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Inflammation compared to low-density lipoprotein cholesterol: two different causes of atherosclerotic cardiovascular

Benjamin N Wadström1,2,3, Kasper M Pedersen1,2,3, Anders B Wulff1,2,3

  • 1Department of Clinical Biochemistry.

Current Opinion in Lipidology
|February 8, 2023
PubMed

Insights

Inflammation, specifically interleukin-6 (IL-6), and low-density lipoprotein (LDL) cholesterol are distinct causes of atherosclerotic cardiovascular disease (ASCVD). Research is ongoing for both anti-inflammatory therapies and improved LDL cholesterol-lowering treatments.

Area of Science:

  • Cardiovascular Science
  • Immunology
  • Genetics

Background:

  • Atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized as a condition influenced by inflammatory processes.
  • This review compares the etiological evidence for inflammation versus low-density lipoprotein (LDL) cholesterol in ASCVD pathogenesis.

Approach:

  • Systematic review of human genetic studies and randomized controlled trials.
  • Analysis of the inflammasome-IL-1-IL-6 inflammatory pathway.
  • Evaluation of current and emerging LDL cholesterol-lowering therapies.

Key Points:

  • Genetic studies and clinical trials implicate the IL-6 inflammatory pathway in ASCVD development.
  • Higher IL-6 levels correlate with increased ASCVD risk; IL-6 inhibitors are in clinical trials.
  • The causal link between LDL cholesterol and ASCVD is well-established, with advancements in RNA/DNA-based therapies.
  • While some lipid-lowering drugs reduce IL-6, these pathways are considered separate contributors to ASCVD.

Conclusions:

  • IL-6 mediated inflammation and LDL cholesterol are parallel causes of ASCVD.
  • High LDL cholesterol affects a larger population segment than elevated IL-6.
  • Future research should optimize anti-inflammatory therapies and enhance the implementation of LDL cholesterol-lowering strategies.
Abstract

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