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. 2023 Jan 17;81(2):136-152.
doi: 10.1016/j.jacc.2022.10.019.

Elevated LDL Triglycerides and Atherosclerotic Risk

Mie Balling  1 , Shoaib Afzal  1 , George Davey Smith  2 , Anette Varbo  1 , Anne Langsted  1 , Pia R Kamstrup  3 , Børge G Nordestgaard  4
Affiliations
Free article

Elevated LDL Triglycerides and Atherosclerotic Risk

Mie Balling et al. J Am Coll Cardiol. .
Free article

Abstract

Background: It is unclear whether elevated low-density lipoprotein (LDL) triglycerides are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD).

Objectives: This study tested the hypothesis that elevated LDL triglycerides are associated with an increased risk of ASCVD and of each ASCVD component individually.

Methods: The study investigators used the Copenhagen General Population Study, which measured LDL triglycerides in 38,081 individuals with a direct automated assay (direct LDL triglycerides) and in another 30,208 individuals with nuclear magnetic resonance (NMR) spectroscopy (NMR LDL triglycerides). Meta-analyses aggregated the present findings with previously reported results.

Results: During a median follow-up of 3.0 and 9.2 years, respectively, 872 and 5,766 individuals in the 2 cohorts received a diagnosis of ASCVD. Per 0.1 mmol/L (9 mg/dL) higher direct LDL triglycerides, HRs were 1.26 (95% CI: 1.17-1.35) for ASCVD, 1.27 (95% CI: 1.16-1.39) for ischemic heart disease, 1.28 (95% CI: 1.11-1.48) for myocardial infarction, 1.22 (95% CI: 1.08-1.38) for ischemic stroke, and 1.38 (95% CI: 1.21-1.58) for peripheral artery disease. Corresponding HRs for NMR LDL triglycerides were 1.26 (95% CI: 1.20-1.33), 1.33 (95% CI: 1.25-1.41), 1.41 (95% CI: 1.31-1.52), 1.13 (95% CI: 1.05-1.23), and 1.26 (95% CI: 1.10-1.43), respectively. The foregoing results were not entirely statistically explained by apolipoprotein B levels. In meta-analyses for the highest quartile vs the lowest quartile of LDL triglycerides, random-effects risk ratios were 1.50 (95% CI: 1.35-1.66) for ASCVD (4 studies; 71,526 individuals; 8,576 events), 1.62 (95% CI: 1.37-1.93) for ischemic heart disease (6 studies; 107,538 individuals; 9,734 events), 1.30 (95% CI: 1.13-1.49) for ischemic stroke (4 studies; 78,026 individuals; 4,273 events), and 1.53 (95% CI: 1.29-1.81) for peripheral artery disease (4 studies; 107,511 individuals; 1,848 events).

Conclusions: Elevated LDL triglycerides were robustly associated with an increased risk of ASCVD and of each ASCVD component individually in 2 prospective cohort studies and in meta-analyses of previous and present studies combined.

Keywords: atherosclerosis; cardiovascular disease; lipids; remnants; triglyceride-rich lipoproteins; very low-density lipoprotein.

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Conflict of interest statement

Funding Support and Author Disclosures This study was funded by the Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital; the Danish Heart Foundation (grant 18-R124-A8511-22089 MB); the Novo Nordisk Foundation (grant NNF18OC0052893 MB); and the Medical Research Council Integrative Epidemiology Unit at the University of Bristol (grant MC_UU_00011/1 GDS). The funders did not participate in the design or conduct of the study; in the collection, analysis, or interpretation of data; and in preparation, review, or approval of the manuscript. Dr Davey Smith has served on the scientific advisory boards of Relation Therapeutics and insitro. Dr Varbo is employed by Novo Nordisk. Dr Kamstrup has received lecture honoraria from Physicians’ Academy for Cardiovascular Education; and has served as a consultant for Silence Therapeutics and Novartis. Dr Nordestgaard has served as a consultant for Akcea, Amarin, Amgen, AstraZeneca, Abbott, Denka, Kowa, Novartis, Novo Nordisk, Sanofi, Regeneron, Esperion, and Silence Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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