Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension

Rationale: Limited information is available on racial/ ethnic differences in pulmonary arterial hypertension (PAH). Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH. Methods: 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. MeasurementsandMainResults: After covariate adjustment, selfreported Hispanic patients (n = 290) exhibited significantly reduced mortality versus NHWpatients (n = 1,970) after global meta-Analysis (HR, 0.60 [95% CI, 0.41 0.87]; P=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]; P = 0.053) in the two national registries. Finally, in the National Inpatient Sample, an inpatient mortality benefit was also observed for Hispanic patients (n = 1,524) versus NHWpatients (n=8,829;OR, 0.65 [95%CI, 0.50 0.84];P = 0.001).Aninpatientmortality benefitwas observed for Native American patients (n = 185; OR, 0.38 [95% CI, 0.15 0.93]; P=0.034). Conclusions: 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.