Lung and Blood Institute Framingham Heart Study

Framingham, MA, United States

Lung and Blood Institute Framingham Heart Study

Framingham, MA, United States
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Rosenquist K.J.,Harvard University | Rosenquist K.J.,Lung and Blood Institute Framingham Heart Study | Pedley A.,Lung and Blood Institute Framingham Heart Study | Massaro J.M.,Boston University | And 6 more authors.
JACC: Cardiovascular Imaging | Year: 2013

Objectives The aim of this study was to evaluate whether computed tomography (CT) attenuation, as a measure of fat quality, is associated with cardiometabolic risk factors above and beyond fat quantity. Background Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are pathogenic fat depots associated with cardiometabolic risk. Adipose tissue attenuation in CT images is variable, similar to adipose tissue volume. However, whether the quality of abdominal fat attenuation is associated with cardiometabolic risk independent of the quantity is uncertain. Methods Participants were drawn from the Framingham Heart Study CT substudy. The VAT and SAT volumes were acquired by semiquantitative assessment. Fat quality was measured by CT attenuation and recorded as mean Hounsfield unit (HU) within each fat depot. Sex-specific linear and logistic multivariable regression models were used to assess the association between standard deviation (SD) decrease in HU and each risk factor. Results Lower CT attenuation of VAT and SAT was correlated with higher body mass index levels in both sexes. Risk factors were generally more adverse with decreasing HU values. For example, in women, per 1 SD decrease in VAT HU, the odds ratio (OR) was increased for hypertension (OR: 1.80), impaired fasting glucose (OR: 2.10), metabolic syndrome (OR: 3.65), and insulin resistance (OR: 3.36; all p < 0.0001). In models that further adjusted for VAT volume, impaired fasting glucose, metabolic syndrome, and insulin resistance remained significant. Trends were similar but less pronounced for SAT and for men. There was evidence of an interaction between HU and fat volume among both women and men. Conclusions Lower CT attenuation of VAT and SAT is associated with adverse cardiometabolic risk above and beyond total adipose tissue volume. Qualitative indices of abdominal fat depots may provide insight regarding cardiometabolic risk independent of fat quantity. © 2013 by The American College of Cardiology Foundation.

PubMed | University of Maryland Baltimore County, McMaster University, Stanford University, Institute of Psychiatry and 53 more.
Type: Journal Article | Journal: American journal of human genetics | Year: 2014

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.

PubMed | Karolinska Institutet, Stanford University, University of Tromsø, University of Pennsylvania and 26 more.
Type: Journal Article | Journal: Journal of the American College of Cardiology | Year: 2016

Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation.The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population.We incorporated participant data from 16 prospective cohorts (n= 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n= 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure.Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p= 2.12 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p=5.95 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p= 0.994), which was statistically different from the observational estimate (p= 1.6 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD.Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD.Assuch, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.

Chun S.,University of Toronto | Tu J.V.,University of Toronto | Tu J.V.,Institute for Health Policy | Wijeysundera H.C.,University of Toronto | And 10 more authors.
Circulation: Heart Failure | Year: 2012

Background-Hospital readmissions for heart failure (HF) contribute to increased morbidity and resource burden. Predictors of hospitalization and patterns of cardiovascular events over the lifetime of patients with HF have not been elucidated. Methods and Results-We examined recurrent hospitalizations, cardiovascular events, and survival among newly discharged (April 1999-March 2001) patients with HF in the Enhanced Feedback For Effective Cardiac Treatment phase 1 study. During 10-year follow-up, we examined all new cardiovascular hospitalizations and selected predictors of readmission. Among 8543 patients (mean age, 77.4±10.5 years; 51.6% women) followed for 22 567 person-years, 60.7% had ischemic etiology, and 67.3% had HF with reduced ejection fraction (left ventricular ejection fraction 45% versus >45% [HF with preserved ejection fraction]). Overall, 10-year mortality was 98.8%, with 35 966 hospital readmissions occurring over the lifetime of the cohort. Adjusted hazards ratios (HRs) for first cardiovascular hospitalization were 1.36 for ischemic HF (95% CI, 1.28-1.44; P<0.001), 1.10 for HF with reduced ejection fraction (95% CI; 1.00-1.20; P=0.045), and 1.00 for men (95% CI, 0.94-1.06; P=0.979). On repeated-events time-to-event analysis, ischemic HF was a predictor of cardiovascular (HR, 1.24; 95% CI, 1.18-1.29), HF (HR, 1.20; 95% CI, 1.13-1.27), and coronary heart disease (HR, 2.01; 95% CI, 1.81-2.24) hospitalizations (all P<0.001). Of all recurrent HF hospitalizations, 26.8% occurred in the first and 39.8% in the last deciles of cohort survival duration. Similarly, 29.7% and 52.3% of all cardiovascular readmissions occurred in the first and last deciles of the cohort survival duration, respectively. Conclusions-Among newly discharged patients with HF, cardiovascular events were clustered at early postdischarge and prefatal time periods, and were increased among those with ischemic etiology. © 2012 American Heart Association, Inc.

Mann D.M.,Mount Sinai School of Medicine | Carson A.P.,University of Alabama at Birmingham | Shimbo D.,Columbia University | Fonseca V.,Tulane University | And 3 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - New clinical practice recommendations include A1C as an alternative to fasting glucose as a diagnostic test for identifying pre-diabetes. The impact of these new recommendations on the diagnosis of pre-diabetes is unknown. RESEARCH DESIGNANDMETHODS - Data from the National Health and Nutrition Examination Survey 1999-2006 (n = 7,029) were analyzed to determine the percentage and number of U.S. adults without diabetes classified as having pre-diabetes by the elevated A1C (5.7-6.4%) and by the impaired fasting glucose (IFG) (fasting glucose 100-125 mg/dl) criterion separately. Test characteristics (sensitivity, specificity, and positive and negative predictive values) using IFG as the reference standard were calculated. RESULTS - The prevalence of pre-diabetes among U.S. adults was 12.6% by the A1C criterion and 28.2% by the fasting glucose criterion. Only 7.7% of U.S. adults, reflecting 61 and 27% of those with pre-diabetes by A1C and fasting glucose, respectively, had pre-diabetes according to both definitions. A1C used alone would reclassify 37.6 million Americans with IFG to not having pre-diabetes and 8.9 million without IFG to having pre-diabetes (46.5 million reclassi-fied). Using IFG as the reference standard, pre-diabetes by the A1C criterion has 27% sensitivity, 93% specificity, 61% positive predictive value, and 77% negative predictive value. CONCLUSIONS - Using A1C as the pre-diabetes criterion would reclassify the prediabetes diagnosis of nearly 50 million Americans. It is imperative that clinicians and health systems understand the differences and similarities in using A1C or IFG in diagnosis of pre-diabetes. © 2010 by the American Diabetes Association.

Lee D.S.,University of Toronto | Gona P.,Lung and Blood Institute Framingham Heart Study | Gona P.,Boston University | Albano I.,University of Padua | And 8 more authors.
Circulation: Heart Failure | Year: 2011

Background-The high mortality rate in patients with heart failure (HF) is influenced by presence of multiple comorbidities. Data are limited on the relative contributions of cardiovascular versus noncardiovascular diseases to death in individuals with HF in the community. Methods and Results-We examined the incidence and predictors of cardiovascular versus noncardiovascular death in participants with HF in the Framingham Heart Study. Underlying, immediate, and contributing causes of death (3 key elements of the World Health Organization classification) were adjudicated by a 3-physician review panel. During 1971 to 2004, 1025 participants with HF died (499 men, mean [SD] age at death 79 [11] years), including 463 participants with left ventricular ejection fraction (LVEF) data. Cardiovascular disease was the cause of death in 66.1% overall. Stratified by LVEF, cardiovascular deaths occurred in 44.5% and 69.9% of those with preserved and reduced LVEF, respectively. Presence of reduced LVEF increased the risk of cardiovascular death, with odds ratios of 3.16 (95% confidence interval [CI], 1.73 to 5.78) in men and 2.39 (95% CI, 1.39 to 4.08) in women. Prior myocardial infarction was associated with increased cardiovascular death in women with HF (odds ratio, 1.87; 95% CI, 1.10 to 3.16) but not in men. The risk of cardiovascular disease death decreased in women (odds ratio after 1980, 0.41; 95% CI, 0.24 to 0.69) and men (odds ratio, 0.66; 95% CI, 0.41 to 1.07, P-0.095) with HF over time. Infections and kidney disease emerged as key immediate and contributing causes of death, respectively. © 2011 American Heart Association, Inc.

Van Himbergen T.M.,Tufts University | Van Himbergen T.M.,Lung and Blood Institute Framingham Heart Study | Beiser A.S.,Boston University | Ai M.,Tufts University | And 9 more authors.
Archives of Neurology | Year: 2012

Objective: To investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 levels) to the risk of developing Alzheimer disease (AD) and all-cause dementia. Design: Prospective cohort study. Setting: Dementia-free Framingham Heart Study participants had sera measured for these biomarkers at the 19th biennial examination (1985-1988) and were followed up prospectively for the development of AD and all-cause dementia. Participants: Eight hundred forty (541 women, median age of 76 years) subjects participated in the study. Main Outcome Measures: We used sex-pooled and sex-specific multivariable Cox proportional hazards models adjusted for age, education, body mass index, recent change in weight, APOE ε4 allele status, and plasma docosahexaenoic acid levels to determine association of these biomarkers with the development of all-cause dementia and AD. Results: Over a mean follow-up period of 13 years, 159 persons developed dementia (including 125 with AD). After adjustment for other risk factors, only adiponectin in women was associated with an increased risk of all-cause dementia (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.00-1.66; P=.054) and AD (HR, 1.33; 95% CI, 1.00-1.76; P=.050) per 1-SD increase in adiponectin level. Women with baseline adiponectin values more than the median had a higher risk of all-cause dementia (HR, 1.63; 95% CI, 1.03-2.56; P=.04) and AD (HR, 1.87; 95% CI, 1.13-3.10; P=.01) as compared with those with values less than the median. Conclusion: In women, increased plasma adiponectin levels are an independent risk factor for the development of both all-cause dementia and AD.

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