IDL Composition and Angiographically Determined Progression of Atherosclerotic Lesions During Simvastatin Therapy

From the Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

Correspondence to Wayne H.F. Sutherland, Department of Medicine, University of Otago, PO Box 913, Dunedin, New Zealand.

Abstract—Some patients with coronary artery disease experience continued progression of one or more coronary lesions despite treatment with drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and markedly lower plasma cholesterol levels. We examined relationships between the progression of coronary artery lesions and plasma lipoproteins, in particular intermediate density lipoprotein (IDL) and its composition, in 38 patients with coronary artery disease who had been treated with simvastatin for 2 years. Patients were given lipid-lowering dietary advice; 3 months later they were started on simvastatin therapy (10 mg/d) for 1 month, and after review of their plasma cholesterol levels, the dose was increased to 20 mg/d and later to 40 mg/d if the target level of plasma cholesterol had not been attained. Progression of lesions was determined by serial quantitative coronary angiography (variability of 5.5%) and was defined as an increase in percent diameter stenosis (%S)10%; regression was defined as a decrease in %S 10%. The proportions of cholesteryl esters (CEs) and free cholesterol decreased significantly (P<.001), and proportions of protein and triglycerides increased significantly (P<.001) in IDL during simvastatin therapy. The CE content of IDL decreased significantly (-7.2 weight [wt]%, n=20, P<.001) in nonprogressors (patients who did not show progression of any lesions) and did not change significantly (-1.8 wt%, n=14, P=.36) in progressors (patients who showed progression of one or more lesions without regression of any lesion). This decrease in IDL CE content in nonprogressors was significantly (P=.01) different compared with the corresponding change in patients classified as progressors. Mean plasma cholesterol concentration tended to increase in progressors (0.47 mmol/L) and tended to decrease in nonprogressors (-0.39 mmol/L) during the initial 3-month diet period, and these changes were significantly different (P=.02). Furthermore, this change in plasma cholesterol level during the initial diet period was correlated significantly with the change in IDL CE content during the entire study (r=.348, n=38, P=.03). These data suggest that IDL CE content may be a determinant of progression of coronary lesions and may be influenced by compliance with or metabolic response to lipid-lowering dietary advice in patients with coronary artery disease during simvastatin treatment.

Key Words: angiography • diet • IDL • lesions • progression

This article has been cited by other articles:

				A. Yates, J. Norwig, J. C. Maroon, J. Bost, J. P. Bradley, M. Duca, D. A. Wecht, R. Grove, A. Iso, I. Cobb, et al. Evaluation of Lipid Profiles and the Use of Omega-3 Essential Fatty Acid in Professional Football Players Sports Health: A Multidisciplinary Approach, January 1, 2009; 1(1): 21 - 30. [Abstract] [Full Text] [PDF]

				J. Frohlich and M. Dobiasova Fractional Esterification Rate of Cholesterol and Ratio of Triglycerides to HDL-Cholesterol Are Powerful Predictors of Positive Findings on Coronary Angiography Clin. Chem., November 1, 2003; 49(11): 1873 - 1880. [Abstract] [Full Text] [PDF]

				U. Ravnskov Is atherosclerosis caused by high cholesterol? QJM, June 1, 2002; 95(6): 397 - 403. [Full Text] [PDF]

				C. Lee, F. Sigari, T. Segrado, S. Horkko, S. Hama, P. V. Subbaiah, M. Miwa, M. Navab, J. L. Witztum, and P. D. Reaven All ApoB-Containing Lipoproteins Induce Monocyte Chemotaxis and Adhesion When Minimally Modified : Modulation of Lipoprotein Bioactivity by Platelet-Activating Factor Acetylhydrolase Arterioscler. Thromb. Vasc. Biol., June 1, 1999; 19(6): 1437 - 1446. [Abstract] [Full Text] [PDF]