{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:08:14Z","timestamp":1788761294383,"version":"build-2803163510"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While conventional lipid parameters are linked to gallstone disease, the specific role of small dense low-density lipoprotein cholesterol (sdLDL-C)\u2014a highly atherogenic subfraction\u2014remains unexplored. We aimed to evaluate the independent association between estimated sdLDL-C and gallstone risk, and to map potential cross-population dose-response relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This dual-source cross-sectional study integrated a strictly defined Chinese clinical sample (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f730, comprising 334 symptomatic surgical cases and 396 healthy controls from routine health check-ups) and the US NHANES database (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f6,799). 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\u202f\u2265\u202f800\u202fmg\/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).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u202f=\u202f1.12, 95% CI: 1.08\u20131.15) and the NHANES cohort (OR\u202f=\u202f1.03, 95% CI: 1.01\u20131.04). Sensitivity analysis excluding individuals with diabetes and hypertension confirmed the stability of this positive association (OR\u202f=\u202f1.11, 95% CI: 1.07\u20131.15). Dose-response analysis revealed a non-linear threshold effect in the Chinese sample, with an inflection point at 34.51\u202fmg\/dL (sdLDL-C\u202f\u2265\u202f34.51\u202fmg\/dL: OR\u202f=\u202f1.27, 95% CI: 1.20\u20131.34,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2026.1922892","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:33:35Z","timestamp":1788759215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross-population heterogeneity in the association between estimated sdLDL-C and gallstone disease: a dual-source two-sample cross-sectional study"],"prefix":"10.3389","volume":"14","author":[{"given":"Wei","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qikai","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqun","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeben","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"16024","DOI":"10.1038\/nrdp.2016.24","article-title":"Gallstones","volume":"2","author":"Lammert","year":"2016","journal-title":"Nat Rev Dis 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