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Area of Science:

  • Cardiology
  • Lipid Metabolism
  • Preventive Medicine

Background:

  • Elevated triglycerides (TGs) and TG-rich lipoprotein cholesterol (TGRL-C) are associated with increased atherosclerotic cardiovascular disease (ASCVD) risk.
  • Observational studies and genetic data suggest a causal link between higher TG and TGRL-C levels and ASCVD.
  • Mechanistic studies support the biological plausibility of this association.

Purpose of the Study:

  • To review the evidence linking lower triglycerides (TGs) and TG-rich lipoprotein cholesterol (TGRL-C) levels to reduced atherosclerotic cardiovascular disease (ASCVD) event risk.
  • To evaluate the current evidence from observational studies and clinical trials regarding the impact of TG and TGRL-C lowering on ASCVD outcomes.

Main Methods:

  • Review of observational studies, including genetic variant analyses.
  • Analysis of subgroup data from randomized controlled trials (RCTs) investigating lipid-lowering therapies.
  • Assessment of mechanistic studies supporting the biological basis of the TG-ASCVD relationship.

Main Results:

  • Observational and genetic data consistently indicate that elevated TG and TGRL-C levels increase ASCVD risk.
  • Evidence from large-scale RCTs specifically targeting TG or TGRL-C elevation is currently limited, with several trials ongoing or in development.
  • Subgroup analyses of existing RCTs suggest potential ASCVD risk reduction with statins, fibrates, omega-3 fatty acid concentrates, and niacin in individuals with high TGs, especially when combined with low HDL-C.

Conclusions:

  • Current data suggest that therapies lowering TG and TGRL-C may offer benefits in reducing ASCVD.
  • Definitive evidence regarding the efficacy of TG- and TGRL-C-lowering therapies for ASCVD risk reduction is anticipated from ongoing outcomes trials.