Racial and Socioeconomic Disparity Associates with Differences in Cardiac DNA Methylation among Men with End-Stage Heart Failure

Heart Failure (HF) is a multifactorial syndrome and that remains a leading cause of worldwide morbidity. Despite its high prevalence, only half 50% of HF patients respond to guideline-directed medical management, prompting therapeutic efforts . Therapeutic avenues are forced to confront the molecular underpinnings of its heterogeneity of HF as a clinical syndrome to identify novel molecular targets. In both pilot (n = 11) and testing (n = 31) cohorts (n = 31), unsupervised multidimensional scaling of genome-wide myocardial DNA methylation exhibited a bimodal distribution of CpG methylation found largely to occur in the promoter regions of metabolic genes.. Among the available patient attributes, only categorical patient race could delineate this methylation signature, with African American (AA) and Caucasian American (CA) samples clustering separately. Because race is a social construct, and thus a poor proxy of human physiology, extensive review of medical records was conducted, but ultimately failed to identify co-variates of race at the time of LVAD surgery. By contrast, retrospective analysis exposed a higher all-cause mortality among AA (56.3%) relative to CA (16.7%) patients at 2 years following LVAD placement (P = 0.03). .G To mitigate concerns of genetic confounding factors, putative single-nucleotide polymorphisms (SNPs) were identified by proximity to CpG methylation sites. Nevertheless, a minor proportion of SNPs (0.15%) was identified, and no evidence of racial dissimilarity was seen among them. By contrast, geocoding-based approximation of patient demographics uncovered disparities in income levels among AA relative to CA patients. Therefore, Although although additional studies studies are warrantedneeded, our multicohort studythe current analysis implicates identifies cardiac DNA methylation as as a previously unrecognized indicator of socioeconomic disparity in human heart failure outcomes. In the current study, we examined epigenetics as a yet unexplored mechanism source of heterogeneity in among patients with end-stage HF. Specifically, a multicohort-based study was designed to analyze quantify cardiac genome-wide cytosine-p-guanine (DNA CpG) methylation of cardiac biopsies from patients undergoing left ventricular assist device (LVAD) implantation.