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Framingham Center, MA, United States

Lam C.S.,Lung and Blood Institute Framingham Heart Study
Circulation. Cardiovascular genetics | Year: 2010

Data regarding the familial aggregation of left ventricular (LV) geometry and its relations to parental heart failure (HF) are limited. We evaluated concordance of LV geometry within 1093 nuclear families in 5758 participants of the original (parents) (n=2351) and offspring (n=3407) cohorts of the Framingham Heart Study undergoing routine echocardiography in mid- to late adulthood. LV geometry was categorized based on cohort- and sex-specific 80th percentile cutoffs of LV mass and relative wall thickness (RWT) into normal (both <80th percentile), concentric remodeling (LV mass <80th percentile; RWT >80th percentile), concentric hypertrophy (both >80th percentile), and eccentric hypertrophy (LV mass >80th percentile; RWT <80th percentile). Within nuclear families, LV geometry was concordant among related pairs (parent-child, sibling-sibling) (P=0.0015) but not among unrelated spousal pairs (P=0.60), a finding that remained unchanged after adjusting for clinical covariates known to influence LV remodeling (age, systolic blood pressure, body mass index), excluding individuals with prevalent HF and myocardial infarction, and varying the thresholds for defining LV geometry. The prevalence of abnormal LV geometry was higher in family members of affected individuals, with recurrence risks of 1.4 for concentric remodeling (95% CI, 1.2 to 1.7) and eccentric hypertrophy (95% CI, 1.1 to 1.8) and 3.9 (95% CI, 3.2 to 4.6) for concentric hypertrophy. In a subset of 1497 offspring, we observed an association between parental HF (n=458) and eccentric hypertrophy in offspring (P<0.0001). Our investigation of a 2-generational community-based sample demonstrates familial aggregation of LV geometry, with the greatest recurrence risk for concentric LV geometry, and establishes an association between eccentric LV geometry and parental HF.


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.


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.


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.


Fox C.S.,Lung and Blood Institute Framingham Heart Study | Fox C.S.,Harvard University | Massaro J.M.,Lung and Blood Institute Framingham Heart Study | Schlett C.L.,Harvard University | And 8 more authors.
Circulation: Cardiovascular Imaging | Year: 2010

Background-Central obesity is associated with peripheral arterial disease, suggesting that ectopic fat depots may be associated with localized diseases of the aorta and lower-extremity arteries. We hypothesized that persons with greater amounts of periaortic fat are more likely to have clinical PAD and a low ankle-brachial index. Methods and Results-We quantified periaortic fat surrounding the thoracic aorta using a novel volumetric quantitative approach in 1205 participants from the Framingham Heart Study Offspring cohort (mean age, 65.9 years; women, 54%); visceral abdominal fat also was measured. Clinical peripheral arterial disease was defined as a history of intermittent claudication, and ankle-brachial index was dichotomized as low (≤0.9) or lower-extremity revascularization versus normal (>0.9 to <1.4). Regression models were created to examine the association between periaortic fat and intermittent claudication or low ankle-brachial index (n=66). In multivariable logistic regression, per 1 SD increase in periaortic fat, the odds ratio for the combined end point was 1.52 (P=0.004); these results were strengthened with additional adjustment for body mass index (odds ratio, 1.69; P=0.002) or visceral abdominal fat (odds ratio, 1.67; P=0.009), whereas no association was observed for visceral abdominal fat (P=0.16). Similarly, per SD increase in body mass index or waist circumference, no association was observed after accounting for visceral abdominal fat (body mass index, P=0.35; waist circumference, P=0.49). Conclusions-Periaortic fat is associated with low ABI and intermittent claudication. © 2010 American Heart Association, Inc.

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