NHLBIs Framingham Heart Study

Framingham, MA, United States

NHLBIs Framingham Heart Study

Framingham, MA, United States
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Romero J.R.,Boston University | Beiser A.,Boston University | Himali J.J.,NHLBIs Framingham Heart Study | Himali J.J.,Boston University | And 3 more authors.
Neurobiology of Aging | Year: 2017

Cerebral microbleeds (CMBs) are MRI markers attributed to the most common cerebral angiopathies in the elderly and in patients with dementia: hypertensive and cerebral amyloid angiopathy. CMB detection in asymptomatic persons may help identify those at risk for dementia and may influence preventive strategies and design of clinical trials testing treatments for dementia. We studied the association of CMB with risk of incident dementia in community dwelling individuals. A total of 1296 dementia-free Framingham Heart Study participants (mean age 72 years; 54% women) with available brain MRI and incident dementia data during a mean follow-up period of 6.7 years were included. Using Cox proportional hazards models, we related CMB presence to incident dementia. Multivariable models were adjusted for age, sex, APOE status, and education, with additional models adjusting for vascular risk factors and MRI markers of ischemic brain injury. CMBs were observed in 10.8% and incident dementia in 85 participants (6.6% over study period). Participants with any CMB had 1.74 times higher risk of dementia (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.00–3.01), whereas those with deep and mixed CMB had a three-fold increased risk (HR 2.99, 95% CI 1.52–5.90). The associations were independent of vascular risk factors, and for deep and mixed CMB also independent of MRI markers of ischemia (HR 2.44, 95% CI 1.22–4.88). Purely lobar CMBs were not associated with incident dementia. Our findings support a role for hypertensive vasculopathy and the interplay of hypertensive and cerebral amyloid angiopathy in risk of dementia and suggest that CMB presence can identify individuals at risk of dementia. © 2017 Elsevier Inc.


Murabito J.M.,Boston University | Beiser A.S.,NHLBIs Framingham Heart Study | Beiser A.S.,Boston University | Decarli C.,University of California at Davis | And 6 more authors.
Age and Ageing | Year: 2014

Background: offspring of long-lived individuals have lower risk for dementia. We examined the relation between parental longevity and cognition and subclinical markers of brain ageing in community-dwelling adult offspring. Methods: offspring participants with both parents in the Framingham Heart Study, aged >55 years and dementia-free underwent baseline and repeat neuropsychological (NP) testing and brain magnetic resonance imaging (MRI). Parental longevity was defined as having at least one parent survive to age >85 years. To test the association between parental longevity and measures of cognition and brain volumes, we used multivariable linear and logistic regression adjusting for age, sex, education and time to NP testing or brain MRI. Results: of 728 offspring (mean age 66 years, 54% women), 407 (56%) had >1 parent achieve longevity. In cross-sectional analysis, parental longevity was associated with better scores on attention (beta 0.21 ± 0.08, P = 0.006) and a lower odds of extensive white matter hyperintensity on brain MRI (odds ratio 0.59, 95% CI: 0.38, 0.92, P = 0.019). The association with white matter hyperintensity was no longer significant in models adjusted for cardiovascular risk factors and disease. In longitudinal analysis (6.7 ± 1.7 years later), offspring with parental longevity had slower decline in attention (0.18 ± 0.08, P = 0.038), executive function (beta 0.19 ± 0.09, P = 0.031) and visual memory (beta -0.18 ± 0.08, P = 0.023), and less increase in temporal horn volume (beta -0.25 ± 0.09, P = 0.005). The associations persisted in fully adjusted models. Conclusion: parental longevity is associated with better brain ageing in middle-aged offspring. © The Author 2013. Published by Oxford University Press on behalf of the British Geriatrics Society.


PubMed | Harvard University, University of Texas at Brownsville, NHLBIs Framingham Heart Study, Health Discovery and 21 more.
Type: Journal Article | Journal: Nature genetics | Year: 2016

Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 10


Yeon S.B.,Beth Israel Deaconess Medical Center | Yeon S.B.,Harvard University | Salton C.J.,Beth Israel Deaconess Medical Center | Gona P.,NHLBIs Framingham Heart Study | And 11 more authors.
Journal of Magnetic Resonance Imaging | Year: 2015

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 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. 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, 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). Conclusion 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. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.


PubMed | University of Minnesota, McGill University, Northwestern University, Harvard University and 7 more.
Type: | Journal: American heart journal | Year: 2016

Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait.We examined 2 dichotomous phenotypes of ideal CV health-clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical+behavioral (clinical plus: not a current smoker, body mass index <25 kg/m(2))-among white participants aged 505 years. We performed a meta-analysis of 4 genome-wide association studies (total n=11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P<2.0 10(-9)). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol.A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.


Chuang M.L.,NHLBIs Framingham Heart Study | Chuang M.L.,Beth Israel Deaconess Medical Center | Gona P.,NHLBIs Framingham Heart Study | Gona P.,University of Massachusetts Medical School | And 9 more authors.
Journal of Magnetic Resonance Imaging | Year: 2014

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. Materials 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 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. Conclusion 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. © 2013 Wiley Periodicals, Inc.


Chuang M.L.,NHLBIs Framingham Heart Study | Chuang M.L.,Beth Israel Deaconess Medical Center | Chuang M.L.,Harvard University | Gona P.,NHLBIs Framingham Heart Study | And 11 more authors.
JACC: Cardiovascular Imaging | Year: 2012

Objectives: 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). Background: 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. Methods: 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. Results: 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. Conclusions: 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. © 2012 American College of Cardiology Foundation.


Rice M.B.,Beth Israel Deaconess Medical Center | Ljungman P.L.,Beth Israel Deaconess Medical Center | Ljungman P.L.,Karolinska Institutet | Wilker E.H.,Beth Israel Deaconess Medical Center | And 10 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2015

Rationale: Few studies have examined associations between longterm exposure to fine particulate matter (PM2.5) and lung function decline in adults. Objectives: To determine if exposure to traffic and PM2.5 is associated with longitudinal changes in lung function in a population-based cohort in the Northeastern United States, where pollution levels are relatively low. Methods: FEV1 and FVC were measured up to two times between 1995 and 2011 among 6,339 participants of the Framingham Offspring or Third Generation studies. We tested associations between residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by a land-use model using satellite measurements of aerosol optical thickness) and lung function. We examined differences in average lung function using mixed-effects models and differences in lung function decline using linear regression models. Current smokers were excluded. Models were adjusted for age, sex, height, weight, pack-years, socioeconomic status indicators, cohort, time, season, and weather. Measurements and Main Results: Living less than 100 m from a major roadway was associated with a 23.2 ml (95% confidence interval [CI], -44.4 to -1.9) lower FEV1 and a 5.0 ml/yr (95% CI, -9.0 to -0.9) faster decline in FEV1 compared with more than 400 m. Each 2 μg/m3 increase in average of PM2.5 was associated with a 13.5 ml (95% CI, -26.6 to -0.3) lower FEV1 and a 2.1 ml/yr (95% CI, -4.1 to -0.2) faster decline in FEV1 There were similar associations with FVC. Associations with FEV1/FVC ratio were weak or absent. Conclusions: Long-term exposure to traffic and PM2.5, at relatively low levels, was associated with lower FEV1 and FVC and an accelerated rate of lung function decline. Copyright © 2015 by the American Thoracic Society.


Ma J.,Tufts University | Fox C.S.,NHLBIs Framingham Heart Study | Fox C.S.,Harvard University | Jacques P.F.,Tufts University | And 6 more authors.
Journal of Hepatology | Year: 2015

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. © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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