Estimated small dense low-density lipoprotein cholesterol in predicting atherosclerotic cardiovascular disease: Longitudinal evidence from over 1 million Japanese adults.

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.