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.

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.