– In a study of end-stage heart failure patients, researchers at the University of Alabama at Birmingham (UAB) found that race and socioeconomic factors may contribute to differences heart failure outcomes in black and white men.
Published in the American Journal of Physiology: Heart and Circulatory Physiology, the findings showed differences in methylation of the DNA in the heart among patients – and that race was the sole variable in patient records that explained the difference.
Researchers subsequently looked at the census tracts where the patients lived and saw that black subjects lived in neighborhoods with more racial diversity and poverty, indicating that the underlying variable may be a socioeconomic difference.
Despite the high prevalence of heart failure, researchers noted that only half of heart failure patients respond to guideline-directed medical management. This disparity has led investigators to examine the underlying molecular differences that contribute to the heterogeneity of heart failure.
Methylation of DNA is a form of epigenetics, an indirect method of gene regulation that can differ with gene-environment interaction.
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The UAB study included a pilot cohort of eleven heart failure patients, followed by a testing cohort of 31 heart failure patients – all of them male. Researchers obtained the heart muscle tissue for the study when patients underwent surgery to install a left ventricular assist device, or LVAD. This device is a small mechanical pump carried outside the body to help a weakened heart pump blood.
Until now, epigenetics has been an unexamined source of heterogeneity among patients with end-stage heart failure. UAB researchers found differential promoter hyper-methylation of genes involved in fatty acid metabolism among black patients’ heart muscle samples compared to white patients’ samples. The team also saw higher expression of lipogenesis genes.
These molecular alterations are pathological signs of end-stage heart failure, because the heart gets more of its energy from glucose sugar as it fails.
This finding led to two hypotheses among the researchers. The first was that epigenetic remodeling of cardiac gene regulation determines the treatment potential of LVADs.
The group also theorized that epigenetic reprogramming of cardiac gene regulation includes a process that may impact a patient’s responsiveness to LVADs, when the heart possibly improves because the pump takes over part of the work.
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In contrast to the hyper-methylated promoters, genes that had differentially hypo-methylated promoters – or lower levels of methylation – in black patients’ hearts disproportionately represented inflammatory signaling cascades.
UAB researchers also conducted a retrospective analysis of deaths from any cause in the 31 testing cohort patients two years after heart pump implantation. The results showed that black patients had higher rates of death, with eight of 15 patients dying. Among white patients, two of 14 patients died.
Researchers emphasized the need for better heart failure treatments, as just half of patients respond to treatments and black patients experience worse outcomes than any race or ethnicity in the US.
“African Americans with heart failure are hospitalized at a rate 2.5-times higher than other races or ethnicities. Furthermore, despite a threefold higher mortality from heart-failure complications, the prevalence of heart failure among African Americans continues to increase,” said Adam R. Wende, PhD, the associate professor in the UAB Department of Pathology who led the study.
“It is estimated that 3.6 percent of this community will live with heart failure by 2030, exceeding the predicted prevalence of any other race or ethnicity in America. Therefore, it is paramount to identify and address the issues that underly these disturbing racial differences in heart-failure morbidity and mortality.”
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The study was limited in that it was a single-center study, but the team expects that their findings will lead to further research into the racial and socioeconomic factors that contribute to heart failure outcomes.
“We provide preliminary evidence that socioeconomic factors are likely associated with racial differences in cardiac DNA methylation among men with end-stage heart failure,” Wende concluded.
Past research suggests that genetic testing may play an important role in addressing disparities in heart failure treatment and diagnosis. A 2019 study published in JAMA showed that a genetic variant found in individuals of African American Latino ancestry was significantly associated with heart failure.
Patients of African American or Latino ancestry who have this genetic variant are two-fold more likely to have heart failure risk.
“Given recent advances in treatment for hereditary transthyretin amyloid cardiomyopathy, it is imperative to identify patients at risk for the disease and intervene before noticeable symptoms of the disease appear,” said study author Ron Do, PhD, Assistant Professor of Genetics and Genomics Sciences, and co-Director of the BioMe Phenomics Center in The Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai.
“Previous studies have proposed utilizing routine genetic testing for individuals with African ancestry; however, this is not current practice and the scope of the under-diagnosis is not clear.”
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