Epigenetic biomarkers of aging (the “epigenetic clock”) have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors. We analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue. Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.

Background: Body Mass Index (BMI) is widely used to assess the impact of obesity on cardiometabolic risk in children but it does not always relate to central obesity and varies with growth and maturation. Waist-to-Height Ratio (WHtR) is a relatively constant anthropometric index of abdominal obesity across different age, sex or racial groups. However, information is scant on the utility of WHtR in assessing the status of abdominal obesity and related cardiometabolic risk profile among normal weight and overweight/obese children, categorized according to the accepted BMI threshold values. Methods: Cross-sectional cardiometabolic risk factor variables on 3091 black and white children (56% white, 50% male), 4-18 years of age were used. Based on the age-, race- and sex-specific percentiles of BMI, the children were classified as normal weight (5th - 85th percentiles) and overweight/obese (≥ 85th percentile). The risk profiles of each group based on the WHtR (<0.5, no central obesity versus ≥ 0.5, central obesity) were compared. Results: 9.2% of the children in the normal weight group were centrally obese (WHtR ≥0.5) and 19.8% among the overweight/obese were not (WHtR < 0.5). On multivariate analysis the normal weight centrally obese children were 1.66, 2.01, 1.47 and 2.05 times more likely to have significant adverse levels of LDL cholesterol, HDL cholesterol, triglycerides and insulin, respectively. In addition to having a higher prevalence of parental history of type 2 diabetes mellitus, the normal weight central obesity group showed a significantly higher prevalence of metabolic syndrome (p < 0.0001). In the overweight/obese group, those without central obesity were 0.53 and 0.27 times less likely to have significant adverse levels of HDL cholesterol and HOMA-IR, respectively (p < 0.05), as compared to those with central obesity. These overweight/obese children without central obesity also showed significantly lower prevalence of parental history of hypertension (p = 0.002), type 2 diabetes mellitus (p = 0.03) and metabolic syndrome (p < 0.0001). Conclusion: WHtR not only detects central obesity and related adverse cardiometabolic risk among normal weight children, but also identifies those without such conditions among the overweight/obese children, which has implications for pediatric primary care practice.

We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.

This study aims to characterize longitudinal blood pressure (BP) trajectories from childhood in black–white and sex groups and examine the association between childhood level–independent trajectories of BP and adult hypertension. The longitudinal cohort consisted of 2732 adults who had body mass index and BP measured 4 to 15 times from childhood (4–19 years) to adulthood (20–51 years). Model-estimated levels and linear slopes of BP and body mass index at childhood age points were calculated at 1-year intervals using the growth curve parameters and their first derivatives, respectively. Linear and nonlinear curve parameters differed significantly between race–sex groups; BP levels showed race and sex differences 15 years of age onward. Hypertensives had higher long-term BP levels than normotensives in race–sex groups. Although linear and nonlinear slope parameters of BP were race and sex specific, they differed consistently, significantly between hypertension and normotension groups. BP trajectories during young adulthood (20–35 years) were significantly greater in hypertensives than in normotensives; however, the trajectories during middle-aged adulthood (36–51 years) were significantly smaller in hypertensives than in normotensives. Level-independent linear slopes of systolic BP showed significantly negative associations (odds ratio=0.50≈0.76; P <0.001) during prepuberty period (4–11 years) but significantly positive associations (odd ratio=1.44≈2.80, P <0.001) during the puberty period (13–19 years) with adult hypertension, adjusting for covariates. These associations were consistent across race–sex groups. These observations indicate that adult hypertension originates in childhood, with different longitudinal BP trajectory profiles during young and middle-aged adulthood in black–white and sex groups. Puberty is a crucial period for the development of hypertension in later life.

This longitudinal study aims to characterize longitudinal blood pressure (BP) trajectories from childhood and examine the impact of level-independent childhood BP trajectories on adult left ventricular hypertrophy (LVH) and remodeling patterns. The longitudinal cohort consisted of 1154 adults (787 whites and 367 blacks) who had repeated measurements of BP 4 to 15 times from childhood (4–19 years) to adulthood (20–51 years) and assessment of echocardiographic LV dimensions in adulthood. Model-estimated levels and linear slopes of BP at childhood age points were calculated in 1-year intervals using the growth curve parameters and their first derivatives, respectively. Linear and nonlinear curve parameters of BP showed significant race and sex differences from age 15 years onwards. Adults with LVH had higher long-term BP levels than adults with normal LVM in race–sex groups. Linear and nonlinear slope parameters of BP differed consistently and significantly between LVH and normal groups. Associations of level-independent linear slopes of systolic BP with adult LVH were significantly inverse (odds ratio=0.75–0.82; P =0.001–0.015) in preadolescent children of 4 to 9 years but significantly positive (odds ratio=1.29–1.46; P =0.001–0.008) in adolescents of 13 to 19 years, adjusting for covariates. These associations were consistent across race–sex groups. Of note, the association of childhood BP linear slopes with concentric LVH was significantly stronger than that with eccentric LVH during the adolescence period of 12 to 19 years. These observations indicate that the impact of BP trajectories on adult LVH and geometric patterns originates in childhood. Adolescence is a crucial period for the development of LVH in later life, which has implications for early prevention.