Predictive value of long-term changes of growth differentiation factor-15 over a 27-year-period for heart failure and death due to coronary heart disease
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Predictive value of long-term changes of growth differentiation factor-15 over a 27-year-period for heart failure and death due to coronary heart disease. / Fluschnik, Nina; Ojeda, Francisco; Zeller, Tanja; Jørgensen, Torben; Kuulasmaa, Kari; Becher, Peter Moritz; Sinning, Christoph; Blankenberg, Stefan; Westermann, Dirk.
In: PLOS ONE, Vol. 13, No. 5, 2018, p. e0197497.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Predictive value of long-term changes of growth differentiation factor-15 over a 27-year-period for heart failure and death due to coronary heart disease
AU - Fluschnik, Nina
AU - Ojeda, Francisco
AU - Zeller, Tanja
AU - Jørgensen, Torben
AU - Kuulasmaa, Kari
AU - Becher, Peter Moritz
AU - Sinning, Christoph
AU - Blankenberg, Stefan
AU - Westermann, Dirk
PY - 2018
Y1 - 2018
N2 - BACKGROUND: 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.METHODS AND RESULTS: Levels 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.CONCLUSIONS: GDF-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.
AB - BACKGROUND: 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.METHODS AND RESULTS: Levels 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.CONCLUSIONS: GDF-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.
KW - Adult
KW - Biomarkers/blood
KW - C-Reactive Protein/metabolism
KW - Coronary Disease/blood
KW - Cystatin C/blood
KW - Female
KW - Growth Differentiation Factor 15/blood
KW - Heart Failure/blood
KW - Humans
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Proportional Hazards Models
KW - Prospective Studies
KW - Risk Factors
U2 - 10.1371/journal.pone.0197497
DO - 10.1371/journal.pone.0197497
M3 - SCORING: Journal article
C2 - 29771963
VL - 13
SP - e0197497
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 5
ER -
