Background— Visceral adipose tissue (VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting. Methods and Results— Participants (n=3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005. Metabolic risk factors were examined in relation to increments of SAT and VAT after multivariable adjustment. Heritability was calculated using variance-components analysis. Among both women and men, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus, and metabolic syndrome ( P range <0.01). In women, relations between VAT and risk factors were consistently stronger than in men. However, VAT was more strongly correlated with most metabolic risk factors than was SAT. For example, among women and men, both SAT and VAT were associated with increased odds of metabolic syndrome. In women, the odds ratio (OR) of metabolic syndrome per 1–standard deviation increase in VAT (OR, 4.7) was stronger than that for SAT (OR, 3.0; P for difference between SAT and VAT <0.0001); similar differences were noted for men (OR for VAT, 4.2; OR for SAT, 2.5). Furthermore, VAT but not SAT contributed significantly to risk factor variation after adjustment for body mass index and waist circumference ( P ≤0.01). Among overweight and obese individuals, the prevalence of hypertension, impaired fasting glucose, and metabolic syndrome increased linearly and significantly across increasing VAT quartiles. Heritability values for SAT and VAT were 57% and 36%, respectively. Conclusions— Although both SAT and VAT are correlated with metabolic risk factors, VAT remains more strongly associated with an adverse metabolic risk profile even after accounting for standard anthropometric indexes. Our findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot. Measurement of VAT may provide a more complete understanding of metabolic risk associated with variation in fat distribution.

Heart failure is a major public health problem. Long-term trends in the incidence of heart failure and survival after its onset in the community have not been characterized. We used statistical models to assess temporal trends in the incidence of heart failure and Cox proportional-hazards regression to evaluate survival after the onset of heart failure among subjects in the Framingham Heart Study. Cases of heart failure were classified according to the date of onset: 1950 through 1969 (223 cases), 1970 through 1979 (222), 1980 through 1989 (307), and 1990 through 1999 (323). We also calculated 30-day, 1-year, and 5-year age-adjusted mortality rates for each period. Heart failure occurred in 1075 subjects (51 percent of whom were women). As compared with the rate for the period from 1950 through 1969, the incidence of heart failure remained virtually unchanged among men in the three subsequent periods but declined by 31 to 40 percent among women (rate ratio for the period from 1990 through 1999, 0.69; 95 percent confidence interval, 0.51 to 0.93). The 30-day, 1-year, and 5-year age-adjusted mortality rates among men declined from 12 percent, 30 percent, and 70 percent, respectively, in the period from 1950 through 1969 to 11 percent, 28 percent, and 59 percent, respectively, in the period from 1990 through 1999. The corresponding rates among women were 18 percent, 28 percent, and 57 percent for the period from 1950 through 1969 and 10 percent, 24 percent, and 45 percent for the period from 1990 through 1999. Overall, there was an improvement in the survival rate after the onset of heart failure of 12 percent per decade (P=0.01 for men and P=0.02 for women). Over the past 50 years, the incidence of heart failure has declined among women but not among men, whereas survival after the onset of heart failure has improved in both sexes. Factors contributing to these trends need further clarification.

Background— Atrial fibrillation (AF) and congestive heart failure (CHF) frequently occur together, but there is limited information regarding their temporal relations and the combined influence of these conditions on mortality. Methods and Results— We studied participants in the Framingham Study with new-onset AF or CHF. Multivariable Cox proportional hazards models with time-dependent variables were used to evaluate whether mortality after AF or CHF was affected by the occurrence and timing of the other condition. Hazard ratios (HRs) were adjusted for time period and cardiovascular risk factors. During the study period, 1470 participants developed AF, CHF, or both. Among 382 individuals with both conditions, 38% had AF first, 41% had CHF first, and 21% had both diagnosed on the same day. The incidence of CHF among AF subjects was 33 per 1000 person-years, and the incidence of AF among CHF subjects was 54 per 1000 person-years. In AF subjects, the subsequent development of CHF was associated with increased mortality (men: HR 2.7; 95% CI, 1.9 to 3.7; women: HR 3.1; 95% CI, 2.2 to 4.2). Similarly, in CHF subjects, later development of AF was associated with increased mortality (men: HR 1.6; 95% CI, 1.2 to 2.1; women: HR 2.7, 95% CI, 2.0 to 3.6). Preexisting CHF adversely affected survival in individuals with AF, but preexisting AF was not associated with adverse survival in those with CHF. Conclusions— Individuals with AF or CHF who subsequently develop the other condition have a poor prognosis. Additional studies addressing the pathogenesis, prevention, and optimal management of the joint occurrence of AF and CHF appear warranted.

ContextPrediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction.ObjectiveTo determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction.Data SourcesRelevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies.Study SelectionStudies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality.Data ExtractionPrespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease.ResultsSixteen population cohort studies fulfilling the inclusion criteria were included. During 480 325 person-years of follow-up of 24 955 men and 23 339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (≤0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (≤0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women.ConclusionMeasurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Background— Congestive heart failure (CHF) is an increasing public health problem. Methods and Results— Among Framingham Heart Study subjects who were free of CHF at baseline, we determined the lifetime risk for developing overt CHF at selected index ages. We followed 3757 men and 4472 women from 1971 to 1996 for 124 262 person-years; 583 subjects developed CHF and 2002 died without prior CHF. At age 40 years, the lifetime risk for CHF was 21.0% (95% CI 18.7% to 23.2%) for men and 20.3% (95% CI 18.2% to 22.5%) for women. Remaining lifetime risk did not change with advancing index age because of rapidly increasing CHF incidence rates. At age 80 years, the lifetime risk was 20.2% (95% CI 16.1% to 24.2%) for men and 19.3% (95% CI 16.5% to 22.2%) for women. Lifetime risk for CHF doubled for subjects with blood pressure ≥160/100 versus <140/90 mm Hg. In a secondary analysis, we only considered those who developed CHF without an antecedent myocardial infarction; at age 40 years, the lifetime risk for CHF was 11.4% (95% CI 9.6% to 13.2%) for men and 15.4% (95% CI 13.5% to 17.3%) for women. Conclusions— When established clinical criteria are used to define overt CHF, the lifetime risk for CHF is 1 in 5 for both men and women. For CHF occurring in the absence of myocardial infarction, the lifetime risk is 1 in 9 for men and 1 in 6 for women, which highlights the risk of CHF that is largely attributable to hypertension. These results should assist in predicting the population burden of CHF and placing greater emphasis on prevention of CHF through hypertension control and prevention of myocardial infarction.

Background: DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age. Results: Here we test whether differences between people’s chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δ_age) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δ_age and mortality. A 5-year higher Δ_age is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δ_age. A pedigree-based heritability analysis of Δ_age was conducted in a separate cohort. The heritability of Δ_age was 0.43. Conclusions: DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors.