Estimated Small Dense LDL-Cholesterol Is Independently Associated With Arterial Stiffness: A Large Japanese Screening Study

Objective: Small dense low-density lipoprotein cholesterol (sdLDL-C) is an established atherogenic marker; however, whether estimated sdLDL-C (EsdLDL-C) is related to atherosclerosis remains unclear. In this study, we assessed the association between EsdLDL-C levels, calculated using the Sampson formula, and brachial–ankle pulse wave velocity (baPWV), an objective indicator of arterial stiffness. Design and method: We conducted a retrospective observational study including health examinees (January 2007 to December 2019). Of 25,472 individuals with baPWV, 23,623 were included in the study after exclusion. The primary outcome was baPWV > 1400 cm/s, and the primary explanatory variable was EsdLDL-C level. A multivariate logistic regression analysis was performed. EsdLDL-C and LDL-C levels were dichotomized at the median values to create four cross-classified groups (low/low, low/high, high/low, high/high, and reference low/low). Results: EsdLDL-C levels were independently associated with an increased risk of arterial stiffness, as measured by baPWV values > 1400 cm/s, in the overall population. Specifically, for every 10 mg/dL increase in EsdLDL-C levels, the risk of arterial stiffness increased by approximately 22%, with a high level of statistical confidence (adjusted odds ratio OR, 1.219 per 10 mg/dL; 95% confidence interval CI, 1.172–1.280). This association was consistently observed in both men and women. In the four-group analysis, a high EsdLDL-C level was associated with increased odds, irrespective of LDL-C levels, whereas a low EsdLDL-C level was not associated with increased risk, even when LDL-C levels were high. Conclusions: In a large Japanese screening cohort, EsdLDL-C was independently associated with elevated baPWV and provided risk information distinct from that of LDL-C, supporting its potential utility in atherosclerosis risk stratification.