Remnant cholesterol-inflammation index and depressive symptoms in middle-aged and older adults with study-defined low...

Low bone mass and depressive symptoms commonly coexist in later life, but their shared metabolic-inflammatory profile is poorly characterized. We examined the remnant cholesterol-inflammation index (RCII) within adults aged ≥50 years with study-defined low bone mass, evaluated its component-specific associations, and assessed directional consistency in a separate outcome-enriched clinical sample.

This cross-sectional analysis used survey-weighted NHANES data. Logistic and linear regression models examined depressive-symptom screening positivity and PHQ-9 scores, respectively. Restricted cubic splines were used to evaluate dose-response associations, and component-specific models jointly included standardized log-transformed calculated remnant cholesterol (RC) and cycle-specific C-reactive protein (CRP). The primary association was examined in an outcome-enriched clinical sample using the fixed NHANES standard-deviation (SD) scale.

Among 1,743 NHANES participants, 139 screened positive (PHQ-9 ≥10). Each survey-weighted SD increment in ln(RCII) was associated with screening positivity (OR, 1.52; 95% CI, 1.15-2.00; P = 0.004). Odds were higher in the highest versus lowest weighted quartile (OR, 3.00; 95% CI, 1.40-6.43; P for trend = 0.002), with no strong evidence of nonlinearity (P = 0.874). Higher ln(RCII) was also associated with higher PHQ-9 scores (β per SD, 0.38; 95% CI, 0.13-0.63; P = 0.004). In the mutually adjusted component model, the cycle-specific CRP measurement remained associated with screening positivity (OR per SD, 1.44; 95% CI, 1.12-1.84; P = 0.005), whereas calculated RC did not (OR, 1.14; 95% CI, 0.89-1.47; P = 0.284); the direct standardized coefficient contrast was imprecise and nonsignificant (P = 0.179). The direction of association was consistent in the outcome-enriched clinical sample (N = 150; 50 events; adjusted OR per fixed NHANES SD, 3.29; 95% CI, 1.92-5.64; P < 0.001).

Higher RCII was associated with greater depressive-symptom burden among adults with low bone mass, with supportive directional clinical corroboration. Prospective studies with clinically confirmed outcomes are needed.