Pulmonary arterial hypertension (PAH) has median survival of only 5-7 years in registries from developed countries. In resource-limited areas, PAH is more frequently encountered and less often treated due to lack of access to therapy. In order to improve global outcomes in PAH, noninvasive, widely available, and inexpensive risk stratification markers should be identified. Serum chloride is a widely available laboratory test that is prognostic in heart failure patietns, buts its widespread utility as a prognostic marker in PAH requires further investigation.
We performed a cohort study of PAH patients (n=630, mean age: 52±14 years, 76% female) evaluated at the University of Minnesota and Vanderbilt University Medical Centers. Kaplan-Meier method and Cox regression analysis were used to assess survival and predictors of mortality, respectively.
PAH patients in the lowest tertile of chloride (≤101 mEq/d) had the lowest six-minute walk distance (145±113 vs 169±133 vs 183±130 meters, p=0.045) and highest right atrial pressure (10±6 vs 8±5 vs 8±5 mm Hg, p=0.002) despite having similar mean pulmonary arterial pressures (48±13 vs 49±15 vs 49±14 mm Hg, p=0.660), pulmonary vascular resistance (9.5±5.7 vs 9.7±6.0 vs 10.0±5.1, p=0.253), and pulmonary arterial compliance (1.5±1.0 vs 1.5±1.2 vs 1.5±0.9 mL/mm Hg, p=0.995). The 1-, 3-, and 5- survival was markedly reduced in patients with serum chloride in the lowest tertiles as compared to patients in the middle and the highest tertiles (84/67/47% vs 94/80/62% vs 91/79/68%). In a multivariate model that adjusted for other noninvasive markers including serum sodium, bicarbonate, use of diuretic, creatinine, age, and gender, the patients in the highest (hazard ratio (HR): 0.65, 95% confidence interval (95%CI): 0.44-0.97, p=0.034) and middle tertile (HR: 0.62, 95% CI: 0.45-0.86, p=0.004) chloride levels had improved survival.
Lower serum chloride is a strong and an independent risk factor for mortality in PAH.