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Remnant Cholesterol, Not LDL Cholesterol, Explains Peripheral Artery Disease Risk Conferred by apoB: A Cohort Study
Benjamin N Wadström1, Kasper M Pedersen1, Anders B Wulff1
1Department of Clinical Biochemistry and the Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Denmark. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Arteriosclerosis, Thrombosis, and Vascular Biology
|March 21, 2024
Summary
Elevated remnant cholesterol significantly increases peripheral artery disease (PAD) risk. Myocardial infarction risk is linked to both remnant and LDL cholesterol, highlighting different lipoprotein roles in cardiovascular disease.
Area of Science:
- Cardiovascular Disease Research
- Lipoprotein Metabolism and Atherosclerosis
Background:
- Elevated apolipoprotein B (apoB)-containing lipoproteins, including remnants and low-density lipoproteins (LDLs), are established risk factors for atherosclerotic cardiovascular diseases.
- Peripheral artery disease (PAD) and myocardial infarction (MI) are significant manifestations of atherosclerotic cardiovascular disease linked to elevated apoB.
- The specific contributions of remnant and LDL cholesterol to the risk of PAD, chronic limb-threatening ischemia, and MI require further elucidation.
Purpose of the Study:
- To test the hypothesis that both remnant and LDL cholesterol partially explain the increased risk of PAD associated with elevated apoB-containing lipoproteins.
- To compare the risk contributions of remnant and LDL cholesterol for PAD, chronic limb-threatening ischemia, and myocardial infarction.
- To validate findings using both cholesterol measurements and particle counts for remnants and LDLs.
Main Methods:
- Analysis of 93,461 individuals without statin use from the Copenhagen General Population Study (2003-2015) and 302,167 from the UK Biobank (2004-2010).
- Measurement of apoB, remnant cholesterol, and LDL cholesterol. Remnant and LDL particle counts were additionally measured in a subset using nuclear magnetic resonance spectroscopy.
- Follow-up for incident PAD, chronic limb-threatening ischemia, and myocardial infarction, with results adjusted for multiple variables.
Main Results:
- In the Copenhagen study, a 1 mmol/L increase in remnant cholesterol was associated with a 1.9-fold increased risk of PAD, while LDL cholesterol showed a 1.1-fold increase.
- Remnant cholesterol explained 73% of the apoB-associated PAD risk, whereas LDL cholesterol explained 8%.
- For myocardial infarction, remnant and LDL cholesterol explained 41% and 54% of the apoB-associated risk, respectively, with findings consistent across both cohorts and measurement methods.
Conclusions:
- The elevated risk of peripheral artery disease (PAD) associated with high apoB-containing lipoproteins is primarily driven by elevated remnant cholesterol.
- In contrast, myocardial infarction risk is influenced by both elevated remnant and LDL cholesterol levels.
- These findings underscore the distinct roles of remnant and LDL particles in mediating different types of atherosclerotic cardiovascular disease.
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