Association of Educational Attainment With Lifetime Risk of Cardiovascular Disease: The Atherosclerosis Risk in Communities Study

Estimates of lifetime risk may help raise awareness of the extent to which educational inequalities are associated with risk of cardiovascular disease (CVD). To estimate lifetime risks of CVD according to categories of educational attainment. Participants were followed from 1987 through December 31, 2013. All CVD events (coronary heart disease, heart failure, and stroke) were confirmed by physician review and International Classification of Diseases codes. A total of 13 948 whites and African Americans who were 45 to 64 years old and free of CVD at baseline were included from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburbs of Minneapolis, Minnesota). The data analysis was performed from June 7 to August 31, 2016. Educational attainment. We used a life table approach to estimate lifetime risks of CVD from age 45 through 85 years according to educational attainment. We adjusted for competing risks of death from underlying causes other than CVD. The sample of 13 948 participants was 56% female and 27% African American. During 269 210 person-years of follow-up, we documented 4512 CVD events and 2401 non-CVD deaths. Educational attainment displayed an inverse dose-response relation with cumulative risk of CVD, which became evident in middle age, with the most striking gap between those not completing vs completing high school. In men, lifetime risks of CVD were 59.0% (95% CI, 54.0%-64.1%) for grade school, 52.5% (95% CI, 47.7%-56.8%) for high school education without graduation, 50.9% (95% CI, 47.3%-53.9%) for high school graduation, 47.2% (95% CI, 41.5%-52.5%) for vocational school, 46.4% (95% CI, 42.8%-49.6%) for college with or without graduation, and 42.2% (95% CI, 36.6%-47.0%) for graduate/professional school; in women, 50.8% (95% CI, 45.7%-55.8%), 49.3% (95% CI, 45.1%-53.1%), 36.3% (95% CI, 33.4%-39.1%), 32.2% (95% CI, 26.0%-37.3%), 32.8% (95% CI, 29.1%-35.9%), and 28.0% (95% CI, 21.9%-33.3%), respectively. Educational attainment was inversely associated with CVD even within categories of family income, income change, occupation, or parental educational level. More than 1 in 2 individuals with less than high school education had a lifetime CVD event. Educational attainment was inversely associated with the lifetime risk of CVD, regardless of other important socioeconomic characteristics. Our findings emphasize the need for further efforts to reduce CVD inequalities related to educational disparities

Lipoprotein-associated phospholipase A2 and venous thromboembolism: A prospective study

Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory marker associated positively with atherothrombotic risk. Whether Lp-PLA2 is related to risk of venous thromboembolism (VTE) is incompletely studied

Elevated hepatic enzymes and incidence of venous thromboembolism: a prospective study

Approximately 10 percent of the general population have elevated blood concentrations of hepatic enzymes, which are linked to increased coagulation markers. We tested whether elevated hepatic enzymes are associated with increased risk of venous thromboembolism (VTE)

Taller height as a risk factor for venous thromboembolism:a Mendelian randomization meta-analysis

Background Taller height is associated with greater risk of venous thromboembolism (VTE). Objectives We used instrumental variable (IV) techniques (Mendelian randomization) to further explore this relationship Methods Participants of European ancestry were included from two cohort studies [Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS)] and one case-control study [Mayo Clinic VTE Study (Mayo)]. We created two weighted genetic risk scores (GRS) for height; the full GRS included 668 single nucleotide polymorphisms (SNPs) from a previously published meta-analysis and the restricted GRS included a subset of 362 SNPs not associated with weight independently of height. Standard logistic regression and IV models were used to estimate odds ratios (ORs) for VTE per 10 cm increment in height. ORs were pooled across the three studies using inverse variance weighted random effects meta-analysis Results Among 9143 ARIC and 3180 CHS participants free of VTE at baseline, there were 367 and 109 incident VTE events. There were 1143 VTE cases and 1292 controls included from Mayo. The pooled ORs from non-IV models and models using the full and restricted GRSs as IVs were 1.27 (95% CI: 1.11, 1.46), 1.34 (95% CI: 1.04, 1.73), and 1.45 (95% CI: 1.04, 2.01) per 10 cm greater height, respectively. Conclusions Taller height is associated with an increased risk of VTE in adults of European ancestry. Possible explanations for this association, including that taller people may have greater venous surface area, greater number of venous valves, or greater hydrostatic pressure, need to be explored further

DNA methylation age is associated with an altered hemostatic profile in a multi-ethnic meta-analysis

Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry–specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P 5 .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P 5 6.6 3 1025) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription

DNA methylation-based measures of biological age:meta-analysis predicting time to death

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 x 10-9), independent of chronological age, even after adjusting for additional risk factors (p < 5.4 x 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 x 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

Venous Thromboembolism: Assessing Novel Risk Factors and Treatments

University of Minnesota Ph.D. dissertation.December 2017. Major: Epidemiology. Advisor: Richard MacLehose. 1 computer file (PDF); ix, 114 pages.Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is the third leading cause of cardiovascular death. This dissertation includes research intended to improve our understanding of two potential risk factors for VTE (body height and endogenous sex hormones) and the comparative safety of novel drugs [direct oral anticoagulants (DOACs)] and warfarin used for treating patients with VTE. Manuscript 1 uses data from two prospective cohorts [the Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS)] and a case-control study (the Mayo Clinic VTE Study) to examine the association between body height and risk of VTE using a Mendelian randomization approach, which may be less influenced by traditional confounding factors. Taller height was associated with an increased risk of VTE. Manuscript 2 uses data from the ARIC study to examine the associations between plasma levels of endogenous testosterone, dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) with incidence of VTE using Cox proportional hazards regression. Plasma hormones were not associated with incidence of VTE among men and postmenopausal women not using exogenous hormones. Lower plasma DHEAS and higher plasma SHBG, when modeled using quartiles, were associated with higher risk of VTE among postmenopausal women using exogenous hormones. Manuscript 3 uses administrative claims data from enrollees in a large, private, nationwide health plan to compare the risk of all-cause mortality during the primary treatment of VTE between groups of enrollees with prescriptions for different oral anticoagulants using marginal structural logistic models. There was no association between having a prescription for warfarin versus any DOAC or between any head-to-head DOAC comparisons with risk of all-cause mortality occurring within 3 or 6 months. This dissertation extends our knowledge on VTE risk factors and the primary treatment of VTE, which could contribute to future preventive efforts and treatment guidelines