Atherogenic lipoprotein heterogeneity beyond LDL-C in coronary heart disease: small dense LDL cholesterol and an internally validated nomogram

Low-density lipoprotein cholesterol (LDL-C) reflects the total cholesterol content of LDL particles but does not fully capture particle composition. Small dense LDL cholesterol (sdLDL-C) may provide complementary information on atherogenic lipoprotein heterogeneity beyond conventional LDL-C. This single-center retrospective case-control study included 22,073 hospitalized adults, comprising 17,631 patients with CHD and 4442 non-CHD controls. Multivariable logistic regression, restricted cubic splines, ROC analysis, lower-LDL-C analysis, and LDL-C-sdLDL-C discordance analysis were performed. Associations were additionally examined after adjustment for triglycerides (TG) and non-HDL-C, and large buoyant LDL cholesterol (lbLDL-C) was evaluated. An sdLDL-C-based nomogram was subsequently developed and internally validated. Patients with CHD had higher sdLDL-C, sdLDL-C/LDL-C ratios, TG, and non-HDL-C, but lower lbLDL-C, whereas between-group differences in LDL-C were small. In Model 3, which included TG, non-HDL-C, and LDL-C, each 1-SD increase in sdLDL-C and the sdLDL-C/LDL-C ratio was associated with higher odds of prevalent CHD (OR 2.37, 95% CI 2.26-2.49, and OR 3.52, 95% CI 3.28-3.76, respectively). lbLDL-C showed an inverse association in its adjusted model (OR 0.39, 95% CI 0.37-0.42). Associations of sdLDL-C and the ratio remained evident among participants with LDL-C < 2.60 mmol/L; those with low LDL-C but high sdLDL-C had higher odds of CHD (OR 6.01, 95% CI 5.29-6.82). Adding sdLDL-C or the ratio to the traditional lipid model increased the apparent AUROC from 0.8159 to 0.8565 or 0.8627, respectively. The eight-variable nomogram achieved a bootstrap-corrected AUROC of 0.879 with a calibration slope of 0.998. sdLDL-C captures atherogenic lipoprotein heterogeneity not fully reflected by LDL-C, with associations persisting after adjustment for TG and non-HDL-C and among participants with lower LDL-C or discordant lipid phenotypes. The sdLDL-C-based nomogram showed good internal discrimination and calibration, although external validation is required.