High Remnant Cholesterol Increases CVD Odds, Especially in Patients With Diabetes

New data presented at the 2025 American Heart Association Scientific Sessions in New Orleans, Louisiana, demonstrates that elevated remnant cholesterol (RC) is independently associated with higher odds of prevalent cardiovascular disease (CVD), with a more pronounced association in patients with diabetes compared with those without.¹

What Is Remnant Cholesterol?

RC is rapidly emerging as a strong predictor of adverse outcomes and increased CVD risk. Research shows that heightened RC can serve as predictors for diseases such as metabolic dysfunction-associated steatotic liver disease and chronic kidney disease. Elevated RC is also associated with a composite of adverse cardiovascular events, such as stroke and myocardial infarction. As an alternative to traditional lipid measures, RC can help better explain the excess CVD risk seen in patients with diabetes.^2-4

Evidence suggests that RC is independently associated with diabetes, even if traditional lipid indicators are at appropriate levels, yet it is unclear how CVD risk attributed to RC differs by diabetes status. In the current investigation, researchers assessed the diabetes-stratified association between RC and prevalent CVD in US adults. Data from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 was used for their analysis.^1,5

How Are Remnant Cholesterol and CVD Risk Associated?

A total of 29,342 survey participants aged 40 or older were analyzed. RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated low-density lipoprotein cholesterol (LDL-C) and was categorized into quartiles for individuals with (n = 10,793) and without diabetes (n = 18,549). CVD was defined as self-reported congestive heart failure, coronary heart disease, angina, myocardial infarction, or stroke. A multivariable logistic regression estimated adjusted odds ratios and confidence intervals for prevalent CVD by RC quartile and was stratified by diabetes status.¹

For participants with and without diabetes, CVD prevalence was 4135 (38.3%) and 4400 (23.7%), respectively. OR for CVD per standard deviation increase in log-transformed RC in patients with diabetes was 1.11 (95% CI, 1.07–1.16; P < .001) and 1.03 (95% CI, 0.99–1.07; P < .001) for patients without diabetes. CVD prevalence was observed to be highest in the highest versus lowest RC quartile, measured at 40.1% versus 37.3% for patients with diabetes and 24.9% versus 23.6% for patients without diabetes.¹

OR for CVD when comparing the highest to lowest RC quartile was 1.38 (95% CI, 1.22–1.56; P < .001) for diabetes and 1.18 (95% CI, 1.07–1.31; P < .001) for patients without diabetes.¹

How Can Pharmacists Manage Remnant Cholesterol?

These data suggest that elevated RC levels are independently associated with higher odds of prevalent CVD, with more significant associations observed in individuals with diabetes. According to the researchers, their results highlight that these patients have increased susceptibility to RC-driven atherogenesis. For individuals with diabetes, utilizing RC in primary and secondary prevention efforts could yield earlier recognition of CVD risk, allowing for prompt and tailored cholesterol reduction.

Given the ease of RC calculation and its growing role as a CVD predictor, pharmacists—especially those in lipid or CVD clinics—can work to integrate RC data into their practices. Patients with diabetes face a heightened risk of CVD when RC is at its highest, so these patients should be especially monitored and counseled on the benefits of lipid-lowering treatment to effectively reduce RC levels.

REFERENCES

1. Cheon P, O’Connor S, Ononye CB et al. Association of remnant cholesterol with prevalent cardiovascular disease in individuals with and without diabetes: A cross-sectional analysis of NHANES 2005–2018. Presented: 2025 American Heart Association Scientific Sessions; November 10, 2025; New Orleans, LA. Accessed via AHA Virtual Platform on November 19, 2025.

2. Halpern L. Remnant cholesterol, independent of LDL-C, serves as predictor of MASLD. Pharmacy Times. Published July 24, 2025. Accessed November 19, 2025. https://www.pharmacytimes.com/view/remnant-cholesterol-independent-of-ldl-c-serves-as-predictor-of-masld

3. Halpern L. Remnant cholesterol directly associated with higher risk of chronic kidney disease development. Pharmacy Times. Published June 19, 2025. Accessed November 19, 2025. https://www.pharmacytimes.com/view/remnant-cholesterol-directly-associated-with-higher-risk-of-chronic-kidney-disease-development

4. Halpern L. Elevated remnant cholesterol, Lp-PLA2 linked to heightened risk of composite adverse events. Pharmacy Times. Published July 4, 2025. Accessed November 19, 2025. https://www.pharmacytimes.com/view/elevated-remnant-cholesterol-lp-pla2-linked-to-heightened-risk-of-composite-adverse-events

5. Li B, Zhou X, Wang W, et al. Remnant cholesterol is independently associated with diabetes, even if the traditional lipid is at the appropriate level: A report from the REACTION study. J Diabetes. 2023;15(3):204-214. doi:10.1111/1753-0407.13362