Growth Differentiation Factor-15 Improves Prognostic Accuracy of Risk Stratification in Pulmonary Arterial Hypertension.

Abstract

The etiology of pulmonary arterial hypertension (PAH) is complex and the risk is heterogeneous. Growth differentiation factor-15 (GDF-15) has been reported to be associated with the prognosis of patients with PAH, but whether the use of GDF-15 as an additional prognostic biomarker can improve preexisting PAH risk stratification remains unclear. Can the addition of GDF-15 improve the performance of existing prediction models for PAH? We conducted a nationwide, multicenter retrospective study in which 435 patients with PAH (218 in the discovery cohort and 217 in the validation cohort) were enrolled from the National Rare Diseases Registry System of China. Serum samples were collected and serum GDF-15 levels were determined. Comprehensive PAH assessments were conducted postenrollment, including right heart catheterization, World Health Organization functional class, and other relevant clinical indicators. C-indexes were used to compare the prediction power of several existing risk models with or without GDF-15 as a predictive biomarker, especially Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA). In the discovery cohort, elevated levels of GDF-15 were significantly associated with an increased risk of mortality, with hazard ratios of 1.658 (95% CI, 1.099-2.499; P = .016) in univariate Cox analysis and 1.678 (95% CI, 1.018-2.765; P = .042) after full adjustment. The corresponding hazard ratios in the validation cohort were 1.982 (95% CI, 1.169-3.361; P = .011) and 1.817 (95% CI, 1.035-3.190; P = .038), respectively. A novel risk model incorporating GDF-15 was developed based on COMPERA, which demonstrated improved discrimination for mortality prediction and enhanced fit, with an increase in C-index from 0.743 to 0.767 in the discovery cohort and from 0.658 to 0.687 in the validation cohort. Our results show that GDF-15 may improve the predictive effects of existing PAH risk assessment strategies on all-cause mortality.