Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension

Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH). Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH. Patients with Group 1 PAH were included from two national registries with genome-wide data and two local cohorts, and further incorporated in a global meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for transplant-free, all-cause mortality in Hispanic patients with non-Hispanic white (NHW) patients as the reference group. Odds ratios (ORs) for inpatient-specific mortality in patients with PAH were also calculated for race/ethnic groups from an additional National Inpatient Sample dataset not included in the meta-analysis. After covariate adjustment, self-reported Hispanic patients ( = 290) exhibited significantly reduced mortality versus NHW patients ( = 1,970) after global meta-analysis (HR, 0.60 [95% CI, 0.41-0.87];  = 0.008). Although not significant, increasing Native American genetic ancestry appeared to account for part of the observed mortality benefit (HR, 0.48 [95% CI, 0.23-1.01];  = 0.053) in the two national registries. Finally, in the National Inpatient Sample, an inpatient mortality benefit was also observed for Hispanic patients ( = 1,524) versus NHW patients ( = 8,829; OR, 0.65 [95% CI, 0.50-0.84];  = 0.001). An inpatient mortality benefit was observed for Native American patients ( = 185; OR, 0.38 [95% CI, 0.15-0.93];  = 0.034). This study demonstrates a reproducible survival benefit for Hispanic patients with Group 1 PAH in multiple clinical settings. Our results implicate contributions of genetic ancestry to differential survival in PAH.