When 'good' cholesterol goes awry: Cross-sectional association of high HDL-C with prevalent sarcopenia in U.S. adults.

Background: Sarcopenia-the progressive loss of muscle mass and function-is linked to metabolic dysregulation. Although high-density lipoprotein cholesterol (HDL-C) is usually protective, emerging data suggest a "U-shaped" association with adverse outcomes. We examined the relation between HDL-C and sarcopenia and evaluated mediation by neutrophil-to-lymphocyte ratio (NLR) and homeostasis model assessment of insulin resistance (HOMA-IR).

Methods: We analyzed 2167 National Health and Nutrition Examination Survey 2011 to 2014 adults (≥20 years) with complete dual-energy X-ray absorptiometry, grip-strength, and lipid data. Sarcopenia followed European Working Group on Sarcopenia in Older People 2 criteria. Survey-weighted logistic models progressed from age-sex-ethnicity (Model 1) to body mass index (BMI) (Model 2) and full socioeconomic and clinical covariates (Model 3). HDL-C was treated continuously and as 5 bands (<40, 40-50, 50-60, 60-70, >70 mg/dL). Bias-corrected bootstrap mediation tested indirect effects via NLR and HOMA-IR.

Results: HDL-C was positively associated with sarcopenia in univariate analysis, but the relation disappeared after full adjustment; adding BMI reduced the coefficient by 23%. HDL-C > 70 mg/dL (n = 327) independently predicted sarcopenia (odds ratio: 1.04 per 1 mg/dL, 95% CI, 1.00-1.08). Lower strata were non-significant. NLR showed no mediation. HOMA-IR exerted a small, negative indirect effect (<1% of total).

Conclusion: Extremely elevated HDL-C levels have been associated with an increased risk of sarcopenia, indicating a potentially complex underlying relationship. HOMA-IR may partially mediate this association, highlighting the need for further mechanistic investigations. These findings underscore the importance of considering insulin resistance and overall metabolic health in the assessment and management of sarcopenia risk.