Abstract
Background and aims: Biomarkers reflecting vascular function and neurohumoral activity may predict cardiovascular disease (CVD). Midregional proadrenomedullin (MR-proADM) is increased in myocardial infarction and correlates with the severity of heart failure (HF).The aim of the present study was to examine the predictive ability of MR-proADM for incident CVD events in a prospective, population-based setting for the first time and to compare the findings on MR-proADM with those of natriuretic peptides. Methods: MR-proADM, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and midregional proatrial natriuretic peptide (MR-proANP) were measured from stored samples of the FINRISK 1997 cohort. After excluding individuals with a history of major adverse cardiovascular event (MACE) and pregnant women at baseline, 7,899 individuals were included. The follow-up was until Dec. 31 st , 2010. We used Cox proportional hazards regression to estimate hazard ratios (HR) per one standard deviation increase in each biomarker and for each type of MACE, adjusting for standard CVD risk factors. Measures of discrimination and reclassification were calculated using ten-fold cross-validation. Results: During follow-up 1,074 incident MACE (529 coronary heart disease (CHD) events, 299 ischemic strokes, 505 cases of HF) occured. Adjusted HRs (and 95% confidence intervals) of outcomes for each biomarker are shown in the table. Adding MR-proADM improved discrimination and reclassification for HF (C-index improved from 0.822 to 0.840, NRI was 12.1%, IDI was also significant, all p<0.001), but not for CHD events or stroke. Conclusions: In the general population of the FINRISK 1997 cohort, MR-proADM had no additional predictive effect for CHD events or stroke beyond natriuretic peptides. However, MR-proADM proved to be strongly predictive for incident HF and improved discrimination and reclassification similarly to NT-proBNP while being more specific.
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