Abstract
BackgroundGrowth differentiation factor-15 (GDF-15), Cystatin C and C-reactive protein (CRP) have been discussed as biomarkers for prediction of cardiac diseases. The aim of this study was to investigate the predictive value of single and repeated measurements of GDF-15 compared to Cystatin C and CRP for incidence of heart failure (HF) and death due to coronary heart disease (CHD) in the general population.Methods and resultsLevels of GDF-15, CRP and Cystatin C were determined in three repeated measurements collected 5 years apart in the DAN-MONICA (Danish-Multinational MONitoring of trends and determinants in Cardiovascular disease) cohort (participants at baseline n = 3785). Cox regression models adjusted for cardiovascular risk factors revealed significantly increased hazard ratios (HR) for GDF-15 for incident HF 1.36 (HR per interquartile range (IQR) increase, 95% confidence interval (CI): 1.16; 1.59) and for death from CHD 1.51 (HR per IQR increase, 95% CI: 1.31, 1.75) (both with p<0.001). Joint modeling of time-to-event and longitudinal GDF-15 over a median 27-year follow-up period showed that the marker evolution was positively associated with death of CHD (HR per IQR increase 3.02 95% CI: (2.26, 4.04), p < 0.001) and HF (HR per IQR increase 2.12 95% CI: (1.54, 2.92), p<0.001). However using Cox models with follow-up time starting at the time of the third examination, serial measurement of GDF-15, modeled as changes between the measurements, did not improve prediction over that of the most recent measurement.ConclusionsGDF-15 is a promising biomarker for prediction of HF and death due to CHD in the general population, which may provide prognostic information to already established clinical biomarkers. Repeated measurements of GDF-15 displayed only a slight improvement in the prediction of these endpoints compared to a single measurement.
Highlights
The prevalence of heart failure (HF) is steadily increasing with the growing elderly population with a current prevalence of over 23 million worldwide [1]
Levels of Growth differentiation factor-15 (GDF-15), C-reactive protein (CRP) and Cystatin C were determined in three repeated measurements collected 5 years apart in the DAN-MONICA (Danish-Multinational MONitoring of trends and determinants in Cardiovascular disease) cohort
Cox regression models adjusted for cardiovascular risk factors revealed significantly increased hazard ratios (HR) for GDF-15 for incident HF 1.36 (HR per interquartile range (IQR) increase, 95% confidence interval (CI): 1.16; 1.59) and for death from coronary heart disease (CHD) 1.51 (HR per IQR increase, 95% CI: 1.31, 1.75)
Summary
The prevalence of heart failure (HF) is steadily increasing with the growing elderly population with a current prevalence of over 23 million worldwide [1]. In community-based populations, Brown and colleagues first described in a prospective case-control study that increased plasma levels of GDF-15 in healthy women were accompanied with a higher risk for future cardiovascular events [14]. Several subsequent studies revealed that increased levels of GDF-15 are associated with increased cardiovascular mortality and all-cause mortality independent of classical cardiovascular risk factors in community-dwelling individuals [8, 15,16,17]. Growth differentiation factor-15 (GDF-15), Cystatin C and C-reactive protein (CRP) have been discussed as biomarkers for prediction of cardiac diseases. The aim of this study was to investigate the predictive value of single and repeated measurements of GDF-15 compared to Cystatin C and CRP for incidence of heart failure (HF) and death due to coronary heart disease (CHD) in the general population
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