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CLINICAL RESEARCH: TRIGLYCERIDES AND RISK

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

Andrei C. Sposito, MD, PhD^*, Pedro A. Lemos, MD, Raul D. Santos, MD, PhD, Whady Hueb, MD, PhD, Carmen G. C. Vinagre, PhD, Edgard Quintella, MD, Otavio Carneiro, MD, M. John Chapman, PhD, DSc, Jose A. F. Ramires, MD, PhD, FACC^* and Raul C. Maranhão, MD, PhD^,*

^* Heart Institute (InCor), Zerbini Foundation, Brasilia, Brazil
Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
INSERM Unité 551, Hôpital de la Pitié-Salpetriere, Paris, France
Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

Manuscript received January 29, 2003; revised manuscript received November 7, 2003, accepted November 13, 2003.

^* Reprint requests and correspondence: Prof. Raul C. Maranhão, Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina USP, Av. Dr. Eneas Carvalho Aguiar, 44., 05403.900 São Paulo, SP, Brazil.
ramarans{at}usp.br

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.

Abbreviations and Acronyms   ACAD = aggravating coronary artery disease   ACE = angiotensin-converting enzyme   CAD = coronary artery disease   CE = cholesterol ester   CI = confidence interval   DI = delipidation index   FCR = fractional clearance rate   HDL = high-density lipoprotein   HR = hazard ratio   LDL = low-density lipoprotein   LPL = lipoprotein lipase   SCAD = stable coronary artery disease   TG = triglyceride   VLDL = very low-density lipoprotein

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