Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease

Juan Wang; Li-Na Han; Dao-Sheng Ai; Xin-Yu Wang; Wan-Jing Zhang; Xiao-Rong Xu; Hong-Bin Liu; Jing Zhang; Pan Wang; Xu Li; Mu-Lei Chen

doi:10.26599/1671-5411.2023.07.007

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease

J Geriatr Cardiol. 2023 Jul 28;20(7):527-537. doi: 10.26599/1671-5411.2023.07.007.

Authors

Juan Wang¹, Li-Na Han², Dao-Sheng Ai³, Xin-Yu Wang¹, Wan-Jing Zhang¹, Xiao-Rong Xu¹, Hong-Bin Liu², Jing Zhang¹, Pan Wang¹, Xu Li¹, Mu-Lei Chen¹

Affiliations

¹ Heart Center of Beijing Chao-Yang Hospital, Capital Medical University, Beijing Key Laboratory of Hypertension, Beijing, China.
² Department of Cardiology, the Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China.
³ Academy for Advanced Interdisciplinary Studies, Peking University National Institute of Biological Sciences, Zhongguancun Life Science Park, Tsinghua University, Beijing, China.

Abstract

Background: Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers.

Methods: A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death.

Results: Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years.

Conclusions: Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Grants and funding

This work was supported by in part, by the National Natural Science Fund (81900382). This research was also supported, in part, by the Yang Talents Program of Beijing (QML20200302) and Beijing Municipal Natural Science Foundation (7222072). There is no other conflict of interest associated with industry and financial associations.