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

Abstract

Background There 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. Methods GDF-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. Results Serum 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. Conclusions In 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. Electronic supplementary material The online version of this article (10.1186/s12933-019-0823-3) contains supplementary material, which is available to authorized users.

Associations between Sex Hormones and Circulating Growth Differentiation Factor-15 in Male Patients with Major Depressive Disorder

“…Moreover, in prostate cancer cells, the upregulation of GDF-15 was directly affected by the downregulation of T and E2 [ 40 ]. Studies have shown that GDF-15 serum levels were negatively associated with T levels and the T/E2 ratio, and the combination of T and E2 could significantly reduce the GDF-15 level [ 41 , 42 ]. Based on the currently available literature, it can therefore be assumed that there is a regulatory interaction between serum GDF-15 and sex hormones.…”

The Association Among Serum Growth Differentiation Factor 15 Level and Suicidal Ideation is Dependent on Testosterone Deficiency in Depressive Patients

“…Serum GDF-15 levels were significantly and negatively associated with testosterone in patients with coronary artery disease or HBV-associated hepatocellular carcinoma. [28][29][30] Thus, the present research was to investigate the association among serum GDF-15 level and testosterone levels in depressive patients with or without suicidal ideation. Our data confirmed depressed subjects with suicidal ideation showed much higher serum GDF-15 levels than those without suicidal ideation, regardless of whether they had a testosterone <314 ng/dL or ≥314 ng/dL.…”

The association between serum growth differentiation factor 15 levels and lower extremity atherosclerotic disease is independent of body mass index in type 2 diabetes

“…The results from previous studies have shown that increased circulating GDF15 levels were closely associated with the development and progression of various cardiovascular diseases (including myocardial ischaemia/reperfusion, heart failure, atherosclerosis, and acute coronary syndrome), and were shown to be a strong and independent predictor of mortality and disease progression in patients with atherosclerosis and coronary artery disease [5][6][7][8][9][10][31][32][33][34][35][36]. In diabetic patients, higher levels of lipids and chronic inflammation may directly damage the cardiovascular system [37].…”