J Clin Lipidol. 2026 Sep 15:S1933-2874(26)00514-3. doi: 10.1016/j.jacl.2026.09.005. Online ahead of print.
ABSTRACT
BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C) is an atherogenic LDL-C subfraction associated with atherosclerotic cardiovascular disease (ASCVD). Although sdLDL-C integration into major routine risk assessments remains limited, partly because of requiring additional lipid tests, a more implementable estimated sdLDL-C equation was recently developed.
OBJECTIVE: This study aimed to evaluate the association between estimated sdLDL-C and incident ASCVD in a health checkup population of Japanese adults.
METHODS: Using the DeSC database in Japan, this study included adults aged 40 to 74 years who underwent health checkups between April 2014 and March 2023. Estimated sdLDL-C was calculated via the Sampson formula, and the primary outcome was the first incident ASCVD hospitalization via claims data. Estimated sdLDL-C was categorized into quartiles, and associations with incident ASCVD were evaluated using Cox regression models adjusted for sex, age, body mass index, hypertension, diabetes, smoking, alcohol, low HDL-C, high LDL-C, lipid-lowering medication, and fasting time. Subgroup analyses were conducted by LDL-C, sex, age, and ASCVD subtypes.
RESULTS: Among 1884,758 participants, 22,596 incident ASCVD events were observed. The Cox model showed ASCVD risk increased across estimated sdLDL-C quartiles, with a hazard ratio of 1.25 (1.20-1.31) for Q4. This association largely continued across sex, age, LDL-C, and ASCVD subtype subgroups, with stronger associations observed in male participants for coronary artery disease (CAD) than ischemic stroke, among younger individuals, and those with higher LDL-C.
CONCLUSION: Higher estimated sdLDL-C was associated with increased ASCVD risk, including among individuals with low LDL-C. Estimated sdLDL-C may improve ASCVD risk stratification beyond LDL-C and inform further primary prevention strategies.
PMID:42816230 | DOI:10.1016/j.jacl.2026.09.005