Testosterone concentrations and risk of cardiovascular events in androgen-deficient men with atherosclerotic cardiovascular disease.

Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest.

Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up.

In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL ["low T"] vs. ≥300 ng/dL ["normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models.

Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively.

In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke.

In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The "low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.

American heart journal. 2020 Mar 20 [Epub ahead of print]

William E Boden, Michael G Miller, Ruth McBride, Christopher Harvey, Michael C Snabes, Jeffrey Schmidt, Mark E McGovern, Jerome L Fleg, Patrice Desvigne-Nickens, Todd Anderson, Moti Kashyap, Jeffrey L Probstfield

VA Boston Healthcare System, Boston University School of Medicine, Boston, MA. Electronic address: ., AbbVie, Chicago, IL., Axio Research, LLC, Seattle, WA., VA Boston Healthcare System, Boston University School of Medicine, Boston, MA., National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD., Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta., Long Beach VA Healthcare System, Los Angeles, CA., University of Washington, Seattle, WA.