The relationship between endothlial ABD erectile dysfunction, levels of testosterone and cardiovascular events in the follow-up

Abstract

Background: Clinical and experimental evidence suggest that testosterone levels play a role in cardiac and vascular pathology. A long history of observational studies investigating serum testosterone level and cardiovascular risks, specifically mortality, reveals important associations between low testosterone and mortality, while higher serum testosterone level appear to be predictive in the majority of studies. On the other hand, it is well documented and accepted that endothelial dysfunction is expression of preclinical atherosclerosis and it is associated with an increased amount of CV events in the follow-up. Erectile dysfunction is also an early manifestation of arteriosclerosis associated with endothelial damage/dysfunction. Endothelial function plays a very important role in the process of erection. Moreover, erectile dysfunction and coronary artery disease (CAD) overlap in risk factors, etiology and clinical outcomes. Endothelial dysfunction is considered to be their shared etiological factor. There is growing evidence that patients presenting with erectile dysfunction should be investigated for CAD, even if with no symptoms of the problem. Earlier diagnosis of erectile dysfunction can facilitate prompt intervention, reduce long-term complications, especially the risk of CAD, and provide effective treatment for erectile dysfunction. Objectives: We aimed to assess whether baseline testosterone levels may be predictors of future CV events in a cohort of patients at intermediate cardiovascular risk. Methods: Our cohort included 802 adult subjects, males from 40 to 80 years (mean age of the whole population was 57.52±13.85 years old). Thy were at intermediate cardiovascular risk, according to the Framingham risk score and all referred between 2009 and 2014. Patients were excluded if they had a past history of peripheral artery disease, coronary revascularization, angina pectoris, myocardial infarction, carotid surgery or cerebrovascular event. The study of the endothelial function was performed by using the method of flow mediated vasodilation. Moreover, it was administered a standard questionnaire for the evaluation of the erectile function and the dosage of the plasma testosterone was carried out. The median follow-up time for major CV events was 5.1 years. Results: Patients with lower serum testosterone levels (n=332) had a higher prevalence of traditional CV risk factors, such as hypertension (p=0.009), diabetes (p=0.03), dyslipidemia (p<0.0001), obesity (p=0.002), endothelial function score (p<0.0001). there were no significant differences in age and in the presence of smoking or family history of CV. Logistic regression analysis showed that testosterone levels, erectile dysfunction and endothelial dysfunction were independent predictor for major adverse cardiac events (MACE) in the follow-up period (p<0.0001). this association was independent of age and CV risk factors (p<0.0001). Conclusions: Lower serum testosterone levels define a group of patients with endothelial dysfunction at higher risk of events during the follow-up, while normal values do not significantly influence the distribution of events. Our results confirm also those of Sharma R. et al. in a very large cohort of patients in whom the normalization of testosterone levels, after replacement therapy, significantly reduced all causes of mortality, myocardial infarction and stroke.