Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension
Jason H. Karnes, Howard W. Wiener, Tae-Hwi Schwantes-An, Balaji Natarajan, Andrew J. Sweatt, Abhishek Chaturvedi, Amit Arora, Ken Batai, Vineet Nair, Heidi E. Steiner, Jason B. Giles, Jeffrey Yu, Maryam Hosseini, Michael W. Pauciulo, Katie A. Lutz, Anna W. Coleman, Jeremy Feldman, Rebecca Vanderpool, Haiyang Tang, Joe G. N. Garcia, Jason X.‐J. Yuan, Rick A. Kittles, Vinicio de Jesús Pérez, Roham T. Zamanian, Franz Rischard, Hemant K. Tiwari, William C. Nichols, Raymond L. Benza, Ankit A. Desai
Abstract
Abstract 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. Measurements and Main Results After covariate adjustment, self-reported Hispanic patients (n = 290) exhibited significantly reduced mortality versus NHW patients (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 NHW patients (n = 8,829; OR, 0.65 [95% CI, 0.50–0.84]; P = 0.001). An inpatient mortality benefit was 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.