Key result
High cholesterol in small remnants linked to ~21% greater ASCVD risk versus low content.
Why the study?
Small remnants may penetrate the arterial intima more efficiently than large TGRL, but whether the ASCVD risk from remnant cholesterol depends on particle size remained to be tested.
Does high cholesterol content in small remnants increase the risk of atherosclerotic cardiovascular disease in the general population?
Cohort (n=248,293)
Yes
Does high cholesterol content in small remnants increase the risk of atherosclerotic cardiovascular disease in the general population?
Hazard Ratio: 1.21 (95% CI 1.07–1.37)
High cholesterol content in small remnants, but not large triglyceride-rich lipoproteins, is associated with an increased risk of atherosclerotic cardiovascular disease.
Does not support remnant cholesterol testing in practice; leaves open whether small-remnant content independently predicts ASCVD.
BACKGROUND: Small remnants may penetrate the arterial intima more efficiently compared to large triglyceride-rich lipoproteins (TGRL). We tested the hypothesis that the importance of remnant cholesterol for the risk of atherosclerotic cardiovascular disease (ASCVD) may depend on the size of the remnants and TGRL carrying cholesterol. METHODS: The cholesterol content of small remnants and large TGRL were measured in 25 572 individuals from the Copenhagen General Population Study (2003-2015) and in 222 721 individuals from the UK Biobank (2006-2010) using nuclear magnetic resonance spectroscopy. In the Copenhagen cohort during up to 15 years of follow-up and in the UK Biobank cohort during up to 16 years of follow-up, the numbers of individuals diagnosed with ASCVD (=myocardial infarction, ischemic stroke, and peripheral artery disease) in national health registries were 3869 and 11 424, respectively. RESULTS: Compared to individuals with low cholesterol content in both small remnants and large TGRL (cutpoints were median cholesterol content), multivariable-adjusted hazard ratios for risk of ASCVD were 1.21 (95% confidence interval: 1.07-1.37) for individuals with high cholesterol content in small remnants only and 0.94 (0.83-1.07) for individuals with high cholesterol content in large TGRL only; the multivariable-adjusted hazard ratio for risk of ASCVD per 10 percentile-units higher cholesterol content in small remnants vs that in large TGRL was 1.04 (1.01-1.07). In the UK Biobank cohort, corresponding hazard ratios were 1.11 (1.03-1.20), 1.01 (0.93-1.09), and 1.05 (1.04-1.07), respectively. CONCLUSION: The importance of remnant cholesterol for the risk of ASCVD may depend on the size of the TGRL and remnants carrying cholesterol.
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Wadström et al. (2025) conducted a cohort in Atherosclerotic cardiovascular disease (ASCVD) (n=248,293). High cholesterol content in small remnants vs. Low cholesterol content in both small remnants and large TGRL was evaluated on Atherosclerotic cardiovascular disease (myocardial infarction, ischemic stroke, and peripheral artery disease) (HR 1.21, 95% CI 1.07-1.37). High cholesterol content in small remnants was associated with increased ASCVD risk compared to low content in both small and large remnants (HR 1.21, 95% CI 1.07-1.37 in the Copenhagen cohort).
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