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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.

SUBMITTER: Liu H

PROVIDER: S-EPMC6394066 | biostudies-other | 2019 Feb

REPOSITORIES: biostudies-other

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

Liu Huan H Lyu Yongnan Y Li Di D Cui Yan Y Huang Yun Y Dai Wen W Li Yan Y

Cardiovascular diabetology 20190228 1

<h4>Background</h4>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.<h4>Methods</h4>GDF-15 and testosterone concentrations we ...[more]

PMID: 30819257

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Project description:BackgroundGrowth 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.MethodsA 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.ResultsBaseline 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.ConclusionsHigher 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.

Project description:ImportanceRecent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk.ObjectiveTo test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume.Design, setting, and participantsDouble-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014.InterventionTestosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months.Main outcomes and measuresThe primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis).ResultsOf 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95% CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group.Conclusions and relevanceAmong older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding.Trial registrationclinicaltrials.gov Identifier: NCT00799617.

Project description:BackgroundFamilial combined hypolipidemia, a Mendelian condition characterized by substantial reductions in all 3 major lipid fractions, is caused by mutations that inactivate the gene angiopoietin-like 3 (ANGPTL3). Whether ANGPTL3 deficiency reduces risk of coronary artery disease (CAD) is unknown.ObjectivesThe study goal was to leverage 3 distinct lines of evidence-a family that included individuals with complete (compound heterozygote) ANGPTL3 deficiency, a population based-study of humans with partial (heterozygote) ANGPTL3 deficiency, and biomarker levels in patients with myocardial infarction (MI)-to test whether ANGPTL3 deficiency is associated with lower risk for CAD.MethodsWe assessed coronary atherosclerotic burden in 3 individuals with complete ANGPTL3 deficiency and 3 wild-type first-degree relatives using computed tomography angiography. In the population, ANGPTL3 loss-of-function (LOF) mutations were ascertained in up to 21,980 people with CAD and 158,200 control subjects. LOF mutations were defined as nonsense, frameshift, and splice-site variants, along with missense variants resulting in <25% of wild-type ANGPTL3 activity in a mouse model. In a biomarker study, circulating ANGPTL3 concentration was measured in 1,493 people who presented with MI and 3,232 control subjects.ResultsThe 3 individuals with complete ANGPTL3 deficiency showed no evidence of coronary atherosclerotic plaque. ANGPTL3 gene sequencing demonstrated that approximately 1 in 309 people was a heterozygous carrier for an LOF mutation. Compared with those without mutation, heterozygous carriers of ANGPTL3 LOF mutations demonstrated a 17% reduction in circulating triglycerides and a 12% reduction in low-density lipoprotein cholesterol. Carrier status was associated with a 34% reduction in odds of CAD (odds ratio: 0.66; 95% confidence interval: 0.44 to 0.98; p = 0.04). Individuals in the lowest tertile of circulating ANGPTL3 concentrations, compared with the highest, had reduced odds of MI (adjusted odds ratio: 0.65; 95% confidence interval: 0.55 to 0.77; p < 0.001).ConclusionsANGPTL3 deficiency is associated with protection from CAD.

Project description:Background and aims Studies on the association between growth-differentiation factor-15 (GDF-15) level and adverse outcomes have yielded conflicting results in patients with stable coronary artery disease (CAD). This meta-analysis aimed to evaluate the association of baseline GDF-15 level with adverse outcomes in stable CAD patients. Methods Two authors independently searched PubMed and Embase databases from inception to May 31, 2021 for available studies that investigated the association of baseline GDF-15 level with all-cause mortality, cardiovascular mortality, or major adverse cardiovascular events (MACEs) in stable CAD patients. Pooled multivariable adjusted hazard ratio (HR) with 95% confidence interval (CI) was calculated for the highest vs. the lowest GDF-15 level. Results Seven studies that involved 28,765 stable CAD patients were identified and analyzed. The meta-analysis showed that the highest GDF-15 level was associated with higher risk of MACEs (HR 1.42; 95% CI 1.29–1.57; p < 0.001), cardiovascular mortality (HR 1.64: 95% CI 1.25–2.14; p < 0.001), and all-cause mortality (HR 2.01; 95% CI 1.67–2.42; p < 0.001) when compared the lowest GDF-15 level. Moreover, the values of GDF-15 level in predicting MACEs were consistently observed in each named subgroup. Conclusions Elevated blood GDF-15 level is an independent predictor of MACEs, cardiovascular mortality, and all-cause mortality in stable CAD patients. The baseline GDF-15 level may play an important role in the risk stratification of stable CAD patients. Graphical abstract Image 1 Highlights • Predictive value of GDF-15 level has not been well-established in stable CAD patients.• Stable CAD patients with the highest GDF-15 had a 42% higher risk of MACEs (p < 0.001).• Stable CAD patients with the highest GDF-15 had a 64% higher risk of cardiovascular death (p < 0.001).• Stable CAD patients with the highest GDF-15 had a 2.01-fold higher risk of all-cause death (p < 0.001).• Baseline GDF-15 level is a promising biomarker of adverse outcomes in stable CAD patients.

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

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

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