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Published on: September 22, 2020
Growth Differentiation Factor 15 May Predict Mortality of Peripheral and Coronary Artery Diseases and Correlate with
Lung-An Hsu1, Semon Wu2, Jyh-Ming Jimmy Juang3
1Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 33305, Taiwan.
Insights
Growth Differentiation Factor 15 (GDF15) levels predict mortality in patients with peripheral artery disease (PAD) and coronary artery disease (CAD). Higher GDF15 levels indicate increased risk, offering better prediction than C-reactive protein.
Area of Science:
- Biochemistry
- Genetics
- Cardiovascular Medicine
Background:
- Plasma Growth Differentiation Factor 15 (GDF15) is a stress-responsive cytokine.
- Factors influencing GDF15 levels and its prognostic value in cardiovascular diseases require further investigation.
Purpose of the Study:
- To investigate the associations between GDF15 levels, genetic variants, and clinical parameters in a Taiwanese population.
- To evaluate the role of GDF15 in predicting all-cause mortality in patients with peripheral artery disease (PAD) and coronary artery disease (CAD).
Main Methods:
- Plasma GDF15 concentrations were measured in 612 healthy Taiwanese individuals.
- GDF15 genetic variants, clinical parameters, and 22 biomarkers were analyzed.
- Prognostic value of GDF15 was assessed in 86 PAD and 481 CAD patients using Kaplan-Meier analysis and reclassification metrics.
Main Results:
- Significant associations were found between GDF15 genotypes/haplotypes and GDF15 levels.
- Circulating GDF15 levels positively correlated with age, smoking, hypertension, diabetes, lipocalin 2, and inflammatory/oxidative stress biomarkers.
- Elevated GDF15 levels (>3096 pg/mL for PAD, >1123 pg/mL for CAD) strongly predicted all-cause mortality.
- GDF15 improved risk reclassification by 17.3% in PAD and 29.2% in CAD compared to C-reactive protein.
Conclusions:
- Both genetic and non-genetic factors influence GDF15 levels.
- High plasma GDF15 is a significant predictor of all-cause mortality in high-risk PAD and angiographically confirmed CAD patients.
- GDF15 offers superior prognostic value compared to C-reactive protein for these patient cohorts.
Abstract:
Plasma GDF15 concentrations were measured in 612 Taiwanese individuals without overt systemic disease. Clinical parameters, GDF15 genetic variants, and 22 biomarker levels were analyzed. We further enrolled 86 patients with PAD and 481 patients with CAD, who received endovascular intervention and coronary angiography, respectively, to examine the role of GDF15 level in predicting all-cause mortality. Significant associations were found between GDF15 genotypes/haplotypes and GDF15 levels. The circulating GDF15 level was positively associated with age, smoking, hypertension, and diabetes mellitus as well as circulating levels of lipocalin 2 and various biomarkers of inflammation and oxidative stress. Kaplan-Meier survival analysis showed that baseline GDF15 levels of above 3096 pg/mL and 1123 pg/mL were strong predictors of death for patients with PAD and CAD, respectively (P = 0.011 and P < 0.001). GDF15 more accurately reclassified 17.3% and 29.2% of patients with PAD and CAD, respectively (P = 0.0046 and P = 0.0197), compared to C-reactive protein. Both genetic and nongenetic factors, including cardiometabolic and inflammatory markers and adipokines, were significantly associated with GDF15 level. A high level of GDF15 was significantly associated with an increase of all-cause mortality in patients with high-risk PAD and in patients with angiographically documented CAD.
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