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Exploring the Causal Roles of Circulating Remnant Lipid Profile on Cardiovascular and Cerebrovascular Diseases:
Shucheng Si1, Lei Hou1, Xiaolu Chen1
1Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University.
Insights
This study found that certain remnant lipids, like those in small and medium very-low-density lipoprotein particles, increase the risk of coronary heart disease (CHD) and myocardial infarction (MI). However, larger remnant particles may have neutral or protective effects, suggesting targeted interventions for cardiovascular disease (CVD) prevention.
Area of Science:
- Cardiovascular epidemiology
- Lipid metabolism and disease
- Genetic epidemiology
Background:
- Causal links between circulating lipids, particularly remnant cholesterol, and cardiovascular/cerebrovascular diseases (CVD) remain unclear.
- Existing research lacks definitive evidence on the specific roles of various lipid profiles in CVD pathogenesis.
- Understanding these associations is crucial for developing effective CVD prevention strategies.
Purpose of the Study:
- To investigate the causal relationships between extensive circulating lipid traits, with a focus on remnant lipids, and the risk of CVD.
- To differentiate the impact of various lipid profiles and remnant particle sizes on coronary heart disease (CHD) and ischemic stroke (IS).
- To identify potential therapeutic targets for CVD intervention based on lipid profiles.
Main Methods:
- Employed a two-sample Mendelian randomization (TSMR) analysis utilizing large-scale meta-analysis datasets from European ancestry populations.
- Assessed the causal effects of 15 circulating lipid profiles (6 conventional, 9 remnant) on coronary heart disease (CHD) and ischemic stroke (IS), including subtypes.
- Utilized genetic variants as instrumental variables to infer causality between lipid traits and cardiovascular outcomes.
Main Results:
- Apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were confirmed as significant risk factors for CHD and myocardial infarction (MI), but not IS.
- Specific remnant lipid subfractions, including TG in medium (M.VLDL.TG), small (S.VLDL.TG), and very small (XS.VLDL.TG) VLDL particles, and TG in intermediate-density lipoprotein (IDL.TG) particles, robustly increased CHD and MI risk.
- Conversely, TG in very/extremely large VLDL particles (XXL.VLDL.TG, XL.VLDL.TG) showed insignificant or negative associations with CHD and IS, indicating a potential protective role or lack of risk.
Conclusions:
- Remnant lipids exhibit heterogeneous and potentially opposing effects on the risk of CHD and IS, influenced by particle size.
- Intervention strategies targeting remnant lipids should be component-specific, considering the varying impact of different particle sizes.
- This research provides strong causal evidence supporting remnant lipids as critical targets for future CVD prevention and therapeutic interventions.
Background:
Causal evidence of circulating lipids especially the remnant cholesterol with cardiovascular and cerebrovascular disease (CVD) is lacking. This research aimed to explore the causal roles of extensive lipid traits especially the remnant lipids in CVD.
Methods:
Two-sample Mendelian randomization (TSMR) analysis was performed based on large-scale meta-analysis datasets in European ancestry. The causal effect of 15 circulating lipid profiles including 6 conventional lipids and 9 remnant lipids on coronary heart disease (CHD) and ischemic stroke (IS), as well as the subtypes, was assessed.
Results:
Apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were still important risk factors for CHD and myocardial infarction (MI) but not for IS. Apo B is the strongest which increased the CHD and MI risk by 44% and 41%, respectively. The odds ratios (ORs) of total TG on CHD and MI were 1.25 (95% confidence interval [CI], 1.13-1.38) and 1.24 (95% CI, 1.11-1.38), respectively. A one standard deviation difference increased TG in medium very-low-density lipoproteins (M.VLDL.TG), TG in small VLDL (S.VLDL.TG), TG in very small VLDL (XS.VLDL.TG), TG in intermediate-density lipoproteins (IDL.TG), TG in very large HDL (XL.HDL.TG), and TG in small HDL (S.HDL.TG) particles also robustly increased the risk of CHD and MI by 9-28% and 9-27%, respectively. TG in very/extremely large VLDL (XXL.VLDL.TG and XL.VLDL.TG) were insignificant or even negatively associated with CHD (in multivariable TSMR), and negatively associated with IS as well.
Conclusion:
The remnant lipids presented heterogeneity and two-sided effects for the risk of CHD and IS that may partially rely on the particle size. The findings suggested that the remnant lipids were required to be intervened according to specific components. This research confirms the importance of remnant lipids and provides causal evidence for potential targets for intervention.
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