Impaired intravascular triglyceride lipolysis constitutes a marker of clinical outcome in patients with stable angina undergoing secondary prevention treatment: a long-term follow-up study

J Am Coll Cardiol. 2004 Jun 16;43(12):2225-32. doi: 10.1016/j.jacc.2003.11.065.

Abstract

Objectives: We sought to verify whether the intravascular metabolism of chylomicron-like emulsion may predict the clinical evolution of patients with coronary artery disease (CAD) undergoing secondary prevention therapy of CAD.

Background: Case-control studies have suggested an association between impaired intravascular catabolism of triglyceride (TG)-rich lipoproteins and CAD. However, evidence is lacking with respect to the potential clinical relevance of this metabolic disorder in CAD patients.

Methods: During a period of 4.5 +/- 0.9 years, we followed up 63 stable CAD patients (mean age 60 +/- 10 years) undergoing secondary prevention therapy (low-density lipoprotein cholesterol <100 mg/dl) in whom kinetic studies of the in vivo catabolism of chylomicron-like emulsions were performed. At enrollment into the study, fasting patients were injected intravenously with a chylomicron-like emulsion labeled with radioactive triglyceride (3H-TG) and cholesteryl esters (14C-CE) to evaluate the efficacy of intravascular TG lipolysis.

Results: At baseline, CAD patients displayed a diminished fractional clearance rate (FCR) for 3H-TG (-26%; p = 0.027), for 14C-CE (-37%; p = 0.015), and for delipidation index (DI) (-26%; p = 0.02) as compared with 35 control subjects. During follow-up of secondary prevention therapy, 33% of CAD patients (n = 21) presented with clinically refractory angina and aggravated coronary angiographic severity. The FCR for 3H-TG (-44%; p = 0.005) and DI (-41%; p = 0.006) in those patients with refractory angina was significantly lower than that observed in those with stable evolution. Moreover, in a Cox multivariate regression analysis, the presence of a DI less than the median value was an independent predictor of an unfavorable clinical evolution (adjusted hazard ratio 3.32; 95% confidence interval 1.21 to 9.14; p = 0.020).

Conclusions: The current study establishes that delayed intravascular TG lipolysis is a strong and independent predictor of evolution to severe angina among patients undergoing secondary prevention therapy of CAD.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angina Pectoris / metabolism*
  • Angina Pectoris / physiopathology
  • Angina Pectoris / prevention & control*
  • Biomarkers / blood
  • Brazil
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / drug effects
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / drug effects
  • Cholesterol, VLDL / blood
  • Cholesterol, VLDL / drug effects
  • Coronary Angiography
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / physiopathology
  • Coronary Artery Disease / prevention & control*
  • Emulsions
  • Female
  • Follow-Up Studies
  • Humans
  • Hypolipidemic Agents / therapeutic use*
  • Lipolysis / drug effects*
  • Lipolysis / physiology*
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Stroke Volume / physiology
  • Time
  • Treatment Outcome
  • Triglycerides / metabolism*

Substances

  • Biomarkers
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Cholesterol, VLDL
  • Emulsions
  • Hypolipidemic Agents
  • Triglycerides