Lauren L Schmitz, Elizabeth Duffie, Wei Zhao
et al.
Abstract Epigenetic biomarkers of accelerated aging have been widely used to predict disease risk and may enhance our understanding of biological mechanisms between early-life adversity and disparities in aging. With respect to childhood adversity, most studies have used parental education or childhood disadvantage and/or have not examined the role played by socioemotional or physical abuse and trauma in epigenetic profiles at older ages. This study leveraged data from the Multi-Ethnic Study of Atherosclerosis (MESA) on experiences of threat and deprivation in participants’ early lives (i.e., before the age of 18 years) to examine whether exposure to specific dimensions of early-life adversity is associated with epigenetic profiles at older ages that are indicative of accelerated biological aging. The sample included 842 MESA respondents with DNA methylation data collected between 2010 and 2012 who answered questions on early-life adversities in a 2018–2019 telephone follow-up. We found that experiences of deprivation, but not threat, were associated with later-life GrimAge epigenetic aging signatures that were developed to predict mortality risk. Results indicated that smoking behavior partially mediates this association, which suggests that lifestyle behaviors may act as downstream mechanisms between parental deprivation in early life and accelerated epigenetic aging in later life.
Lyndia C Brumback, David R Jacobs, Daniel A Duprez
AbstractSystolic and diastolic blood pressures provide information about cardiovascular disease (CVD) but are only extremes of the pressure waveform during the cardiac cycle. We developed summaries of the pressure decay, called PTC1 and PTC2, that are related to arterial compliance and to an existing proprietary summary that has been shown to predict CVD. We derived the summaries from a Windkessel model (consisting of a decaying exponential plus a dampened cosine, with an intercept so they are independent of calibration with blood pressure, unlike the proprietary measures), and we estimated them using nonlinear least squares with standard, free software. Among 6,228 adults from the Multi-Ethnic Study of Atherosclerosis, initially free of CVD in 2000–2002, mean PTC2 was 94 (standard deviation, 46) milliseconds. During median 15-year follow-up, there were 911 CVD events (including 609 incidents of coronary heart disease and 270 strokes). One-standard-deviation higher PTC2 was associated with 17% (95% confidence interval: 10, 24) lower CVD risk, after adjustment for traditional risk factors. Results were similar for PTC1. PTC1 and PTC2 are relatively straightforward to compute and add information beyond traditional risk factors for prediction of CVD. Our work enables others to replicate and extend our results with waveforms from any suitable device.
Isac C Thomas, Michelle L Takemoto, Nketi I Forbang
et al.
Abstract Aims The benefits of physical activity (PA) on cardiovascular disease (CVD) are well known. However, studies suggest PA is associated with coronary artery calcium (CAC), a subclinical marker of CVD. In this study, we evaluated the associations of self-reported recreational and non-recreational PA with CAC composition and incident CVD events. Prior studies suggest high CAC density may be protective for CVD events. Methods and results We evaluated 3393 participants of the Multi-Ethnic Study of Atherosclerosis with prevalent CAC. After adjusting for demographics, the highest quintile of recreational PA was associated with 0.07 (95% confidence interval 0.01–0.13) units greater CAC density but was not associated with CAC volume. In contrast, the highest quintile of non-recreational PA was associated with 0.08 (0.02–0.14) units lower CAC density and a trend toward 0.13 (−0.01 to 0.27) log-units higher CAC volume. There were 520 CVD events over a 13.7-year median follow-up. Recreational PA was associated with lower CVD risk (hazard ratio 0.88, 0.79–0.98, per standard deviation), with an effect size that was not changed with adjustment for CAC composition or across levels of prevalent CAC. Conclusion Recreational PA may be associated with a higher density but not a higher volume of CAC. Non-recreational PA may be associated with lower CAC density, suggesting these forms of PA may not have equivalent associations with this subclinical marker of CVD. While PA may affect the composition of CAC, the associations of PA with CVD risk appear to be independent of CAC.
Ehimare Akhabue, Thanh-Huyen T Vu, Anand Vaidya
et al.
Abstract BACKGROUND Higher fibroblast growth factor-23 (FGF23) concentrations have been found to be associated with incident heart failure (HF). Experimental data suggest FGF23 directly stimulates myocardial hypertrophy. FGF23 may also enhance renin–angiotensin–aldosterone system activity. Whether FGF23 is associated with increased HF risk in populations with hypertension and whether this association is weaker in the presence of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy is unknown. METHODS We studied 2,858 adults with hypertension free of cardiovascular disease at baseline (65.6 ± 9.5 years, 46.2% male) participating in the Multi-Ethnic Study of Atherosclerosis (MESA). We investigated the association of baseline serum intact FGF23 with incident HF over a 14-year median follow-up and whether ACEI/ARB therapy modified this risk. We also investigated the relationship of FGF23 with aldosterone and plasma renin activity in a random subgroup of the entire MESA cohort with available assays (N = 1,642). RESULTS In adjusted Cox regression models, higher FGF23 was associated with a 63% greater hazard of incident HF (hazard ratio: 1.63, 95% confidence interval: [1.13–2.36] per 1-unit increase in log-transformed FGF23), which persisted after exclusion of participants with chronic kidney disease (hazard ratio: 1.94 [1.10–3.43]). There was no heterogeneity by ACEI/ARB use (Pinteraction = 0.438). FGF23 improved model fit over covariables (likelihood ratio χ2 = 6.67, P = 0.010). In multivariable linear regression models, there was no association between FGF23 and aldosterone or plasma renin activity. CONCLUSIONS Higher FGF23 concentrations are associated with a significantly increased risk of HF in hypertension but this risk did not differ by ACEI/ARB treatment status. FGF23 may be a useful biomarker for HF risk in hypertensive populations.
Christina M Eckhardt, Pallavi Balte, Jack E Morris
et al.
Introduction Cigarette smoking leads to altered DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) gene. However, it remains unknown whether pipe or cigar smoking is associated with AHRR methylation. We evaluated associations of non-cigarette tobacco use with AHRR methylation and determined if AHRR methylation was associated with smoking-related health outcomes. Methods Data were pooled across four population-based cohorts that enrolled participants from 1985 to 2002. Tobacco exposures were evaluated using smoking questionnaires. AHRR cg05575921 methylation was measured in peripheral blood leucocyte DNA. Spirometry and respiratory symptoms were evaluated at the time of methylation measurements and in subsequent visits. Vital status was monitored using the National Death Index. Results Among 8252 adults (mean age 56.7±10.3 years, 58.1% women, 40.6% black), 4857 (58.9%) participants used cigarettes and 634 (7.7%) used non-cigarette tobacco products. Exclusive use of non-cigarette tobacco products was independently associated with lower AHRR methylation (−2.44 units, 95% CI −4.42 to −0.45), though to a lesser extent than exclusive use of cigarettes (−6.01 units, 95% CI −6.01 to −4.10). Among participants who exclusively used non-cigarette tobacco products, reduced AHRR methylation was associated with increased respiratory symptom burden (OR 1.60, 95% CI 1.03 to 2.68) and higher all-cause mortality (log-rank p=0.02). Conclusion Pipe and cigar smoking were independently associated with lower AHRR methylation in a multiethnic cohort of US adults. Among users of non-cigarette tobacco products, lower AHRR methylation was associated with poor respiratory health outcomes and increased mortality. AHRR methylation may identify non-cigarette tobacco users with an increased risk of adverse smoking-related health outcomes.