Elevated LDL Triglycerides and Atherosclerotic Risk

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis* / complications
  • Atherosclerosis* / diagnosis
  • Cholesterol, LDL
  • Humans
  • Hypertriglyceridemia* / complications
  • Hypertriglyceridemia* / diagnosis
  • Ischemic Stroke*
  • Lipoproteins, LDL* / blood
  • Lipoproteins, LDL* / chemistry
  • Myocardial Ischemia / diagnosis
  • Peripheral Arterial Disease / diagnosis
  • Prospective Studies
  • Risk Factors
  • Triglycerides* / blood
  • Triglycerides* / chemistry

Substances

  • Cholesterol, LDL
  • low density lipoprotein triglyceride
  • Triglycerides
  • Lipoproteins, LDL