NEW YORK (Reuters Health) SHBG levels (SHBG) could be a biomarker of cardiovascular disease (CVD) risks for older and middle-aged men, regardless of total testosterone levels in a large observational study.
For men between 40 and 70 years the endogenous total testosterone levels were not associated with risk of CVD events, however, those who had lower SHBG levels were at greater risk of developing myocardial infarction (MI), the study team writes in Annals of Internal Medicine.
SHBG is the major binding protein for circulating testosterone however, only a few studies have examined whether the SHBG level, independent of testosterone, is linked to CVD events.
To study the issue the issue, Dr. Bu Yeap of the University of Western Australia in Crawley and his colleagues utilized UK Biobank data to analyze the correlation between serum testosterone and SHBG levels with CVD events in more than 210,000 men aged 40 to 69 years.
Over nine years, 8,790 (4.2 percent) men had an CVD event. After adjustment for lifestyle, sociodemographic and medical factors, and for SHBG the total testosterone levels did not correlate with the risk of any CVD events.
In contrast after adjusting for all these factors and also for total testosterone, men with lower SHBG levels were at a significantly higher risk of MI (hazard ratio, 1.23) but at lower risk of having an ischemic stroke (HR, 0.79) and heart failure (HR, 0.69), when compared to those who had higher levels of SHBG.
Researchers conclude that, while testosterone levels alone cannot predict CVD events in middle-aged men and older men, SHBG levels may be a biomarker to predict CVD risk.
The study’s strengths are its large sample size, the long follow-up period and large number of outcomes. The researchers stress that the study’s observational nature cannot address causality and that the serum total testosterone and SHBG along with other covariates, were taken at the time of baseline.
In a related editorial Dr. Di Zhao and Dr. Eliseo Guallar of Johns Hopkins University in Baltimore, Maryland, say the finding that endogenous testosterone levels in men of middle age and older were not directly linked to CV events indicates that it is “unlikely that the decrease in serum testosterone levels is a major explanation for the increase in age-related CVD.”
These findings also warn against using testosterone as a preventive measure for CVD in men. They state that the cardiovascular safety profile of testosterone therapy remains uncertain and that it is crucial to determine each patient’s cardiovascular risk profile prior to initiating testosterone therapy.
Funding for the study was provided by the Western Australian Health Translation Network, Medical Research Future Fund and Lawley Pharmaceuticals.
SOURCE: https://bit.ly/3sAbsY0 and https://bit.ly/3mzFUhc Annals of Internal Medicine, online December 27, 2021.
