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BackgroundDNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.MethodsNine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.ResultsAmong 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate

Background: Exposure to black carbon (BC), a tracer of vehicular-traffic pollution, is associated with increased blood pressure (BP). Identifying biological factors that attenuate BC effects on BP can inform prevention. We evaluated the role of mitochondrial abundance, an adaptive mechanism compensating for cellular-redox imbalance, in the BC-BP relationship., Methods and Results: At ≥ 1 visits among 675 older men from the Normative Aging Study (observations=1252), we assessed daily BP and ambient BC levels from a stationary monitor. To determine blood mitochondrial abundance, we used whole blood to analyze mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA) using quantitative polymerase chain reaction. Every standard deviation increase in the 28-day BC moving average was associated with 1.97 mm Hg (95% confidence interval [CI], 1.23-2.72; P<0.0001) and 3.46 mm Hg (95% CI, 2.06-4.87; P<0.0001) higher diastolic and systolic BP, respectively. Positive BC-BP associations existed throughout all time windows. BC moving averages (5-day to 28-day) were associated with increased mtDNA/nDNA; every standard deviation increase in 28-day BC moving average was associated with 0.12 standard deviation (95% CI, 0.03-0.20; P=0.007) higher mtDNA/nDNA. High mtDNA/nDNA significantly attenuated the BC-systolic BP association throughout all time windows. The estimated effect of 28-day BC moving average on systolic BP was 1.95-fold larger for individuals at the lowest mtDNA/nDNA quartile midpoint (4.68 mm Hg; 95% CI, 3.03-6.33; P<0.0001), in comparison with the top quartile midpoint (2.40 mm Hg; 95% CI, 0.81-3.99; P=0.003)., Conclusions: In older adults, short-term to moderate-term ambient BC levels were associated with increased BP and blood mitochondrial abundance. Our findings indicate that increased blood mitochondrial abundance is a compensatory response and attenuates the cardiac effects of BC., (© 2015 American Heart Association, Inc.)

Background: Several methods exist by which to assess type A behavior (TAB). Although the videotaped clinical interview is regarded as the "gold standard," self-report measures have also proved useful in assessing TAB in large population studies. The purpose of this study was to examine prospectively the relationship of TAB to risk of coronary heart disease (CHD) incidence with the use of the revised Minnesota Multiphasic Personality Inventory (MMPI-2) Type A Scale. To the best of our knowledge, this is the first test of this scale in the context of predicting CHD incidence., Methods and Results: The study was performed in the VA Normative Aging Study, an ongoing cohort of older (mean age, 61 years) community-dwelling men. A total of 1305 men who were free of diagnosed CHD in 1986 completed the MMPI-2 Type A Scale. During an average 7.0 years of follow-up, 110 cases of incident CHD occurred. Compared with men in the lowest quartile of type A scores, men in the highest quartile had multivariate adjusted relative risks of 2.86 (95% CI, 1.19 to 6.89; P for trend=0.016) for combined CHD death and nonfatal myocardial infarction (MI) and 2.30 (95% CI, 1.32 to 4.01; P for trend=0.001) for combined CHD death/nonfatal MI plus angina pectoris. The relationship of TAB to CHD was independent of measures of anger and cynicism., Conclusions: The MMPI-2 Type A Scale predicts CHD incidence. Further research is warranted to examine the correlation, if any, between this scale and the videotaped clinical interview.

Background: Worry is an important component of anxiety, which recent work suggests is related to increased incidence of coronary heart disease (CHD). Chronic worry has also been associated with decreased heart rate variability. We hypothesized that high levels of worry may increase CHD risk., Method and Results: We examined prospectively the relationship of worry with CHD incidence in the Normative Aging Study, an ongoing cohort of older men. In 1975, 1759 men free of diagnosed CHD completed a Worries Scale, indicating the extent to which they worried about each of five worry domains: social conditions, health, financial, self-definition, and aging. During 20 years of follow-up, 323 cases of incident CHD occurred: 113 cases of nonfatal myocardial infarction (MI); 86 cases of fatal CHD; and 124 cases of angina pectoris. Worry about social conditions was the domain most strongly associated with incident CHD. Compared with men reporting the lowest levels of social conditions worry, men reporting the highest levels had multivariate adjusted relative risks of 2.41 (95% CI, 1.40 to 4.13) for nonfatal MI and 1.48 (95% CI, 0.99 to 2.20) for total CHD (nonfatal MI and fatal CHD). A dose-response relation was found between level of worry and both nonfatal MI (P for trend, .002) and total CHD (P for trend, .04)., Conclusions: These results suggest that high levels of worry in specific domains may increase the risk of CHD in older men.

Background: Recent laboratory and epidemiological studies have suggested that high levels of anger may increase the risk of coronary heart disease (CHD)., Methods and Results: We examined prospectively the relationship of anger to CHD incidence in the Veterans Administration Normative Aging Study, an ongoing cohort of older (mean age, 61 years) community-dwelling men. A total of 1305 men who were free of diagnosed CHD completed the revised Minnesota Multiphasic Personality Inventory (MMPI-2) in 1986. Subjects were categorized according to their responses to the MMPI-2 Anger Content Scale, which measures the degree to which individuals have problems controlling their anger. During an average of 7 years of follow-up, 110 cases of incident CHD occurred, including 30 cases of nonfatal myocardial infarction hostility. (MI), 20 cases of fatal CHD, and 60 cases of angina pectoris. Compared with men reporting the lowest levels of anger, the multivariate-adjusted relative risks among men reporting the highest levels of anger were 3.15 (95% confidence interval) [CI]: 0.94 to 10.5) for total CHD (nonfatal MI plus fatal CHD) and 2.66 (95% CI: 1.26 to 5.61) for combined incident coronary events including angina pectoris. A dose-response relation was found between level of anger and overall CHD risk (P for trend, .008)., Conclusions: These data suggest that high levels of expressed anger may be a risk factor for CHD among older men.

The results from the Beta-Blocker Heart Attack Trial for patients ages 60-69 years indicate a significant beneficial effect of propranolol and an overall reduction in mortality of 33%. This beneficial effect appears to begin early and continues through 3 years of follow-up. Examination of patient complaints and medical reasons for withdrawing study medication indicates that side effects resulting from propranolol use were infrequent in both the younger and older age groups, and there were no major differences between the two groups. Given these results, and considering the large number of hospital-diagnosed myocardial infarctions that occur each year in persons older than 60 years of age, it appears that the use of propranolol, where not contraindicated, could delay mortality in a substantial number of older postinfarction patients.