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An independent, inverse association of high-density-lipoprotein-cholesterol concentration with nonadipose body mass^1,2,3

Background: Increasing body mass index (BMI) is associated with progressively lower serum HDL-cholesterol concentrations, although the underlying body-composition compartment accounting for this unfavorable lipid change remains uncertain.

Objective: Because growing evidence favors a role of lean tissue in HDL homeostasis, the hypothesis was tested that non–adipose tissue components of body mass explain the inverse association of HDL cholesterol and BMI.

Design: Fasting serum lipid concentrations and body composition [total, subcutaneous, and visceral adipose tissue; adipose tissue–free mass (ATFM); and skeletal muscle by whole-body magnetic resonance imaging and body cell mass by ⁴⁰K counting) were evaluated in healthy adults. Body-composition compartments were expressed as height²-normalized indexes.

Results: An inverse correlation was observed between serum HDL cholesterol and BMI in women (n = 68; R² = 0.08, P = 0.023) and men (n = 61; R² = 0.07, P = 0.046). Significant inverse correlations (P = 0.005–0.02) were also observed between HDL cholesterol and nonadipose components (ie, ATFM, skeletal muscle, and body cell mass) but not between HDL cholesterol and any adipose tissue component. The association between HDL cholesterol and ATFM remained significant after serum triacylglycerol was controlled for. When BMI was entered into the HDL cholesterol–ATFM regression model, BMI was not a significant independent variable. The strongest correlate of serum triacylglycerol was visceral adipose tissue (P = 0.002 for both women and men).

Conclusions: Lean tissues and body cell mass appear to account in part for the long-observed inverse association of HDL cholesterol and BMI. These observations suggest a link between nonadipose tissue compartments and the greater cardiovascular risk associated with high BMI.

Key Words: HDL cholesterol • high-density-lipoprotein cholesterol • serum lipids • cardiovascular disease • body composition • skeletal muscle • adipose tissue • body mass index • magnetic resonance imaging