central

Stack, Conor M.; Lim, Maria A.; Cuasay, Katrina; Stone, Madeleine M.; Seibert, Kimberly. M.; Spivak-Pohis, Irit; Crawley, Jacqueline N.; Waschek, James A.; Hill, Joanna M.

2008-01-01

Blockage of vasoactive intestinal peptide (VIP) receptors during early embryogenesis in the mouse has been shown to result in developmental delays in neonates, and social behavior deficits selectively in adult male offspring. Offspring of VIP deficient mothers (VIP +/−) also exhibited developmental delays, and reductions in maternal affiliation and play behavior. In the current study, comparisons among the offspring of VIP deficient mothers (VIP +/−) mated to VIP +/− males with the offspring of wild type (WT) mothers mated to VIP +/− males allowed assessment of the contributions of both maternal and offspring VIP genotype to general health measures, social behavior, fear conditioning, and spatial learning and memory in the water maze. These comparisons revealed few differences in general health among offspring of WT and VIP deficient mothers, and all offspring exhibited normal responses in fear conditioning and in the acquisition phase of spatial discrimination in the water maze. WT mothers produced offspring that were normal in all tests; the reduced VIP in their VIP +/− offspring apparently did not contribute to any defects in the measures under study. However, regardless of their own VIP genotype, all male offspring of VIP deficient mothers exhibited severe deficits in social approach behavior and reversal learning. The deficits in these behaviors in the female offspring of VIP deficient mothers were less severe than in their male littermates, and the extent of their impairment was related to their own VIP genotype. This study has shown that intrauterine conditions had a greater influence on behavioral outcome than did genetic inheritance. In addition, the greater prevalence of deficits in social behavior and the resistance to change seen in reversal learning in the male offspring of VIP deficient mothers indicate a potential usefulness of the VIP knockout mouse in furthering the understanding of neurodevelopmental disorders such as autism. PMID:18316078

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.

Assessing the roles of population density and predation risk in the evolution of offspring size in populations of a placental fish

PubMed Central

Schrader, Matthew; Travis, Joseph

2012-01-01

Population density is an ecological variable that is hypothesized to be a major agent of selection on offspring size. In high-density populations, high levels of intraspecific competition are expected to favor the production of larger offspring. In contrast, lower levels of intraspecific competition and selection for large offspring should be weaker and more easily overridden by direct selection for increased fecundity in low-density populations. Some studies have found associations between population density and offspring size consistent with this hypothesis. However, their interpretations are often clouded by a number of issues. Here, we use data from a 10-year study of nine populations of the least killifish, Heterandria formosa, to describe the associations of offspring size with habitat type, population density, and predation risk. We found that females from spring populations generally produced larger offspring than females from ponds; however, the magnitude of this difference varied among years. Across all populations, larger offspring were associated with higher densities and lower risks of predation. Interestingly, the associations between the two ecological variables (density and predation risk) and offspring size were largely independent of one another. Our results suggest that previously described genetic differences in offspring size are due to density-dependent natural selection. PMID:22957156

Intergenerational Transmission of Overweight and Obesity from Parents to Their Adolescent Offspring - The HUNT Study.

PubMed

Næss, Marit; Holmen, Turid Lingaas; Langaas, Mette; Bjørngaard, Johan Håkon; Kvaløy, Kirsti

2016-01-01

The main aim of this study was to examine weight associations between parents and offspring at two time points: 1995-97 and 2006-08, taking into account body mass index (BMI) and waist circumference. The study included 8425 parent-offspring trios who participated in the population based Health Study of Nord Trøndelag (the HUNT Study), Norway, at either the HUNT2 (1995-97) or the HUNT3 (2006-08) survey. We used linear mixed effects models with siblings clustered within mothers to analyze the associations between 1) parental grouped BMI and offspring BMI z-scores and 2) parental grouped waist circumference and offspring waist circumference z-scores. Adolescent and adult overweight and obesity were higher in 2006-08 than in 1995-97, with the greatest increase observed in waist circumference. Both mother's and father's BMI and waist circumference were strongly associated with corresponding measures in offspring. Compared with both parents being normal weight (BMI <25 kg/m2), having two overweight or obese parents (BMI ≥25 kg/m2) was associated with a higher offspring BMI z-score of 0.76 (95% CI; 0.65, 0.87) and 0.64 (95% CI; 0.48, 0.80) in daughters, and 0.76 (95% CI; 0.65, 0.87) and 0.69 (95% CI; 0.53, 0.80) in sons, in 1995-97 and 2006-08 respectively. Offspring with one parent being overweight/obese had BMI z-scores of approximately half of offspring with two parents categorized as overweight/obese. The results of the waist circumference based analyses did not differ substantially from the BMI based analyses. Parental overweight was strongly positively associated with offspring weight both in 1995-97 and 2006-08 where both parents being overweight/obese gave the largest effect. This seemingly stable association, strongly address the importance of public health initiatives towards preventing obesity in parents of both sexes to decrease further obesity expansion in offspring.

Temperament and major depression: How does difficult temperament affect frequency, severity, and duration of major depressive episodes among offspring of parents with or without depression?

PubMed

Sherman, Brian J; Vousoura, Eleni; Wickramaratne, Priya; Warner, Virginia; Verdeli, Helen

2016-08-01

The current study examined the relationships between parental depression, offspring depression, and offspring temperament among 203 offspring of parents with or without depression. The specific aim was to investigate how parental depression and offspring difficult temperament affect frequency, severity, and duration of offspring major depressive episodes (MDEs). As part of an ongoing multigenerational study assessing familial transmission of depression, offspring were assessed over a 20-year study period. Offspring temperament was assessed at baseline using the Dimensions of Temperament Survey and diagnostic interviews were conducted at each of the four waves using best estimate procedures. Difficult temperament predicted greater frequency of lifetime MDEs. Parental depression moderated the relationship between offspring difficult temperament and severity of MDEs, such that difficult temperament was associated with increased severity ratings among high-risk, but not low-risk offspring. Dimensional analysis revealed that lower rhythmicity and adaptability were associated with greater number of lifetime MDEs, higher inattention/distractibility was associated with shorter duration of MDEs, and greater activity was associated with decreased severity of MDEs. Certain limitations must be noted, namely the self-report nature of temperament data and the relatively small sample size drawn from a clinical and predominantly Caucasian and Christian sample. Notwithstanding these limitations, our results suggest that the clinical presentation of major depression may reflect temperamental profiles and should be considered in diagnostic and treatment settings. Copyright © 2016 Elsevier B.V. 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...

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…

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...

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

A theoretical model of the evolution of maternal effects under parent-offspring conflict.

PubMed

Uller, Tobias; Pen, Ido

2011-07-01

The evolution of maternal effects on offspring phenotype should depend on the extent of parent-offspring conflict and costs and constraints associated with maternal and offspring strategies. Here, we develop a model of maternal effects on offspring dispersal phenotype under parent-offspring conflict to evaluate such dependence. In the absence of evolutionary constraints and costs, offspring evolve dispersal rates from different patch types that reflect their own, rather than the maternal, optima. This result also holds true when offspring are unable to assess their own environment because the maternal phenotype provides an additional source of information. Consequently, maternal effects on offspring diapause, dispersal, and other traits that do not necessarily represent costly resource investment are more likely to maximize offspring than maternal fitness. However, when trait expression was costly, the evolutionarily stable dispersal rates tended to deviate from those under both maternal and offspring control. We use our results to (re)interpret some recent work on maternal effects and their adaptive value and provide suggestions for future work. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Antenatal depression and offspring psychopathology: the influence of childhood maltreatment.

PubMed

Pawlby, Susan; Hay, Dale; Sharp, Deborah; Waters, Cerith S; Pariante, Carmine M

2011-08-01

Antenatal depression and childhood maltreatment have each been associated with offspring psychopathology, but have never been examined in the same sample. To determine whether childhood maltreatment influences the association between antenatal depression and offspring psychopathology. Prospectively collected data on antenatal depression, offspring maltreatment (age 11) and offspring psychopathology (age 11 and 16) were analysed in 120 mother-offspring dyads from the community-based South London Child Development Study. Antenatal depression increased the risk of maltreatment in the offspring by almost four times. Children exposed only to antenatal depression or only to childhood maltreatment were no more at risk of developing psychopathology; however, children exposed to both antenatal depression and childhood maltreatment were at almost 12 times greater risk of developing psychopathology than offspring not so exposed. Research investigating exposure to adverse events in utero and offspring psychopathology should take account of postnatal adverse events such as maltreatment.

Paternal stress prior to conception alters DNA methylation and behaviour of developing rat offspring.

PubMed

Mychasiuk, R; Harker, A; Ilnytskyy, S; Gibb, R

2013-06-25

Although there has been an abundance of research focused on offspring outcomes associated with maternal experiences, there has been limited examination of the relationship between paternal experiences and offspring brain development. As spermatogenesis is a continuous process, experiences that have the ability to alter epigenetic regulation in fathers may actually change developmental trajectories of offspring. The purpose of this study was to examine the effects of paternal stress prior to conception on behaviour and the epigenome of both male and female developing rat offspring. Male Long-Evans rats were stressed for 27 consecutive days and then mated with control female rats. Early behaviour was tested in offspring using the negative geotaxis task and the open field. At P21 offspring were sacrificed and global DNA methylation levels in the hippocampus and frontal cortex were analysed. Paternal stress prior to conception altered behaviour of all offspring on the negative geotaxis task, delaying acquisition of the task. In addition, male offspring demonstrated a reduction in stress reactivity in the open field paradigm spending more time than expected in the centre of the open field. Paternal stress also altered DNA methylation patterns in offspring at P21, global methylation was reduced in the frontal cortex of female offspring, but increased in the hippocampus of both male and female offspring. The results from this study clearly demonstrate that paternal stress during spermatogenesis can influence offspring behaviour and DNA methylation patterns, and these affects occur in a sex-dependent manner. Development takes place in the centre of a complex interaction between maternal, paternal, and environmental influences, which combine to produce the various phenotypes and individual differences that we perceive. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Gray Matter Volume Decrease Distinguishes Schizophrenia From Bipolar Offspring During Childhood and Adolescence.

PubMed

Sugranyes, Gisela; de la Serna, Elena; Romero, Soledad; Sanchez-Gistau, Vanessa; Calvo, Anna; Moreno, Dolores; Baeza, Inmaculada; Diaz-Caneja, Covadonga M; Sanchez-Gutierrez, Teresa; Janssen, Joost; Bargallo, Nuria; Castro-Fornieles, Josefina

2015-08-01

There is increasing support toward the notion that schizophrenia and bipolar disorder share neurodevelopmental underpinnings, although areas of divergence remain. We set out to examine gray matter volume characteristics of child and adolescent offspring of patients with schizophrenia or bipolar disorder comparatively. In this 2-center study, magnetic resonance structural neuroimaging data were acquired in 198 children and adolescents (aged 6-17 years): 38 offspring of patients with schizophrenia, 77 offspring of patients with bipolar disorder, and 83 offspring of community controls. Analyses of global brain volumes and voxel-based morphometry (using familywise error correction) were conducted. There was an effect of group on total cerebral gray matter volume (F = 3.26, p = .041), driven by a decrease in offspring of patients with schizophrenia relative to offspring of controls (p = .035). At a voxel-based level, we observed an effect of group in the left inferior frontal cortex/anterior insula (F = 14.7, p < .001), which was driven by gray matter volume reduction in offspring of patients with schizophrenia relative to both offspring of controls (p = .044) and of patients with bipolar disorder (p < .001). No differences were observed between offspring of patients with bipolar disorder and offspring of controls in either global or voxel-based gray matter volumes. This first comparative study between offspring of patients with schizophrenia and bipolar disorder suggests that gray matter volume reduction in childhood and adolescence may be specific to offspring of patients with schizophrenia; this may index a greater neurodevelopmental impact of risk for schizophrenia relative to bipolar disorder during youth. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Obesity and abnormal glucose tolerance in offspring of diabetic mothers: A systematic review and meta-analysis.

PubMed

Kawasaki, Maki; Arata, Naoko; Miyazaki, Celine; Mori, Rintaro; Kikuchi, Toru; Ogawa, Yoshihiro; Ota, Erika

2018-01-01

Rising prevalence of childhood obesity and type 2 diabetes mellitus (T2DM) is an emerging public health issue. To investigate the association of maternal hyperglycemia exposure during pregnancy with obesity and abnormal glucose tolerance in offspring, and the age at occurrence. We searched MEDLINE and EMBASE for observational studies on obesity and diabetes in offspring of diabetic mothers (gestational diabetes mellitus (GDM), type 1 diabetes mellitus (T1DM) and T2DM), and those on non-diabetic mothers. We performed fixed effect meta-analysis for all studies except when heterogeneity was detected. The quality of studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). Twenty observational studies were included involving a total of 26,509 children. Offspring of GDM mother had higher BMI z-score in childhood (pooled MD: 0.14, 95%CI: 0.04-0.24, seven studies, 21,691children, low quality of evidence). Offspring of T1DM mothers had higher BMI z-score from prepubertal to adolescent (pooled MD: 0.35, 95% CI: 0.13-0.58, three studies, 844 children, low quality of evidence) compared with control. After adjustment for maternal pre-pregnancy BMI, this association remained in offspring of T1DM, but disappeared in those of GDM mothers. Offspring of GDM mother had higher 2-hour plasma glucose from prepubertal to early adulthood (pooled MD: 0.43 mmol/L, 95% CI: 0.18-0.69, five studies, 890 children), while those of T1DM mothers had higher rate of T2DM in 2-5 years old to early adulthood (pooled odds ratio [OR], 6.10: 95% CI: 1.23-30.37, two studies, 448 children, very low quality of evidence) compared with control. As there was only one study with offspring of T2DM mothers, evidence is sparse. Only observational studies were included, with a few adequately adjusted for covariables. Exposure to maternal hyperglycemia was associated with offspring obesity and abnormal glucose tolerance especially in offspring of T1DM mothers, but the evidence relies on observational studies with low quality of evidence only.

A Study on Mediation by Offspring BMI in the Association between Maternal Obesity and Child Respiratory Outcomes in the Amsterdam Born and Their Development Study Cohort.

PubMed

Harskamp-van Ginkel, Margreet W; London, Stephanie J; Magnus, Maria C; Gademan, Maaike G; Vrijkotte, Tanja G

2015-01-01

A causal relationship between maternal obesity and offspring asthma is hypothesized to begin during early development, but no underlying mechanism for the found association is identified. We quantitatively examined mediation by offspring body mass index (BMI) in the association of maternal pre-pregnancy BMI on risk of asthma and wheezing during the first 7-8 years of life in a large Amsterdam born birth cohort. For 3185 mother-child pairs, mothers reported maternal pre-pregnancy BMI and offspring outcomes "ever being diagnosed with asthma" and "wheezing in the past 12 months" on questionnaires. We measured offspring height and weight at age 5-6 years. We performed a multivariate log linear regression comparing outcomes in offspring of mothers with different BMI categories. For each category we quantified and tested mediation by offspring BMI and also investigated interaction by parental asthma. At the age of 7-8 years, 8% of the offspring ever had asthma and 7% had current wheezing. Maternal pre-pregnancy obesity was associated with higher risks of asthma (adjusted RR 2.32 (95% CI: 1.49-3.61) and wheezing (adjusted RR 2.16 (95% CI: 1.28-3.64). Offspring BMI was a mediator in the association between maternal BMI and offspring wheezing, but not for asthma. There was no interaction by parental asthma. Maternal pre-pregnancy obesity was associated with higher risks of offspring asthma and wheezing. The association between maternal obesity and offspring wheezing was both direct and indirect (mediated) through the child's own BMI.

Exploring the association between maternal prenatal multivitamin use and early infant growth: The Healthy Start Study.

PubMed

Sauder, K A; Starling, A P; Shapiro, A L; Kaar, J L; Ringham, B M; Glueck, D H; Dabelea, D

2016-10-01

Prenatal multivitamin supplementation is recommended to improve offspring outcomes, but effects on early infant growth are unknown. We examined whether multivitamin supplementation in the year before delivery predicts offspring mass, body composition and early infant growth. Multivitamin use was assessed longitudinally in 626 women from the Healthy Start Study. Offspring body size and composition was measured with air displacement plethysmography at birth (<3 days) and postnatally (median 5.2 months). Separate multiple linear regressions assessed the relationship of weeks of daily multivitamin use with offspring mass, body composition and postnatal growth, after adjustment for potential confounders (maternal age, race, pre-pregnant body mass index; offspring gestational age at birth, sex; breastfeeding exclusivity). Maternal multivitamin use was not related to offspring mass or body composition at birth, or rate of change in total or fat-free mass in the first 5 months. Multivitamin use was inversely associated with average monthly growth in offspring percent fat mass (β = -0.009, p = 0.049) between birth and postnatal exam. Offspring of non-users had a monthly increase in percent fat mass of 3.45%, while offspring at the top quartile of multivitamin users had a monthly increase in percent fat mass of 3.06%. This association was not modified by exclusive breastfeeding. Increased multivitamin use in the pre-conception and prenatal periods was associated with a slower rate of growth in offspring percent fat mass in the first 5 months of life. This study provides further evidence that in utero nutrient exposures may affect offspring adiposity beyond birth. © 2015 World Obesity.

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.

Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring.

PubMed

Akitake, Yoshiharu; Katsuragi, Shinji; Hosokawa, Masato; Mishima, Kenichi; Ikeda, Tomoaki; Miyazato, Mikiya; Hosoda, Hiroshi

2015-01-01

Intrauterine growth retardation (IUGR) occurs in 3% to 7% of all pregnancies. Recent human studies have indicated that neurodevelopmental disabilities, learning disorders, memory impairment, and mood disturbance are common in IUGR offspring. However, the interactions between IUGR and neurodevelopmental disorders are unclear because of the wide range of causes of IUGR, such as maternal malnutrition, placental insufficiency, pregnancy toxemia, and fetal malformations. Meanwhile, many studies have shown that moderate food restriction enhances spatial learning and improves mood disturbance in adult humans and animals. To date, the effects of maternal moderate food restriction on fetal brain remain largely unknown. In this study, we hypothesized that IUGR would be caused by even moderate food restriction in pregnant females and that the offspring would have neurodevelopmental disabilities. Mid-pregnant mice received moderate food restriction through the early lactation period. The offspring were tested for aspects of physical development, behavior, and neurodevelopment. The results showed that moderate maternal food restriction induced IUGR. Offspring had low birth weight and delayed development of physical and coordinated movement. Moreover, IUGR offspring exhibited mental disabilities such as anxiety and poor cognitive function. In particular, male offspring exhibited significantly impaired cognitive function at 3 weeks of age. These results suggested that a restricted maternal diet could be a risk factor for developmental disability in IUGR offspring and that male offspring might be especially susceptible. Copyright © 2015 Elsevier Inc. All rights reserved.

Total and Trimester-Specific Gestational Weight Gain and Offspring Birth and Early Childhood Weight: A Prospective Cohort Study on Monozygotic Twin Mothers and Their Offspring.

PubMed

Scheers Andersson, Elina; Silventoinen, Karri; Tynelius, Per; Nohr, Ellen A; Sørensen, Thorkild I A; Rasmussen, Finn

2016-08-01

Gestational weight gain (GWG) has in numerous studies been associated with offspring birth weight (BW) and childhood weight. However, these associations might be explained by genetic confounding as offspring inherit their mother's genetic potential to gain weight. Furthermore, little is known about whether particular periods of pregnancy could influence offspring body weight differently. We therefore aimed to explore total and trimester-specific effects of GWG in monozygotic (MZ) twin mother-pairs on their offspring's BW, weight at 1 year and body mass index (BMI) at 5 and 10 years. MZ twin mothers born 1962-1975 were identified in national Swedish registers, and data on exposure and outcome variables was collected from medical records. We analyzed associations within and between twin pairs. We had complete data on the mothers' GWG and offspring BW for 82 pairs. The results indicated that total, and possibly also second and third trimester GWG were associated with offspring BW within the twin pairs in the fully adjusted model (β = 0.08 z-score units, 95% CI: 0.001, 0.17; β = 1.32 z-score units, 95% CI: -0.29, 2.95; and β = 1.02 z-score units, 95% CI: -0.50, 2.54, respectively). Our findings, although statistically weak, suggested no associations between GWG and offspring weight or BMI during infancy or childhood. Our study suggests that total, and possibly also second and third trimester, GWG are associated with offspring BW when taking shared genetic and environmental factors within twin pairs into account. Larger family-based studies with long follow-up are needed to confirm our findings.

Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison.

PubMed

Mesman, Esther; Birmaher, Boris B; Goldstein, Benjamin I; Goldstein, Tina; Derks, Eske M; Vleeschouwer, Marloes; Hickey, Mary Beth; Axelson, David; Monk, Kelly; Diler, Rasim; Hafeman, Danella; Sakolsky, Dara J; Reichart, Catrien G; Wals, Marjolein; Verhulst, Frank C; Nolen, Willem A; Hillegers, Manon H J

2016-11-15

Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10-18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, p<.05), older age of the offspring (OR: 1.19, p<.05), and country of origin (US; OR: 2.17, p<.001). Regarding comorbidity, only country of origin (OR: 7.84, p<.001) was a significant predictor. In general, we found no differences in dimensional psychopathology based on CBCL reports. Preliminary measure of inter-site reliability. We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study. Copyright © 2016 Elsevier B.V. All rights reserved.

Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison✩

PubMed Central

Mesman, Esther; Birmaher, Boris B.; Goldstein, Benjamin I.; Goldstein, Tina; Derks, Eske M.; Vleeschouwer, Marloes; Hickey, Mary Beth; Axelson, David; Monk, Kelly; Diler, Rasim; Hafeman, Danella; Sakolsky, Dara J.; Reichart, Catrien G.; Wals, Marjolein; Verhulst, Frank C.; Nolen, Willem A.; Hillegers, Manon H.J.

2017-01-01

Objective Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. Methods We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10–18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). Results Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, p<.05), older age of the offspring (OR: 1.19, p<.05), and country of origin (US; OR: 2.17, p<.001). Regarding comorbidity, only country of origin (OR: 7.84, p<.001) was a significant predictor. In general, we found no differences in dimensional psychopathology based on CBCL reports. Limitations Preliminary measure of inter-site reliability. Conclusions We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study. PMID:27423424

The effect of pre-laying maternal immunization on offspring growth and immunity differs across experimentally altered postnatal rearing conditions in a wild songbird.

PubMed

Martyka, Rafał; Śliwińska, Ewa B; Martyka, Mirosław; Cichoń, Mariusz; Tryjanowski, Piotr

2018-01-01

Prenatal antibody transfer is an immune-mediated maternal effect by which females can shape postnatal offspring resistance to pathogens and parasites. Maternal antibodies passed on to offspring provide primary protection to neonates against diverse pathogenic antigens, but they may also affect offspring growth and influence the development of an offspring's own immune response. The effects of maternal antibodies on offspring performance commonly require that the disease environment experienced by a mother prior to breeding matches the environment encountered by her offspring after hatching/birth. However, other circumstances, like postnatal rearing conditions that affect offspring food availability, may also determine the effects of maternal antibodies on offspring growth and immunity. To date, knowledge about how prenatal immune-mediated maternal effects interact with various postnatal rearing conditions to affect offspring development and phenotype in wild bird population remains elusive. Here we experimentally studied the interactive effects of pre-laying maternal immunization with a bacterial antigen (lipopolysaccharide) and post-hatching rearing conditions, altered by brood size manipulation, on offspring growth and humoral immunity of wild great tits ( Parus major ). We found that maternal immunization and brood size manipulation interactively affected the growth and specific humoral immune response of avian offspring. Among nestlings reared in enlarged broods, only those that originated from immunized mothers grew better and were heavier at fledging stage compared to those that originated from non-immunized mothers. In contrast, no such effects were observed among nestlings reared in non-manipulated (control) broods. Moreover, offspring of immunized females had a stronger humoral immune response to lipopolysaccharide during postnatal development than offspring of non-immunized females, but only when the nestling was reared in control broods. This study demonstrates that offspring development and their ability to cope with pathogens after hatching are driven by mutual influences of pathogen-induced prenatal maternal effects and post-hatching rearing conditions. Our findings suggest that immune-mediated maternal effects may have context-dependent influences on offspring growth and immune function, related to the postnatal environmental conditions experienced by the progeny.

Baseline Levels, and Changes Over Time in Body Mass Index and Fasting Insulin, and Their Relationship to Change in Metabolic Trait Clustering

PubMed Central

Sullivan, Lisa M.; Fox, Caroline S.; Wilson, Peter W.F.; Nathan, David M.; Vasan, Ramachandran S.; D'Agostino, Ralph B.; Meigs, James B.

2014-01-01

Abstract Background: Multiple abnormal metabolic traits are found together or “cluster” within individuals more often than is predicted by chance. The individual and combined role of adiposity and insulin resistance (IR) on metabolic trait clustering is uncertain. We tested the hypothesis that change in trait clustering is a function of both baseline level and change in these measures. Methods: In 2616 nondiabetic Framingham Offspring Study participants, body mass index (BMI) and fasting insulin were related to a within-person 7-year change in a trait score of 0–4 Adult Treatment Panel III metabolic syndrome traits (hypertension, high triglycerides, low high-density lipoprotein cholesterol, hyperglycemia). Results: At baseline assessment, mean trait score was 1.4 traits, and 7-year mean (SEM) change in trait score was +0.25 (0.02) traits, P<0.0001. In models with BMI predictors only, for every quintile difference in baseline BMI, the 7-year trait score increase was 0.14 traits, and for every quintile increase in BMI during 7-year follow-up, the trait score increased by 0.3 traits. Baseline level and change in fasting insulin were similarly related to trait score change. In models adjusted for age–sex–baseline cluster score, 7-year change in trait score was significantly related to both a 1-quintile difference in baseline BMI (0.07 traits) and fasting insulin (0.18 traits), and to both a 1-quintile 7-year increase in BMI (0.21 traits) and fasting insulin (0.18 traits). Conclusions: Change in metabolic trait clustering was significantly associated with baseline levels and changes in both BMI and fasting insulin, highlighting the importance of both obesity and IR in the clustering of metabolic traits. PMID:25007010

Relations Between Aortic Stiffness and Left Ventricular Mechanical Function in the Community.

PubMed

Bell, Vanessa; McCabe, Elizabeth L; Larson, Martin G; Rong, Jian; Merz, Allison A; Osypiuk, Ewa; Lehman, Birgitta T; Stantchev, Plamen; Aragam, Jayashri; Benjamin, Emelia J; Hamburg, Naomi M; Vasan, Ramachandran S; Mitchell, Gary F; Cheng, Susan

2017-01-09

Aortic stiffness impairs optimal ventricular-vascular coupling and left ventricular systolic function, particularly in the long axis. Left ventricular global longitudinal strain (GLS) has recently emerged as a sensitive measure of early cardiac dysfunction. In this study, we investigated the relation between aortic stiffness and GLS in a large community-based sample. In 2495 participants (age 39-90 years, 57% women) of the Framingham Offspring and Omni cohorts, free of cardiovascular disease, we performed tonometry to measure arterial hemodynamics and echocardiography to assess cardiac function. Aortic stiffness was evaluated as carotid-femoral pulse wave velocity and as characteristic impedance, and GLS was calculated using speckle tracking-based measurements. In multivariable analyses adjusting for age, sex, height, systolic blood pressure, augmentation index, left ventricular structure, and additional cardiovascular risk factors, increased carotid-femoral pulse wave velocity (B±SE: 0.122±0.030% strain per SD, P<0.0001) and characteristic impedance (0.090±0.029, P=0.002) were both associated with worse GLS. We observed effect modification by sex on the relation between characteristic impedance and GLS (P=0.004); in sex-stratified multivariable analyses, the relation between greater characteristic impedance and worse GLS persisted in women (0.145±0.039, P=0.0003) but not in men (P=0.73). Multiple measures of increased aortic stiffness were cross-sectionally associated with worse GLS after adjusting for hemodynamic variables. Parallel reductions in left ventricular long axis shortening and proximal aortic longitudinal strain in individuals with a stiffened proximal aorta, from direct mechanical ventricular-vascular coupling, offers an alternative explanation for the observed relations. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Long-term exposure to fine particulate matter, residential proximity to major roads and measures of brain structure.

PubMed

Wilker, Elissa H; Preis, Sarah R; Beiser, Alexa S; Wolf, Philip A; Au, Rhoda; Kloog, Itai; Li, Wenyuan; Schwartz, Joel; Koutrakis, Petros; DeCarli, Charles; Seshadri, Sudha; Mittleman, Murray A

2015-05-01

Long-term exposure to ambient air pollution is associated with cerebrovascular disease and cognitive impairment, but whether it is related to structural changes in the brain is not clear. We examined the associations between residential long-term exposure to ambient air pollution and markers of brain aging using magnetic resonance imaging. Framingham Offspring Study participants who attended the seventh examination were at least 60 years old and free of dementia and stroke were included. We evaluated associations between exposures (fine particulate matter [PM2.5] and residential proximity to major roadways) and measures of total cerebral brain volume, hippocampal volume, white matter hyperintensity volume (log-transformed and extensive white matter hyperintensity volume for age), and covert brain infarcts. Models were adjusted for age, clinical covariates, indicators of socioeconomic position, and temporal trends. A 2-μg/m(3) increase in PM2.5 was associated with -0.32% (95% confidence interval, -0.59 to -0.05) smaller total cerebral brain volume and 1.46 (95% confidence interval, 1.10 to 1.94) higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 (95% confidence interval, 0.01 to 0.19) greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter. Exposure to elevated levels of PM2.5 was associated with smaller total cerebral brain volume, a marker of age-associated brain atrophy, and with higher odds of covert brain infarcts. These findings suggest that air pollution is associated with insidious effects on structural brain aging even in dementia- and stroke-free persons. © 2015 American Heart Association, Inc.

Dietary Patterns of Women Are Associated with Incident Abdominal Obesity but Not Metabolic Syndrome123

PubMed Central

Kimokoti, Ruth W.; Gona, Philimon; Zhu, Lei; Newby, P. K.; Millen, Barbara E.; Brown, Lisa S.; D’Agostino, Ralph B.; Fung, Teresa T.

2012-01-01

Data on the relationship between empirical dietary patterns and metabolic syndrome (MetS) and its components in prospective study designs are limited. In addition, demographic and lifestyle determinants of MetS may modify the association between dietary patterns and the syndrome. We prospectively examined the relationship between empirically derived patterns and MetS and MetS components among 1146 women in the Framingham Offspring/Spouse cohort. They were aged 25–77 y with BMI ≥18.5 kg/m2 and free of cardiovascular disease, diabetes, cancer, and MetS at baseline, and followed for a mean of 7 y. Five dietary patterns, Heart Healthier, Lighter Eating, Wine and Moderate Eating, Higher Fat, and Empty Calorie, were previously identified using cluster analysis from food intake collected using a FFQ. After adjusting for potential confounders, we observed lower odds for abdominal obesity for Higher Fat [OR = 0.48 (95% CI: 0.25, 0.91)] and Wine and Moderate Eating clusters [OR = 0.28 (95% CI: 0.11, 0.72)] compared with the Empty Calorie cluster. Additional adjustment for BMI somewhat attenuated these OR [Higher Fat OR = 0.52 (95% CI: 0.27, 1.00); Wine and Moderate Eating OR = 0.34 (95% CI: 0.13, 0.89)]. None of the clusters was associated with MetS or other MetS components. Baseline smoking status and age did not modify the relation between dietary patterns and MetS. The Higher Fat and Wine and Moderate Eating patterns showed an inverse association with abdominal obesity; certain foods might be targeted in these habitual patterns to achieve optimal dietary patterns for MetS prevention. PMID:22833658

Apolipoprotein epsilon 4 allele modifies waist-to-hip ratio effects on cognition and brain structure.

PubMed

Zade, David; Beiser, Alexa; McGlinchey, Regina; Au, Rhoda; Seshadri, Sudha; Palumbo, Carole; Wolf, Philip A; DeCarli, Charles; Milberg, William

2013-02-01

This study aimed to determine whether relationships between obesity, as measured by waist-to-hip ratio (WHR), and cognition and brain structure were modified by the apolipoprotein epsilon 4 allele (apoE4). The sample included 1969 stroke- and dementia-free participants from the Framingham Offspring Cohort who underwent neuropsychological (NP) testing and structural magnetic resonance imaging (MRI) between 1999 and 2002. WHR was categorized into sex-specific quartiles with those in Q4 representing central obesity. Multivariate linear regression estimated the relationships between Q4-WHR, cognitive, and MRI measures; interaction terms examined modification of these relationships by the presence of apoE4. All analyses were cross sectional. ApoE4 status significantly modified a number of associations. Specifically, we observed a significant negative relationship between Q4-WHR and a measure of executive function in the apoE4(+) group but not in the apoE4(-) group. Similarly, we observed a stronger negative relationship between Q4-WHR and a measure of memory function for those in the apoE4(+) group compared to those in the apoE4(-) group. In addition, apoE4 status modified the relationship between Q4-WHR and 2 measures of structural brain integrity. First, a paradoxical finding of a negative association between WHR and frontal brain volume that was significant only for those in the apoE4(-) group, and a second finding that WHR was significantly associated with greater white matter hyperintensity volume only in the apoE4(+) group. These findings suggest that associations between central adiposity and both neuropsychological performance and underlying brain structure are highly complex and must be considered in the context of possible modifying genetic influences. Published by Elsevier Inc.

Face-Emotion Processing in Offspring at Risk for Panic Disorder.

ERIC Educational Resources Information Center

Pine, Daniel S.; Klein, Rachel G.; Mannuzza, Salvatore; Moulton, John L., III; Lissek, Shmuel; Guardino, Mary; Woldehawariat, Girma

2005-01-01

Objective: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. Method: Offspring of adults with PD, major depressive disorder (MDD), or no…

Long-term influences of parental divorce on offspring affective disorders: A systematic review and meta-analysis.

PubMed

Sands, Amy; Thompson, Ellen J; Gaysina, Darya

2017-08-15

The prevalence of divorce in Western countries has increased in recent decades. However, there is no recent systematic review and/or meta-analysis of studies testing for long-term effects of parental divorce on offspring affective disorders. The present study conducted a systematic review and meta-analysis of studies published since 1980 testing for the association between parental divorce and offspring depression and anxiety in adulthood. PUBMED, Science Direct, Medline, PsychInfo, and PsychArticles databases were searched for eligible studies. Random-effect meta-analyses were used to synthesize effect sizes and to test whether associations of parental divorce with offspring affective disorders differed among three publication periods (i.e., before 1996, 1996-2005, 2006-2015). In total, 29 studies were eligible for the systematic review, and 18 studies were included in the meta-analyses (depression: n=21,581; anxiety: n=2472). There was significant association between parental divorce and offspring depression (OR=1.56; 95%CI [1.31, 1.86]), but not anxiety (OR=1.16; 95%CI [0.98, 1.38]). The effect of parental divorce on offspring depression was not weaker in the reports published in more recent decades. There is limited research in relation to offspring anxiety in adulthood. Parental divorce is associated with an increased risk of adult offspring depression, with no indication of the effect being weaker in recent publications. Copyright © 2017 Elsevier B.V. All rights reserved.

Transgenerational effects of parent and grandparent gender on offspring development in a biparental beetle species.

PubMed

Lock, Judith E

2012-06-23

Parental effects on offspring life-history traits are common and increasingly well-studied. However, the extent to which these effects persist into offspring in subsequent generations has received less attention. In this experiment, maternal and paternal effects on offspring and grand-offspring were investigated in the biparental burying beetle Nicrophorus vespilloides, using a split-family design. This allowed the separation of prenatal and postnatal transgenerational effects. Grandparent and parent gender were found to have a cumulative effect on offspring development and may provide a selection pressure on the division of parental investment in biparental species.

Maternal depression during pregnancy and the postnatal period: risks and possible mechanisms for offspring depression at age 18 years.

PubMed

Pearson, Rebecca M; Evans, Jonathan; Kounali, Daphne; Lewis, Glyn; Heron, Jon; Ramchandani, Paul G; O'Connor, Tom G; Stein, Alan

2013-12-01

Some small studies suggest that maternal postnatal depression is a risk factor for offspring adolescent depression. However, to our knowledge, no large cohort studies have addressed this issue. Furthermore, only 1 small study has examined the association between antenatal depression and later offspring depression. Understanding these associations is important to inform prevention. To investigate the hypothesis that there are independent associations between antenatal and postnatal depression with offspring depression and that the risk pathways are different, such that the risk is moderated by disadvantage (low maternal education) with postnatal depression but not with antenatal depression. Prospective investigation of associations between symptoms of antenatal and postnatal parental depression with offspring depression at age 18 years in a UK community-based birth cohort (Avon Longitudinal Study of Parents and Children) with data from more than 4500 parents and their adolescent offspring. Diagnosis of offspring aged 18 years with major depression using the International Classification of Diseases, 10th Revision. Antenatal depression was an independent risk factor. Offspring were 1.28 times (95% CI, 1.08-1.51; P = .003) more likely to have depression at age 18 years for each standard deviation increase in maternal depression score antenatally, independent of later maternal depression. Postnatal depression was also a risk factor for mothers with low education, with offspring 1.26 times (95% CI, 1.06-1.50; P = .01) more likely to have depression for each standard deviation increase in postnatal depression score. However, for more educated mothers, there was little association (odds ratio, 1.09; 95% CI, 0.88-1.36; P = .42). Analyses found that maternal education moderated the effects of postnatal but not antenatal depression. Paternal depression antenatally was not associated with offspring depression, while postnatally, paternal depression showed a similar pattern to maternal depression. The findings suggest that treating maternal depression antenatally could prevent offspring depression during adulthood and that prioritizing less advantaged mothers postnatally may be most effective.

Familial Risk of Chronic Musculoskeletal Pain and the Importance of Physical Activity and Body Mass Index: Prospective Data from the HUNT Study, Norway.

PubMed

Lier, Ragnhild; Mork, Paul Jarle; Holtermann, Andreas; Nilsen, Tom Ivar Lund

2016-01-01

The main objectives of the current study was i) to prospectively examine if chronic musculoskeletal pain in parents is associated with risk of chronic musculoskeletal pain in their adult offspring, and ii) to assess if these parent-offspring associations are modified by offspring body mass index and leisure time physical activity. We used data on 4,742 adult offspring linked with their parents who participated in the population-based HUNT Study in Norway in 1995-97 and in 2006-08. Family relations were established through the national Family Registry. A Poisson regression model was used to estimate relative risk (RR) with 95% confidence interval (CI). In total, 1,674 offspring (35.3%) developed chronic musculoskeletal pain during the follow-up period of approximately 11 years. Both maternal (RR: 1.26, 95% CI: 1.03, 1.55) and paternal chronic musculoskeletal pain (RR: 1.29, 95% CI: 1.06, 1.57) was associated with increased risk of offspring chronic musculoskeletal pain. Compared to offspring of parents without chronic musculoskeletal pain, the adverse effect of parental pain was somewhat stronger among offspring who reported a low (RR: 1.82, 95% CI: 1.32, 2.52) versus high (RR: 1.32, 95% CI: 0.95, 1.84) level of leisure time physical activity. Offspring of parents with chronic musculoskeletal pain and who were classified as obese had more than twofold increased risk (RR: 2.33, 95% CI: 1.68, 3.24) of chronic musculoskeletal pain compared to normal weight offspring of parents without pain. In conclusion, parental chronic musculoskeletal pain is positively associated with risk of chronic musculoskeletal pain in their adult offspring. Maintenance of normal body weight may reduce the risk of chronic musculoskeletal pain in offspring of pain-afflicted parents.

Familial Risk of Chronic Musculoskeletal Pain and the Importance of Physical Activity and Body Mass Index: Prospective Data from the HUNT Study, Norway

PubMed Central

Lier, Ragnhild; Mork, Paul Jarle; Holtermann, Andreas; Nilsen, Tom Ivar Lund

2016-01-01

The main objectives of the current study was i) to prospectively examine if chronic musculoskeletal pain in parents is associated with risk of chronic musculoskeletal pain in their adult offspring, and ii) to assess if these parent-offspring associations are modified by offspring body mass index and leisure time physical activity. We used data on 4,742 adult offspring linked with their parents who participated in the population-based HUNT Study in Norway in 1995–97 and in 2006–08. Family relations were established through the national Family Registry. A Poisson regression model was used to estimate relative risk (RR) with 95% confidence interval (CI). In total, 1,674 offspring (35.3%) developed chronic musculoskeletal pain during the follow-up period of approximately 11 years. Both maternal (RR: 1.26, 95% CI: 1.03, 1.55) and paternal chronic musculoskeletal pain (RR: 1.29, 95% CI: 1.06, 1.57) was associated with increased risk of offspring chronic musculoskeletal pain. Compared to offspring of parents without chronic musculoskeletal pain, the adverse effect of parental pain was somewhat stronger among offspring who reported a low (RR: 1.82, 95% CI: 1.32, 2.52) versus high (RR: 1.32, 95% CI: 0.95, 1.84) level of leisure time physical activity. Offspring of parents with chronic musculoskeletal pain and who were classified as obese had more than twofold increased risk (RR: 2.33, 95% CI: 1.68, 3.24) of chronic musculoskeletal pain compared to normal weight offspring of parents without pain. In conclusion, parental chronic musculoskeletal pain is positively associated with risk of chronic musculoskeletal pain in their adult offspring. Maintenance of normal body weight may reduce the risk of chronic musculoskeletal pain in offspring of pain-afflicted parents. PMID:27082110

Maternal effects on offspring depend on female mating pattern and offspring environment in yellow dung flies.

PubMed

Tregenza, Tom; Wedell, Nina; Hosken, David J; Ward, Paul I

2003-02-01

Direct costs and benefits to females of multiple mating have been shown to have large effects on female fecundity and longevity in several species. However, with the exception of studies examining genetic benefits of polyandry, little attention has been paid to the possible effects on offspring of multiple mating by females. We propose that nongenetic effects of maternal matings on offspring fitness are best viewed in the same context as other maternal phenotype effects on offspring that are well known even in species lacking parental care. Hence, matings can exert effects on offspring in the same way as other maternal environment variables, and are likely to interact with such effects. We have conducted a study using yellow dung flies (Scathophaga stercoraria), in which we independently manipulated female mating rate, number of mates and maternal thermal environment and measured subsequent fecundity, hatching success, and offspring life-history traits. To distinguish between direct effects of matings and potential genetic benefits of polyandry we split broods and reared offspring at three different temperature regimes. This allowed us to demonstrate that although we could not detect any simple benefits or costs to matings, there are effects of maternal environment on offspring and these effects interact with female mating regime affecting offspring fitness. Such interactions between female phenotype and the costs and benefits of matings have potentially broad implications for understanding female behavior.

[Psychopathological Profiles of Offspring of Subjects with Bipolar Disorder].

PubMed

Villa, Esteban Uribe; Briceño, Paola Gutiérrez; Palacio, Juan David; García, Jenny

2012-03-01

Bipolar Disorder (BD) has a high heritability and is more prevalent in first-degree relatives with family history. This makes the bipolar offspring (BO) an ideal study group to evaluate the natural history and the prodromal symptoms of this disorder. The main psychopathological findings for this group in various studies are described in this review. Articles comparing the psychopathology of bipolar offspring to either the offspring of other psychiatric patients or the offspring of healthy controls were reviewed. The reviewed studies showed that the BO group had higher rates of affective disorders when compared to the offspring of other psychiatric patients or the offspring of healthy controls. The high prevalence of anxiety disorders, ADHD, and disruptive behavior disorders in this population suggest that such disorders could be considered prodromes of mood disorders. The group of BO had a significantly higher risk of developing a wide range of psychiatric disorders besides BD. More longitudinal studies are needed to characterize this population at risk for BD and to elucidate the risk factors in the progression of this disorder. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

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

Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines

PubMed Central

McBride, Shawna M.; Culver, Bruce; Flynn, Francis W.

2008-01-01

This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams (n = 6–8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low- and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors. PMID:18614766

Maternal or paternal suicide and offspring's psychiatric and suicide-attempt hospitalization risk.

PubMed

Kuramoto, S Janet; Stuart, Elizabeth A; Runeson, Bo; Lichtenstein, Paul; Långström, Niklas; Wilcox, Holly C

2010-11-01

We examined whether the risk for psychiatric morbidity requiring inpatient care was higher for offspring who experienced parental suicide, compared with offspring of fatal accident decedents, and whether the association varied according to the deceased parent's gender. Children and adolescents (0-17 years of age) who experienced maternal (N = 5600) or paternal (N = 17,847) suicide in 1973-2003 in Sweden were identified by using national, longitudinal, population-based registries. Cox regression modeling was used to compare psychiatric hospitalization risks among offspring of suicide decedents and propensity score-matched offspring of accident decedents. Offspring of maternal suicide decedents had increased risk of suicide-attempt hospitalization, after controlling for psychiatric hospitalization for decedents and surviving parents, compared with offspring of maternal accidental decedents. Offspring of paternal suicide decedents had similar risk of suicide-attempt hospitalization, compared with offspring of accident decedents, but had increased risk of hospitalization attributable to depressive and anxiety disorders. The magnitude of risks for offspring suicide-attempt hospitalization was greater for those who experienced maternal versus paternal suicide, compared with their respective control offspring (interaction P = .05; offspring of maternal decedents, adjusted hazard ratio: 1.80 [95% confidence interval: 1.19-2.74]; offspring of paternal decedents, adjusted hazard ratio: 1.14 [95% confidence interval: 0.96-1.35]). Maternal suicide is associated with increased risk of suicide-attempt hospitalization for offspring, beyond the risk associated with maternal accidental death. However, paternal suicide is not associated with suicide-attempt hospitalization. Future studies should examine factors that might differ between offspring who experience maternal versus paternal suicide, including genetic or early environmental determinants.

Parental depression and offspring psychopathology: a children of twins study.

PubMed

Singh, A L; D'Onofrio, B M; Slutske, W S; Turkheimer, E; Emery, R E; Harden, K P; Heath, A C; Madden, P A F; Statham, D J; Martin, N G

2011-07-01

Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations. A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds. In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20-1.93] and conduct disorder (CD; HR 2.27, CI 1.31-3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00-1.94). Logistic regression analysis suggested that the parental depression-offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63-3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95-6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses. The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.

Maternal Age at Holocaust Exposure and Maternal PTSD Independently Influence Urinary Cortisol Levels in Adult Offspring

PubMed Central

Bader, Heather N.; Bierer, Linda M.; Lehrner, Amy; Makotkine, Iouri; Daskalakis, Nikolaos P.; Yehuda, Rachel

2014-01-01

Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal posttraumatic stress disorder (PTSD) appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association with offspring ambient cortisol and PTSD-associated symptom expression. Method: Ninety-five Holocaust offspring and Jewish comparison subjects received diagnostic and psychological evaluations, and 24 h urinary cortisol was assayed by RIA. Offspring completed the parental PTSD questionnaire to assess maternal PTSD status. Maternal Holocaust exposure was identified as having occurred in childhood, adolescence, or adulthood and examined in relation to offspring psychobiology. Results: Urinary cortisol levels did not differ for Holocaust offspring and comparison subjects but differed significantly in offspring based on maternal age of exposure and maternal PTSD status. Increased maternal age of exposure and maternal PTSD were each associated with lower urinary cortisol in offspring, but did not exhibit a significant interaction. In addition, offspring PTSD-associated symptom severity increased with maternal age at exposure and PTSD diagnosis. A regression analysis of correlates of offspring cortisol indicated that both maternal age of exposure and maternal PTSD were significant predictors of lower offspring urinary cortisol, whereas childhood adversity and offspring PTSD symptoms were not. Conclusion: Offspring low cortisol and PTSD-associated symptom expression are related to maternal age of exposure, with the greatest effects associated with increased age at exposure. These effects are relatively independent of the negative consequences of being raised by a trauma survivor. These observations highlight the importance of maternal age of exposure in determining a psychobiology in offspring that is consistent with increased risk for stress-related pathology. PMID:25071719

Maternal age at first birth and offspring criminality: Using the children-of-twins design to test causal hypotheses

PubMed Central

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D’Onofrio, Brian M

2013-01-01

Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behaviour. It is not clear if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children-of-siblings and children-of-twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant MZ twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association. PMID:23398750

Reduced Intellectual Ability in Offspring of Ovarian Hyperstimulation Syndrome: A Cohort Study.

PubMed

Xu, Gu-Feng; Zhou, Cheng-Liang; Xiong, Yi-Meng; Li, Jing-Yi; Yu, Tian-Tian; Tian, Shen; Lin, Xian-Hua; Liao, Yun; Lv, Yuan; Zhang, Fang-Hong; Liu, Zhi-Wei; Shi, Yin-Yin; Shen, Yan; Sha, Jin; Zhang, Dan; Zhu, Yi-Min; Sheng, Jian-Zhong; Huang, He-Feng

2017-06-01

Ovarian hyperstimulation syndrome (OHSS), a complication of ovarian stimulation, has various adverse effects on both pregnant women and their offspring. However, whether OHSS will affect intellectual ability in offspring is still unknown. We recruited 86 Chinese children born to OHSS women and 172 children conceived with non-OHSS In Vitro Fertilization (IVF) in this cohort study. Their intellectual ability was assessed according to the Revised Chinese Version of the Wechsler Intelligence Scale for Children (C-WISC). Verbal Intelligence Quotient (VIQ), Performance Intelligence Quotient (PIQ), and Full Intelligence Quotient (FIQ) were calculated. The investigation was registered in Chinese Clinical Trial Registry (ChiCTR-SOC-16009555). OHSS offspring scored less on C-WISC (mean (standard deviation [SD]): (VIQ=92.7 (14.7), PIQ=108.9 (13.1), FIQ=100.6 (13.4)) compared with non-OHSS IVF offspring (VIQ=100.1 (13.2), PIQ=113.7 (10.8), FIQ=107.4 (11.5)). The prevalence of low IQ (<80) children was 4.7 times higher in OHSS offspring compared with non-OHSS offspring. Maternal estradiol level on hCG administration day was negatively associated with FIQ in offspring. OHSS offspring displayed reduced intellectual ability. Prenatal estradiol exposure might be involved in underlying mechanism. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Maternal age at first birth and offspring criminality: using the children of twins design to test causal hypotheses.

PubMed

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D'Onofrio, Brian M

2013-02-01

Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behavior. It is not clear, however, if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children of siblings and children of twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant monozygotic twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association.

Current Parental Depression and Offspring Perceived Self-Competence: A Quasi-Experimental Examination

PubMed Central

Class, Quetzal A.; D’Onofrio, Brian M.; Singh, Amber L.; Ganiban, Jody M.; Spotts, E. L.; Lichtenstein, Paul; Reiss, David; Neiderhiser, Jenae M.

2013-01-01

A genetically-informed, quasi-experimental design was used to examine the genetic and environmental processes underlying associations between current parental depressive symptoms and offspring perceived self-competence. Participants, drawn from a population-based Swedish sample, were 852 twin pairs and their male (52%) and female offspring aged 15.7 ± 2.4 years. Parental depressive symptoms were measured using the Center for Epidemiological Studies Depression scale. Offspring perceived self-competence was measured using a modified Harter Perceived Competence Scale. Cousin comparisons and Children of Twins (CoT) designs suggested that associations between maternal depressive symptoms and offspring perceived self-competence were due to shared genetic/environmental liability. The mechanism responsible for father-offspring associations, however, was independent of genetic factors and of extended-family environmental factors, supporting a causal inference. Thus, mothers and fathers may impact offspring perceived self-competence via different mechanisms and unmeasured genetic and environmental selection factors must be considered when studying the intergenerational transmission of cognitive vulnerabilities for depression. PMID:22692226

Emotional and behavioral functioning of offspring of African American mothers with depression.

PubMed

Boyd, Rhonda C; Diamond, Guy S; Ten Have, Thomas R

2011-10-01

Extensive research demonstrates the negative impact of maternal depression on their offspring. Unfortunately, few studies have been explored in African American families. This study examined emotional and behavioral functioning among children of African American mothers with depression. African American mothers (n = 63), with a past year diagnosis of a depressive disorder, and one of their children (ages 7-14) completed behavioral rating scales in a cross-sectional design. Results showed that 6.5 and 15% scored within the clinical range for depression and anxiety symptoms, respectively. Approximately a third of the offspring reported suicidal ideation. Based on mothers' report, 25.4 and 20.6% of the offspring exhibited internalizing and externalizing symptoms in the clinical range, respectively. Offspring whose mothers were in treatment exhibited higher levels of self-reported anxiety symptoms. Offspring of African American mothers with depression were exhibiting socioemotional problems in ways that are similar to offspring of European American mothers with depression.

Suicidal risk in young adult offspring of mothers with bipolar or major depressive disorder: a longitudinal family risk study.

PubMed

Klimes-Dougan, Bonnie; Lee, Chih-Yuan S; Ronsaville, Donna; Martinez, Pedro

2008-04-01

Recent evidence has highlighted suicidal risk associated with bipolar disorder (BD). Using a family risk approach, the goal of this study was to evaluate suicidal thoughts and behaviors longitudinally from childhood to young adulthood in children of mothers with BD, Major depressive disorder (MDD), and well mothers. Few group differences were found for cross-sectional assessments of suicidal thoughts and behavior in young adulthood; the offspring of MDD demonstrate an earlier onset and more persistent suicidality than other groups, but by young adulthood, BD offspring appear to be comparable to MDD offspring in their rates of suicidality. The longitudinal assessments reveal a pattern of higher suicidal risk in MDD offspring, more intermediate risk in BD offspring, and lower risk in well offspring. Precursors and correlates of suicidal thoughts and behaviors were also examined. These findings suggest diverse developmental trajectories based on family risk and have implications for planning preventive intervention.

Emotional and Behavioral Functioning of Offspring of African American Mothers with Depression

PubMed Central

Boyd, Rhonda C.; Diamond, Guy S.; Ten Have, Thomas R.

2011-01-01

Extensive research demonstrates the negative impact of maternal depression on their offspring. Unfortunately, few studies have been explored in African American families. This study examined emotional and behavioral functioning among children of African American mothers with depression. African American mothers (n = 63), with a past year diagnosis of a depressive disorder, and one of their children (ages 7–14) completed behavioral rating scales in a cross-sectional design. Results showed that 6.5% and 15% scored within the clinical range for depression and anxiety symptoms, respectively. Approximately a third of the offspring reported suicidal ideation. Based on mothers’ report, 25.4% and 20.6% of the offspring exhibited internalizing and externalizing symptoms in the clinical range, respectively. Offspring whose mothers were in treatment exhibited higher levels of self-reported anxiety symptoms Offspring of African American mothers with depression were exhibiting socioemotional problems in ways that are similar to offspring of European American mothers with depression. PMID:21671005

Current parental depression and offspring perceived self-competence: a quasi-experimental examination.

PubMed

Class, Quetzal A; D'Onofrio, Brian M; Singh, Amber L; Ganiban, Jody M; Spotts, E L; Lichtenstein, Paul; Reiss, David; Neiderhiser, Jenae M

2012-09-01

A genetically-informed, quasi-experimental design was used to examine the genetic and environmental processes underlying associations between current parental depressive symptoms and offspring perceived self-competence. Participants, drawn from a population-based Swedish sample, were 852 twin pairs and their male (52 %) and female offspring aged 15.7 ± 2.4 years. Parental depressive symptoms were measured using the Center for Epidemiological Studies Depression scale. Offspring perceived self-competence was measured using a modified Harter Perceived Competence Scale. Cousin comparisons and Children of Twins designs suggested that associations between maternal depressive symptoms and offspring perceived self-competence were due to shared genetic/environmental liability. The mechanism responsible for father-offspring associations, however, was independent of genetic factors and of extended family environmental factors, supporting a causal inference. Thus, mothers and fathers may impact offspring perceived self-competence via different mechanisms and unmeasured genetic and environmental selection factors must be considered when studying the intergenerational transmission of cognitive vulnerabilities for depression.

Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring

PubMed Central

Dasinger, John Henry; Intapad, Suttira; Backstrom, Miles A.; Carter, Anthony J.

2016-01-01

Placental insufficiency programs an increase in blood pressure associated with a twofold increase in serum testosterone in male growth-restricted offspring at 4 mo of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth restriction programs an age-related increase in blood pressure in male offspring. Growth-restricted offspring retained a significantly higher blood pressure at 12 but not at 18 mo of age compared with age-matched controls. Blood pressure was significantly increased in control offspring at 18 mo of age relative to control counterparts at 12 mo; however, blood pressure was not increased in growth-restricted at 18 mo relative to growth-restricted counterparts at 12 mo. Serum testosterone levels were not elevated in growth-restricted offspring relative to control at 12 mo of age. Thus, male growth-restricted offspring no longer exhibited a positive association between blood pressure and testosterone at 12 mo of age. Unlike hypertension in male growth-restricted offspring at 4 mo of age, inhibition of the renin-angiotensin system with enalapril (250 mg/l for 2 wk) did not abolish the difference in blood pressure in growth-restricted offspring relative to control counterparts at 12 mo of age. Therefore, these data suggest that intrauterine growth restriction programs an accelerated age-related increase in blood pressure in growth-restricted offspring. Furthermore, this study suggests that the etiology of increased blood pressure in male growth-restricted offspring at 12 mo of age differs from that at 4 mo of age. PMID:27147668

Female partner preferences enhance offspring ability to survive an infection.

PubMed

Raveh, Shirley; Sutalo, Sanja; Thonhauser, Kerstin E; Thoß, Michaela; Hettyey, Attila; Winkelser, Friederike; Penn, Dustin J

2014-01-23

It is often suggested that mate choice enhances offspring immune resistance to infectious diseases. To test this hypothesis, we conducted a study with wild-derived house mice (Mus musculus musculus) in which females were experimentally mated either with their preferred or non-preferred male, and their offspring were infected with a mouse pathogen, Salmonella enterica (serovar Typhimurium). We found that offspring sired by preferred males were significantly more likely to survive the experimental infection compared to those sired by non-preferred males. We found no significant differences in the pathogen clearance or infection dynamics between the infected mice, suggesting that offspring from preferred males were better able to cope with infection and had improved tolerance rather than immune resistance. Our results provide the first direct experimental evidence within a single study that partner preferences enhance offspring resistance to infectious diseases.

Association between parental psychopathology and suicidal behavior among adult offspring: results from the cross-sectional South African Stress and Health survey

PubMed Central

2014-01-01

Background Prior studies have demonstrated a link between parental psychopathology and offspring suicidal behavior. However, it remains unclear what aspects of suicidal behavior among adult offspring are predicted by specific parental mental disorders, especially in Africa. This study set out to investigate the association between parental psychopathology and suicidal behavior among their adult offspring in a South African general population sample. Method Parental psychopathology and suicidal behavior in offspring were assessed using structured interviews among 4,315 respondents from across South Africa. The WHO CIDI was used to collect data on suicidal behavior, while the Family History Research Diagnostic Criteria Interview was used to assess prior parental psychopathology. Bivariate and multivariate survival models tested the associations between the type and number parental mental disorders (including suicide) and lifetime suicidal behavior in the offspring. Associations between a range of parental disorders and the onset of subsequent suicidal behavior (suicidal ideation, plans, and attempts) among adult offspring were tested. Results The presence of parental psychopathology significantly increased the odds of suicidal behavior among their adult offspring. More specifically, parental panic disorder was associated with offspring suicidal ideation, while parental panic disorder, generalized anxiety disorder and suicide were significantly associated with offspring suicide attempts. Among those with suicidal ideation, none of the tested forms of parental psychopathology was associated with having suicide plans or attempts. There was a dose–response relationship between the number of parental disorders and odds of suicidal ideation. Conclusions Parental psychopathology increases the odds of suicidal behavior among their adult offspring in the South African context, replicating results found in other regions. Specific parental disorders predicted the onset and persistence of suicidal ideation or attempts in their offspring. Further research into these associations is recommended in order to determine the mechanisms through which parent psychopathology increases the odds of suicidal behavior among offspring. PMID:24592882

Obesity and abnormal glucose tolerance in offspring of diabetic mothers: A systematic review and meta-analysis

PubMed Central

Kawasaki, Maki; Miyazaki, Celine; Mori, Rintaro; Kikuchi, Toru; Ogawa, Yoshihiro; Ota, Erika

2018-01-01

Background Rising prevalence of childhood obesity and type 2 diabetes mellitus (T2DM) is an emerging public health issue. Objectives To investigate the association of maternal hyperglycemia exposure during pregnancy with obesity and abnormal glucose tolerance in offspring, and the age at occurrence. Methods We searched MEDLINE and EMBASE for observational studies on obesity and diabetes in offspring of diabetic mothers (gestational diabetes mellitus (GDM), type 1 diabetes mellitus (T1DM) and T2DM), and those on non-diabetic mothers. We performed fixed effect meta-analysis for all studies except when heterogeneity was detected. The quality of studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) Results Twenty observational studies were included involving a total of 26,509 children. Offspring of GDM mother had higher BMI z-score in childhood (pooled MD: 0.14, 95%CI: 0.04–0.24, seven studies, 21,691children, low quality of evidence). Offspring of T1DM mothers had higher BMI z-score from prepubertal to adolescent (pooled MD: 0.35, 95% CI: 0.13–0.58, three studies, 844 children, low quality of evidence) compared with control. After adjustment for maternal pre-pregnancy BMI, this association remained in offspring of T1DM, but disappeared in those of GDM mothers. Offspring of GDM mother had higher 2-hour plasma glucose from prepubertal to early adulthood (pooled MD: 0.43 mmol/L, 95% CI: 0.18–0.69, five studies, 890 children), while those of T1DM mothers had higher rate of T2DM in 2–5 years old to early adulthood (pooled odds ratio [OR], 6.10: 95% CI: 1.23–30.37, two studies, 448 children, very low quality of evidence) compared with control. As there was only one study with offspring of T2DM mothers, evidence is sparse. Limitations Only observational studies were included, with a few adequately adjusted for covariables. Conclusions Exposure to maternal hyperglycemia was associated with offspring obesity and abnormal glucose tolerance especially in offspring of T1DM mothers, but the evidence relies on observational studies with low quality of evidence only. PMID:29329330

Offspring of Parents with Chronic Pain: A Systematic Review and Meta-Analysis of Pain, Health, Psychological, and Family Outcomes

PubMed Central

Higgins, Kristen S.; Birnie, Kathryn A.; Chambers, Christine T.; Wilson, Anna C.; Caes, Line; Clark, Alexander J.; Lynch, Mary; Stinson, Jennifer; Campbell-Yeo, Marsha

2015-01-01

Offspring of parents with chronic pain may be at risk for poorer outcomes than offspring of healthy parents. The objective of this research was to provide a comprehensive mixed-methods, systematic synthesis of all available research on outcomes in offspring of parents with chronic pain. A systematic search was conducted for published articles in English examining pain, health, psychological, or family outcomes in offspring of parents with chronic pain. Fifty-nine eligible articles were identified (31 population-based, 25 clinical, 3 qualitative), including offspring from birth to adulthood and parents with varying chronic pain diagnoses (e.g., mixed pain samples, arthritis). Meta-analysis was used to synthesize the results from population-based and clinical studies, while meta-ethnography was used to synthesize the results of qualitative studies. Increased pain complaints were found in offspring of mothers and of fathers with chronic pain, and when both parents had chronic pain. Newborns of mothers with chronic pain were more likely to have adverse birth outcomes, including low birthweight, preterm delivery, caesarean section, intensive care admission, and mortality. Offspring of parents with chronic pain had greater externalizing and internalizing problems and poorer social competence and family outcomes. No significant differences were found on teacher-reported externalizing problems. The meta-ethnography identified six key concepts (developing independence, developing compassion, learning about health and coping, missing out, emotional health, and struggles communicating with parents). Across study designs, offspring of parents with chronic pain had poorer outcomes than other offspring, although the meta-ethnography noted some constructive impact of having a parent with chronic pain. PMID:26172553

Association of secondary sex ratio with smoking and parity.

PubMed

Beratis, Nicholas G; Asimacopoulou, Aspasia; Varvarigou, Anastasia

2008-03-01

To assess the sex ratio in offspring of smoking and nonsmoking mothers in relationship to parity. Prospective study. University hospital. The authors studied 2,108 term singleton neonates born between 1993 and 2002, 665 from smoking mothers and 1,443 from nonsmoking mothers. A prospective recording of maternal age, parity and smoking status, and gender of neonates delivered over a 10-year period. Secondary sex ratio in regard to maternal smoking and parity. The offspring sex ratio in the total sample studied was 1.09; in the offspring of smoking and nonsmoking mothers, it was 1.26 and 1.03, respectively, a statistically significant difference. In the offspring of smoking women who had parity 1, 2, and >or=3, it was 1.47, 1.35, and 0.92, whereas in those of nonsmoking women, it was 1.04, 1.00, and 1.03, respectively (the differences of the parity 1 and 2 groups between the offspring of smoking and nonsmoking mothers were statistically significant). Logistic regression analysis showed that the possibility of a boy being delivered by a mother who smoked was significantly greater in primiparous women than in women who had parity >or=3, independent of the maternal age. Conversely, parity did not affect significantly the sex ratio in the offspring of nonsmoking women. The findings suggest that among women who smoked, significantly more male than female offspring are born from primiparous women, whereas women who had parity >or=3 gave birth to more female offspring; biparous women give birth to significantly more male offspring, but the offspring sex ratio declined with the number of cigarettes when the mothers smoked >or=10 cigarettes per day.

Both paternal exercise and healthy diet are required to protect offspring from high fat diet-induced obesity and type 2 diabetes risk in mice

USDA-ARS?s Scientific Manuscript database

Objective: Paternal eating and physical activity behaviors peri-conception may influence offspring obesity and type 2 diabetes (T2D) risk. A recent study showed that paternal exercise increased offspring susceptibility to obesity when the offspring consumed a high fat (HF) diet. However, it is not y...

The relationship between parental depressive symptoms and offspring psychopathology: evidence from a children-of-twins study and an adoption study.

PubMed

McAdams, T A; Rijsdijk, F V; Neiderhiser, J M; Narusyte, J; Shaw, D S; Natsuaki, M N; Spotts, E L; Ganiban, J M; Reiss, David; Leve, L D; Lichtenstein, P; Eley, T C

2015-01-01

Parental depressive symptoms are associated with emotional and behavioural problems in offspring. However, genetically informative studies are needed to distinguish potential causal effects from genetic confounds, and longitudinal studies are required to distinguish parent-to-child effects from child-to-parent effects. We conducted cross-sectional analyses on a sample of Swedish twins and their adolescent offspring (n = 876 twin families), and longitudinal analyses on a US sample of children adopted at birth, their adoptive parents, and their birth mothers (n = 361 adoptive families). Depressive symptoms were measured in parents, and externalizing and internalizing problems measured in offspring. Structural equation models were fitted to the data. Results of model fitting suggest that associations between parental depressive symptoms and offspring internalizing and externalizing problems remain after accounting for genes shared between parent and child. Genetic transmission was not evident in the twin study but was evident in the adoption study. In the longitudinal adoption study child-to-parent effects were evident. We interpret the results as demonstrating that associations between parental depressive symptoms and offspring emotional and behavioural problems are not solely attributable to shared genes, and that bidirectional effects may be present in intergenerational associations.

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers.

PubMed

de Almeida Chaves Rodrigues, Aline Fernanda; de Lima, Ingrid Lauren Brites; Bergamaschi, Cássia Toledo; Campos, Ruy Ribeiro; Hirata, Aparecida Emiko; Schoorlemmer, Guus Hermanus Maria; Gomes, Guiomar Nascimento

2013-01-15

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

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.

Filial anxiety and sense of obligation among offspring of Holocaust survivors.

PubMed

Shrira, Amit; Menashe, Ravit; Bensimon, Moshe

2018-03-13

Much is known about adult children caring for their aging parents, yet the potentially unique experience of offspring caring for traumatized parents is underexplored. Therefore, the current studies assessed filial anxiety and sense of obligation among offspring of Holocaust survivors (OHS) in caring for their parents. In Study 1, we interviewed 10 OHS (mean age = 61.0) in order to extract themes of filial anxiety. Based on Study 1's data, a newly constructed scale of filial anxiety was administered in Study 2 to 59 adult offspring (mean age = 56.4): 28 OHS and 31 comparisons. Study 3 included 143 dyads of parents and offspring (mean age = 55.4 and 81.7, respectively): 86 Holocaust dyads and 57 comparison dyads. Parents reported posttraumatic stress disorder (PTSD) symptoms and offspring reported filial anxiety and sense of obligation. In Study 1, interviewees referred to concerns about parent experiencing decline alongside caregiving difficulties. In Study 2, OHS reported higher filial anxiety and sense of obligation relative to comparisons. This group difference was mediated by sense of obligation. In Study 3, OHS with parental PTSD reported higher filial anxiety and sense of obligation relative to comparisons. Once more, filial sense of obligation served as a mediator. In Studies 2-3, results remained significant after adjusting for offspring symptoms. Parental exposure to the Holocaust, and especially parental PTSD, related to higher filial obligation, which in turn was related to higher filial anxiety. These findings bear important implications for practitioners working with survivors' families.

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.

Psychiatric morbidity, violent crime, and suicide among children and adolescents exposed to parental death.

PubMed

Wilcox, Holly C; Kuramoto, Satoko J; Lichtenstein, Paul; Långström, Niklas; Brent, David A; Runeson, Bo

2010-05-01

This retrospective cohort study examined the risk for suicide, psychiatric hospitalization, and violent criminal convictions among offspring of parents who died from suicide, accidents, and other causes. Population-based data from multiple Swedish national registers were linked from 1969 to 2004. Participants were 44,397 offspring of suicide decedents, 41,467 offspring of accident decedents, 417,365 offspring of parents who died by other causes, and 3,807,867 offspring of alive parents. We estimated risk by mode of parental death (suicide, accident, other) and offspring age at parental death (childhood, adolescence, young adulthood). Offspring of suicide decedents were at greater risk for suicide than offspring of alive parents (incidence rate ratio [IRR] = 1.9; 95% confidence interval [CI] = 1.4 to 2.5), whereas offspring of accident decedents and other parental death were not at increased risk (p < .001). The risk for offspring suicide differed by the developmental period during which parental suicide occurred. Child and adolescent offspring of suicide decedents were at threefold greater risk for suicide (IRR = 3.0; 95% CI = 1.7 to 5.3; IRR = 3.1, 95% CI = 2.1 to 4.6, respectively). Young adults were not at increased risk for suicide (IRR = 1.3; 95% CI = 0.9 to 1.9). Offspring of suicide decedents had an especially high risk of hospitalization for suicide attempt, depressive, psychotic, and personality disorders. Child survivors of parental suicide were at particularly high risk for hospitalization for drug disorders and psychosis. All offspring who experienced parental death, regardless of mode or age, were at increased risk for violent criminal convictions. Mode of parental death and offspring age at parental death are associated with offspring long-term risk for suicide and hospitalization for specific psychiatric disorders.

Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats.

PubMed

Santos, Mery; Rodríguez-González, Guadalupe L; Ibáñez, Carlos; Vega, Claudia C; Nathanielsz, Peter W; Zambrano, Elena

2015-02-01

Exercise improves health but few data are available regarding benefits of exercise in offspring exposed to developmental programming. There is currently a worldwide epidemic of obesity. Obesity in pregnant women predisposes offspring to obesity. Maternal obesity has well documented effects on offspring reproduction. Few studies address ability of offspring exercise to reduce adverse outcomes. We observed increased oxidative stress and impaired sperm function in rat offspring of obese mothers. We hypothesized that regular offspring exercise reverses adverse effects of maternal obesity on offspring sperm quality and fertility. Female Wistar rats ate chow (C) or high-energy, obesogenic diet (MO) from weaning through lactation, bred at postnatal day (PND) 120, and ate their pregnancy diet until weaning. All offspring ate C diet from weaning. Five male offspring (different litters) ran on a wheel for 15 min, 5 times/week from PND 330 to 450 and were euthanized at PND 450. Average distance run per session was lower in MO offspring who had higher body weight, adiposity index, and gonadal fat and showed increases in testicular oxidative stress biomarkers. Sperm from MO offspring had reduced antioxidant enzyme activity, lower sperm quality, and fertility. Exercise in MO offspring decreased testicular oxidative stress, increased sperm antioxidant activity and sperm quality, and improved fertility. Exercise intervention has beneficial effects on adiposity index, gonadal fat, oxidative stress markers, sperm quality, and fertility. Thus regular physical exercise in male MO offspring recuperates key male reproductive functions even at advanced age: it's never too late. Copyright © 2015 the American Physiological Society.

Adiposity, Dysmetabolic Traits, and Earlier Onset of Female Puberty in Adolescent Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within the Danish National Birth Cohort.

PubMed

Grunnet, Louise G; Hansen, Susanne; Hjort, Line; Madsen, Camilla M; Kampmann, Freja B; Thuesen, Anne Cathrine B; Granstrømi, Charlotta; Strøm, Marin; Maslova, Ekaterina; Frikke-Schmidt, Ruth; Damm, Peter; Chavarro, Jorge E; Hu, Frank B; Olsen, Sjurdur F; Vaag, Allan

2017-12-01

Offspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring. We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models. After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs. In summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy. © 2017 by the American Diabetes Association.

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.

Association of Maternal Exposure to Childhood Abuse With Elevated Risk for Attention Deficit Hyperactivity Disorder in Offspring.

PubMed

Roberts, Andrea L; Liew, Zeyan; Lyall, Kristen; Ascherio, Alberto; Weisskopf, Marc G

2018-05-14

Children whose mothers experienced childhood abuse are more likely to suffer various neurodevelopmental deficits. Whether an association exists specifically for attention deficit hyperactivity disorder (ADHD) is unknown. We examined the association of maternal experience of childhood abuse with ADHD in offspring, assessed by maternal report of diagnosis and validated with the ADHD Rating Scale-IV in a subsample, in the Nurses' Health Study II (n = 49,497 mothers, N offspring cases = 7,607, N offspring controls = 102,151). We examined whether ten adverse perinatal circumstances (e.g., prematurity, smoking) or socioeconomic factors accounted for a possible association. Exposure to abuse was associated with greater prevalence of ADHD in offspring (8.7% of offspring of women exposed to severe abuse vs. 5.5% of offspring of women not abused, P = 0.0001) and with greater risk for ADHD adjusted for demographic factors (male offspring, risk ratio (RR) = 1.6; 95% CI: 1.3, 1.9; female offspring, RR = 2.3, 95% CI: 1.7, 3.0). Adjusted for perinatal factors, the association of maternal childhood abuse with ADHD in offspring was slightly attenuated (male offspring, RR = 1.5; 95% CI: 1.2, 1.8; female offspring, RR = 2.1, 95% CI: 1.6, 2.8). We identified an association between maternal experience of childhood abuse and risk for ADHD in offspring, which was not explained by several important perinatal risk factors or socioeconomic status.

Family environment and psychopathology in offspring of parents with bipolar disorder.

PubMed

Lau, Phoebe; Hawes, David J; Hunt, Caroline; Frankland, Andrew; Roberts, Gloria; Wright, Adam; Costa, Daniel S J; Mitchell, Philip B

2018-01-15

The aim of this study was to examine the relationship between family environment (cohesion and parental bonding), high-risk status, and psychopathology (internalizing and externalizing problems) among offspring of parents with bipolar disorder (BD), from the perspective of both offspring and their parents. We further tested if family environment mediated the relationship between bipolar risk status and internalizing and externalizing problems. High-risk (n = 90) BD offspring and control (n = 56) offspring aged 12-21 years old, and their parents, completed questionnaires on family cohesion and offspring internalizing and externalizing problems. Offspring also completed a parental bonding questionnaire. Group differences were examined, followed by multi-level mediation analysis with maximum likelihood and robust standard errors. Both offspring and parents in the high-risk group reported higher levels of internalizing and externalizing problems than controls. According to offspring reports, high-risk status, lower maternal and paternal care in parental bonding, was independently associated with internalizing problems. Lower maternal care alone predicted externalizing problems. Family environment did not mediate the relationship between bipolar risk status, and offspring problems. Due to rates of missing data from parent reports of offspring psychopathology, mediation analysis was completed using offspring reports. The offspring-report data presented indicate that low parental warmth and connection were associated with internalizing and externalizing problems as an independent risk factor, in addition to bipolar risk status. The parent-child relationship therefore warrants attention as a potential target for prevention strategies with such families. Copyright © 2017 Elsevier B.V. All rights reserved.

Offspring ADHD as a risk factor for parental marital problems: controls for genetic and environmental confounds.

PubMed

Schermerhorn, Alice C; D'Onofrio, Brian M; Slutske, Wendy S; Emery, Robert E; Turkheimer, Eric; Harden, K Paige; Heath, Andrew C; Martin, Nicholas G

2012-12-01

Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. However, the reasons for this association are unclear. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Data were drawn from the Australian Twin Registry, including 1,296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD.Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds,as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology,when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems.

Are there subtle genome-wide epigenetic alterations in normal offspring conceived by assisted reproductive technologies?

PubMed

Batcheller, April; Cardozo, Eden; Maguire, Marcy; DeCherney, Alan H; Segars, James H

2011-12-01

To review recent data regarding subtle, but widespread, epigenetic alterations in phenotypically normal offspring conceived by assisted reproductive technologies (ART) compared with offspring conceived in vivo. A PubMed computer search was performed to identify relevant articles. Research institution. Not applicable. None. Not applicable. Studies in animals indicate that in vitro culture may be associated with widespread alterations in imprinted genes compared with in vivo-conceived offspring. Recently, studies in humans have likewise demonstrated widespread changes in DNA methylation, including genes linked to adipocyte development, insulin signaling, and obesity in offspring conceived by ART compared with in vivo-conceived children. Changes in multiple imprinted genes after ART also were noted in additional studies, which suggested that the diagnosis of infertility may explain the differences between in vivo-conceived and ART offspring. These data suggest that ART is associated with widespread epigenetic modifications in phenotypically normal children, and that these modifications may increase the risk of adverse cardiometabolic outcomes. Further research is needed to elucidate the possible relationship between ART, genome-wide alterations in imprinted genes, and their potential relevance to subtle cardiometabolic consequences reported in ART offspring. Published by Elsevier Inc.

Offspring ADHD as a Risk Factor for Parental Marital Problems: Controls for Genetic and Environmental Confounds

PubMed Central

Schermerhorn, Alice C.; D’Onofrio, Brian M.; Slutske, Wendy S.; Emery, Robert E.; Turkheimer, Eric; Harden, K. Paige; Heath, Andrew C.; Martin, Nicholas G.

2013-01-01

Background Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. The reasons for this association are unclear, however. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Method Data were drawn from the Australian Twin Registry, including 1296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD. Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds, as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Results Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology, when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. Conclusion The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems. PMID:22958575

A developmental approach to dimensional expression of psychopathology in child and adolescent offspring of parents with bipolar disorder.

PubMed

Morón-Nozaleda, María Goretti; Díaz-Caneja, Covadonga M; Rodríguez-Toscano, Elisa; Arango, Celso; Castro-Fornieles, Josefina; de la Serna, Elena; Espliego, Ana; Sanchez-Gistau, Vanessa; Romero, Soledad; Baeza, Immaculada; Sugranyes, Gisela; Moreno, Carmen; Moreno, Dolores

2017-10-01

The aim of this is to describe psychopathology, functioning and symptom dimensions accounting for subthreshold manifestations and developmental status in child and adolescent offspring of parents with bipolar disorder ("high-risk offspring"). The study population comprised 90 high-risk offspring (HR-offspring) and 107 offspring of community control parents (CC-offspring). Direct clinical observations and parental and offspring reports based on selected standardized clinical scales were used to assess offspring threshold and subthreshold diagnoses, symptoms and functioning. All outcomes were compared between the whole HR-offspring and CC-offspring samples and then by developmental status. After controlling for potential confounders, HR-offspring showed significantly poorer adjustment for childhood (r = 0.18, p = 0.014) and adolescence (r = 0.21, p = 0.048) than CC-offspring, as well as more emotional problems (r = 0.24, p = 0.001) and higher depression scores (r = 0.16, p = 0.021). As for differences in lifetime categorical diagnoses (threshold and subthreshold) between HR-offspring and CC-offspring, the prevalence of disruptive disorders was higher in pre-pubertal HR-offspring (OR 12.78 [1.45-112.42]), while prevalence of mood disorders was higher in post-pubertal HR-offspring (OR 3.39 [1.14-10.06]). Post-pubertal HR-offspring presented more prodromal (r = 0.40, p = 0.001), negative (r = 0.38, p = 0.002), manic (r = 0.22, p = 0.035) and depressive (r = 0.23, p = 0.015) symptoms than pre-pubertal HR-offspring, as well as more peer relationship problems (r = 0.31, p = 0.004), poorer childhood adjustment (r = 0.22, p = 0.044) and worse current psychosocial functioning (r = 0.27, p = 0.04). Externalizing psychopathology is more prevalent in pre-pubertal HR-offspring, while depressive and prodromal symptoms leading to functional impairment are more prominent in post-pubertal HR-offspring. Developmental approaches and dimensional measures may be useful for identifying children at high risk of developing bipolar disorder and help guide specific preventive strategies.

Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring

PubMed Central

Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

2014-01-01

While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. PMID:24661622

Interspecific competition alters nonlinear selection on offspring size in the field.

PubMed

Marshall, Dustin J; Monro, Keyne

2013-02-01

Offspring size is one of the most important life-history traits with consequences for both the ecology and evolution of most organisms. Surprisingly, formal estimates of selection on offspring size are rare, and the degree to which selection (particularly nonlinear selection) varies among environments remains poorly explored. We estimate linear and nonlinear selection on offspring size, module size, and senescence rate for a sessile marine invertebrate in the field under three different intensities of interspecific competition. The intensity of competition strongly modified the strength and form of selection acting on offspring size. We found evidence for differences in nonlinear selection across the three environments. Our results suggest that the fitness returns of a given offspring size depend simultaneously on their environmental context, and on the context of other offspring traits. Offspring size effects can be more pervasive with regards to their influence on the fitness returns of other traits than previously recognized, and we suggest that the evolution of offspring size cannot be understood in isolation from other traits. Overall, variability in the form and strength of selection on offspring size in nature may reduce the efficacy of selection on offspring size and maintain variation in this trait. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Investigation of implicit avoidance of displacement-related stimuli in offspring of trauma exposed, forcibly-displaced individuals.

PubMed

Wittekind, Charlotte E; Muhtz, Christoph; Moritz, Steffen; Jelinek, Lena

2017-04-01

There is an ongoing debate as to whether traumatization also affects the close relatives of trauma survivors who have symptoms of PTSD. Although many studies provide evidence favoring a transgenerational transmission, other studies have not found evidence to support this idea. The present study examined whether adult offspring of individuals exposed to trauma during forced displacement with (n=22) and without PTSD (n=24) exhibit an implicit avoidance of stimuli related to the parental trauma compared to children of non-trauma exposed control participants (n=23) using an Approach-Avoidance task (AAT). Offspring participants were requested to push (i.e., avoidance) or pull (i.e., approach) displacement-related and neutral pictures, whereby response direction depended on a non-affective dimension (color of the pictures). Results suggest that the offspring of non-PTSD participants exhibit implicit avoidance of displacement-related stimuli. This rather unexpected finding might either indicate resilience amongst offspring of PTSD participants or that offspring of non-PTSD participants are particularly affected. If these results were to replicate, they suggest that implicit avoidance tendencies amongst the offspring of trauma exposed participants might partially contribute to their heightened PTSD vulnerability. Longitudinal studies are needed to elucidate whether implicit avoidance tendencies are associated with increased stress vulnerability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of maternal obesity on the long-term health of offspring

PubMed Central

Godfrey, Keith M.; Reynolds, Rebecca M.; Prescott, Susan L.; Nyirenda, Moffat; Jaddoe, Vincent W.V.; Eriksson, Johan G.; Broekman, Birit F.P

2017-01-01

Alongside its immediate implications for pregnancy complications, increasing evidence implicates maternal obesity as a major determinant of health in the offspring during childhood and later adult life. Observational studies provide evidence for effects of maternal obesity on the offspring’s risks of obesity, coronary heart disease, stroke, type 2 diabetes and asthma. Maternal obesity may also lead to poorer cognitive performance in the offspring and an increased risk of neurodevelopmental disorders including cerebral palsy. Preliminary evidence suggests potential implications for immune and infectious disease related outcomes. Insights from experimental studies support causal effects of maternal obesity on offspring outcomes, mediated at least in part through changes in epigenetic processes including alternations in DNA methylation, and perhaps through alterations in the gut microbiome. Although the offspring of obese women who lose weight prior to pregnancy have a reduced risk of obesity, to date few controlled intervention studies have reversed maternal obesity and examined the consequences for the offspring. The long term effects of maternal obesity may have profound public health implications and indicate the urgency of studies on causality, underlying mechanisms and effective interventions to reverse the epidemic of obesity in women of child-bearing age and to mitigate its consequences for the offspring. PMID:27743978

Maternal Obesity: Lifelong Metabolic Outcomes for Offspring from Poor Developmental Trajectories During the Perinatal Period.

PubMed

Zambrano, Elena; Ibáñez, Carlos; Martínez-Samayoa, Paola M; Lomas-Soria, Consuelo; Durand-Carbajal, Marta; Rodríguez-González, Guadalupe L

2016-01-01

The prevalence of obesity in women of reproductive age is increasing in developed and developing countries around the world. Human and animal studies indicate that maternal obesity adversely impacts both maternal health and offspring phenotype, predisposing them to chronic diseases later in life including obesity, dyslipidemia, type 2 diabetes mellitus, and hypertension. Several mechanisms act together to produce these adverse health effects including programming of hypothalamic appetite-regulating centers, increasing maternal, fetal and offspring glucocorticoid production, changes in maternal metabolism and increasing maternal oxidative stress. Effective interventions during human pregnancy are needed to prevent both maternal and offspring metabolic dysfunction due to maternal obesity. This review addresses the relationship between maternal obesity and its negative impact on offspring development and presents some maternal intervention studies that propose strategies to prevent adverse offspring metabolic outcomes. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Neck/upper back and low back pain in parents and their adult offspring: Family linkage data from the Norwegian HUNT Study.

PubMed

Lier, R; Nilsen, T I L; Vasseljen, O; Mork, P J

2015-07-01

Chronic pain in the neck and low back is highly prevalent. Although heritable components have been identified, knowledge about generational transmission of spinal pain between parents and their adult offspring is sparse. This study examined the intergenerational association of spinal pain using data from 11,081 parent-offspring trios participating in the population-based HUNT Study in Norway. Logistic regression was used to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for offspring spinal pain associated with parental spinal pain. In total, 3654 (33%) offspring reported spinal pain at participation. Maternal and paternal spinal pain was consistently associated with higher ORs for offspring spinal pain. The results suggest a slightly stronger association for parental multilevel spinal pain (i.e., both neck/upper back pain and low back pain) than for pain localized to the neck/upper back or low back. Multilevel spinal pain in both parents was associated with ORs of 2.6 (95% CI, 2.1-3.3), 2.4 (95% CI, 1.9-3.1) and 3.1 (95% CI, 2.2-4.4) for offspring neck/upper back, low back and multilevel spinal pain, respectively. Parental chronic spinal pain was consistently associated with increased occurrence of chronic spinal pain in their adult offspring, and this association was particularly strong for multilevel spinal pain. © 2014 European Pain Federation - EFIC®

Animal models of maternal high fat diet exposure and effects on metabolism in offspring: a meta-regression analysis.

PubMed

Ribaroff, G A; Wastnedge, E; Drake, A J; Sharpe, R M; Chambers, T J G

2017-06-01

Animal models of maternal high fat diet (HFD) demonstrate perturbed offspring metabolism although the effects differ markedly between models. We assessed studies investigating metabolic parameters in the offspring of HFD fed mothers to identify factors explaining these inter-study differences. A total of 171 papers were identified, which provided data from 6047 offspring. Data were extracted regarding body weight, adiposity, glucose homeostasis and lipidaemia. Information regarding the macronutrient content of diet, species, time point of exposure and gestational weight gain were collected and utilized in meta-regression models to explore predictive factors. Publication bias was assessed using Egger's regression test. Maternal HFD exposure did not affect offspring birthweight but increased weaning weight, final bodyweight, adiposity, triglyceridaemia, cholesterolaemia and insulinaemia in both female and male offspring. Hyperglycaemia was found in female offspring only. Meta-regression analysis identified lactational HFD exposure as a key moderator. The fat content of the diet did not correlate with any outcomes. There was evidence of significant publication bias for all outcomes except birthweight. Maternal HFD exposure was associated with perturbed metabolism in offspring but between studies was not accounted for by dietary constituents, species, strain or maternal gestational weight gain. Specific weaknesses in experimental design predispose many of the results to bias. © 2017 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

Does Male Care, Provided to Immature Individuals, Influence Immature Fitness in Rhesus Macaques?

PubMed Central

Langos, Doreen; Kulik, Lars; Ruiz-Lambides, Angelina; Widdig, Anja

2015-01-01

Among many mammals, maternal care strongly impacts infant survival; however, less is known about whether adult males also affect infant fitness. Paternal care is expected when providing care enhances offspring survival and reproduction, which likewise increases fathers’ fitness. Males might also care for unrelated immature individuals to increase their mating probability with the immature individuals’ mothers. Studies in multimale primate groups showed that sires enhance food access for offspring and provide protection in conflicts. Furthermore, fathers’ presence during infancy has been suggested to accelerate offspring sexual maturation. However, no study has yet directly linked the degree of father-offspring bonds to offspring fitness in primates. We previously reported father-offspring affiliation in rhesus macaques, pronounced during early infancy and independent of mothers’ presence. The present study aims at investigating whether affiliation with fathers or other males affects proxies of immature fitness (body mass gain, body fat and testis size). First, we combined behavioral, genetic and morphometric data from 55 subjects of one group. Second, using demographic and genetic data, we investigated for 92 individuals of the population whether mother- and father-offspring co-residence during immaturity influenced offspring lifetime reproductive success (LRS). Our results show that focal rank and higher amounts of affiliation with high-ranking males during infancy tend to positively impact body mass gain of female, but not male focal animals. In contrast, body mass gain of male focal individuals, but not females’, appeared to be higher when affiliation of male immature individuals was evenly distributed across their adult male partners. Moreover, we found mothers’, but not fathers’, presence during immaturity to predict offspring LRS. Our results suggest that male-immature affiliation, but not father-offspring co-residence, potentially impacts proxies of immature fitness. However, future studies should investigate the underlying mechanisms of male-immature relationships and their impact on immature fitness in more detail. PMID:26367536

Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor.

PubMed

Chechi, Kanta; McGuire, John J; Cheema, Sukhinder K

2009-04-01

We have previously shown that a maternal high-fat diet, rich in saturated fatty acids (SFA), alters the lipid metabolism of their adult offspring. The present study was designed to investigate 1) whether alterations in hepatic LDL-receptor (LDL-r) expression may serve as a potential mechanism of developmental programming behind the altered lipid metabolism of the offspring, 2) whether altered lipid metabolism leads to aortic vascular dysfunction in the offspring, 3) whether deleterious effects of SFA exposure preweaning are influenced by postweaning diet, and 4) whether gender-specific programming effects are observed. Female C57Bl/6 mice were fed a high-SFA diet or regular chow during gestation and lactation while their pups, both male and female, received either SFA or a chow diet after weaning. Male offspring obtained from mothers fed an SFA diet and those who continued on chow postweaning had higher plasma triglycerides and total cholesterol, whereas female offspring had higher plasma total and LDL cholesterol levels, lower hepatic LDL-r mRNA expression, and reduced aortic contractile responses compared with the offspring that were fed chow throughout the study. A comparison of the postweaning diet revealed significantly lower hepatic LDL-r expression along with significantly higher plasma LDL-cholesterol concentration in the female offspring that were obtained from mothers fed an SFA diet and who continued on an SFA diet postweaning, compared with the female offspring that were obtained from mothers fed an SFA diet but who continued on chow postweaning. In conclusion, we report a novel observation of hepatic LDL-r-mediated programming of altered lipid metabolism, along with aortic vascular dysfunction, in the female offspring of mothers fed a high-SFA diet. Male offspring only exhibited dyslipidemia, suggesting gender-mediated programming. This study further highlighted the role of postweaning diets in overriding the effects of maternal programming.

Offspring from mothers fed a 'junk food' diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females.

PubMed

Bayol, S A; Simbi, B H; Bertrand, J A; Stickland, N C

2008-07-01

We have shown previously that a maternal junk food diet during pregnancy and lactation plays a role in predisposing offspring to obesity. Here we show that rat offspring born to mothers fed the same junk food diet rich in fat, sugar and salt develop exacerbated adiposity accompanied by raised circulating glucose, insulin, triglyceride and/or cholesterol by the end of adolescence (10 weeks postpartum) compared with offspring also given free access to junk food from weaning but whose mothers were exclusively fed a balanced chow diet in pregnancy and lactation. Results also showed that offspring from mothers fed the junk food diet in pregnancy and lactation, and which were then switched to a balanced chow diet from weaning, exhibited increased perirenal fat pad mass relative to body weight and adipocyte hypertrophy compared with offspring which were never exposed to the junk food diet. This study shows that the increased adiposity was more enhanced in female than male offspring and gene expression analyses showed raised insulin-like growth factor-1 (IGF-1), insulin receptor substrate (IRS)-1, vascular endothelial growth factor (VEGF)-A, peroxisome proliferator-activated receptor-gamma (PPARgamma), leptin, adiponectin, adipsin, lipoprotein lipase (LPL), Glut 1, Glut 3, but not Glut 4 mRNA expression in females fed the junk food diet throughout the study compared with females never given access to junk food. Changes in gene expression were not as marked in male offspring with only IRS-1, VEGF-A, Glut 4 and LPL being up-regulated in those fed the junk food diet throughout the study compared with males never given access to junk food. This study therefore shows that a maternal junk food diet promotes adiposity in offspring and the earlier onset of hyperglycemia, hyperinsulinemia and/or hyperlipidemia. Male and female offspring also display a different metabolic, cellular and molecular response to junk-food-diet-induced adiposity.

Offspring from mothers fed a ‘junk food’ diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females

PubMed Central

Bayol, S A; Simbi, B H; Bertrand, J A; Stickland, N C

2008-01-01

We have shown previously that a maternal junk food diet during pregnancy and lactation plays a role in predisposing offspring to obesity. Here we show that rat offspring born to mothers fed the same junk food diet rich in fat, sugar and salt develop exacerbated adiposity accompanied by raised circulating glucose, insulin, triglyceride and/or cholesterol by the end of adolescence (10 weeks postpartum) compared with offspring also given free access to junk food from weaning but whose mothers were exclusively fed a balanced chow diet in pregnancy and lactation. Results also showed that offspring from mothers fed the junk food diet in pregnancy and lactation, and which were then switched to a balanced chow diet from weaning, exhibited increased perirenal fat pad mass relative to body weight and adipocyte hypertrophy compared with offspring which were never exposed to the junk food diet. This study shows that the increased adiposity was more enhanced in female than male offspring and gene expression analyses showed raised insulin-like growth factor-1 (IGF-1), insulin receptor substrate (IRS)-1, vascular endothelial growth factor (VEGF)-A, peroxisome proliferator-activated receptor-γ (PPARγ), leptin, adiponectin, adipsin, lipoprotein lipase (LPL), Glut 1, Glut 3, but not Glut 4 mRNA expression in females fed the junk food diet throughout the study compared with females never given access to junk food. Changes in gene expression were not as marked in male offspring with only IRS-1, VEGF-A, Glut 4 and LPL being up-regulated in those fed the junk food diet throughout the study compared with males never given access to junk food. This study therefore shows that a maternal junk food diet promotes adiposity in offspring and the earlier onset of hyperglycemia, hyperinsulinemia and/or hyperlipidemia. Male and female offspring also display a different metabolic, cellular and molecular response to junk-food-diet-induced adiposity. PMID:18467362

Effects of bisphenol A treatment during pregnancy on kidney development in mice: a stereological and histopathological study.

PubMed

Nuñez, P; Fernandez, T; García-Arévalo, M; Alonso-Magdalena, P; Nadal, A; Perillan, C; Arguelles, J

2018-04-01

Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9-16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.

Colorectal cancer knowledge, attitudes, screening, and intergenerational communication among Japanese American families: an exploratory, community-based participatory study.

PubMed

Lau, Denys T; Machizawa, Sayaka; Demonte, William; Cameron, Kenzie A; Muramatsu, Naoko; Henker, Raymond D; Chikahisa, Frances; Tanimura, Michael

2013-03-01

Adults of Japanese descent (Nikkei) in the United States have higher risk for colorectal cancer (CRC) than their white counterparts. Family norms toward CRC screening may influence screening behaviors of Nikkei adults. This community-based participatory research study explores if mailing educational pamphlets to Nikkei families can influence CRC knowledge, attitudes, and screening adherence; and trigger intergenerational communication about CRC. Among 56 parent-offspring dyads contacted, 24 were eligible (e.g., no prior CRC screening/diagnosis) and were randomized into 3 cohorts defined by the "target recipient(s)" of study pamphlets about CRC screening: parent only, offspring only, and both parent and offspring. Among the 19 completed dyads (79.2 % = 19/24), results showed that CRC knowledge of most pamphlet recipients increased in all cohorts; however, some misinformation and attitudinal barriers persisted. Although some parent-offspring communication about CRC increased after mailing pamphlets to offspring, only spousal communication occurred after mailing pamphlets to parents. Additional benefits were not observed in increasing parental screening intent/behavior after mailing pamphlets to both parent and offspring. At the end, among the 10 parents who reported developing CRC screening intent or having scheduled a CRC screening, 8 attributed to study pamphlets and 2 to communication with their offspring. Self-reported barriers preventing screening and parent-offspring communication about CRC were identified. This exploratory study describes preliminary findings that will inform future research aimed to promote CRC screening and reduce racial/ethnic disparities at the community level by enhancing intergenerational communication among Nikkei families.

Colorectal cancer knowledge, attitudes, screening, and intergenerational communication among Japanese American families: an exploratory, community-based participatory study

PubMed Central

Lau, Denys T.; Machizawa, Sayaka; Demonte, William; Cameron, Kenzie A.; Muramatsu, Naoko; Henker, Raymond D.; Chikahisa, Frances; Tanimura, Michael

2012-01-01

Adults of Japanese descent (Nikkei) in the United States have higher risk for colorectal cancer (CRC) than their white counterparts. Family norms toward CRC screening may influence screening behaviors of Nikkei adults. This community-based participatory research study explores if mailing educational pamphlets to Nikkei families can influence CRC knowledge, attitudes, and screening adherence; and trigger intergenerational communication about CRC. Among 56 parent-offspring dyads contacted, 24 were eligible (e.g., no prior CRC screening/diagnosis) and were randomized into 3 cohorts defined by the “target recipient(s)” of study pamphlets about CRC screening: parent only, offspring only, and both parent and offspring. Among the 19 completed dyads (79.2%=19/24), results showed that CRC knowledge of most pamphlet recipients increased in all cohorts; however, some misinformation and attitudinal barriers persisted. Although some parent-offspring communication about CRC increased after mailing pamphlets to offspring, only spousal communication occurred after mailing pamphlets to parents. Additional benefits were not observed in increasing parental screening intent/behavior after mailing pamphlets to both parent and offspring. At the end, among the 10 parents who reported developing CRC screening intent or having scheduled a CRC screening, 8 attributed to study pamphlets and 2 to communication with their offspring. Self-reported barriers preventing screening and parent-offspring communication about CRC were identified. This exploratory study describes preliminary findings that will inform future research aimed to promote CRC screening and reduce racial/ethnic disparities at the community level by enhancing intergenerational communication among Nikkei families. PMID:23263883

Maternal smoking during pregnancy and self-reported delinquency by offspring.

PubMed

Ellis, Lee; Widmayer, Alan; Das, Shyamal

2012-12-01

Several studies have reported significant positive correlations between smoking during pregnancy by mothers and the involvement of their offspring in criminal/delinquent behaviour later in life, but these findings have been described as modest and the criminality based on official conviction statistics. We sought to verify this relationship and probe for more details on the basis of self-reported offending among college students. Independently completed questionnaires were collected from 6332 students and their mothers. The students provided information about their delinquent acts, if any, according to eight categories. Their mothers provided retrospective reports of their smoking habits, if any, during pregnancy. Mothers who recalled having smoked during pregnancy were significantly more likely than non-smoking mothers to have offspring who self-reported engaging in some types of delinquency. This relationship was more evident for female offspring than for male offspring and was most pronounced for illegal drug use by the offspring. There was, however, no relationship between offspring offending and estimated number of cigarettes smoked by mothers, month of pregnancy when smoked or consistency of smoking throughout pregnancy. Overall, our study confirms that maternal smoking during pregnancy is associated with offspring involvement in delinquency, but the lack of critical timing or dose-response relationships between maternal smoking and later offspring delinquency cast doubt on the possibility that the associations are due to teratogenic effects of tobacco smoke. Copyright © 2012 John Wiley & Sons, Ltd.

The experiences of adolescents and adults conceived by sperm donation: comparisons by age of disclosure and family type.

PubMed

Jadva, Vasanti; Freeman, Tabitha; Kramer, Wendy; Golombok, Susan

2009-08-01

This study presents findings from a large sample of donor offspring who are aware of the nature of their conception. Importantly, this is one of the first studies to compare the views of offspring told of their origins during childhood to those who found out during adulthood. Online questionnaires were completed anonymously by donor offspring who were members of the Donor Sibling Registry, a US-based worldwide registry that helps donor-conceived individuals search for and contact their donor and donor siblings (i.e. half-siblings). Data were obtained on offspring's feelings about being donor conceived and their feelings towards their parents. Offspring of single mothers and lesbian couples learnt of their donor origins earlier than offspring of heterosexual couples. Those told later in life reported more negative feelings regarding their donor conception than those told earlier. Offspring's feelings towards their parents were less clear, with some of those told later reporting more positive feelings and others reporting more negative feelings. Offspring from heterosexual-couple families were more likely to feel angry at being lied to by their mothers than by their fathers. The most common feeling towards fathers was 'sympathetic'. Age of disclosure is important in determining donor offspring's feelings about their donor conception. It appears it is less detrimental for children to be told about their donor conception at an early age.

Parental history of lupus and rheumatoid arthritis and risk in offspring in a nationwide cohort study: does sex matter?

PubMed

Somers, Emily C; Antonsen, Sussie; Pedersen, Lars; Sørensen, Henrik Toft

2013-04-01

To examine the familial risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), including juvenile rheumatoid/idiopathic arthritis (JRA), in a population-based setting; and to determine whether patterns of transmission differ according to the sex of the parent or offspring, in order to provide insight into the potential impact of X-chromosomal factors on sex disparities in these autoimmune diseases. A population-based cohort of parent-offspring triads from Denmark (1977-2010) was established. SLE and RA incidence rates among offspring were calculated, and Cox regression was performed to assess the sex-specific risk of disease in offspring according to maternal or paternal disease history. Among 3 513 817 parent-offspring triads, there were 1258 SLE cases among offspring (1095 female, 163 male) and 9118 cases of RA/JRA (6086 female, 3032 male). Among female offspring, SLE risk was nearly the same according to maternal (HR 14.1) or paternal (HR 14.5) history (p=NS); likewise among male offspring, risk according to maternal (HR 5.5) and paternal (no cases) history were similar (p=NS). For RA, all risk estimates were similar, regardless of the sex of the offspring or parent (HR 2.6-2.9; p=NS). The authors quantified the familial risk of SLE and RA in a nationwide cohort study. For both diseases, transmission was comparable among both female and male offspring of maternal and paternal cases. These data provide evidence at the population level that X-chromosomal factors do not play a major role in sex disparities associated with the risk of SLE and RA.

The association between teenage motherhood and poor offspring outcomes: A national cohort study across 30 years

PubMed Central

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D’Onofrio, Brian M

2013-01-01

Teenage motherhood is associated with poor offspring outcomes but these associations may be influenced by offspring birth year because of substantial social changes in recent decades. Existing research also has not examined whether these associations are due to the specific effect of mother’s age at childbirth or factors shared by siblings in a family. We used a population-based cohort study in Sweden comprising all children born from 1960–1989 (N=3,162,239), and a subsample of siblings differentially exposed to maternal teenage childbearing (N=485,259) to address these limitations. We examined the effect of teenage childbearing on offspring violent and nonviolent criminal convictions, poor academic performance, and substance-related problems. Population-wide, teenage childbearing was associated with offspring criminal convictions, poor academic performance, and substance-related problems. The magnitude of these associations increased over time. Comparisons of differentially exposed siblings indicated no within-family association between teenage childbearing and offspring violent and nonviolent criminal convictions or poor academic performance, although offspring born to teenage mothers were more likely to experience substance-related problems than their later-born siblings. Being born to a teenage mother in Sweden has become increasingly associated with negative outcomes across time, but the nature of this association may differ by outcome. Teenage childbearing may be associated with offspring violent and nonviolent criminal convictions and poor academic performance because of shared familial risk factors but may be causally associated with offspring substance-related problems. The findings suggest that interventions to improve offspring outcomes should delay teenage childbearing and target risk factors influencing all offspring of teenage mothers. PMID:23632141

Time to hospitalization for suicide attempt by the timing of parental suicide during offspring early development

PubMed Central

Kuramoto, S. Janet; Runeson, Bo; Stuart, Elizabeth A.; Lichtenstein, Paul; Wilcox, Holly C.

2013-01-01

Context Previous studies have suggested that children who experience parental suicide at earlier ages are at higher risk of future hospitalization for suicide attempt. However, how the trajectories of risk differ by offspring age at the time of parental suicide is currently unknown. Objective To study time at risk to hospitalization for suicide attempt among offspring after experiencing parental suicide or accidental death by offspring developmental period at the time of parental death. Design Population-based retrospective cohort study Setting Sweden Participants 26,096 offspring who experienced parental suicide and 32,395 offspring of accident decedents prior to age 25 from 1973-2003. Main Outcome Measures Hospitalization for suicide attempt. Parametric survival analysis was used to model the time to hospitalization for suicide attempt across offspring who lost a parent during early childhood (0-5 years old), later childhood (6-12), adolescence (13-17) and young adulthood (18-24). Results The risk in offspring who lost a parent during early or late childhood surpassed the other two age groups’ hazards approximately 5 years after the origin and, for the youngest group, continued to rise over the course of decades. Offspring who lost a parent during adolescence or young adulthood were at greatest risk within 1 to 2 years after parental suicide, and risk declined over time. The shape of hospitalization risk was similar among those who experienced parental fatal accident. When the shape of hospitalization for suicide attempt at each developmental period was fixed to be the same between the two groups, offspring who lost a parent to suicide had earlier risk to hospitalization for suicide attempt hospitalization than offspring who lost a parent to an accident. Conclusion The hospitalization risk for suicide attempt in offspring who lost a parent during their childhood is different from those who lost a parent during adolescence or young adulthood. The results suggest critical windows for careful monitoring and intervention for suicide attempt risk, especially 1-2 years after parental death for the older age groups and over decades for childhood survivors of parental death. PMID:23229861

Cognitive-emotional hyperarousal in the offspring of parents vulnerable to insomnia: a nuclear family study.

PubMed

Fernandez-Mendoza, Julio; Shaffer, Michele L; Olavarrieta-Bernardino, Sara; Vgontzas, Alexandros N; Calhoun, Susan L; Bixler, Edward O; Vela-Bueno, Antonio

2014-10-01

Cognitive-emotional hyperarousal is believed to be a predisposing factor for insomnia; however, there is limited information on the association of familial vulnerability to insomnia and cognitive-emotional hyperarousal. The aim of this study was to estimate the heritability of stress-related insomnia and examine whether parental vulnerability to stress-related insomnia is associated with cognitive-emotional hyperarousal in their offspring. We studied a volunteer sample of 135 nuclear families comprised of 270 middle-aged (51.5 ± 5.4 years) fathers and mothers and one of their biological offspring (n = 135, 20.2 ± 1.1 years). We measured vulnerability to stress-related insomnia (i.e. Ford Insomnia Response to Stress Test: FIRST), perceived stress, depression and anxiety in all participants, and arousability, presleep cognitive and somatic arousal, coping and personality in the offspring. We found a heritability estimate of 29% for FIRST scores. High FIRST parents had three to seven times the odds of having offspring highly vulnerable to stress-related insomnia. Offspring of high FIRST parents showed higher arousability, presleep cognitive arousal and emotion-oriented coping. Furthermore, high FIRST mothers contributed to offspring's higher anxiety and lower task-oriented coping, while high FIRST fathers contributed to offspring's higher presleep somatic arousal and conscientiousness. Vulnerability to stress-related insomnia is significantly heritable. Parents vulnerable to stress-related insomnia have offspring with cognitive-emotional hyperarousal who rely upon emotion-oriented coping. These data give support to the notion that arousability and maladaptive coping are key factors in the aetiology of insomnia. © 2014 European Sleep Research Society.

Paternal and maternal alcohol abuse and offspring mental distress in the general population: the Nord-Trøndelag health study

PubMed Central

2012-01-01

Background The degree to which parental alcohol abuse is a risk factor for offspring mental distress is unclear, due to conflicting results of previous research. The inconsistencies in previous findings may be related to sample characteristics and lack of control of confounding or moderating factors. One such factor may be the gender of the abusing parent. Also, other factors, such as parental mental health, divorce, adolescent social network, school functioning or self-esteem, may impact the outcome. This study examines the impact of maternal and paternal alcohol abuse on adolescent mental distress, including potentially confounding, mediating or moderating effects of various variables. Methods Data from the Nord-Trøndelag Health Study (HUNT), a Norwegian population based health survey, from 4012 offspring and their parents were analyzed. Parental alcohol abuse was measured by numerical consumption indicators and CAGE, whereas offspring mental distress was measured by SCL-5, an abbreviated instrument tapping symptoms of anxiety and depression. Statistical method was analysis of variance. Results Maternal alcohol abuse was related to offspring mental distress, whereas no effect could be shown of paternal alcohol abuse. Effects of maternal alcohol abuse was partly mediated by parental mental distress, offspring social network and school functioning. However, all effects were relatively small. Conclusions The results indicate graver consequences for offspring of alcohol abusing mothers compared to offspring of alcohol abusing fathers. However, small effect sizes suggest that adolescent offspring of alcohol abusing parents in general manage quite well. PMID:22708789

A maternal "junk food" diet in pregnancy and lactation promotes nonalcoholic Fatty liver disease in rat offspring.

PubMed

Bayol, Stéphanie A; Simbi, Bigboy H; Fowkes, Robert C; Stickland, Neil C

2010-04-01

With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring.

Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

PubMed Central

Thompson, Jacqueline R.; Gustafsson, Hanna C.; DeCapo, Madison; Takahashi, Diana L.; Bagley, Jennifer L.; Dean, Tyler A.; Kievit, Paul; Fair, Damien A.; Sullivan, Elinor L.

2018-01-01

Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes) increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD), metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC) exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation. PMID:29740395

A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring

PubMed Central

Bayol, Stéphanie A.; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.

2010-01-01

With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring. PMID:20207831

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

Like mother, like offspring: maternal and offspring wound healing correlate in snakes.

PubMed

Hopkins, Brittney C; Chin, Stephanie Y; Willson, John D; Hopkins, William A

2013-07-15

Immune function early in life can be influenced by parental effects and the environment, but it remains unclear how these two factors may interact to influence immunocompetence. We evaluated maternal and environmental contributions to offspring healing ability in a viviparous reptile, the northern watersnake (Nerodia sipedon). We measured wound healing rates, a highly integrative and biologically relevant measure of innate immunity, of females and their offspring collected from sites contaminated with a toxic heavy metal and compared them with those of individuals from reference sites. We found that female watersnakes that healed the fastest produced offspring that also exhibited faster healing rates. However, we detected no influence of environmental pollution on maternal or offspring healing rates. To our knowledge, our study is the first to correlate maternal and offspring wound healing ability in a wild vertebrate.

Helpers increase the reproductive potential of offspring in cooperative meerkats

PubMed Central

Russell, A.F; Young, A.J; Spong, G; Jordan, N.R; Clutton-Brock, T.H

2006-01-01

In both animal and human societies, individuals may forego personal reproduction and provide care to the offspring of others. Studies aimed at investigating the adaptive nature of such cooperative breeding systems in vertebrates typically calculate helper ‘fitness’ from relationships of helper numbers and offspring survival to independence. The aim of this study is to use observations and supplemental feeding experiments in cooperatively breeding meerkats, Suricata suricatta, to investigate whether helpers influence the long-term reproductive potential of offspring during adulthood. We show that helpers have a significant and positive influence on the probability that offspring gain direct reproductive success in their lifetimes. This effect arises because helpers both reduce the age at which offspring begin to reproduce as subordinates and increase the probability that they will compete successfully for alpha rank. Supplemental feeding experiments confirm the causality of these results. Our results suggest that one can neither discount the significance of helper effects when none is found nor necessarily estimate accurately the fitness benefit that helpers accrue, unless their effects on offspring are considered in the long term. PMID:17476771

Personality profile of the children of long-lived parents.

PubMed

Antoniou, Evangelia E; Dutta, Ambarish; Langa, Kenneth M; Melzer, David; Llewellyn, David

2013-09-01

Past research has shown that parental longevity is related to offspring physical health and longevity. Preliminary studies suggest that parental longevity may be linked to the offspring's personality traits. A comprehensive 5-factor personality model has been related to physical health, but the association with parental longevity has not yet been investigated. We used a 5-factor personality model to investigate the relationship between parental longevity and offspring personality. Data from the longitudinal Health and Retirement Study (HRS) was used in the analyses. Using the Midlife Development Inventory and the Life Orientation test, the relationship between parental attained age and offspring personality was assessed using regression models for both men and women. Male offspring of long-lived fathers and mothers were more likely to be open to new experiences (p < .01) and be more extroverted (p = .03) compared with male offspring of short-lived fathers or mothers. Maternal or paternal attained age had no effect on the female offspring personality traits. Personality is an important phenotype to consider when investigating genetic and environmental determinants of longevity. Further research is needed to investigate the potential of gender-specific mechanisms.

Maternal Blood Pressure During Pregnancy and Early Childhood Blood Pressures in the Offspring

PubMed Central

Lim, Wai-Yee; Lee, Yung-Seng; Yap, Fabian Kok-Peng; Aris, Izzudin Mohd; Ngee, Lek; Meaney, Michael; Gluckman, Peter D.; Godfrey, Keith M.; Kwek, Kenneth; Chong, Yap-Seng; Saw, Seang-Mei; Pan, An

2015-01-01

Abstract Although epidemiological studies suggest that offspring of women with preeclampsia are at increased risk to higher blood pressures and cardiovascular disease, little is known about the nature of blood pressures between the mother and her offspring. As blood pressures comprise of both pulsatile (systolic blood pressure [SBP] and pulse pressure [PP]) and stable (diastolic blood pressure [DBP]) components, and they differ between central and peripheral sites, we sought to examine maternal peripheral and central blood pressure components in relation to offspring early childhood blood pressures. A prospective birth cohort of 567 Chinese, Malay, and Indian mother–offspring with complete blood pressure information were studied. Maternal brachial artery SBP, DBP, and PP were measured at 26 to 28 weeks gestation; and central SBP and PP were estimated from radial artery waveforms. Offspring brachial artery SBP, DBP, and PP were measured at 3 years of age. Associations between continuous variables of maternal blood pressures (peripheral SBP, DBP, PP, central SBP, and PP) and offspring blood pressures (peripheral SBP, DBP, and PP) were examined using multiple linear regression with adjustment for maternal characteristics (age, education level, parity, smoking status, alcohol consumption and physical activity during pregnancy, and pre-pregnancy BMI) and offspring characteristics (sex, ethnicity, BMI, and height at 3 years of age). In the multivariate models, offspring peripheral SBP increased by 0.08 (95% confidence interval 0.00–0.17, P = 0.06) mmHg with every 1-mmHg increase in maternal central SBP, and offspring peripheral PP increased by 0.10 (0.01–0.18, P = 0.03) mmHg for every 1-mmHg increase in maternal central PP. The relations of maternal-offspring peripheral blood pressures (SBP, DBP, and PP) were positive but not statistically significant, and the corresponding values were 0.05 (−0.03 to 0.13; P = 0.21), 0.03 (−0.04 to 0.10; P = 0.35), and 0.05 (−0.02 to 0.13; P = 0.14), respectively. Maternal central pulsatile blood pressure components (SBP and PP) during pregnancy are associated with higher blood pressures in the offspring. This positive correlation is already evident at 3-years old. Studies are needed to further evaluate the effects of maternal central pulsatile blood pressure components during pregnancy and long-term cardiovascular health in the offspring. PMID:26559279

Prenatal stress accelerates offspring growth to compensate for reduced maternal investment across mammals

PubMed Central

Berghänel, Andreas; Heistermann, Michael; Schülke, Oliver; Ostner, Julia

2017-01-01

Across mammals, prenatal maternal stress (PREMS) affects many aspects of offspring development, including offspring growth. However, how PREMS translates to offspring growth is inconsistent, even within species. To explain the full range of reported effects of prenatal adversity on offspring growth, we propose an integrative hypothesis: developmental constraints and a counteracting adaptive growth plasticity work in opposition to drive PREMS effects on growth. Mothers experiencing adversity reduce maternal investment leading to stunted growth (developmental constraints). Concomitantly, the pace of offspring life history is recalibrated to partly compensate for these developmental constraints (adaptive growth plasticity). Moreover, the relative importance of each process changes across ontogeny with increasing offspring independence. Thus, offspring exposed to PREMS may grow at the same rate as controls during gestation and lactation, but faster after weaning when direct maternal investment has ceased. We tested these predictions with a comparative analysis on the outcomes of 719 studies across 21 mammal species. First, the observed growth changes in response to PREMS varied across offspring developmental periods as predicted. We argue that the observed growth acceleration after weaning is not “catch-up growth,” because offspring that were small for age grew slower. Second, only PREMS exposure early during gestation produced adaptive growth plasticity. Our results suggest that PREMS effects benefit the mother’s future reproduction and at the same time accelerate offspring growth and possibly maturation and reproductive rate. In this sense, PREMS effects on offspring growth allow mother and offspring to make the best of a bad start. PMID:29180423

Maternal BMI, parity, and pregnancy weight gain: influences on offspring adiposity in young adulthood.

PubMed

Reynolds, R M; Osmond, C; Phillips, D I W; Godfrey, K M

2010-12-01

The prevalence of obesity among women of childbearing age is increasing. Emerging evidence suggests that this has long-term adverse influences on offspring health. The aim was to examine whether maternal body composition and gestational weight gain have persisting effects on offspring adiposity in early adulthood. The Motherwell birth cohort study was conducted in a general community in Scotland, United Kingdom. We studied 276 men and women whose mothers' nutritional status had been characterized in pregnancy. Four-site skinfold thicknesses, waist circumference, and body mass index (BMI), were measured at age 30 yr; sex-adjusted percentage body fat and fat mass index were calculated. Indices of offspring adiposity at age 30 yr were measured. Percentage body fat was greater in offspring of mothers with a higher BMI at the first antenatal visit (rising by 0.35%/kg/m2; P<0.001) and in offspring whose mothers were primiparous (difference, 1.5% in primiparous vs. multiparous; P=0.03). Higher offspring percentage body fat was also independently associated with higher pregnancy weight gain (7.4%/kg/wk; P=0.002). There were similar significant associations of increased maternal BMI, greater pregnancy weight gain, and parity with greater offspring waist circumference, BMI, and fat mass index. Adiposity in early adulthood is influenced by prenatal influences independently of current lifestyle factors. Maternal adiposity, greater gestational weight, and parity all impact on offspring adiposity. Strategies to reduce the impact of maternal obesity and greater pregnancy weight gain on offspring future health are required.

Maternal high-fat diet and offspring expression levels of vitamin K-dependent proteins.

PubMed

Lanham, S A; Cagampang, F R; Oreffo, R O C

2014-12-01

Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

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...

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...

Longitudinal Pathways between Maternal Mental Health in Infancy and Offspring Romantic Relationships in Adulthood: A 30-Year Prospective Study

ERIC Educational Resources Information Center

Slominski, Lisa; Sameroff, Arnold; Rosenblum, Katherine; Kasser, Tim

2011-01-01

Longitudinal pathways between maternal mental health in infancy and offspring romantic relationship outcomes in adulthood were examined using a 30-year prospective longitudinal study of 196 mothers and their children. Structural equation modeling revealed that maternal mental health at 30 months was related to offspring relationship status and…

Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring.

PubMed

Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

2014-08-01

While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Paternal alcoholism and offspring conduct disorder: evidence for the 'common genes' hypothesis.

PubMed

Haber, Jon R; Jacob, Theodore; Heath, Andrew C

2005-04-01

Not only are alcoholism and externalizing disorders frequently comorbid, they often co-occur in families across generations; for example, paternal alcoholism predicts offspring conduct disorder just as it does offspring alcoholism. To clarify this relationship, the current study examined the 'common genes' hypothesis utilizing a children-of-twins research design. Participants were male monozygotic (MZ) and dizygotic (DZ) twins from the Vietnam Era Twin Registry who were concordant or discordant for alcohol dependence together with their offspring and the mothers of those offspring. All participants were conducted through a structured psychiatric interview. Offspring risk of conduct disorder was examined as a function of alcoholism genetic risk (due to paternal and co-twin alcohol dependence) and alcoholism environmental risk (due to being reared by a father with an alcohol dependence diagnosis). After controlling for potentially confounding variables, the offspring of alcohol-dependent fathers were significantly more likely to exhibit conduct disorder diagnoses than were offspring of nonalcohol-dependent fathers, thus indicating diagnostic crossover in generational family transmission. Comparing offspring at high genetic and high environmental risk with offspring at high genetic and low environmental risk indicated that genetic factors were most likely responsible for the alcoholism-conduct disorder association. The observed diagnostic crossover (from paternal alcoholism to offspring conduct disorder) across generations in the context of both high and low environmental risk (while genetic risk remained high) supported the common genes hypothesis.

Parental Smoking and Adult Offspring's Smoking Behaviors in Ethnic Minority Groups: An Intergenerational Analysis in the HELIUS Study.

PubMed

Ikram, Umar Z; Snijder, Marieke B; Derks, Eske M; Peters, Ron J G; Kunst, Anton E; Stronks, Karien

2018-05-03

To understand smoking behaviors among ethnic minority groups, studies have largely focused on societal factors, with little attention to family influences. Yet studies among majority groups have identified parental smoking as an important risk factor. It is unknown whether this applies to ethnic minority groups. We investigated the association between parental smoking and adult offspring's smoking behaviors among ethnic minority groups with an immigrant background. We used data from the Healthy Life in an Urban Setting study from Amsterdam (the Netherlands) from January 2011 to December 2015. The sample consisted of 2184 parent-offspring pairs from South-Asian Surinamese, African Surinamese, Turkish, Moroccan, and Ghanaian origin. We collected self-reported smoking data: current status, duration of exposure to parental smoking, number of daily cigarettes, heavy smoking ( > 10 cigarettes/day), and nicotine dependency (using the Fagerström Test). Analyses were stratified by offspring's age, cohabitation with parent, education (parent/offspring), offspring's cultural orientation, and gender concordance within pairs. Logistic regression was used. Overall, parental smoking was associated with offspring's smoking behaviors (eg, current smoking: odds ratio 2.33; 95% confidence interval 1.79-3.03), with little ethnic variation. We found dose-response associations between exposure to parental smoking and offspring's smoking. The associations were similar across different strata but stronger in gender-concordant pairs (3.16; 2.12-4.51 vs. 1.73; 1.15-2.59 in gender-discordant pairs; p-value for interaction .017). Parental smoking is associated with offspring's smoking behaviors in ethnic minority groups across different strata but particularly in gender-concordant pairs. Similar to majority groups, family influences matter to smoking behaviors in ethnic minority groups. Our findings have deepened our understanding of smoking behaviors among ethnic minority groups. Future studies should simultaneously consider societal factors and parental influences, to comprehensively understand their impact on smoking among ethnic minority groups. Also, smoking patterns among family members should be addressed in individual counselling, irrespective of ethnicity.

MTHFR deficiency or reduced intake of folate or choline in pregnant mice results in impaired short-term memory and increased apoptosis in the hippocampus of wild-type offspring.

PubMed

Jadavji, N M; Deng, L; Malysheva, O; Caudill, M A; Rozen, R

2015-08-06

Genetic or nutritional disturbances in one-carbon metabolism, with associated hyperhomocysteinemia, can result in complex disorders including pregnancy complications and neuropsychiatric diseases. In earlier work, we showed that mice with a complete deficiency of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate and homocysteine metabolism, had cognitive impairment with disturbances in choline metabolism. Maternal demands for folate and choline are increased during pregnancy and deficiencies of these nutrients result in several negative outcomes including increased resorption and delayed development. The goal of this study was to investigate the behavioral and neurobiological impact of a maternal genetic deficiency in MTHFR or maternal nutritional deficiency of folate or choline during pregnancy on 3-week-old Mthfr(+/+) offspring. Mthfr(+/+) and Mthfr(+/-) females were placed on control diets (CD); and Mthfr(+/+) females were placed on folate-deficient diets (FD) or choline-deficient diets (ChDD) throughout pregnancy and lactation until their offspring were 3weeks of age. Short-term memory was assessed in offspring, and hippocampal tissue was evaluated for morphological changes, apoptosis, proliferation and choline metabolism. Maternal MTHFR deficiency resulted in short-term memory impairment in offspring. These dams had elevated levels of plasma homocysteine when compared with wild-type dams. There were no differences in plasma homocysteine in offspring. Increased apoptosis and proliferation was observed in the hippocampus of offspring from Mthfr(+/-) mothers. In the maternal FD and ChDD study, offspring also showed short-term memory impairment with increased apoptosis in the hippocampus; increased neurogenesis was observed in ChDD offspring. Choline acetyltransferase protein was increased in the offspring hippocampus of both dietary groups and betaine was decreased in the hippocampus of FD offspring. Our results reveal short-term memory deficits in the offspring of dams with MTHFR deficiency or dietary deficiencies of critical methyl donors. We suggest that deficiencies in maternal one-carbon metabolism during pregnancy can contribute to hippocampal dysfunction in offspring through apoptosis or altered choline metabolism. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A systematic review of the parenting and outcomes experienced by offspring of mothers with borderline personality pathology: Potential mechanisms and clinical implications.

PubMed

Eyden, Julie; Winsper, Catherine; Wolke, Dieter; Broome, Matthew R; MacCallum, Fiona

2016-07-01

There is growing interest in whether the parenting strategies and offspring outcomes of mothers with borderline personality disorder (BPD) differ from those of mothers without BPD. We searched PsychINFO, PubMed, EMBASE, Web of Science, Scopus and ASSIA databases for studies examining parenting skills and attitudes among mothers with BPD/BPD symptoms and/or offspring outcomes. PRISMA reporting guidelines were followed. Of 10,067 abstracts screened, 101 full-text articles were retrieved and 33 met pre-determined criteria for qualitative synthesis. Overall, studies suggest that mothers with BPD/BPD symptoms are more likely to engage in maladaptive interactions with their offspring characterised by insensitive, overprotective, and hostile parenting compared to mothers without BPD/BPD symptoms. Adverse offspring outcomes include BPD symptoms, internalising (including depression) and externalising problems, insecure attachment patterns, and emotional dysregulation. Findings suggest that vulnerability from mother to offspring may be partly transmitted via maladaptive parenting and maternal emotional dysfunction. Conclusions were limited by study heterogeneity in methodology and construct definitions, as well as a paucity of clinical comparison groups. Prospective studies of mothers with BPD and their offspring from pregnancy onwards may further elucidate mechanisms of transmission and identify resilience factors across development. Parenting behaviour awareness, improving attachment behaviours and emotional regulation strategies may be important intervention targets. Copyright © 2016 Elsevier Ltd. All rights reserved.

Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers.

PubMed

Leveque, Lucie; Hodgson, Samantha; Peyton, Stephen; Koyama, Motoko; MacDonald, Kelli P A; Khosrotehrani, Kiarash

2014-05-01

The origins of autoimmunity are not yet understood despite significant advances in immunology. The trafficking of maternal cells to the offspring represents the very first immunological event in foetal life and is reinforced during lactation. The persistence of maternal cells in offspring's tissues and circulation has been associated with several autoimmune disorders. However a direct causal effect has never been demonstrated. Maternal T cells specifically targeting foetal insulin producing cells have been shown to generate islet inflammation without directly participating in this process. Our objective was to evaluate if alloreactive maternal cells could directly trigger a graft-versus host like reaction or indirectly influence the development of the offspring's regulatory T cells favouring autoimmunity. We adopted a breeding strategy comparing genetically identical offspring from either strongly alloreactive transgenic mothers compared to immunodeficient mothers. We detected maternal alloreactive T cells in the offspring and early signs of inflammation in small intestine of 6 weeks old offspring. Interestingly, CD4(+) Foxp3(+) regulatory T cell frequency was diminished in mesenteric lymph nodes from eight months old offspring born of alloreactive mothers compared to offspring of immunodeficient mothers. Our study favours a hypothesis where highly alloreactive maternal cell microchimerism indirectly predisposes offspring to autoimmunity. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Brain Structural and Vascular Anatomy Is Altered in Offspring of Pre-Eclamptic Pregnancies: A Pilot Study.

PubMed

Rätsep, M T; Paolozza, A; Hickman, A F; Maser, B; Kay, V R; Mohammad, S; Pudwell, J; Smith, G N; Brien, D; Stroman, P W; Adams, M A; Reynolds, J N; Croy, B A; Forkert, N D

2016-05-01

Pre-eclampsia is a serious clinical gestational disorder occurring in 3%-5% of all human pregnancies and characterized by endothelial dysfunction and vascular complications. Offspring born of pre-eclamptic pregnancies are reported to exhibit deficits in cognitive function, higher incidence of depression, and increased susceptibility to stroke. However, no brain imaging reports exist on these offspring. We aimed to assess brain structural and vascular anatomy in 7- to 10-year-old offspring of pre-eclamptic pregnancies compared with matched controls. Offspring of pre-eclamptic pregnancies and matched controls (n = 10 per group) were recruited from an established longitudinal cohort examining the effects of pre-eclampsia. Children underwent MR imaging to identify brain structural and vascular anatomic differences. Maternal plasma samples collected at birth were assayed for angiogenic factors by enzyme-linked immunosorbent assay. Offspring of pre-eclamptic pregnancies exhibited enlarged brain regional volumes of the cerebellum, temporal lobe, brain stem, and right and left amygdalae. These offspring displayed reduced cerebral vessel radii in the occipital and parietal lobes. Enzyme-linked immunosorbent assay analysis revealed underexpression of the placental growth factor among the maternal plasma samples from women who experienced pre-eclampsia. This study is the first to report brain structural and vascular anatomic alterations in the population of offspring of pre-eclamptic pregnancies. Brain structural alterations shared similarities with those seen in autism. Vascular alterations may have preceded these structural alterations. This pilot study requires further validation with a larger population to provide stronger estimates of brain structural and vascular outcomes among the offspring of pre-eclamptic pregnancies. © 2016 by American Journal of Neuroradiology.

Effect of Gestational Weight Gain and Prepregnancy Body Mass Index in Adolescent Mothers on Weight and Body Mass Index of Adolescent Offspring.

PubMed

Groth, Susan W; Holland, Margaret L; Smith, Joyce A; Meng, Ying; Kitzman, Harriet

2017-11-01

The purpose of the study was to examine the association of the gestational weight gain and prepregnancy body mass index (BMI) of low-income adolescent mothers with the risk of their children being overweight and/or obese in late adolescence. Study subjects were low-income, primiparous adolescents (n = 360) who self-identified as black and participated in the New Mothers Study in Memphis, Tennessee, and their children. Gestational weight gain was examined as a continuous variable and also categorized into overgain, recommended gain, and undergain following the 2009 Institute of Medicine guidelines. The effects of maternal prepregnancy BMI percentiles and calculated BMI were also considered. Multivariable logistic and linear regression models were used. The main outcome measures were offspring overweight, obesity, and BMI. Thirty-nine percent of offspring were overweight or obese. Higher maternal gestational weight gain increased the risk for offspring overweight and obesity. There was an interaction between gestational weight gain and prepregnancy BMI: offspring of mothers with a BMI percentile ≤76 were at greater risk of obesity with higher maternal weight gain. If mothers with a BMI percentile between the 29th and 83rd percentiles overgained, offspring were at greater risk for overweight. Using calculated BMIs, if a mother's BMI was ≤26 kg/m 2 , offspring risk for obesity was greater with higher gestational weight gain. High gestational weight gain had a larger effect on offspring overweight and obesity if maternal prepregnancy BMI percentile was ≤76. The gestational weight gain of primiparous adolescents who self-identified as black had an effect on offspring weight. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

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.

Maternal Postnatal Depression and the Development of Depression in Offspring up to 16 Years of Age

ERIC Educational Resources Information Center

Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Goodyer, Ian; Cooper, Peter

2011-01-01

Objective: The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers. Method: This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702…

A Genetically Informed Study of the Processes Underlying the Association between Parental Marital Instability and Offspring Adjustment

ERIC Educational Resources Information Center

D'Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Slutske, Wendy S.; Heath, Andrew C.; Madden, Pamela A.; Martin, Nicholas G.

2006-01-01

Parental divorce is associated with problematic offspring adjustment, but the relation may be due to shared genetic or environmental factors. One way to test for these confounds is to study offspring of twins discordant for divorce. The current analyses used this design to separate the mechanisms responsible for the association between parental…

Transgenerational effects of caloric restriction on appetite: a meta-analysis.

PubMed

Lagisz, M; Blair, H; Kenyon, P; Uller, T; Raubenheimer, D; Nakagawa, S

2014-04-01

Maternal undernutrition can result in significant alterations to the post-natal offspring phenotype, including body size and behaviour. For example, maternal food restriction has been implicated in offspring hyperphagia, potentially causing increased weight gain and fat accumulation. This could result in obesity and other adverse long-term health effects in offspring. We investigated the link between maternal caloric restriction during gestation and offspring appetite by conducting the first meta-analysis on this topic using experimental data from mammalian laboratory models (i.e. rats and mice). We collected 89 effect sizes from 35 studies, together with relevant moderators. Our analysis revealed weak and statistically non-significant overall effect on offspring's appetite. However, we found that lower protein content of restricted diets is associated with higher food intake in female offspring. Importantly, we show that a main source of variation among studies arises from whether, and how, food intake was adjusted for body mass. This probably explains many of the contradictory results in the field. Based on our results, we recommend using allometric scaling of food intake to body mass in future studies. © 2014 The Authors. obesity reviews © 2014 International Association for the Study of Obesity.

Clinical study report on milk production in the offspring of a somatic cell cloned Holstein cow.

PubMed

Takahashi, Masahiro; Tsuchiya, Hideki; Hamano, Seizo; Inaba, Toshio; Kawate, Noritoshi; Tamada, Hiromichi

2013-12-17

This study examined two female offspring of a somatic cell cloned Holstein cow that had reproduction problems and milk production performance issues. The two offspring heifers, which showed healthy appearances and normal reproductive characteristics, calved on two separate occasions. The mean milk yields of the heifers in the first lactation period were 9,037 kg and 7,228 kg. The relative mean milk yields of these cows were 111.2% and 88.9%, respectively, when compared with that of the control group. No particular clinical abnormalities were revealed in milk yields and milk composition rate [e.g., fat, protein and solids-not-fat (SNF)], and reproductive characteristics of the offspring of the somatic cell cloned Holstein cow suggested that the cloned offspring had normal milk production.

Maternal inflammatory bowel disease has short and long-term effects on the health of their offspring: a multicenter study in Israel.

PubMed

Dotan, Iris; Alper, Arik; Rachmilewitz, Daniel; Israeli, Eran; Odes, Shmuel; Chermesh, Irit; Naftali, Timna; Fraser, Gerald; Shitrit, Ariella Bar-Gil; Peles, Vardit; Reif, Shimon

2013-08-01

There are concerns about the effect of inflammatory bowel diseases (IBD) on fertility, pregnancy and pregnancy outcomes, but no long-term data on the health of offspring born to IBD mothers. The aims were to assess the short- and long-term effects of maternal IBD on the morbidity and development of their offspring. Female IBD patients and controls completed questionnaires on their pregnancy outcome, and their offspring's short- and long-term health and development. IBD and control mothers (159 and 175, respectively) were recruited. Medical data of 412 IBD and 417 control offspring were recorded. IBD mothers had significantly more singleton pregnancies, their offspring's birth weight was significantly lower, and they breastfed significantly less compared to controls (P=0.028, 0.007, and <0.0001, respectively). There were significantly more congenital anomalies (mainly limb deformities) among the IBD offspring (P<0.035). Offspring born post-maternal IBD diagnosis, compared to pre-diagnosis, tended to have more neurodevelopmental problems (e.g., gross motor delay, P=0.03). IBD was significantly more prevalent in the offspring of IBD mothers, while allergies and atopic dermatitis were more frequent in offspring of control mothers. More offspring of IBD mothers taking medications during pregnancy were born preterm and had lower birth weights compared to offspring of IBD mothers not taking medications during pregnancy. Children of mothers taking steroids had the lowest birth weights, compared to those of IBD mothers taking 5ASAs or immunomodulators. Maternal IBD affects pregnancy and the offspring's immediate and long-term morbidity, specifically, congenital anomalies and neurodevelopmental problems. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

A Maternal Low-Fiber Diet Predisposes Offspring to Improved Metabolic Phenotypes in Adulthood in an Herbivorous Rodent.

PubMed

Zhang, Xue-Ying; Lou, Mei-Fang; Shen, Wei; Fu, Rong-Shu; Wang, De-Hua

The maternal or paternal dietary composition can have important effects on various aspects of their offspring's physiology. Studies from animal models and humans showed that a maternal high-fiber diet protected offspring against fat accumulation. However, little is known about how a maternal low-fiber diet modifies the metabolism of offspring in herbivorous rodents. We hypothesized that a maternal low-fiber diet would confer long-lasting beneficial effects on offspring metabolic phenotypes in herbivorous Brandt's vole (Lasiopodomys brandtii). Female voles were fed either a control (12.4% fiber) or a low-fiber (3.5% fiber) diet throughout pregnancy and lactation, and all offspring were fed the control diet after weaning till 14 wk old. Offspring were sampled from each litter at 18 d and 14 wk of age. Another subset of adult offspring at 15 wk of age was fed a high-fat diet for 8 wk. We found that there was no difference in litter size, litter mass, or pup mass before weaning between the two maternal diet groups. Offspring from the maternal low-fiber diet increased energy intake, body mass, and lean mass; suppressed fat accumulation; and improved glucose tolerance compared with those from the control diet. Moreover, the maternal low-fiber diet alleviated high-fat diet-induced obesity in the adult offspring. Serum leptin concentration and uncoupling protein 1 content in brown adipose tissue of offspring were not affected by a maternal low-fiber diet. We demonstrate that herbivorous females fed a low-fiber diet during pregnancy and lactation may predispose their offspring to accelerated growth of lean tissue, which may increase the opportunity for survival and reproduction in offspring.

Administration of Non-Absorbable Antibiotics to Pregnant Mice to Perturb the Maternal Gut Microbiota Is Associated with Alterations in Offspring Behavior.

PubMed

Tochitani, Shiro; Ikeno, Takahiro; Ito, Tatsuhito; Sakurai, Asuka; Yamauchi, Tomoki; Matsuzaki, Hideo

2016-01-01

There is increasing evidence that the gut microbiota plays a major role in host health and disease. In this study, we examined whether perturbation of the maternal gut microbiota during pregnancy, induced by administration of non-absorbable antibiotics to pregnant dams, influences the behavior of offspring. Terminal restriction fragment length polymorphism analyses of fecal bacterial composition showed that the relative abundance of the bacterial order Lactobacillales was lower in offspring born from antibiotic-treated dams (20.7 ± 3.4%) than in control offspring (42.1 ± 6.2%) at P24, while the relative abundance of the bacterial family Clostridium subcluster XIVa was higher in offspring born from antibiotic-treated dams (34.2 ± 5.0%) than in control offspring (16.4 ± 3.3%). Offspring born from antibiotic-treated dams exhibited low locomotor activity in both familiar and novel environments, and preferred to explore in the peripheral area of an unfamiliar field at postnatal week 4. At postnatal weeks 7-8, no difference was observed in the level of locomotor activity between control offspring and offspring from antibiotic-treated dams, while the tendency for the offspring from antibiotic-treated dams to be less engaged in exploring the inside area was still observed. The behavioral phenotypes of the offspring from antibiotic-treated dams at postnatal week 4 could be rescued to a considerable extent through fostering of these offspring by normal dams from postnatal day 1. Although the detailed underlying mechanisms are not fully elucidated, the present results suggest that administration of non-absorbable antibiotics to pregnant dams to perturb the maternal gut microbiota during pregnancy leads to alterations in the behavior of their offspring.

Parental longevity and offspring's home blood pressure: the Ohasama study.

PubMed

Watanabe, Yumiko; Metoki, Hirohito; Ohkubo, Takayoshi; Hirose, Takuo; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Hara, Azusa; Obara, Taku; Hoshi, Haruhisa; Totsune, Kazuhito; Imai, Yutaka

2010-02-01

Longevity is clustered in particular families. Some studies using conventional blood pressure (BP) reported an association between parental longevity and offspring's BP. No study has used self-measurement of BP at home (home BP). We examined the association between parental longevity and home BP values of adult Japanese offspring. Home and conventional BPs were measured in 1961 residents aged 40 years and over in the general population of Ohasama, Japan. Information about the ages of offspring's parents (age at death or current age) was obtained from a standardized questionnaire. The mean +/- SD values of systolic/diastolic home BP in offspring whose mothers died at less than 69 years of age, at 69-84 years of age, and in offspring whose mothers were alive at age 84 years were 127.4 +/- 13.2/76.2 +/- 9.1, 124.8 +/- 15.0/74.4 +/- 10.0, and 123.4 +/- 15.2/74.4 +/- 10.3 mmHg (P = 0.0002/0.009), respectively. Corresponding values in offspring whose fathers died at less than 66 years of age, at 66-80 years of age, and in offspring whose fathers were alive at age 80 years were 125.7 +/- 15.2/75.6 +/- 10.6, 124.7 +/- 14.1/75.0 +/- 9.2 and 122.4 +/- 14.6/73.6 +/- 9.5 mmHg (P = 0.001/0.003), respectively. Multivariate analysis demonstrated associations that were only weakly observed for conventional BP values (conventional BP: P = 0.3/0.4 for maternal and P = 0.3/0.3 for paternal longevity; home BP: P = 0.05/0.2 for maternal and P = 0.0004/0.007 for paternal longevity). Parental premature death was significantly associated with higher home BP levels in adult offspring, suggesting that parental longevity might be a useful additional marker for screening adult offspring at higher risk of hypertension.

The association between parental history of diagnosed mood/anxiety disorders and psychiatric symptoms and disorders in young adult offspring

PubMed Central

2012-01-01

Background Parental history of mood or anxiety disorders is one of the strongest and most consistent risk factors for the development of these disorders in offspring. Gaps remain however in our knowledge of whether maternal or paternal disorders are more strongly associated with offspring disorders, and whether the association exists in non-clinical samples. This study uses a large population-based sample to test if maternal or paternal history of mood and/or anxiety disorders increases the risk of mood and/or anxiety disorders, or symptoms of specific anxiety disorders, in offspring. Methods Data were drawn from the Nicotine Dependence in Teens Study, a prospective cohort investigation of 1293 grade 7 students. Data on mental health outcomes were collected in mailed self-report questionnaires when participants were aged 20.4 (0.7) years on average. Parental data were collected in mailed self-report questionnaires. This current analysis pertains to 564 participants with maternal and/or paternal data. The association between maternal and paternal history and each of diagnosed anxiety disorder, diagnosed mood disorder, and symptoms of specific anxiety disorders in offspring was studied in multivariate logistic regression. Results A higher proportion of mothers than fathers had a diagnosed mood/anxiety disorder (23% versus 12%). Similarly, 14% of female offspring had a diagnosed mood/anxiety disorder, compared to 6% of male offspring. The adjusted odds ratio (95% confidence interval) for maternal history was 2.2 (1.1, 4.5) for diagnosed mood disorders, 4.0 (2.1, 7.8) for diagnosed anxiety disorders, and 2.2 (1.2, 4.0) for social phobia symptoms. Paternal history was not associated with any of the mental health outcomes in offspring. Conclusion Maternal, but not paternal mood/anxiety disorders were associated with diagnosed psychiatric disorders, as well as symptoms of specific anxiety disorders, in offspring. Efforts to detect mood and anxiety disorders in offspring with a maternal history should be encouraged. PMID:23126640

Aerobic exercise training performed by parents reduces mice offspring adiposity.

PubMed

Romero, Paulo Vitor da Silva; Guariglia, Débora Alves; Da Rocha, Francielli Ferreira; Picoli, Caroline de Carvalho; Gilio, Gustavo Renan; Fabricio, Gabriel Sergio; Mathias, Paulo Cesar de Freitas; Moraes, Solange Marta Franzói de; Peres, Sidney Barnabé

2018-07-01

The present study aimed to determine the effects of physical training performed by parents on mice offspring adiposity. Male and female parents underwent an aerobic training protocol for 7 weeks. The trained and sedentary parents were allowed to mate and the resultant offspring divided in: S (Offspring from Sedentary Parents), T (Offspring from Trained Parents), ST (Offspring from Sedentary Father and Trained Mother) and TS (Offspring from Trained Father and Sedentary Mother). After weaning, offspring was euthanized, blood collected and samples of mesenteric and inguinal fat pads used to isolate adipocytes for morphologic and histological analyses. Lee index, mesenteric fat pad, sum of visceral fat and total fat weight of female T was reduced in comparison to the other groups (p < 0.05). Periepididymal and sum of visceral fat in male T group was also reduced when compared to the other groups (p < 0.05). The diameter of mesenteric and inguinal adipocytes of T group was smaller compared to all groups comparisons for both sexes (p < 0.05). In summary, exercise training performed by parents reduced visceral offspring adiposity, the diameter of subcutaneous adipocytes and improved metabolic parameters associated to metabolic syndrome.

Developmental cigarette smoke exposure II: Hepatic proteome profiles in 6 month old adult offspring.

PubMed

Neal, Rachel E; Chen, Jing; Webb, Cindy; Stocke, Kendall; Gambrell, Caitlin; Greene, Robert M; Pisano, M Michele

2016-10-01

Utilizing a mouse model of 'active' developmental cigarette smoke exposure (CSE) [gestational day (GD) 1 through postnatal day (PD) 21] characterized by offspring low birth weight, the impact of developmental CSE on liver proteome profiles of adult offspring at 6 months of age was determined. Liver tissue was collected from Sham- and CSE-offspring for 2D-SDS-PAGE based proteome analysis with Partial Least Squares-Discriminant Analysis (PLS-DA). A similar study conducted at the cessation of exposure to cigarette smoke documented decreased gluconeogenesis coupled to oxidative stress in weanling offspring. In the current study, exposure throughout development to cigarette smoke resulted in impaired hepatic carbohydrate metabolism, decreased serum glucose levels, and increased gluconeogenic regulatory enzyme abundances during the fed-state coupled to decreased expression of SIRT1 as well as increased PEPCK and PGC1α expression. Together these findings indicate inappropriately timed gluconeogenesis that may reflect impaired insulin signaling in mature offspring exposed to 'active' developmental CSE. Copyright © 2016 Elsevier Inc. All rights reserved.

Motorboat noise impacts parental behaviour and offspring survival in a reef fish.

PubMed

Nedelec, Sophie L; Radford, Andrew N; Pearl, Leanne; Nedelec, Brendan; McCormick, Mark I; Meekan, Mark G; Simpson, Stephen D

2017-06-14

Anthropogenic noise is a pollutant of international concern, with mounting evidence of disturbance and impacts on animal behaviour and physiology. However, empirical studies measuring survival consequences are rare. We use a field experiment to investigate how repeated motorboat-noise playback affects parental behaviour and offspring survival in the spiny chromis ( Acanthochromis polyacanthus ), a brooding coral reef fish. Repeated observations were made for 12 days at 38 natural nests with broods of young. Exposure to motorboat-noise playback compared to ambient-sound playback increased defensive acts, and reduced both feeding and offspring interactions by brood-guarding males. Anthropogenic noise did not affect the growth of developing offspring, but reduced the likelihood of offspring survival; while offspring survived at all 19 nests exposed to ambient-sound playback, six of the 19 nests exposed to motorboat-noise playback suffered complete brood mortality. Our study, providing field-based experimental evidence of the consequences of anthropogenic noise, suggests potential fitness consequences of this global pollutant. © 2017 The Authors.

Giving offspring a head start in life: field and experimental evidence for selection on maternal basking behaviour in lizards.

PubMed

Wapstra, E; Uller, T; While, G M; Olsson, M; Shine, R

2010-03-01

The timing of birth is often correlated with offspring fitness in animals, but experimental studies that disentangle direct effects of parturition date and indirect effects mediated via variation in female traits are rare. In viviparous ectotherms, parturition date is largely driven by female thermal conditions, particularly maternal basking strategies. Our field and laboratory studies of a viviparous lizard (Niveoscincus ocellatus) show that earlier-born offspring are more likely to survive through their first winter and are larger following that winter, than are later-born conspecifics. Thus, the association between parturition date and offspring fitness is causal, rather than reflecting an underlying correlation between parturition date and maternal attributes. Survival selection on offspring confers a significant advantage for increased maternal basking in this species, mediated through fitness advantages of earlier parturition. We discuss the roles of environmentally imposed constraints and parent-offspring conflict in the evolution of maternal effects on parturition date.

Maternal handling during pregnancy reduces DMBA-induced mammary tumorigenesis among female offspring.

PubMed Central

Hilakivi-Clarke, L.

1997-01-01

The present study investigated whether handling of pregnant rats would affect mammary tumorigenesis in their female offspring. Pregnant Sprague-Dawley rats were injected daily with 0.05 ml of vehicle between days 14 and 20 of gestation or were left undisturbed. Handling did not have any effects on pregnancy or early development of the offspring. The female offspring were administered 10 mg of 7,12-dimethylbenz(a)anthracene (DMBA) at the age of 55 days. The rats whose mothers were handled during pregnancy had a significantly reduced mammary tumour incidence when compared with the offspring of non-handled mothers. Thus, on week 18 after DMBA exposure, 15% of the handled offspring had developed mammary tumours, whereas 44% of the non-handled offspring had tumours. No significant differences in the latency to tumour appearance, in the size of the tumours or in their growth rates were noted. Daily handling performed during post-natal days 5 and 20 produced similar data to that obtained for prenatal handling; on week 18 after DMBA exposure, the mammary tumour incidence among the post-natally handled rats was 22% and among the non-handled rats 44%. Possible deviations in hormonal parameters were also studied in adult female rats exposed in utero to handling. The onset of puberty tended to occur later among the handled offspring, but no differences in the uterine wet weights or serum oestradiol levels between the groups were noted. In conclusion, maternal handling reduced the offspring's risk to develop mammary tumours, and this effect was independent of the oestrogenic environment at adulthood. We propose that handling of a pregnant rat reduces mammary tumorigenesis in her offspring by means of changing the morphology of the mammary gland, the pattern of expression of specific genes and/or immune functions. PMID:9231913

Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring.

PubMed

Ramos, Débora R; Costa, Nauilo L; Jang, Karen L L; Oliveira, Ivone B; da Silva, Alexandre A; Heimann, Joel C; Furukawa, Luzia N S

2012-05-22

The goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin-angiotensin-aldosterone-system (RAAS) of the adult offspring. Female Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.16% NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study. TcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA, ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff. High maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring. Copyright © 2012 Elsevier Inc. All rights reserved.

Maternal depression in childhood and aggression in young adulthood: evidence for mediation by offspring amygdala-hippocampal volume ratio.

PubMed

Gilliam, Mary; Forbes, Erika E; Gianaros, Peter J; Erickson, Kirk I; Brennan, Lauretta M; Shaw, Daniel S

2015-10-01

There is abundant evidence that offspring of depressed mothers are at increased risk for persistent behavior problems related to emotion regulation, but the mechanisms by which offspring incur this risk are not entirely clear. Early adverse caregiving experiences have been associated with structural alterations in the amygdala and hippocampus, which parallel findings of cortical regions altered in adults with behavior problems related to emotion regulation. This study examined whether exposure to maternal depression during childhood might predict increased aggression and/or depression in early adulthood, and whether offspring amygdala:hippocampal volume ratio might mediate this relationship. Participants were 258 mothers and sons at socioeconomic risk for behavior problems. Sons' trajectories of exposure to maternal depression were generated from eight reports collected prospectively from offspring ages 18 months to 10 years. Offspring brain structure, aggression, and depression were assessed at age 20 (n = 170). Persistent, moderately high trajectories of maternal depression during childhood predicted increased aggression in adult offspring. In contrast, stable and very elevated trajectories of maternal depression during childhood predicted depression in adult offspring. Increased amygdala: hippocampal volume ratios at age 20 were significantly associated with concurrently increased aggression, but not depression, in adult offspring. Offspring amygdala: hippocampal volume ratio mediated the relationship found between trajectories of moderately elevated maternal depression during childhood and aggression in adult offspring. Alterations in the relative size of brain structures implicated in emotion regulation may be one mechanism by which offspring of depressed mothers incur increased risk for the development of aggression. © 2014 Association for Child and Adolescent Mental Health.

Explaining risk for suicidal ideation in adolescent offspring of mothers with depression.

PubMed

Hammerton, G; Zammit, S; Thapar, A; Collishaw, S

2016-01-01

It is well-established that offspring of depressed mothers are at increased risk for suicidal ideation. However, pathways involved in the transmission of risk for suicidal ideation from depressed mothers to offspring are poorly understood. The aim of this study was to examine the contribution of potential mediators of this association, including maternal suicide attempt, offspring psychiatric disorder and the parent-child relationship. Data were utilized from a population-based birth cohort (ALSPAC). Three distinct classes of maternal depression symptoms across the first 11 years of the child's life had already been identified (minimal, moderate, chronic-severe). Offspring suicidal ideation was assessed at age 16 years. Data were analysed using structural equation modelling. There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms compared to offspring of mothers with minimal symptoms (odds ratio 3.04, 95% confidence interval 2.19-4.21). The majority of this association was explained through maternal suicide attempt and offspring psychiatric disorder. There was also evidence for an independent indirect effect via the parent-child relationship in middle childhood. There was no longer evidence of a direct effect of maternal depression on offspring suicidal ideation after accounting for all three mediators. The pattern of results was similar when examining mechanisms for maternal moderate depression symptoms. Findings highlight that suicide prevention efforts in offspring of depressed mothers should be particularly targeted at both offspring with a psychiatric disorder and offspring whose mothers have made a suicide attempt. Interventions aimed at improving the parent-child relationship may also be beneficial.

Prenatal and early postnatal dietary sodium restriction sensitizes the adult rat to amphetamines.

PubMed

McBride, Shawna M; Culver, Bruce; Flynn, Francis W

2006-10-01

Acute sodium deficiency sensitizes adult rats to psychomotor effects of amphetamine. This study determined whether prenatal and early life manipulation of dietary sodium sensitized adult offspring to psychomotor effects of amphetamine (1 or 3 mg/kg ip) in two strains of rats. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) dams were fed chow containing low NaCl (0.12%; LN), normal NaCl (1%; NN), or high NaCl (4%; HN) throughout breeding, gestation, and lactation. Male offspring were maintained on the test diet for an additional 3 wk postweaning and then fed standard chow thereafter until testing began. Overall, blood pressure (BP), total fluid intake, salt preference, and adrenal gland weight were greater in SHR than in WKY. WKY LN offspring had greater water intake and adrenal gland weight than did WKY NN and HN offspring, whereas WKY HN offspring had increased BP, salt intake, and salt preference compared with other WKY offspring. SHR HN offspring also had increased BP compared with other SHR offspring; all other measures were similar for SHR offspring. The low-dose amphetamine increased locomotor and stereotypical behavior compared with baseline and saline injection in both WKY and SHR offspring. Dietary sodium history affected the rats' psychomotor response to the higher dose of amphetamine. Injections of 3 mg/kg amphetamine in both strains produced significantly more behavioral activity in the LN offspring than in NN and HN offspring. These results show that early life experience with low-sodium diets produce long-term changes in adult rats' behavioral responses to amphetamine.

Effects of maternal cortisol treatment on offspring size, responses to stress, and anxiety-related behavior in wild largemouth bass (Micropterus salmoides).

PubMed

Redfern, Julia C; Cooke, Steven J; Lennox, Robert J; Nannini, Michael A; Wahl, David H; Gilmour, Kathleen M

2017-10-15

Cortisol, the main glucocorticoid stress hormone in teleost fish, is of interest as a mediator of maternal stress on offspring characteristics because it plays an organizational role during early development. The present study tested the hypothesis that maternal exposure to cortisol treatment prior to spawn affects offspring phenotype using wild largemouth bass (Micropterus salmoides). Baseline and stress-induced cortisol concentrations, body size (i.e. length and mass), and behavior (i.e. anxiety, exploration, boldness, and aggression) were assessed at different offspring life-stages and compared between offspring of control and cortisol-treated females. Cortisol administration did not affect spawning success or timing, nor were whole-body cortisol concentrations different between embryos from cortisol-treated and control females. However, maternal cortisol treatment had significant effects on offspring stress responsiveness, mass, and behavior. Compared to offspring of control females, offspring of cortisol-treated females exhibited larger mass right after hatch, and young-of-the-year mounted an attenuated cortisol response to an acute stressor, and exhibited less thigmotaxic anxiety, exploratory behavior, boldness and aggression. Thus, offspring phenotype was affected by elevated maternal cortisol levels despite the absence of a significant increase in embryo cortisol concentrations, suggesting that a mechanism other than the direct deposition of cortisol into eggs mediates effects on offspring. The results of the present raise questions about the mechanisms through which maternal stress influences offspring behavior and physiology, as well as the impacts of such phenotypic changes on offspring fitness. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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.

Hair Mercury Concentrations in Western Hudson Bay Polar Bear Family Groups.

PubMed

Bechshoft, Thea; Derocher, Andrew E; Richardson, Evan; Lunn, Nicholas J; St Louis, Vincent L

2016-05-17

Methylmercury is one of the more toxic forms of mercury (Hg), the biomagnification of which is prevalent in the Arctic where apex predators such as polar bears (Ursus maritimus) can carry high loads. The maternal transfer of contaminants to offspring is a concern, as offspring may be particularly sensitive to the effects of environmental pollutants during early development. However, few studies of polar bears report on Hg in dependent young. We examined hair total Hg (THg) concentrations in 24 polar bear family groups in western Hudson Bay: mother, cub-of-the-year (COY), yearling, and 2 year old. THg concentrations increased with bear age, with COYs having lower concentrations than other offspring groups (p ≤ 0.008). Using AICc-based regression models, we found maternal THg to be positively related to body condition and litter size, while overall offspring THg was positively related to maternal body condition in addition to being dependent on the sex and age of the offspring. COY THg concentrations were positively related to maternal THg while also depending on the sex of the offspring. Considering our results, future studies in polar bear ecotoxicology are encouraged to include offspring of different ages and sexes.

Sexual conflict and consistency of offspring desertion in Eurasian penduline tit Remiz pendulinus.

PubMed

Pogány, Akos; Szentirmai, István; Komdeur, Jan; Székely, Tamás

2008-09-01

The trade-off between current and future parental investment is often different between males and females. This difference may lead to sexual conflict between parents over care provisioning in animals that breed with multiple mates. One of the most obvious manifestations of sexual conflict over care is offspring desertion whereby one parent deserts the young to increase its reproductive success at the expense of its mate. Offspring desertion is a wide-spread behavior, and its frequency often varies within populations. We studied the consistency of offspring desertion in a small passerine bird, the Eurasian penduline tit Remiz pendulinus, that has an extremely variable breeding system. Both males and females are sequentially polygamous, and a single parent (either the male or the female) incubates the eggs and rears the young. About 28-40% of offspring are abandoned by both parents, and these offspring perish. Here we investigate whether the variation in offspring desertion in a population emerges either by each individual behaving consistently between different broods, or it is driven by the environment. Using a three-year dataset from Southern Hungary we show that offspring desertion by females is consistent between nests. Male desertion, however, depends on ambient environment, because all males desert their nests early in the season and some of them care late in the season. Therefore, within-population variation in parental care emerges by sexually different mechanisms; between-individual variation was responsible for the observed pattern of offspring desertion in females, whereas within-individual variation was responsible for the observed pattern in males. To our knowledge, our study is the first that investigates repeatability of offspring desertion behavior in nature. The contrasting strategies of the sexes imply complex evolutionary trajectories in breeding behavior of penduline tits. Our results raise an intriguing question whether the sexual difference in caring/deserting decisions explain the extreme intensity of sexual conflict in penduline tits that produces a high frequency of biparentally deserted (and thus wasted) offspring.

Maternal lipopolysaccharide exposure results in glucose metabolism disorders and sex hormone imbalance in male offspring.

PubMed

Zhao, Mei; Yuan, Li; Yuan, Man-Man; Huang, Li-Li; Su, Chang; Chen, Yuan-Hua; Yang, Yu-Ying; Hu, Yan; Xu, De-Xiang

2018-04-01

An adverse intrauterine environment may be an important factor contributing to the development of type 2 diabetes in later life. The present study investigated the longitudinal effects of maternal lipopolysaccharide (LPS) exposure during the third trimester on glucose metabolism and sex hormone balance in the offspring. Pregnant mice were intraperitoneally injected with LPS (50 μg/kg) daily from gestational day (GD) 15 to GD17. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were assessed at postnatal day (PND) 60 and PND120. Sex hormones, their receptors, and metabolic enzymes (aromatase) were measured in male offspring at different phases of development (PND14: juvenile; PND35: adolescence; PND60: adulthood; and PND120: middle age). LPS-exposed male offspring exhibited glucose intolerance and insulin resistance by GTT and ITT at middle age, accompanied by an increase in fasting blood glucose and reductions in serum insulin levels and hepatic phosphorylated (p) -AKT/AKT ratio. However, glucose intolerance and insulin resistance were not observed in LPS-exposed female offspring. Maternal LPS exposure upregulated hepatic aromatase proteins and mRNA levels in male offspring at all time points. At adolescence, the testosterone/estradiol ratio (T/E2) was markedly reduced in LPS-exposed male offspring. Moreover, maternal LPS exposure significantly increased hepatic estrogen receptor (ER) α expressions and decreased hepatic androgen receptor (AR) expressions in male offspring. At adulthood, maternal LPS exposure increased serum estradiol levels, decreased serum testosterone levels and elevated hepatic ERβ expressions in male offspring. In conclusion, maternal LPS exposure upregulated aromatase expressions, followed by a reduction in the T/E2 ratio and an alteration in sex hormone receptor activity, which might be involved in the development of glucose metabolism disorders in middle-aged male offspring. This study provides a novel clue and direction to clarify the pathogenesis of maternal infection-related diabetes in male offspring. Copyright © 2018 Elsevier B.V. All rights reserved.

Sexual conflict and consistency of offspring desertion in Eurasian penduline tit Remiz pendulinus

PubMed Central

2008-01-01

Background The trade-off between current and future parental investment is often different between males and females. This difference may lead to sexual conflict between parents over care provisioning in animals that breed with multiple mates. One of the most obvious manifestations of sexual conflict over care is offspring desertion whereby one parent deserts the young to increase its reproductive success at the expense of its mate. Offspring desertion is a wide-spread behavior, and its frequency often varies within populations. We studied the consistency of offspring desertion in a small passerine bird, the Eurasian penduline tit Remiz pendulinus, that has an extremely variable breeding system. Both males and females are sequentially polygamous, and a single parent (either the male or the female) incubates the eggs and rears the young. About 28–40% of offspring are abandoned by both parents, and these offspring perish. Here we investigate whether the variation in offspring desertion in a population emerges either by each individual behaving consistently between different broods, or it is driven by the environment. Results Using a three-year dataset from Southern Hungary we show that offspring desertion by females is consistent between nests. Male desertion, however, depends on ambient environment, because all males desert their nests early in the season and some of them care late in the season. Therefore, within-population variation in parental care emerges by sexually different mechanisms; between-individual variation was responsible for the observed pattern of offspring desertion in females, whereas within-individual variation was responsible for the observed pattern in males. Conclusion To our knowledge, our study is the first that investigates repeatability of offspring desertion behavior in nature. The contrasting strategies of the sexes imply complex evolutionary trajectories in breeding behavior of penduline tits. Our results raise an intriguing question whether the sexual difference in caring/deserting decisions explain the extreme intensity of sexual conflict in penduline tits that produces a high frequency of biparentally deserted (and thus wasted) offspring. PMID:18761745

Helpers benefit offspring in both the short and long-term in the cooperatively breeding banded mongoose.

PubMed

Hodge, Sarah J

2005-12-07

Helpers in cooperative and communal breeding species are thought to accrue fitness benefits through improving the condition and survival of the offspring that they care for, yet few studies have shown conclusively that helpers benefit the offspring they rear. Using a novel approach to control for potentially confounding group-specific variables, I compare banded mongoose (Mungos mungo) offspring within the same litter that differ in the amount of time they spend with a helper, and hence the amount of care they receive. I show that pups that spend more time in close proximity to a helper are fed more, grow faster and have a higher probability of survival to independence than their littermates. Moreover, high growth rates during development reduce the age at which females breed for the first time, suggesting that helpers can improve the future fecundity of the offspring for which they care. These results provide strong evidence that it is the amount of investment per se that benefits offspring, rather than some correlate such as territory quality, and validate the assumption that helpers improve the reproductive success of breeders, and hence may gain fitness benefits from their actions. Furthermore, the finding that helpers may benefit offspring in the long-term suggests that current studies underestimate the fitness benefits that helpers gain from rearing the offspring of others.

Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors.

PubMed

Lehrner, Amy; Bierer, Linda M; Passarelli, Vincent; Pratchett, Laura C; Flory, Janine D; Bader, Heather N; Harris, Iris R; Bedi, Aarti; Daskalakis, Nikolaos P; Makotkine, Iouri; Yehuda, Rachel

2014-02-01

Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24-h urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-h urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation. Published by Elsevier Ltd.

Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors

PubMed Central

Lehrner, Amy; Bierer, Linda M.; Passarelli, Vincent; Pratchett, Laura C.; Flory, Janine D.; Bader, Heather; Harris, Iris R.; Bedi, Aarti; Daskalakis, Nikolaos P.; Makotkine, Iouri; Yehuda, Rachel

2014-01-01

Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24 hour urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-hr urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation. PMID:24485493

Coping strategies and self-esteem in the high-risk offspring of bipolar parents.

PubMed

Goodday, Sarah M; Bentall, Richard; Jones, Steven; Weir, Arielle; Duffy, Anne

2018-03-01

This study investigated whether there were differences in coping strategies and self-esteem between offspring of parents with bipolar disorder (high-risk) and offspring of unaffected parents (control), and whether these psychological factors predicted the onset and recurrence of mood episodes. High-risk and control offspring were followed longitudinally as part of the Flourish Canadian high-risk bipolar offspring cohort study. Offspring were clinically assessed annually by a psychiatrist using semi-structured interviews and completed a measure of coping strategies and self-esteem. In high-risk offspring, avoidant coping strategies significantly increased the hazard of a new onset Diagnostic and Statistical Manual of Mental Disorders, 4th Edition twice revised mood episode or recurrence (hazard ratio: 1.89, p = 0.04), while higher self-esteem significantly decreased this hazard (hazard ratio: 2.50, p < 0.01). Self-esteem and avoidant coping significantly interacted with one another ( p < 0.05), where the risk of a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition twice revised new onset mood episode or recurrence was only significantly increased among high-risk offspring with both high avoidant coping and low self-esteem. A reduction of avoidant coping strategies in response to stress and improvement of self-esteem may be useful intervention targets for preventing the new onset or recurrence of a clinically significant mood disorder among individuals at high familial risk.

Altered amygdala-prefrontal response to facial emotion in offspring of parents with bipolar disorder.

PubMed

Manelis, Anna; Ladouceur, Cecile D; Graur, Simona; Monk, Kelly; Bonar, Lisa K; Hickey, Mary Beth; Dwojak, Amanda C; Axelson, David; Goldstein, Benjamin I; Goldstein, Tina R; Bebko, Genna; Bertocci, Michele A; Hafeman, Danella M; Gill, Mary Kay; Birmaher, Boris; Phillips, Mary L

2015-09-01

This study aimed to identify neuroimaging measures associated with risk for, or protection against, bipolar disorder by comparing youth offspring of parents with bipolar disorder versus youth offspring of non-bipolar parents versus offspring of healthy parents in (i) the magnitude of activation within emotional face processing circuitry; and (ii) functional connectivity between this circuitry and frontal emotion regulation regions. The study was conducted at the University of Pittsburgh Medical Centre. Participants included 29 offspring of parents with bipolar disorder (mean age = 13.8 years; 14 females), 29 offspring of non-bipolar parents (mean age = 13.8 years; 12 females) and 23 healthy controls (mean age = 13.7 years; 11 females). Participants were scanned during implicit processing of emerging happy, sad, fearful and angry faces and shapes. The activation analyses revealed greater right amygdala activation to emotional faces versus shapes in offspring of parents with bipolar disorder and offspring of non-bipolar parents than healthy controls. Given that abnormally increased amygdala activation during emotion processing characterized offspring of both patient groups, and that abnormally increased amygdala activation has often been reported in individuals with already developed bipolar disorder and those with major depressive disorder, these neuroimaging findings may represent markers of increased risk for affective disorders in general. The analysis of psychophysiological interaction revealed that offspring of parents with bipolar disorder showed significantly more negative right amygdala-anterior cingulate cortex functional connectivity to emotional faces versus shapes, but significantly more positive right amygdala-left ventrolateral prefrontal cortex functional connectivity to happy faces (all P-values corrected for multiple tests) than offspring of non-bipolar parents and healthy controls. Taken together with findings of increased amygdala-ventrolateral prefrontal cortex functional connectivity, and decreased amygdala-anterior cingulate cortex functional connectivity previously shown in individuals with bipolar disorder, these connectivity patterns in offspring of parents with bipolar disorder may be risk markers for, rather than markers conferring protection against, bipolar disorder in youth. The patterns of activation and functional connectivity remained unchanged after removing medicated participants and those with current psychopathology from analyses. This is the first study to demonstrate that abnormal functional connectivity patterns within face emotion processing circuitry distinguish offspring of parents with bipolar disorder from those of non-bipolar parents and healthy controls. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The relationship between offspring size and fitness: integrating theory and empiricism.

PubMed

Rollinson, Njal; Hutchings, Jeffrey A

2013-02-01

How parents divide the energy available for reproduction between size and number of offspring has a profound effect on parental reproductive success. Theory indicates that the relationship between offspring size and offspring fitness is of fundamental importance to the evolution of parental reproductive strategies: this relationship predicts the optimal division of resources between size and number of offspring, it describes the fitness consequences for parents that deviate from optimality, and its shape can predict the most viable type of investment strategy in a given environment (e.g., conservative vs. diversified bet-hedging). Many previous attempts to estimate this relationship and the corresponding value of optimal offspring size have been frustrated by a lack of integration between theory and empiricism. In the present study, we draw from C. Smith and S. Fretwell's classic model to explain how a sound estimate of the offspring size--fitness relationship can be derived with empirical data. We evaluate what measures of fitness can be used to model the offspring size--fitness curve and optimal size, as well as which statistical models should and should not be used to estimate offspring size--fitness relationships. To construct the fitness curve, we recommend that offspring fitness be measured as survival up to the age at which the instantaneous rate of offspring mortality becomes random with respect to initial investment. Parental fitness is then expressed in ecologically meaningful, theoretically defensible, and broadly comparable units: the number of offspring surviving to independence. Although logistic and asymptotic regression have been widely used to estimate offspring size-fitness relationships, the former provides relatively unreliable estimates of optimal size when offspring survival and sample sizes are low, and the latter is unreliable under all conditions. We recommend that the Weibull-1 model be used to estimate this curve because it provides modest improvements in prediction accuracy under experimentally relevant conditions.

Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism

PubMed Central

Vega, Claudia C; Reyes-Castro, Luis A; Bautista, Claudia J; Larrea, Fernando; Nathanielsz, Peter W; Zambrano, Elena

2013-01-01

BACKGROUND Maternal obesity (MO) impairs maternal and offspring health. Mechanisms and interventions to prevent adverse maternal and offspring outcomes need to be determined. Human studies are confounded by socio-economic status providing the rationale for controlled animal data on effects of maternal exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO. HYPOTHESIS MO produces metabolic and endocrine dysfunction, increases maternal and offspring glucocorticoid exposure, oxidative stress and adverse offspring outcomes by postnatal day (PND) 36. MEx prevents these outcomes. METHODS F0 female rats ate either control or obesogenic diet from weaning through lactation. Half of each group wheel ran (from day ninety of life through pregnancy beginning day 120) providing four groups (n=8/group) – i) controls, ii) obese, iii) exercised controls and iv) exercised obese. After weaning, PND 21, F1 offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of lactation and F1 offspring at PND 36 were analyzed. RESULTS Exercise did not change maternal weight. Before breeding, MO elevated F0 glucose, insulin, triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely prevented the triglyceride rise and partially glucose, insulin, cholesterol and oxidative stress increases. MO decreased fertility, recovered by exercise. At the end of lactation, exercise returned all metabolic variables except leptin to control levels. Exercise partially prevented MO elevated corticosterone. F1 Offspring weights were similar at birth. At PND 36 MO increased F1 male but not female offspring leptin, triglycerides and fat mass. In controls exercise reduced male and female offspring glucose, prevented the offspring leptin increase and partially the triglyceride rise. CONCLUSIONS MEx before and during pregnancy has beneficial effects on maternal and offspring metabolism and endocrine function occurring with no weight change in mothers and offspring indicating the importance of body composition rather than weight in evaluations of metabolic status. PMID:23949616

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...

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.

Parenting behaviours associated with the development of adaptive and maladaptive offspring personality traits.

PubMed

Johnson, Jeffrey G; Liu, Lydia; Cohen, Patricia

2011-08-01

To investigate the associations of beneficial parenting behaviours with adaptive and maladaptive offspring personality traits that persist into adulthood among individuals in the community. Families (n = 669) participating in the Children in the Community Study were interviewed during the childhood, adolescence, emerging adulthood, and adulthood of the offspring at the mean ages of 6, 14, 16, 22, and 33 years. Twelve types of beneficial maternal and paternal child-rearing behaviour, reported by offspring at the mean age of 16 years, were associated with elevated offspring personality resiliency, at the mean ages of 22 and 33 years, and with low offspring personality disorder trait levels. These longitudinal associations remained significant when histories of childhood behaviour problems and parental psychiatric disorder were controlled statistically. Similar linear (that is, dose-dependent) associations were observed between the number of beneficial parenting behaviours during childhood and adaptive and maladaptive offspring traits at the mean ages of 22 and 33 years. Maternal and paternal behaviours were independently associated with both adaptive and maladaptive offspring traits. Beneficial maternal and paternal child-rearing behaviours may promote the development of adaptive offspring personality traits that endure into adulthood, and they may be prospectively associated with reduced levels of maladaptive offspring traits. These associations may not be attributable to childhood behaviour problems or parental psychiatric disorders, and they may be equally evident during early and middle adulthood.

High dietary fat intake during lactation promotes development of diet-induced obesity in male offspring of mice.

PubMed

Tsuduki, Tsuyoshi; Kitano, Yasuna; Honma, Taro; Kijima, Ryo; Ikeda, Ikuo

2013-01-01

The maternal nutritional status during pregnancy and lactation influences the risk of obesity in offspring, but the details of this phenomenon are unclear. In particular, there is little information on the influence on the offspring of the maternal nutritional status during lactation only. Therefore, in this study, we examined the influence of high dietary fat intake in dams during lactation on the risk of obesity in offspring, using C57BL/6J mice. The mice were fed a control diet (CD) during pregnancy. After birth, dams were fed a CD or a high-fat diet (HD) during lactation (3 wk). Fat and energy were significantly increased in milk from dams fed a HD during lactation. Male offspring were weaned at 3 wk old and fed a CD for 4 wk, which resulted in no significant difference in their physique. Four weeks after weaning, the offspring (7 wk old) were fed a CD or HD for 4 wk to induce obesity. High dietary fat intake in dams and offspring promoted lipid accumulation in white adipose tissue and adipocyte hypertrophy in male offspring. The underlying mechanism may involve an increase in expression of Lpl and a decrease in expression of Hsl in white adipose tissue of offspring. In conclusion, our results show that high dietary fat intake during lactation promotes development of diet-induced obesity in male offspring.

APOA2, dietary fat, and body mass index: replication of a gene-diet interaction in 3 independent populations.

PubMed

Corella, Dolores; Peloso, Gina; Arnett, Donna K; Demissie, Serkalem; Cupples, L Adrienne; Tucker, Katherine; Lai, Chao-Qiang; Parnell, Laurence D; Coltell, Oscar; Lee, Yu-Chi; Ordovas, Jose M

2009-11-09

Nutrigenetics studies the role of genetic variation on interactions between diet and health, aiming to provide more personalized dietary advice. However, replication has been low. Our aim was to study interaction among a functional APOA2 polymorphism, food intake, and body mass index (BMI) in independent populations to replicate findings and to increase their evidence level. Cross-sectional, follow-up (20 years), and case-control analyses were undertaken in 3 independent populations. We analyzed gene-diet interactions between the APOA2 -265T>C polymorphism and saturated fat intake on BMI and obesity in 3462 individuals from 3 populations in the United States: the Framingham Offspring Study (1454 whites), the Genetics of Lipid Lowering Drugs and Diet Network Study (1078 whites), and Boston-Puerto Rican Centers on Population Health and Health Disparities Study (930 Hispanics of Caribbean origin). Prevalence of the CC genotype in study participants ranged from 10.5% to 16.2%. We identified statistically significant interactions between the APOA2 -265T>C and saturated fat regarding BMI in all 3 populations. Thus, the magnitude of the difference in BMI between the individuals with the CC and TT+TC genotypes differed by saturated fat. A mean increase in BMI of 6.2% (range, 4.3%-7.9%; P = .01) was observed between genotypes with high- (> or =22 g/d) but not with low- saturated fat intake in all studies. Likewise, the CC genotype was significantly associated with higher obesity prevalence in all populations only in the high-saturated fat stratum. Meta-analysis estimations of obesity for individuals with the CC genotype compared with the TT+TC genotype were an odds ratio of 1.84 (95% confidence interval, 1.38-2.47; P < .001) in the high-saturated fat stratum, but no association was detected in the low-saturated fat stratum (odds ratio, 0.81; 95% confidence interval, 0.59-1.11; P = .18). For the first time to our knowledge, a gene-diet interaction influencing BMI and obesity has been strongly and consistently replicated in 3 independent populations.

Maternal exercise during pregnancy promotes physical activity in adult offspring

USDA-ARS?s Scientific Manuscript database

Previous rodent studies have shown that maternal voluntary exercise during pregnancy leads to metabolic changes in adult offspring. We set out to test whether maternal voluntary exercise during pregnancy also induces persistent changes in voluntary physical activity in the offspring. Adult C57BL/6J ...

Paternal Body Mass Index (BMI) Is Associated with Offspring Intrauterine Growth in a Gender Dependent Manner

PubMed Central

Chen, You-Peng; Xiao, Xiao-Min; Li, Jian; Reichetzeder, Christoph; Wang, Zi-Neng; Hocher, Berthold

2012-01-01

Background Environmental alternations leading to fetal programming of cardiovascular diseases in later life have been attributed to maternal factors. However, animal studies showed that paternal obesity may program cardio-metabolic diseases in the offspring. In the current study we tested the hypothesis that paternal BMI may be associated with fetal growth. Methods and Results We analyzed the relationship between paternal body mass index (BMI) and birth weight, ultrasound parameters describing the newborn's body shape as well as parameters describing the newborns endocrine system such as cortisol, aldosterone, renin activity and fetal glycated serum protein in a birth cohort of 899 father/mother/child triplets. Since fetal programming is an offspring sex specific process, male and female offspring were analyzed separately. Multivariable regression analyses considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal total glycated serum protein, parity and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding showed that paternal BMI is associated with growth of the male but not female offspring. Paternal BMI correlated with birth parameters of male offspring only: birth weight; biparietal diameter, head circumference; abdominal diameter, abdominal circumference; and pectoral diameter. Cortisol was likewise significantly correlated with paternal BMI in male newborns only. Conclusions Paternal BMI affects growth of the male but not female offspring. Paternal BMI may thus represent a risk factor for cardiovascular diseases of male offspring in later life. It remains to be demonstrated whether this is linked to an offspring sex specific paternal programming of cortisol secretion. PMID:22570703

Gestational weight gain and the risk of offspring obesity at 10 and 16 years: a prospective cohort study in low-income women.

PubMed

Diesel, J C; Eckhardt, C L; Day, N L; Brooks, M M; Arslanian, S A; Bodnar, L M

2015-09-01

To study the association between gestational weight gain (GWG) and offspring obesity risk at ages chosen to approximate prepuberty (10 years) and postpuberty (16 years). Prospective pregnancy cohort. Pittsburgh, PA, USA. Low-income pregnant women (n = 514) receiving prenatal care at an obstetric residency clinic and their singleton offspring. Gestational weight gain was classified based on maternal GWG-for-gestational-age Z-score charts and was modelled using flexible spline terms in modified multivariable Poisson regression models. Obesity at 10 or 16 years, defined as body mass index (BMI) Z-scores ≥95th centile of the 2000 CDC references, based on measured height and weight. The prevalence of offspring obesity was 20% at 10 years and 22% at 16 years. In the overall sample, the risk of offspring obesity at 10 and 16 years increased when GWG exceeded a GWG Z-score of 0 SD (equivalent to 30 kg at 40 weeks); but for gains below a Z-score of 0 SD there was no relationship with child obesity risk. The association between GWG and offspring obesity varied by prepregnancy BMI. Among mothers with a pregravid BMI <25 kg/m(2) , the risk of offspring obesity increased when GWG Z-score exceeded 0 SD, yet among overweight women (BMI ≥25 kg/m(2) ), there was no association between GWG Z-scores and offspring obesity risk. Among lean women, higher GWG may have lasting effects on offspring obesity risk. © 2015 Royal College of Obstetricians and Gynaecologists.

Facial emotion labeling in unaffected offspring of adults with bipolar I disorder.

PubMed

Sharma, Aditya Narain; Barron, Evelyn; Le Couteur, James; Close, Andrew; Rushton, Steven; Grunze, Heinz; Kelly, Thomas; Nicol Ferrier, Ian; Le Couteur, Ann Simone

2017-01-15

Young people 'at risk' for developing Bipolar Disorder have been shown to have deficits in facial emotion labeling across emotions with some studies reporting deficits for one or more particular emotions. However, these have included a heterogeneous group of young people (siblings of adolescents and offspring of adults with bipolar disorder), who have themselves diagnosed psychopathology (mood disorders and neurodevelopmental disorders including ADHD). 24 offspring of adults with bipolar I disorder and 34 offspring of healthy controls were administered the Diagnostic Analysis of Non Verbal Accuracy 2 (DANVA 2) to investigate the ability of participants to correctly label 4 emotions: happy, sad, fear and anger using both child and adult faces as stimuli at low and high intensity. Mixed effects modelling revealed that the offspring of adults with bipolar I disorder made more errors in both the overall recognition of facial emotions and the specific recognition of fear compared with the offspring of healthy controls. Further more errors were made by offspring that were male, younger in age and also in recognition of emotions using 'child' stimuli. The sample size, lack of blinding of the study team and the absence of any stimuli that assess subjects' response to a neutral emotional stimulus are limitations of the study. Offspring (with no history of current or past psychopathology or psychotropic medication) of adults with bipolar I disorder displayed facial emotion labeling deficits (particularly fear) suggesting facial emotion labeling may be an endophenotype for bipolar disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Family dissolution and offspring depression and depressive symptoms: A systematic review of moderation effects.

PubMed

Di Manno, Laura; Macdonald, Jacqui A; Knight, Tess

2015-12-01

Parental separation is associated with increased risk for offspring depression; however, depression outcomes are divergent. Knowledge of moderators could assist in understanding idiosyncratic outcomes and developing appropriately targeted prevention programs for those at heightened risk of depression following parental separation. Therefore, the objective of the review was to identify and evaluate studies that examined moderators of the relationship between parental separation and offspring depression A search of scientific, medical and psychological databases was conducted in April 2015 for longitudinal research that had evaluated any moderator/s of the relationship between parental separation or divorce and offspring depression or depressive symptoms. Papers were assessed for quality by evaluating the study's sample, attrition rates, methodology and measurement characteristics. Fourteen quantitative studies from five countries assessed sixteen moderating factors of the relationship between parental separation and offspring depression or depressive symptoms. A number of factors were found to moderate this relationship, including offspring gender, age (at assessment and at depression onset), genotype, preadolescent temperament, IQ, emotional problems in childhood and maternal sensitivity. While robust longitudinal research was selected for inclusion, common issues with longitudinal studies such as low rates of participation and attrition were among the methodological concerns evident in some of the reviewed papers. The current review is the first to assess interaction effects of the relationship between parental separation and offspring depression or depressive symptoms. While further research is recommended, this assessment is critical in understanding variation in heterogeneous populations and can inform targeted policy and prevention.

Maternal infection during late pregnancy increases anxiety- and depression-like behaviors with increasing age in male offspring.

PubMed

Enayati, Mohsen; Solati, Jalal; Hosseini, Mohammad-Hassan; Shahi, Hamid-Reza; Saki, Golshid; Salari, Ali-Akbar

2012-02-10

Scientific reports suggest that the exposure to long-term stressors throughout or during late gestation increase anxiety- and depression-like behaviors of offspring in their later life. Moreover, several studies concluded that increasing age correlates with increased anxiety behaviors in humans and rodents. In the present study, we assessed the effects of prenatally administration of equal lipopolysaccharide (LPS) doses in various points of late gestation (days 15, 16, and 17) period, on neuroendocrine and immunological responses of pregnant mice, and subsequent long-lasting consequences of anxiety and depression with increasing age in male offspring at postnatal days (PD) 40 and 80. Four hours after the LPS injection, levels of corticosterone (COR) and pro-inflammatory cytokines (PIC) in pregnant mice, as compared to the control dams, were increased significantly. Furthermore, maternal inflammation raised the levels of COR, anxiety- and depression-like behaviors with increasing age in male offspring in comparison with saline male offspring. These data support other studies demonstrating that maternal stress increases the levels of anxiety and depression in offspring. Additionally, our data confirm other findings indicating that increasing age correlates with increased anxiety or depression behaviors in humans and rodents. Findings of this study suggest that time course of an inflammation response or stressor application during various stages of gestation and ages of offspring are important factors for assessing neuropsychiatric disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

[Study of genome instability using DNA fingerprinting of the offspring of male mice subjected to chronic low dose gamma irradiation].

PubMed

Bezlepkin, V G; Vasil'eva, G V; Lomaeva, M G; Sirota, N P; Gaziev, A I

2000-01-01

By a polymerase chain reaction with an arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F1 generation) from male parents of mice exposed to chronic low-level gamma-radiation was studied. Male BALB/c mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old offspring mice and DNA was isolated. The primer in the AP-PCR was a 20-mer oligonucleotide flanking the microsatellite locus Atp1b2 on chromosome 11 of the mouse. A comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of microsatellite-associated sequences in the genome of the offspring of the males exposed to 25 and 50 cGy. The DNA-fingerprints of the offspring of male mice exposed to chronic irradiation with the doses 10 and 25 cGy 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of "non-parent bands". The results of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-level radiation prior to fertilization.

Circadian rhythm of autonomic activity in non diabetic offsprings of type 2 diabetic patients

PubMed Central

Fiorentini, A; Perciaccante, A; Paris, A; Serra, P; Tubani, L

2005-01-01

The aim of the present study was to evaluate, by heart rate variability (HRV) with 24-hours ECG Holter (HRV), the circadian autonomic activity in offspring of type 2 diabetic subjects and the relation with insulin-resistance. METHODS: 50 Caucasian offsprings of type 2 diabetic subjects were divided in two groups: insulin-resistant offsprings (IR) and non insulin-resistant offsprings (NIR). Autonomic nervous activity was studied by HRV. Time domain and spectral analysis (low frequency, LF, and high frequency, HF, provide markers of sympathetic and parasympathetic modulation when assessed in normalized units) were evaluated. RESULTS. Time domain showed a reduction of total SDNN in IR (p < 0.001) and NIR (p 0.047) versus controls. Spectral analysis showed a total and night LF higher in IR and NIR than in control group (all p < 0.001). CONCLUSION. In frequency domain, the analysis of sympathetic (LF) and parasympathetic (HF) component evidenced an association between the offspring of type 2 diabetic subjects and a sympathetic overactivity. A global reduction and alteration of circadian rhythm of autonomic activity are present in offspring of type 2 diabetic patients with and without insulin resistance. The data of our study suggested that an autonomic impairment is associated with the familiarity for type 2 diabetes independently to insulin resistance and that an impairment of autonomic system activity could precede the insulin resistance. PMID:16197556

Quantifying inbreeding avoidance through extra-pair reproduction.

PubMed

Reid, Jane M; Arcese, Peter; Keller, Lukas F; Germain, Ryan R; Duthie, A Bradley; Losdat, Sylvain; Wolak, Matthew E; Nietlisbach, Pirmin

2015-01-01

Extra-pair reproduction is widely hypothesized to allow females to avoid inbreeding with related socially paired males. Consequently, numerous field studies have tested the key predictions that extra-pair offspring are less inbred than females' alternative within-pair offspring, and that the probability of extra-pair reproduction increases with a female's relatedness to her socially paired male. However, such studies rarely measure inbreeding or relatedness sufficiently precisely to detect subtle effects, or consider biases stemming from failure to observe inbred offspring that die during early development. Analyses of multigenerational song sparrow (Melospiza melodia) pedigree data showed that most females had opportunity to increase or decrease the coefficient of inbreeding of their offspring through extra-pair reproduction with neighboring males. In practice, observed extra-pair offspring had lower inbreeding coefficients than females' within-pair offspring on average, while the probability of extra-pair reproduction increased substantially with the coefficient of kinship between a female and her socially paired male. However, simulations showed that such effects could simply reflect bias stemming from inbreeding depression in early offspring survival. The null hypothesis that extra-pair reproduction is random with respect to kinship therefore cannot be definitively rejected in song sparrows, and existing general evidence that females avoid inbreeding through extra-pair reproduction requires reevaluation given such biases. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children

PubMed Central

Sharp, Gemma C; Lawlor, Debbie A; Richmond, Rebecca C; Fraser, Abigail; Simpkin, Andrew; Suderman, Matthew; Shihab, Hashem A; Lyttleton, Oliver; McArdle, Wendy; Ring, Susan M; Gaunt, Tom R; Davey Smith, George; Relton, Caroline L

2015-01-01

Background: Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposity in later life. Epigenetic modification is suggested as a plausible mediating mechanism. Methods: We used multivariable linear regression and a negative control design to examine offspring epigenome-wide DNA methylation in relation to maternal and offspring adiposity in 1018 participants. Results: Compared with neonatal offspring of normal weight mothers, 28 and 1621 CpG sites were differentially methylated in offspring of obese and underweight mothers, respectively [false discovert rate (FDR)-corrected P-value < 0.05), with no overlap in the sites that maternal obesity and underweight relate to. A positive association, where higher methylation is associated with a body mass index (BMI) outside the normal range, was seen at 78.6% of the sites associated with obesity and 87.9% of the sites associated with underweight. Associations of maternal obesity with offspring methylation were stronger than associations of paternal obesity, supporting an intrauterine mechanism. There were no consistent associations of gestational weight gain with offspring DNA methylation. In general, sites that were hypermethylated in association with maternal obesity or hypomethylated in association with maternal underweight tended to be positively associated with offspring adiposity, and sites hypomethylated in association with maternal obesity or hypermethylated in association with maternal underweight tended to be inversely associated with offspring adiposity. Conclusions: Our data suggest that both maternal obesity and, to a larger degree, underweight affect the neonatal epigenome via an intrauterine mechanism, but weight gain during pregnancy has little effect. We found some evidence that associations of maternal underweight with lower offspring adiposity and maternal obesity with greater offspring adiposity may be mediated via increased DNA methylation. PMID:25855720

Maternal immunomodulation of the offspring's immunological system.

PubMed

Campos, Sylvia M N; de Oliveira, Vivian L; Lessa, Leonardo; Vita, Melissa; Conceição, Marcia; Andrade, Luiz Antonio Botelho; Teixeira, Gerlinde Agate Platais Brasil

2014-11-01

The mother's and the offspring's immunological system are closely related thus one can influence the other. This hypothesis drove our aim to study the impact of the mother's immunological status over the immunological response of their offspring. For this, female mice tolerant or allergic to peanuts were exposed or not to a challenge diet containing peanuts during the gestation-lactation period (TEP/AEP; TNEP/ANEP, respectively). After weaning the offspring was submitted to the peanut allergy or peanut tolerization protocol and then challenged with a peanut diet. Our results showed that when the offspring is submitted to the allergy induction protocol, they behave differently depending on their mother's immunological status. Offspring born to TEP mothers produced the lowest antibody titters while those born to AEP mothers produced the highest antibody titters compared to mice born to TNEP and ANEP. On the other hand when the offspring was submitted to the tolerization protocol all groups presented low antibody titers with no significant difference between groups, independent of the mothers immunological status and/or contact with peanuts during the gestation-lactation period. The analysis of the histological profile of the offspring correlates well to the serological response. In other words, offspring born to TEP mothers and submitted to the allergy induction protocol presented a normal histological profile, while the offspring born to AEP mothers produced the worst gut inflammation. These results indicate that mothers, exposed to the antigen (by the oral route) during gestation, actively influence the immune response of their offspring. This work sheds some light on the importance of the immunomodulation induced by dietary antigens during gestation and their influence on the immunological response of their offspring. However, more work is needed to elucidate the molecular and cellular components of this regulatory phenomenon. Copyright © 2014 Elsevier GmbH. All rights reserved.

Maternal smoking during pregnancy and the risk of pediatric cardiovascular diseases of the offspring: A population-based cohort study with up to 18-years of follow up.

PubMed

Leybovitz-Haleluya, Noa; Wainstock, Tamar; Landau, Daniella; Sheiner, Eyal

2018-06-01

Cigarette smoke is a well-known reproductive toxicant. We aimed to study the long-term effect of cigarette smoking during pregnancy on the risk for childhood cardiovascular morbidity of the offspring. A population-based cohort analysis was performed comparing total and subtypes of cardiovascular related pediatric hospitalizations among offspring of smoking mothers versus offspring of non-smoking mothers. The analysis included all singletons born between the years 1999-2014.A Kaplan-Meier survival curve was used to compare the cumulative cardiovascular morbidity, and a Cox proportional hazards model was constructed to adjust for confounders. The study population included 242,342 newborns which met inclusion criteria; among them 2861 were born to smoking mothers. Offspring of smoking mothers had higher rates of cardiovascular-related hospitalizations (1.3% vs. 0.6%, OR 2.1, 95% CI 1.5-2.9; p < 0.001; Kaplan-Meier log-rank test p < 0.001). Smoking exposure during pregnancy is associated with an increased risk for long-term pediatric cardiovascular morbidity of the offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

Is there a link between biological parents' insight into their offspring's schizophrenia and their cognitive functioning, expressed emotion and knowledge about disorder?

PubMed

Macgregor, Alexandra; Norton, Joanna; Raffard, Stéphane; Capdevielle, Delphine

2017-07-01

Recent studies suggest that parents' awareness of their offspring's schizophrenia could influence their offspring's insight. Low patient insight is linked to impairment of specific cognitive abilities, and biological parents of schizophrenia patients have impaired capacities in these same domains. However, little is known about what specific socio-demographic, affective or cognitive factors may influence biological parents' awareness of their offspring's disease. Data were drawn from 41 patient-parent dyads. Insight was assessed with a modified version of Amador's Scale to assess Unawareness of Mental Disorders, exploring dimensions of parents' awareness and attribution of their offspring's illness and symptoms. Higher educational levels, better working memory and executive functioning of parents were associated with better attribution of their offspring's symptoms to schizophrenia. Parents' insight into their offspring's schizophrenia is associated with cognitive abilities. This must be taken into account when developing family interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Does major depressive disorder in parents predict specific fears and phobias in offspring?

PubMed

Biel, Matthew G; Klein, Rachel G; Mannuzza, Salvatore; Roizen, Erica R; Truong, Nhan L; Roberson-Nay, Roxann; Pine, Daniel S

2008-01-01

Evidence suggests a relationship between parental depression and phobias in offspring as well as links between childhood fears and risk for major depression. This study examines the relationship between major depressive disorder (MDD) and anxiety disorders in parents and specific fears and phobias in offspring. Three hundred and eighteen children of parents with lifetime MDD, anxiety disorder, MDD+anxiety disorder, or neither were psychiatrically assessed via parent interview. Rates of specific phobias in offspring did not differ significantly across parental groups. Specific fears were significantly elevated in offspring of parents with MDD+anxiety disorder relative to the other groups (MDD, anxiety disorder, and controls, which did not differ). We failed to find increased phobias in offspring of parents with MDD without anxiety disorder. Elevated rates of specific fears in offspring of parents with MDD+anxiety disorder may be a function of more severe parental psychopathology, increased genetic loading, or unmeasured environmental influences. (c) 2007 Wiley-Liss, Inc.

Disturbed nitric oxide and homocysteine production are involved in the increased risk of cardiovascular diseases in the F1 offspring of maternal obesity and malnutrition.

PubMed

Moussa, Y Y; Tawfik, S H; Haiba, M M; Saad, M I; Hanafi, M Y; Abdelkhalek, T M; Oriquat, G A; Kamel, M A

2017-06-01

The present study aimed to evaluate the changes in levels of different independent risk factors for vascular diseases in the rat offspring of maternal obesity and malnutrition as maternal health disturbances are thought to have direct consequences on the offspring health. The effect of postnatal diet on the offspring was also assessed. Three groups of female Wistar rats were used (control, obese and malnourished). After the pregnancy and delivery, the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks postnatal, 20 pups (10 males and 10 females) of each subgroup were sacrificed after overnight fasting, the blood sample was obtained, and the rats were dissected out to obtain heart muscle. The following parameters were assessed; lipid profile, NEFA, homocysteine (Hcy), nitric oxide end product (NOx) and myocardial triglyceride content. Maternal obesity and malnutrition caused significant elevation in the body weight, triglycerides, NEFA, Hcy and NOx in the F1 offspring especially those maintained under HCD. Also, the male offspring showed more prominent changes than female offspring. Maternal malnutrition and obesity may increase the risk of the development of cardiovascular diseases in the offspring, especially the male ones.

Demographic analysis of arrhenotokous parthenogenesis and bisexual reproduction of Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae).

PubMed

Ding, Tianbo; Chi, Hsin; Gökçe, Ayhan; Gao, Yulin; Zhang, Bin

2018-02-20

Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) is a serious pest that is capable of bisexual and arrhenotokous reproduction. In arrhenotokous reproduction, virgin females initially produce male offspring; later, when their sons are sexually mature, the mothers begin bisexual reproduction by carrying out oedipal mating with their sons. Because a virgin female produces many male offspring before oedipal mating occurs, multiple oedipal mating is common. In this study, we investigated the effect of multiple oedipal mating on the population growth of F. occidentalis by using the age-stage, two-sex life table theory. In the arrhenotokous cohorts, all unfertilized eggs developed into males. In the bisexual cohorts, the offspring sex ratio was significantly female biased with the mean number of female offspring and male offspring being 72.68 and 29.00, respectively. These were the same as the net reproductive rate of female offspring and male offspring. In arrhenotokous cohorts, the number of males available for oedipal mating significantly affected the production of female offspring. The number of female offspring increased as the number of sons available for oedipal mating increased. Correctly characterizing this unique type of reproduction will provide important information for predicting the timing of future outbreaks of F. occidentalis, as well as aiding in formulating successful management strategies against the species.

Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring

PubMed Central

Sabet, Julia A.; Park, Lara K.; Iyer, Lakshmanan K.; Tai, Albert K.; Koh, Gar Yee; Pfalzer, Anna C.; Parnell, Laurence D.; Mason, Joel B.; Liu, Zhenhua; Byun, Alexander J.; Crott, Jimmy W.

2016-01-01

Background The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well. Objective In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content. Methods Male Apc1638N mice (prone to intestinal tumor formation) were fed diets containing replete (control, CTRL), mildly deficient (DEF), or supplemental (SUPP) quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden. Results No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring. Conclusions In this animal model, modulation of paternal B vitamin intake prior to mating alters offspring weight gain, lipid metabolism and tumor growth in a sex-specific fashion. These results highlight the need to better define how paternal nutrition affects the health of offspring. PMID:26968002

Female fecundity and offspring survival are not increased through sexual cannibalism in the spider Larinioides sclopetarius.

PubMed

Deventer, S A; Herberstein, M E; Mayntz, D; O'Hanlon, J C; Schneider, J M

2017-12-01

Many hypotheses explaining the evolution and maintenance of sexual cannibalism incorporate the nutritional aspect of the consumption of males. Most studies have focused on a fecundity advantage through consumption of a male; however, recent studies have raised the intriguing possibility that consumption of a male may also affect offspring quality. In particular, recent studies suggest prolonged survival for offspring from sexually cannibalistic females. Here, we measured the protein and lipid content of males compared to insect prey (crickets), quantified female nutrient intake of both prey types and finally assessed how sexual cannibalism affects female fecundity and spiderling quality in the orb-web spider Larinioides sclopetarius. We found no evidence that sexual cannibalism increased fecundity when compared to a female control group fed a cricket. Contrary to previous studies, spiderlings from females fed a male showed reduced survival under food deprivation compared to spiderlings from the control group. Offspring from females fed a male also tended to begin web construction sooner. The low lipid content of males compared to crickets may have reduced offspring survival duration. Whether additional proteins obtained through consumption of a male translate to enhanced silk production in offspring requires further investigation. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

MATERNAL EXPERIENCE OF ABUSE IN CHILDHOOD AND DEPRESSIVE SYMPTOMS IN ADOLESCENT AND ADULT OFFSPRING: A 21-YEAR LONGITUDINAL STUDY

PubMed Central

Roberts, Andrea L.; Chen, Ying; Slopen, Natalie; McLaughlin, Katie A.; Koenen, Karestan C.; Austin, Sydney Bryn

2015-01-01

Background Intergenerational effects of child abuse have been documented, but it is unknown whether maternal childhood abuse influences offspring mental health in adolescence or adulthood. Methods To examine whether maternal experience of childhood abuse is associated with depressive symptoms in adolescent and young adult offspring, we linked data from two large longitudinal cohorts of women (N = 8,882) and their offspring (N = 11,402), and we examined three possible pathways by which maternal experience of abuse might be associated with offspring depressive symptoms: maternal mental health, family characteristics, and offspring’s own experience of abuse. Results Offspring of women who experienced severe versus no childhood abuse had greater likelihood of high depressive symptoms (RR = 1.78, 95% CI = 1.47, 2.16) and persistent high depressive symptoms (RR = 2.47, 95% CI = 1.37, 4.44). Maternal mental health accounted for 20.9% and offspring’s exposure to abuse accounted for 30.3% of the elevated risk of high depressive symptoms. Disparities in offspring depressive symptoms by maternal abuse exposure were evident at age 12 years and persisted through age 31 years. Conclusions Findings provide evidence that childhood abuse adversely affects the mental health of the victim’s offspring well into adulthood. As offspring exposure to abuse and maternal mental health accounted for more than 50% of the elevated risk of high depressive symptoms among offspring of women who experienced abuse, improving maternal mental health and parenting practices may reduce offspring risk for depressive symptoms in these families. PMID:26220852

Parental Depression as a Moderator of Secondary Deficits of Depression in Adult Offspring

ERIC Educational Resources Information Center

Timko, Christine; Cronkite, Ruth C.; Swindle, Ralph; Robinson, Rebecca L.; Sutkowi, Anne; Moos, Rudolf H.

2009-01-01

This study examined whether having a depressed parent intensifies the secondary deficits that often co-occur with offspring's depression symptoms. The sample was adult offspring of parents who had been diagnosed with depression 23 years earlier (N = 143) and demographically matched nondepressed parents (N = 197). Respondents completed mailed…

Psychopathology in the Adolescent Offspring of Parents with Panic Disorder and Depression

ERIC Educational Resources Information Center

Bhat, Amritha S.; Srinivasan, K.

2006-01-01

Aim: To study the prevalence of psychiatric diagnosis and psychopathology in adolescent offspring of parents with panic disorder, depression and normal controls. Methods: Adolescent offspring (11-16 years) of parents with a diagnosis of panic disorder and major depression, and normal controls were interviewed using Missouri Assessment of Genetics…

Postpartum maternal fat distribution and its association with offspring body fat through the first year of life

USDA-ARS?s Scientific Manuscript database

Maternal obesity is known to increase the risk of offspring obesity. Despite the evidence supporting the impact of maternal obesity on infant health, there are no studies examining the effects of maternal fat distribution on the programming of offspring obesity. We hypothesized that increased matern...

The cumulative burden borne by offspring whose mothers were sexually abused as children: descriptive results from a multigenerational study.

PubMed

Noll, Jennie G; Trickett, Penelope K; Harris, William W; Putnam, Frank W

2009-03-01

This multigenerational study empirically demonstrates the extent to which offspring whose parents experienced childhood abuse are at increased risk of being abused or neglected. Females with substantiated childhood sexual abuse and non abused comparison females were assessed at six points spanning 18 years in a prospective, longitudinal study. Non abusing parents or caregivers and offspring were also assessed. Descriptive results indicate that offspring born to mothers with histories of sexual abuse were more likely to be born preterm, have a teenage mother, and be involved in protective services. Abused mothers were more likely to be high-school dropouts, be obese, and have experienced psychiatric problems, substance dependence, and domestic violence. Results provide evidence for the advantages of intervention and prevention programs for victims of childhood maltreatment and their families. Primary prevention/intervention efforts extending throughout development and focusing on the cumulative risk to offspring will likely improve victim outcomes and curtail intergenerational transmission of adversity.

Quantifying inbreeding avoidance through extra-pair reproduction

PubMed Central

Reid, Jane M; Arcese, Peter; Keller, Lukas F; Germain, Ryan R; Duthie, A Bradley; Losdat, Sylvain; Wolak, Matthew E; Nietlisbach, Pirmin

2015-01-01

Extra-pair reproduction is widely hypothesized to allow females to avoid inbreeding with related socially paired males. Consequently, numerous field studies have tested the key predictions that extra-pair offspring are less inbred than females’ alternative within-pair offspring, and that the probability of extra-pair reproduction increases with a female's relatedness to her socially paired male. However, such studies rarely measure inbreeding or relatedness sufficiently precisely to detect subtle effects, or consider biases stemming from failure to observe inbred offspring that die during early development. Analyses of multigenerational song sparrow (Melospiza melodia) pedigree data showed that most females had opportunity to increase or decrease the coefficient of inbreeding of their offspring through extra-pair reproduction with neighboring males. In practice, observed extra-pair offspring had lower inbreeding coefficients than females’ within-pair offspring on average, while the probability of extra-pair reproduction increased substantially with the coefficient of kinship between a female and her socially paired male. However, simulations showed that such effects could simply reflect bias stemming from inbreeding depression in early offspring survival. The null hypothesis that extra-pair reproduction is random with respect to kinship therefore cannot be definitively rejected in song sparrows, and existing general evidence that females avoid inbreeding through extra-pair reproduction requires reevaluation given such biases. PMID:25346331

Cortical thickness in symptomatic and asymptomatic bipolar offspring.

PubMed

Hanford, Lindsay C; Sassi, Roberto B; Minuzzi, Luciano; Hall, Geoffrey B

2016-05-30

Children of parents diagnosed with bipolar disorder are at greater risk for developing a variety of psychiatric disorders, however, the reasons remain unknown. The present study aimed to investigate gray matter integrity in high-risk bipolar offspring (HRO) and healthy offspring (HCO) using cortical thickness techniques. Here we examined healthy control offspring (HCO; n=20) and HRO with (n=17) or without (n=13) psychiatric symptoms. T1-weighted images were collected from all offspring, and cortical thickness and age-cortical thickness correlations were compared. HRO showed cortical thinning in superior and inferior temporal regions, supramarginal, and caudal and rostral middle frontal regions compared to HCO. When comparing HRO with and without psychiatric symptoms, we found cortical thinning in symptomatic offspring in the superior frontal and somatosensory related cortices. Age-thickness correlations showed a relatively consistent negative relationship in most regions in HCO, while the reverse was true for the HRO. These regions included parahippocampal, lateral orbitofrontal, and inferior temporal regions. Our study provides evidence of cortical thickness reductions among symptomatic and asymptomatic high-risk offspring during youth. Some of these alterations, found in regions of emotion processing and regulation, are evident only when associated with the presence of psychiatric symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Associations between postnatal maternal depression and psychological outcomes in adolescent offspring: a systematic review.

PubMed

Sanger, Camilla; Iles, Jane E; Andrew, Catharina S; Ramchandani, Paul G

2015-04-01

Postnatal depression (PND) affects approximately 10-20 % of new mothers in developed countries, with accumulating research documenting its adverse impact on not only the mother but also the wider family. Longitudinal studies assessing potential effects of maternal PND on offspring are mounting, and it is therefore timely to investigate the long-term psychological outcomes for adolescent offspring who were exposed to PND in infancy. PsycINFO, Medline, and Embase databases were searched with key terms for English language abstracts. Papers of 16 were identified that examined associations between PND and internalising problems, externalising problems, psychopathology, psychosocial, and cognitive outcomes of adolescent offspring. Impaired offspring cognitive outcomes reflected some of the most consistent findings. Conflicting evidence was found for an effect of PND on adolescent offspring internalising and externalising problems and overall psychopathology. Psychosocial outcomes in offspring adolescents indicated a specific adverse effect, although based on only two studies. Significant gender differences across outcomes were found. It was concluded that PND possibly increases risk vulnerability in the presence of recurrent, concurrent, and antenatal maternal depression but that these latter factors alone may be the stronger specific predictors. Limitations of the review are discussed as well as implications for future research and clinical practice.

Young Adults’ Provision of Support to Middle-Aged Parents

PubMed Central

Birditt, Kira S.; Zarit, Steven H.; Fingerman, Karen L.

2015-01-01

Objectives. Middle-aged adults often provide support to aging parents, but researchers know little about support that young adults provide middle-aged parents. This study examined support that young adults provide parents and explanations for that support from both offspring’s and parents’ perspectives. Method. Young adults (n = 515, mean age = 22.34) and their parents (n = 364, mean age = 50.09) from the Family Exchanges Study reported support that offspring provide parents. Participants also reported parental personal problems, parental disability status, relationship quality, and support that parents provide offspring. Results. Offspring provided parents with emotional support and listening more often than other forms of support. Offspring reported providing more frequent support than parents reported receiving. We examined factors associated with support using multilevel models. Both offspring and parents reported more frequent support provided to parents when they had higher quality relationships and when parents gave more frequent support to offspring. Offspring (but not parents) reported providing more frequent support to parents when parents were disabled. Discussion. Findings are consistent with solidarity theory, which suggests that high-quality relationships may explain support. The concept of self-enhancement and generativity in middle-aged parents may explain the intergenerational differences in the association between parental disability and support. PMID:24162441

Female offspring desertion and male-only care increase with natural and experimental increase in food abundance

PubMed Central

Eldegard, Katrine; Sonerud, Geir A.

2009-01-01

In species with biparental care, one parent may escape the costs of parental care by deserting and leaving the partner to care for the offspring alone. A number of theoretical papers have suggested a link between uniparental offspring desertion and ecological factors, but empirical evidence is scarce. We investigated the relationship between uniparental desertion and food abundance in a natural population of Tengmalm's owl Aegolius funereus, both by means of a 5-year observational study and a 1-year experimental study. Parents and offspring were fitted with radio-transmitters in order to reveal the parental care strategy (i.e. care or desert) of individual parents, and to keep track of the broods post-fledging. We found that 70 per cent of the females from non-experimental nests deserted, while their partner continued to care for their joint offspring alone. Desertion rate was positively related to natural prey population densities and body reserves of the male partner. In response to food supplementation, a larger proportion of the females deserted, and females deserted the offspring at an earlier age. Offspring survival during the post-fledging period tended to be lower in deserted than in non-deserted broods. We argue that the most important benefit of deserting may be remating (sequential polyandry). PMID:19324835

Female offspring desertion and male-only care increase with natural and experimental increase in food abundance.

PubMed

Eldegard, Katrine; Sonerud, Geir A

2009-05-07

In species with biparental care, one parent may escape the costs of parental care by deserting and leaving the partner to care for the offspring alone. A number of theoretical papers have suggested a link between uniparental offspring desertion and ecological factors, but empirical evidence is scarce. We investigated the relationship between uniparental desertion and food abundance in a natural population of Tengmalm's owl Aegolius funereus, both by means of a 5-year observational study and a 1-year experimental study. Parents and offspring were fitted with radio-transmitters in order to reveal the parental care strategy (i.e. care or desert) of individual parents, and to keep track of the broods post-fledging. We found that 70 per cent of the females from non-experimental nests deserted, while their partner continued to care for their joint offspring alone. Desertion rate was positively related to natural prey population densities and body reserves of the male partner. In response to food supplementation, a larger proportion of the females deserted, and females deserted the offspring at an earlier age. Offspring survival during the post-fledging period tended to be lower in deserted than in non-deserted broods. We argue that the most important benefit of deserting may be remating (sequential polyandry).