Jason H Karnes1, Howard W Wiener2, Tae-Hwi Schwantes-An3, Balaji Natarajan4, Andrew J Sweatt5,6, Abhishek Chaturvedi7, Amit Arora8, Ken Batai9, Vineet Nair10, Heidi E Steiner1, Jason B Giles1, Jeffrey Yu1, Maryam Hosseini10, Michael W Pauciulo11, Katie A Lutz11, Anna W Coleman11, Jeremy Feldman12, Rebecca Vanderpool10, Haiyang Tang10, Joe G N Garcia10, Jason X-J Yuan13, Rick Kittles14, Vinicio de Jesus Perez5,6, Roham T Zamanian5,6, Franz Rischard10, Hemant K Tiwari2, William C Nichols11, Raymond L Benza7, Ankit A Desai15. 1. Department of Pharmacy Practice and Science. 2. Department of Biostatistics, University of Alabama-Birmingham, Birmingham, Alabama. 3. Department of Medical and Molecular Genetics and. 4. Department of Cardiology, University of California Riverside School of Medicine, Riverside, California. 5. Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University School of Medicine, Stanford, California. 6. Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, California. 7. Allegheny General Hospital, Pittsburgh, Pennsylvania. 8. Department of Epidemiology and Biostatistics. 9. Department of Surgery, and. 10. Department of Medicine, University of Arizona, Tucson, Arizona. 11. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. 12. Arizona Pulmonary Specialists, Tucson, Arizona. 13. Department of Medicine, University of California-San Diego, La Jolla, California; and. 14. Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California. 15. Department of Medicine, Indiana University, Indianapolis, Indiana.
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.
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.
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