TY - JOUR
T1 - Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension
AU - Karnes, Jason H.
AU - Wiener, Howard W.
AU - Schwantes-An, Tae Hwi
AU - Natarajan, Balaji
AU - Sweatt, Andrew J.
AU - Chaturvedi, Abhishek
AU - Arora, Amit
AU - Batai, Ken
AU - Nair, Vineet
AU - Steiner, Heidi E.
AU - Giles, Jason B.
AU - Yu, Jeffrey
AU - Hosseini, Maryam
AU - Pauciulo, Michael W.
AU - Lutz, Katie A.
AU - Coleman, Anna W.
AU - Feldman, Jeremy
AU - Vanderpool, Rebecca
AU - Tang, Haiyang
AU - Garcia, Joe G.N.
AU - Yuan, Jason X.J.
AU - Kittles, Rick
AU - De Jesus Perez, Vinicio
AU - Zamanian, Roham T.
AU - Rischard, Franz
AU - Tiwari, Hemant K.
AU - Nichols, William C.
AU - Benza, Raymond L.
AU - Desai, Ankit A.
N1 - Funding Information:
Supported by NIH–NHLBI, including HL136603 (A.A.D.), HL478946 (R.L.B.), and HL125208 (J.X.-J.Y. and F.R.). Data are from the National Biological Sample and Data Repository for Pulmonary Arterial Hypertension, which receives government support under an investigator-initiated grant, R24 HL105333 (W.C.N.), awarded by the NHLBI. Research was supported by NHLBI Award Number K01HL143137 (J.H.K.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. None of the external funders or sponsors had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Publisher Copyright:
© 2020 American Thoracic Society. All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - health disparities
KW - Hispanic American
KW - Native American
KW - pulmonary arterial hypertension
KW - survival
UR - http://www.scopus.com/inward/record.url?scp=85085714661&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085714661&partnerID=8YFLogxK
U2 - 10.1164/rccm.201907-1447OC
DO - 10.1164/rccm.201907-1447OC
M3 - Article
C2 - 31916850
AN - SCOPUS:85085714661
VL - 201
SP - 1407
EP - 1415
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 11
ER -