학술논문
Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension
Document Type
article
Author
Karnes, Jason H; Wiener, Howard W; Schwantes-An, Tae-Hwi; Natarajan, Balaji; Sweatt, Andrew J; Chaturvedi, Abhishek; Arora, Amit; Batai, Ken; Nair, Vineet; Steiner, Heidi E; Giles, Jason B; Yu, Jeffrey; Hosseini, Maryam; Pauciulo, Michael W; Lutz, Katie A; Coleman, Anna W; Feldman, Jeremy; Vanderpool, Rebecca; Tang, Haiyang; Garcia, Joe GN; Yuan, Jason X-J; Kittles, Rick; de Jesus Perez, Vinicio; Zamanian, Roham T; Rischard, Franz; Tiwari, Hemant K; Nichols, William C; Benza, Raymond L; Desai, Ankit A
Source
American Journal of Respiratory and Critical Care Medicine. (ja)
Subject
Language
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.