| Title: | Quantifying Triglyceride-Rich Lipoprotein Atherogenicity, Associations With Inflammation, and Implications for Risk Assessment Using Non-HDL Cholesterol |
| Journal: | Journal of the American College of Cardiology |
| Published: | 1 Oct 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39322327/ |
| DOI: | https://doi.org/10.1016/j.jacc.2024.07.034 |
Publication 13295
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Abstract
BACKGROUND: Triglyceride-rich lipoproteins and remnants (TRL/remnants) have a causal, but not yet quantified, relationship with coronary heart disease (CHD): myocardial infarction plus revascularization.</p>
OBJECTIVES: The authors sought to estimate TRL/remnant per-particle atherogenicity, investigate causal relationships with inflammation, and determine whether differences in the atherogenicity of TRL/remnants and low-density lipoprotein (LDL) impact the causal association of non-high-density lipoprotein cholesterol (non-HDL-C) with CHD.</p>
METHODS: Single nucleotide polymorphisms (SNPs) (N = 1,357) identified by genome-wide association in the UK Biobank were ranked into 10 clusters according to the effect on TRL/remnant-C vs LDL-C. Mendelian randomization analysis was used to estimate for each SNP cluster CHD ORs per 10 mg/dL apolipoprotein B (apoB) and per 0.33 mmol/L non-HDL-cholesterol, and to evaluate association of TRL/remnants with biomarkers of systemic inflammation.</p>
RESULTS: SNPs in cluster 1 predominantly affected LDL-C, whereas SNPs in cluster 10 predominantly affected TRL/remnant-C. CHD risk per genetically predicted increase in apoB and in non-HDL-C rose across clusters. ORs per 10 mg/dL higher apoB was 1.15 (95% CI: 1.11-1.19) in cluster 1 vs 1.70 (95% CI: 1.52-1.90) in cluster 10. Comparing ORs between these TRL/remnant-predominant and LDL-predominant clusters, we estimated that TRL/remnants were at least 3.9 (95% CI: 2.8-5.4) times more atherogenic than LDL on a per-particle basis. For non-HDL-C, CHD ORs per 0.33 mmol/L rose from 1.15 (95% CI: 1.11-1.19) for cluster 1 to 1.40 (95% CI: 1.30-1.50) for cluster 10. TRL/remnants exhibited causal relationships with inflammation, but this did not explain their greater atherogenicity.</p>
CONCLUSIONS: TRL/remnants are about 4 times more atherogenic than LDL. Variation in the causal association of non-HDL-C with CHD indicates that adjustment for percentage TRL/remnant-C may be needed for accurate risk prediction.</p>
19 Keywords
- Aged
- Atherosclerosis
- Biomarkers
- Cholesterol
- Cholesterol, HDL
- Cholesterol, LDL
- Coronary Disease
- Female
- Genome-Wide Association Study
- Humans
- Inflammation
- Lipoproteins
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Polymorphism, Single Nucleotide
- Risk Assessment
- Triglycerides
- United Kingdom
7 Authors
- Elias Björnson
- Martin Adiels
- Anders Gummesson
- Marja-Riitta Taskinen
- Stephen Burgess
- Chris J Packard
- Jan Borén
1 Application
| Application ID | Title |
|---|---|
| 82018 | Improved biomarkers of cardiovascular disease |
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