Potential relation between soluble growth differentiation factor-15 and testosterone deficiency in male patients with coronary artery disease

Huan Liu,Yan Cui,Yongnan Lyu,Wen Dai,Yun Huang,Yan Li,Di Li

doi:10.1186/s12933-019-0823-3

Abstract

BackgroundThere is a mutual interaction between inflammation and endocrine disorders in the development of coronary artery disease (CAD). Growth differentiation factor-15 (GDF-15) is associated with CAD, and the effects of testosterone on CAD as reported in literature have been considered as anti-atherosclerotic. The present study aimed to examine the possible association between serum GDF-15 and testosterone in male CAD patients.MethodsGDF-15 and testosterone concentrations were determined in blood samples of 426 male patients with CAD and 220 male controls. Serum concentrations of hs-CRP, and other baseline characteristics were also measured.ResultsSerum levels of GDF-15 were higher in CAD patients when compared to controls, and testosterone concentrations were lower (p < 0.001). Patients with low testosterone levels had higher concentrations of GDF-15 (p < 0.001). In stratified analyses, inverse relations between GDF-15 levels and testosterone were noted for almost all strata, stratified by categories of hs-CRP, leukocytes, neutrophils, neutrophil to lymphocyte ratio, glucose, HDL-c, and LDL-c, and whether had hypertension, diabetes, and underwent percutaneous coronary intervention (PCI). Furthermore, in the linear regression models with bootstrap resampling with 1000 replications, high GDF-15 levels were independently associated with testosterone deficiency in male patients with CAD.ConclusionsIn male patients with CAD, high GDF-15 levels were associated with testosterone deficiency. These results support that upregulation of GDF-15 in the presence of low testosterone levels during CAD progression is a potential mechanism by which GDF-15 affects CAD.

Highlights

There is a mutual interaction between inflammation and endocrine disorders in the development of coronary artery disease (CAD)
We hypothesize that higher circulating levels of Growth differentiation factor-15 (GDF-15) are associated with a greater prevalence of testosterone deficiency, and that is a potential mechanism by which GDF-15 affect CAD
Age and most other cardiovascular risk factors, such as hypertension, and diabetes did not differ between controls and CAD patients

Summary

Introduction

There is a mutual interaction between inflammation and endocrine disorders in the development of coronary artery disease (CAD). A low testosterone status is associated with an increase in atherosclerosis and cardiovascular risk, and the risk of CAD rises dramatically after 50 years of age [4]. Liu et al Cardiovasc Diabetol (2019) 18:21 age might mediate the increased CAD risk later in life in older men. This theory has been supported by observational studies that demonstrate associations between lower androgen and CAD risk factors, including elevated high sensitivity C-reactive protein (hs-CRP), arterial stiffness, adiposity, insulin resistance, and beta-cell failure [5,6,7,8]. We hypothesize that higher circulating levels of GDF-15 are associated with a greater prevalence of testosterone deficiency, and that is a potential mechanism by which GDF-15 affect CAD. To verify our hypothesis, we compared GDF-15 levels across different testosterone tertiles and analyzed the association of GDF-15 with testosterone

Methods

Results

Conclusion