Predictive value of midregional pro-adrenomedullin compared to natriuretic peptides for incident cardiovascular disease and heart failure in the population-based FINRISK 1997 cohort

INTRODUCTION: To examine whether midregional pro-adrenomedullin (MR-proADM) plasma concentrations predict incident cardiovascular outcomes in the general population. Natriuretic peptides (N-terminal pro-brain natriuretic peptide (NT-proBNP), B-type natriuretic peptide (BNP), and midregional pro-atrial natriuretic peptide (MR-proANP)) were analyzed for comparison. MATERIAL AND METHODS: MR-proADM plasma concentrations and those of the natriuretic peptides were determined in 8444 individuals of the FINRISK 1997 cohort. Patients were followed for 14 years (median). Cox regression analyses, discrimination, and reclassification analyses adjusting for Framingham risk factors were performed to evaluate the additional benefit from MR-proADM. RESULTS: MR-proADM concentrations significantly predicted all-cause death (hazard ratio highest quintile versus lowest 1.18, 95% confidence interval 1.08-1.28), stroke (1.20, 1.05-1.38), major adverse cardiac events (MACE) (1.27, 1.17-1.37), and heart failure (1.67, 1.49-1.87). MR-proADM remained associated with MACE, death, and heart failure even after additional adjustment for NT-proBNP and C-reactive protein. Adding MR-proADM to the Framingham risk factors significantly improved discrimination (P < 0.001 for C-statistics and integrated discrimination improvement) and risk reclassification for heart failure (net reclassification improvement 12.12%, P < 0.001). CONCLUSIONS: In a healthy general population sample of the FINRISK 1997 cohort MR-proADM significantly predicted all-cause death, MACE, and especially heart failure even beyond NT- proBNP. It also improved risk reclassification for heart failure.