Evaluation of Temporal Changes in Cardiovascular Biomarker Concentrations Improves Risk Prediction in an Elderly Population from the Community

BACKGROUND: There is increasing interest in measurements of cardiovascular (CV) biomarker concentrations for risk prediction in the general population. We investigated the prognostic utility of a panel of novel CV biomarkers including biomarker changes over time. METHODS: We measured concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional proadrenomedullin, high-sensitivity cardiac troponin I, growth-differentiation factor-15 (GDF-15), soluble ST2 (sST2), and galectin-3 at baseline and 5 years later in 1016 elderly individuals participating in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Assessed outcomes included all-cause mortality and fatal and nonfatal CV events (in participants without CV disease at baseline) during 10 years of follow-up. RESULTS: GDF-15 exhibited the strongest association with all-cause mortality (n = 158) with a hazard ratio (HR) per 1-SD increase in standardized ln GDF-15 of 1.68 (95% CI, 1.44-1.96). NT-proBNP was the only biomarker to predict CV events (n = 163; HR 1.54 [95% CI, 1.30-1.84]). GDF-15 and NT-proBNP also improved metrics of discrimination and reclassification of the respective outcomes. Changes in GDF-15 concentrations between 70 and 75 years predicted all-cause mortality whereas changes in NT-proBNP predicted both outcomes. The other biomarkers and their temporal changes provided only moderate prognostic value apart from sST2 which had a neutral relationship with adverse events. CONCLUSIONS: Evaluation of temporal changes in GDF-15 and NT-proBNP concentrations improves risk prediction in an elderly population. These findings are of considerable interest given the emphasis on biomarkers as tools to identify and monitor at-risk individuals with preclinical and potentially modifiable stages of CV disease.