Bradley A Maron1, Edward Hess2, Thomas M Maddox2, Alexander R Opotowsky2, Ryan J Tedford2, Tim Lahm2, Karen E Joynt2, Daniel J Kass2, Thomas Stephens2, Maggie A Stanislawski2, Erik R Swenson2, Ronald H Goldstein2, Jane A Leopold2, Roham T Zamanian2, Jean M Elwing2, Mary E Plomondon2, Gary K Grunwald2, Anna E Barón2, John S Rumsfeld2, Gaurav Choudhary2. 1. From Veterans Affairs Boston Healthcare System, MA (B.A.M., R.H.G.); Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.M., A.R.O., T.S., J.A.L.); Veterans Affairs Eastern Colorado Health Care System, Denver (E.H., T.M.M., M.A.S., M.E.P., G.K.G., A.E.B., J.R.); University of Colorado School of Medicine (T.M.M.); Boston Children's Hospital, MA (A.R.O.); Department of Medicine, Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD (R.J.T.); Indiana University School of Medicine and Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis (T.L.); Office of the Assistant Secretary for Planning and Evaluation, United States Department of Health and Human Services, Washington, DC (K.E.J.); Veterans Affairs Pittsburgh Healthcare System, PA (D.J.K.); VA Puget Sound Health Care System and University of Washington, Seattle (E.R.S.); Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, CA (R.T.Z.); Cincinnati Veterans Affairs Medical Center and University of Cincinnati, OH (J.M.E.); and Providence Veterans Affairs Medical Center and Alpert Medical School of Brown University, Providence, RI (G.C.). Bradley.Maron@va.gov. 2. From Veterans Affairs Boston Healthcare System, MA (B.A.M., R.H.G.); Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.M., A.R.O., T.S., J.A.L.); Veterans Affairs Eastern Colorado Health Care System, Denver (E.H., T.M.M., M.A.S., M.E.P., G.K.G., A.E.B., J.R.); University of Colorado School of Medicine (T.M.M.); Boston Children's Hospital, MA (A.R.O.); Department of Medicine, Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD (R.J.T.); Indiana University School of Medicine and Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis (T.L.); Office of the Assistant Secretary for Planning and Evaluation, United States Department of Health and Human Services, Washington, DC (K.E.J.); Veterans Affairs Pittsburgh Healthcare System, PA (D.J.K.); VA Puget Sound Health Care System and University of Washington, Seattle (E.R.S.); Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, CA (R.T.Z.); Cincinnati Veterans Affairs Medical Center and University of Cincinnati, OH (J.M.E.); and Providence Veterans Affairs Medical Center and Alpert Medical School of Brown University, Providence, RI (G.C.).
Abstract
BACKGROUND: Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based primarily on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) ≥25 mm Hg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP <25 mm Hg to clinical outcome is unknown. METHODS AND RESULTS: We analyzed retrospectively all US veterans undergoing right heart catheterization (2007-2012) in the Veterans Affairs healthcare system (n=21,727; 908-day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mm Hg (hazard ratio [HR]=1.183; 95% confidence interval [CI], 1.004-1.393) relative to 10 mm Hg. Therefore, patients were stratified into 3 groups: (1) referent (≤18 mm Hg; n=4,207); (2) borderline PH (19-24 mm Hg; n=5,030); and (3) PH (≥25 mm Hg; n=12,490). The adjusted mortality hazard was increased for borderline PH (HR=1.23; 95% CI, 1.12-1.36; P<0.0001) and PH (HR=2.16; 95% CI, 1.96-2.38; P<0.0001) compared with the referent group. The adjusted hazard for hospitalization was also increased in borderline PH (HR=1.07; 95% CI, 1.01-1.12; P=0.0149) and PH (HR=1.15; 95% CI, 1.09-1.22; P<0.0001). The borderline PH cohort remained at increased risk for mortality after excluding the following high-risk subgroups: (1) patients with pulmonary artery wedge pressure >15 mm Hg; (2) pulmonary vascular resistance ≥3.0 Wood units; or (3) inpatient status at the time of right heart catheterization. CONCLUSIONS: These data illustrate a continuum of risk according to mPAP level and that borderline PH is associated with increased mortality and hospitalization. Future investigations are needed to test the generalizability of our findings to other populations and study the effect of treatment on outcome in borderline PH.
BACKGROUND:Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based primarily on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) ≥25 mm Hg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP <25 mm Hg to clinical outcome is unknown. METHODS AND RESULTS: We analyzed retrospectively all US veterans undergoing right heart catheterization (2007-2012) in the Veterans Affairs healthcare system (n=21,727; 908-day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mm Hg (hazard ratio [HR]=1.183; 95% confidence interval [CI], 1.004-1.393) relative to 10 mm Hg. Therefore, patients were stratified into 3 groups: (1) referent (≤18 mm Hg; n=4,207); (2) borderline PH (19-24 mm Hg; n=5,030); and (3) PH (≥25 mm Hg; n=12,490). The adjusted mortality hazard was increased for borderline PH (HR=1.23; 95% CI, 1.12-1.36; P<0.0001) and PH (HR=2.16; 95% CI, 1.96-2.38; P<0.0001) compared with the referent group. The adjusted hazard for hospitalization was also increased in borderline PH (HR=1.07; 95% CI, 1.01-1.12; P=0.0149) and PH (HR=1.15; 95% CI, 1.09-1.22; P<0.0001). The borderline PH cohort remained at increased risk for mortality after excluding the following high-risk subgroups: (1) patients with pulmonary artery wedge pressure >15 mm Hg; (2) pulmonary vascular resistance ≥3.0 Wood units; or (3) inpatient status at the time of right heart catheterization. CONCLUSIONS: These data illustrate a continuum of risk according to mPAP level and that borderline PH is associated with increased mortality and hospitalization. Future investigations are needed to test the generalizability of our findings to other populations and study the effect of treatment on outcome in borderline PH.
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