Estimates of biological age based on DNA methylation patterns, often referred to as “epigenetic age”, “DNAm age”, have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2×10−9), independent of chronological age, even after adjusting for additional risk factors (p<5.4×10−4), and within the racial/ethnic groups that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic age estimates that incorporated information on blood cell composition led to the smallest p-values for time to death (p=7.5×10−43). Overall, this study a) strengthens the evidence that epigenetic age predicts all-cause mortality above and beyond chronological age and traditional risk factors, and b) demonstrates that epigenetic age estimates that incorporate information on blood cell counts lead to highly significant associations with all-cause mortality.

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Objective Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between mid-life cardiovascular risk factors and AAAs. Approach and Results In ARIC, 15,792 participants were recruited at Visit 1 in 1987–89 and followed-up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from Visit 1 (1987–89) to Visit 4 (1996–1998). We followed participants for incident, clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident AAAs. An abdominal ultrasound was conducted in 2011–2013 in 5,911 surviving participants and 75 asymptomatic AAAs were identified. We estimated the lifetime risk of AAA from the index age 45 years through age 85. At age 45, the lifetime risk for AAA was 5.6% (95% confidence interval: 4.8–6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between Visit 1 and Visit 4 had a 29% lower AAA lifetime risk compared to continuous smokers but had a higher risk than pre-Visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% CI: 1.2, 1.8). Smoking, white race, male gender, and greater height, LDL or total cholesterol were associated with an increased risk of clinical AAA and asymptomatic AAA. Conclusions At least one in 9 middle-aged current smokers developed AAA in their lifetime. Smoking cessation reduced the lifetime risk of AAA.

BACKGROUND Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association’s Life’s Simple 7 guidelines -- on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose -- is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. METHODS We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults aged 45-64 years in 1987-89. From the 1987-89 risk factor measurements, we created a Life’s Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2,218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4,855 participants free of clinical cardiovascular disease in 2011-13, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. RESULTS One in four participants (25.5%) developed heart failure through age 85. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life’s Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life’s Simple 7 score compared with an inadequate score. CONCLUSIONS Greater achievement of American Heart Association’s Life’s Simple 7 in middle-age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function.