Mild Pulmonary Hypertension Is Associated With Increased Mortality: A Systematic Review and Meta‐Analysis

BACKGROUND: Recent studies have demonstrated a continuum in clinical risk related to mean pulmonary artery pressure that begins at >19 mm Hg, which is below the traditional threshold used to define pulmonary hypertension (PH) of 25 mm Hg. Because of the implications on patient diagnosis and prognosis, the generalizability and validity of these data need further confirmation. METHODS AND RESULTS: Databases were searched from inception through January 31, 2018, to identify studies comparing all‐cause mortality between patients with mildly elevated mean pulmonary artery pressure near but <25 mm Hg versus the referent group. The meta‐analysis included 15 nonrandomized studies and 16 482 patients (7451 [45.2%] with measured or calculated mean pulmonary artery pressure of 19–24 mm Hg by right heart catheterization [n=6037] and echocardiography [n=1414] [mild PH]). The mean duration of follow‐up was 5.2 years. Compared with the referent group, mild PH was associated with an increased risk of mortality (risk ratio, 1.52; 95% confidence interval, 1.32–1.74; P<0.001; I(2)=47%). Secondary analysis using risk‐adjusted time‐to‐event estimates showed a similar result (hazard ratio, 1.19; 95% confidence interval, 1.09–1.31; P<0.001; I(2)=42%). The findings were consistent between subgroups of right heart catheterization and echocardiography studies (P (interaction)>0.05). There was evidence of publication bias; however, this did not influence the risk estimate (Duval and Tweedie's trim and fill adjusted risk ratio, 1.34; 95% confidence interval, 1.15–1.56). CONCLUSIONS: The risk of mortality is increased in patients with mild PH, defined as measured or calculated mean pulmonary artery pressure >19 mm Hg. These data emphasize a need for diagnosing patients with mild PH with consideration to enrollment in PH clinical studies investigating pharmacological and nonpharmacological interventions to attenuate clinical risk and improve outcomes.