Philipp Douschan1,2, Gabor Kovacs1,2, Alexander Avian3, Vasile Foris1,2, Fabian Gruber1,2, Andrea Olschewski2,4, Horst Olschewski1,2. 1. 1 Division of Pulmonology, Department of Internal Medicine, and. 2. 2 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; and. 3. 3 Institute for Medical Informatics, Statistics, and Documentation, Medical University of Graz, Graz, Austria. 4. 4 Medical School, Johannes Kepler University Linz, Linz, Austria.
Abstract
RATIONALE: Normal mean pulmonary arterial pressure (mPAP) is 14.0 ± 3.3 mm Hg (mean ± SD). The prognostic relevance of mildly elevated mPAP not fulfilling the definition of pulmonary hypertension (PH; mPAP ≥ 25 mm Hg) has not been prospectively evaluated in a real-world setting. OBJECTIVES: To assess the association of resting mPAP with all-cause mortality in a retrospective and a prospective cohort of patients with unexplained dyspnea and/or at risk of PH. METHODS: Prognostic cutoffs were calculated by means of 1) classification and regression tree (CART) analysis without any preset thresholds, and 2) preset thresholds on the basis of literature data defining mPAP as lower-normal (≤mean + 1 SD), upper-normal (between mean + 1 SD and mean + 2 SD), borderline (between mean + 2 SD and 25 mm Hg), and manifest PH (≥25 mm Hg). We performed univariate and multivariate survival analysis adjusted for age and comorbidities. MEASUREMENTS AND MAIN RESULTS: We enrolled 547 patients, of whom 137, 56, 64, and 290 presented with lower-normal, upper-normal, or borderline mPAP, and manifest PH, respectively. The CART analysis on mPAP discriminated three prognostic groups: mPAP less than 17 mm Hg, 17 to 26 mm Hg, and greater than 26 mm Hg, with significantly decreasing survival. The univariate analysis on the basis of preset thresholds showed that upper-normal mPAP, borderline mPAP, and manifest PH were significantly associated with poor survival compared with lower-normal mPAP. In the multivariate model, considering age and comorbidities, only borderline mPAP (hazard ratio, 2.37; 95% confidence interval, 1.14-4.97; P = 0.022) and manifest PH (hazard ratio, 5.05; 95% confidence interval, 2.79-9.12; P < 0.001) were significantly associated with poor survival. CONCLUSIONS: In patients at risk for PH and/or with unexplained dyspnea, CART analysis detects prognostic thresholds at a resting mPAP of 17 mm Hg and 26 mm Hg, and values between 20 mm Hg and 25 mm Hg represent an independent predictor of poor survival. Clinical trial registered with www.clinicaltrials.gov (NCT 01607502).
RATIONALE: Normal mean pulmonary arterial pressure (mPAP) is 14.0 ± 3.3 mm Hg (mean ± SD). The prognostic relevance of mildly elevated mPAP not fulfilling the definition of pulmonary hypertension (PH; mPAP ≥ 25 mm Hg) has not been prospectively evaluated in a real-world setting. OBJECTIVES: To assess the association of resting mPAP with all-cause mortality in a retrospective and a prospective cohort of patients with unexplained dyspnea and/or at risk of PH. METHODS: Prognostic cutoffs were calculated by means of 1) classification and regression tree (CART) analysis without any preset thresholds, and 2) preset thresholds on the basis of literature data defining mPAP as lower-normal (≤mean + 1 SD), upper-normal (between mean + 1 SD and mean + 2 SD), borderline (between mean + 2 SD and 25 mm Hg), and manifest PH (≥25 mm Hg). We performed univariate and multivariate survival analysis adjusted for age and comorbidities. MEASUREMENTS AND MAIN RESULTS: We enrolled 547 patients, of whom 137, 56, 64, and 290 presented with lower-normal, upper-normal, or borderline mPAP, and manifest PH, respectively. The CART analysis on mPAP discriminated three prognostic groups: mPAP less than 17 mm Hg, 17 to 26 mm Hg, and greater than 26 mm Hg, with significantly decreasing survival. The univariate analysis on the basis of preset thresholds showed that upper-normal mPAP, borderline mPAP, and manifest PH were significantly associated with poor survival compared with lower-normal mPAP. In the multivariate model, considering age and comorbidities, only borderline mPAP (hazard ratio, 2.37; 95% confidence interval, 1.14-4.97; P = 0.022) and manifest PH (hazard ratio, 5.05; 95% confidence interval, 2.79-9.12; P < 0.001) were significantly associated with poor survival. CONCLUSIONS: In patients at risk for PH and/or with unexplained dyspnea, CART analysis detects prognostic thresholds at a resting mPAP of 17 mm Hg and 26 mm Hg, and values between 20 mm Hg and 25 mm Hg represent an independent predictor of poor survival. Clinical trial registered with www.clinicaltrials.gov (NCT 01607502).
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Authors: Bernard Thébaud; Kara N Goss; Matthew Laughon; Jeffrey A Whitsett; Steven H Abman; Robin H Steinhorn; Judy L Aschner; Peter G Davis; Sharon A McGrath-Morrow; Roger F Soll; Alan H Jobe Journal: Nat Rev Dis Primers Date: 2019-11-14 Impact factor: 52.329