Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors.

The sex-specific effect of skeletal muscle mass (SMM) index (SMI) on 4-year first fatal/non-fatal cardiovascular disease (CVD) event in free-of-disease individuals was examined. In 2009, n = 1411 inhabitants (mean age = 64(12)) from Ikaria were selected. Follow-up was performed in 2013. SMI was created to reflect SMM through appendicular skeletal muscle mass (indirectly calculated through formulas) divided by body mass index (BMI). Fifteen and six tenths percent of participants exhibited CVD (19.8% in men/12% in women, p = 0.002). Significant U-shape trends were observed in participants >65 years old and women irrespective to age confirmed through multi-adjusted Cox regression analysis; in age >65 years, Hazard Ratio (HR)(2nd vs. 1st SMI tertile) = 0.80, 95% Confidence Interval (95%CI) (0.45, 0.96) and in women HR(2nd vs. 1st SMI tertile) = 0.71, 95% CI (0.33, 0.95), while, as for the 3rd SMI tertile, no significant trends were observed. Mediation analysis revealed that mediators of the aforementioned associations in men were the arterial distensibility and total testosterone, while, in women, inflammation, insulin resistance, and arterial distensibility. High SMM accompanied by obesity may not guarantee lower CVD risk. Specific cardiometabolic factors seem to explain this need for balance between lean and fat mass.

Low total testosterone levels are associated with the metabolic syndrome in elderly men: the role of body weight, lipids, insulin resistance, and inflammation; the Ikaria study.

BACKGROUND: The prevalence of the metabolic syndrome (MetS) increases with age. Among other changes, testosterone levels decline with age. The relationship between testosterone levels and MetS components in older subjects has not been clearly defined until today. OBJECTIVES: The aim of this work was to evaluate the relationship between total serum testosterone levels and MetS and its components. METHODS: The working sample consisted of 467 elderly individuals (mean age 75 ± 6 years old, n = 220 men) from Ikaria Island, Greece. MetS was defined according to the NCEP ATPIII criteria. RESULTS: MetS prevalence was 52% in men and 64% in women. Those with MetS had lower testosterone levels; a 10 ng/dl increase in testosterone was associated with a 3% reduction in odds of having MetS in men (95% CI: 0.95-0.99), but not in women. This remained the result after various adjustments had been made, including daily hours of sleep. Testosterone was inversely associated with abnormal waist circumference, high-sensitivity C-reactive protein (hs-CRP), insulin, and HDL cholesterol levels in men only. When lipid categories, hs-CRP, BMI, and insulin resistance levels were taken into account, testosterone lost its significance in predicting MetS (p < 0.20), suggesting that these markers possess a mediating effect. CONCLUSIONS: In elderly men, low serum testosterone was associated with MetS. Lipids, BMI, inflammation, and insulin resistance levels seem to explain this relationship, suggesting a potential mediating effect. This finding may support a research hypothesis relating serum testosterone to cardiovascular disease, which requires further research.