| Title: | Association of Apolipoprotein B-Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis |
| Journal: | JAMA Cardiology |
| Published: | 1 Mar 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34773460/ |
| DOI: | https://doi.org/10.1001/jamacardio.2021.5083 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590731 |
| Citations: | 136 (101 in last 2 years) as of 8 Aug 2024 |
Publication 4174
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
IMPORTANCE: Lipid management typically focuses on levels of low-density lipoprotein cholesterol (LDL-C) and, to a lesser extent, triglycerides (TG). However, animal models and genetic studies suggest that the atherogenic particle subpopulations (LDL and very-low-density lipoprotein [VLDL]) are both important and that the number of particles is more predictive of cardiac events than their lipid content.</p>
OBJECTIVE: To determine whether common measures of cholesterol concentration, TG concentration, or their ratio are associated with cardiovascular risk beyond the number of apolipoprotein B (apoB)-containing lipoproteins.</p>
DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort analysis included individuals from the population-based UK Biobank and from 2 large international clinical trials, FOURIER and IMPROVE-IT. The median (IQR) follow-up was 11.1 (10.4-11.8) years in UK Biobank and 2.5 (2.0-4.7) years in the clinical trials. Two populations were studied in this analysis: 389 529 individuals in the primary prevention group who were not taking lipid-lowering therapy and 40 430 patients with established atherosclerosis who were receiving statin treatment.</p>
EXPOSURES: ApoB, non-high-density lipoprotein cholesterol (HDL-C), LDL-C, and TG.</p>
MAIN OUTCOME AND MEASURES: The primary study outcome was incident myocardial infarction (MI).</p>
RESULTS: Of the 389 529 individuals in the primary prevention group, 224 097 (58%) were female, and the median (IQR) age was 56.0 (49.5-62.5) years. Of the 40 430 patients with established atherosclerosis, 9647 (24%) were female, and the median (IQR) age was 63 (56.2-69.0) years. In the primary prevention cohort, apoB, non-HDL-C, and TG each individually were associated with incident MI. However, when assessed together, only apoB was associated (adjusted hazard ratio [aHR] per 1 SD, 1.27; 95% CI, 1.15-1.40; P < .001). Similarly, only apoB was associated with MI in the secondary prevention cohort. Adjusting for apoB, there was no association between the ratio of TG to LDL-C (a surrogate for the ratio of TG-rich lipoproteins to LDL) and risk of MI, implying that for a given concentration of apoB-containing lipoproteins, the relative proportions of particle subpopulations may no longer be a predictor of risk.</p>
CONCLUSIONS AND RELEVANCE: In this cohort study, risk of MI was best captured by the number of apoB-containing lipoproteins, independent from lipid content (cholesterol or TG) or type of lipoprotein (LDL or TG-rich). This suggests that apoB may be the primary driver of atherosclerosis and that lowering the concentration of all apoB-containing lipoproteins should be the focus of therapeutic strategies.</p>
11 Keywords
- Apolipoproteins B
- Atherosclerosis
- Cholesterol
- Cholesterol, LDL
- Cohort Studies
- Female
- Humans
- Lipoproteins
- Male
- Myocardial Infarction
- Prospective Studies
14 Authors
- Nicholas A. Marston
- Robert P. Giugliano
- Giorgio E. M. Melloni
- Jeong-Gun Park
- Valerie Morrill
- Michael A. Blazing
- Brian Ference
- Evan Stein
- Erik S. Stroes
- Eugene Braunwald
- Patrick T. Ellinor
- Steven A. Lubitz
- Christian T. Ruff
- Marc S. Sabatine
Enabling scientific discoveries that improve human health