For a study, it was determined that although APOL1 genotypes were linked to kidney illness in African Americans and may influence cardiovascular disease and mortality risk, results have been mixed. The objective was to determine if high-risk APOL1 genotypes are linked to cardiovascular disease and stroke in postmenopausal African American women who are at high risk for both.  Between 1993 and 1998, 1,61,838 postmenopausal women were included in clinical trials and observational research as part of the Women’s Health Initiative. From enrollment until June 2014, 11,137 African American women who had a clinical incident were included in the outline. From January to August 2017, data analysis was done. Whole-exome sequencing was used to genotype or impute APOL1 variations. Hospital records and death certificates were used to determine the incidence of coronary heart disease, stroke, and heart failure subtypes, as well as total and cause-specific mortality. For the relationships of APOL1 groups with outcomes, hazard ratios (HR) and 95% CIs were calculated for each outcome. Participants were 61.7 (7.1) years old on average. High-risk APOL1 variant carriers (n=1370; 12.3%) had a greater prevalence of hypertension, used cholesterol-lowering medicines more frequently, and had a poorer estimated glomerular filtration rate (eGFR). Carriers of high-risk APOL1 mutations exhibited a greater incidence rate of hospitalized heart failure with preserved ejection fraction (HFpEF) than low-risk carriers after a mean (SD) of 11.0 (3.6) years, but no differences in other outcomes. In adjusted models, carriers of high-risk APOL1 variants had a 58% higher risk of hospitalized HFpEF (HR, 1.58 [95% CI, 1.03-2.41]) compared to carriers of low-risk APOL1 variants. When adjusted for baseline eGFR, the link with HFpEF was decreased (HR = 1.50 [95% CI, 0.98-2.30]) and no longer significant. The presence of a high-risk APOL1 genotype was linked to HFpEF hospitalization in postmenopausal women, which was partially explained by baseline kidney function. For a study, the researchers do not suggest a link between high-risk APOL1 genotypes and postmenopausal African American women’s coronary heart disease, stroke, or mortality.