Race, Common Genetic Variation, and Therapeutic Response Disparities in Heart Failure

Abstract

Because of its relatively recent evolution, Homo sapiens exhibits relatively little within-species genomic diversity. However, because of genome size, a proportionally small amount of variation creates ample opportunity for both rare mutations that may be disease-causative as well as more common genetic variation that may be important in disease modification or pharmacogenetics. Primarily because of the East African origin of modern humans, individuals of African ancestry (AA) exhibit greater degrees of genetic diversity than more recently established populations, such as those of European ancestry (EA) or Asian ancestry. These population effects extend to differences in the frequency of common gene variants that may be important in heart failure natural history or therapy. For cell-signaling mechanisms important in heart failure, we review and present new data on genetic variation between AA and EA populations. The data indicate that 1) neurohormonal signaling mechanisms frequently (16 of the 19 investigated polymorphisms) exhibit racial differences in the allele frequencies of variants comprising key constituents, 2) some of these differences in allele frequency may differentially affect the natural history of heart failure in AA vs. EA individuals, and 3) in many cases these differences likely play a role in observed racial differences in drug or device response.

Racial Differences in the Prevalence and Outcomes of Atrial Fibrillation in Patients Hospitalized With Heart Failure

“…18,19 Compared with patients with HF of European ancestry, African patients with HF have been associated with allele frequency-based genetic profiles that possibly alter the natural history of HF and attenuate certain medical therapies. 20 Previous studies have also found racial differences in left atrial size and atrial automaticity, which may contribute to a pro-arrhythmic state. 21,22 …”

Microvascular complications in diabetes patients with heart failure and reduced ejection fraction—insights from the Beta‐blocker Evaluation of Survival Trial

“…In addition, microvascular disease may particularly affect the myocardium in patients with diabetes which is clearly of greatest danger in patients with already dysfunctional myocardium . Due to the suggestion of less benefit of drug therapy and higher rates of diabetic complications in African‐Americans, we repeated analyses without these patients with similar results . Another potential risk factor for developing heart failure in diabetes patients with microvascular complications is their presumed more severe diabetes and for this reason intensified glucose‐lowering therapy, where some drug classes including pioglitazones have been linked to an increased risk of heart failure …”

Changes in Left Ventricular Ejection Fraction Predict Survival and Hospitalization in Heart Failure With Reduced Ejection Fraction

“…However, these findings could also be due to racial genetic differences that influence the response to neurohormonal inhibitors. 43 To date, the BEST trial contains one of the largest populations of AA patients, representing 23% of the entire cohort and 22% of the LVEF analysis cohort, but may be underpowered to assess the full benefit of LVEF change by race. The ability to calculate risk in in the AA population is vital, as they may have the greatest benefit given their higher risk for the development and severity of HF.…”