Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program

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.

Keywords: outcome assessment; pulmonary heart disease; pulmonary hypertension.

Figure 1

The adjusted hazard ratio for mortality according to mean pulmonary artery pressure (mPAP). The hazard ratio (95% CI) for all-cause mortality is plotted for mPAP between 11–60 mmHg relative to a reference value of 10 mmHg.

Figure 2

Time to event plot for unadjusted mortality and hospitalization-free survival for referent, borderline pulmonary hypertension (PH), and PH patients. The study cohort was stratified according to mean pulmonary artery pressure (mPAP) ≤18 mmHg (referent), mPAP=19–24 mmHg (borderline PH), and mPAP ≥25 mmHg (PH), and Kaplan–Meier analysis of the probability of (A) all-cause mortality (log-rank test X²=886.0, P<0.0001) and (B) combined all-cause mortality or hospitalization (log-rank test X²=362.1, P<0.0001) was performed. Censoring begins at and beyond 1 year, and is indicated by thickening of the curve.