Cross-population heterogeneity in the association between estimated sdLDL-C and gallstone disease: a dual-source two-sample cross-sectional study.

Authors

Wei Dai, Weihao Guo, Hang Shen, Qikai Sun, Yanqun Duan, Yeben Qian

Published in

Frontiers in public health. Volume 14. Pages 1922892. Epub Sep 07, 2026.

Abstract

While conventional lipid parameters are linked to gallstone disease, the specific role of small dense low-density lipoprotein cholesterol (sdLDL-C)-a highly atherogenic subfraction-remains unexplored. We aimed to evaluate the independent association between estimated sdLDL-C and gallstone risk, and to map potential cross-population dose-response relationships.
This dual-source cross-sectional study integrated a strictly defined Chinese clinical sample (n = 730, comprising 334 symptomatic surgical cases and 396 healthy controls from routine health check-ups) and the US NHANES database (n = 6,799). To facilitate large-scale, cost-effective screening, serum sdLDL-C was estimated using the internationally validated Sampson equation, strictly excluding subjects with extreme hypertriglyceridemia (TG ≥ 800 mg/dL). Multivariate logistic regression and two-piecewise models were utilized to evaluate independent associations and potential non-linear patterns. Sensitivity analyses rigorously excluded patients with major metabolic comorbidities (hypertension, diabetes, and clinical dyslipidemia).
In the multivariable-adjusted models, when analyzed as a continuous variable, elevated estimated sdLDL-C was significantly and positively associated with gallstone risk in both the Chinese sample (OR = 1.12, 95% CI: 1.08-1.15) and the NHANES cohort (OR = 1.03, 95% CI: 1.01-1.04). Sensitivity analysis excluding individuals with diabetes and hypertension confirmed the stability of this positive association (OR = 1.11, 95% CI: 1.07-1.15). Dose-response analysis revealed a non-linear threshold effect in the Chinese sample, with an inflection point at 34.51 mg/dL (sdLDL-C ≥ 34.51 mg/dL: OR = 1.27, 95% CI: 1.20-1.34, p < 0.001), whereas a steady linear association was observed in the NHANES population. Stratified analyses indicated that this positive association was particularly prominent in females and diabetic individuals.
Estimated sdLDL-C exhibits an independent and positive association with gallstone disease, suggesting it might be more than merely a secondary manifestation of late-stage metabolic syndrome. The identification of a specific non-linear threshold in the Chinese population, juxtaposed with a linear pattern in the US, suggests the potential value of exploring sdLDL-C for risk stratification in biliary diseases, though these cross-sectional findings require prospective validation.

PMID:
42769186
Bibliographic data and abstract were imported from PubMed on 22 Sep 2026.

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