Abstract Body (Do not enter title and authors here): Background: Both diabetes and dyslipidemia are well-established risk factors for cardiovascular disease (CVD). However, traditional lipid measures do not fully explain the excess CVD risk observed in individuals with diabetes. Remnant cholesterol (RC) is an emerging contributor to this residual risk, and evidence shows that RC levels are higher in those with diabetes. Despite this, the extent to which the cardiovascular risk attributed to RC differs by diabetes status remains unclear.

Objective: To assess the diabetes-stratified association between RC and prevalent CVD in U.S. adults.

Methods: We analyzed 29,342 participants aged ≥40 years from the National Health and Nutrition Examination Survey (NHANES) 2005–2018. RC (mg/dL) was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated low-density lipoprotein cholesterol (LDL-C) and categorized into quartiles for individuals with (n=10,793) and without diabetes (n=18,549). Prevalent CVD was defined as self-reported congestive heart failure, coronary heart disease, angina, myocardial infarction, or stroke. Multivariable logistic regression estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for prevalent CVD by RC quartile and per standard deviation (SD) increase in log-transformed RC, stratified by diabetes status.

Results: The prevalence of CVD was 4135 (38.3%) and 4400 (23.7%) among participants with and without diabetes, respectively. The OR (95% CI) for CVD per SD increase in log-transformed RC in those with and without diabetes was 1.11 (1.07–1.16; P < 0.001) and 1.03 (0.99–1.07; P = 0.11), respectively. CVD prevalence was higher in the highest vs. lowest RC quartile: 40.1% vs. 37.3% (diabetes), and 24.9% vs. 23.6% (non-diabetes). The OR for CVD comparing highest to lowest RC quartile was 1.38 (1.22–1.56; P < 0.001) for diabetes and 1.18 (1.07–1.31; P = 0.001) for non-diabetes. (Table). The interaction p-value between RC and diabetes status was < 0.001.

Conclusion: Elevated RC levels were independently associated with higher odds of prevalent CVD, with a more pronounced association observed among individuals with diabetes compared to those without. This suggests increased susceptibility to RC-driven atherogenesis in the setting of diabetes. These findings support the potential utility of RC in both primary and secondary prevention efforts, especially for individuals with diabetes.