Circulation, Vol 90, 42-49, Copyright © 1994 by American Heart Association
HN Hodis, WJ Mack, SP Azen, P Alaupovic, JM Pogoda, L LaBree, LC Hemphill, DM Kramsch and DH Blankenhorn
BACKGROUND: The Monitored Atherosclerosis Regression Study, a randomized,
double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy,
found that coronary lesions < 50% diameter stenosis (%S) and coronary
lesions > or = 50% S at baseline had different responses to therapy. We
now report on clinical, lipid, and nonlipid risk factors of treatment
response in these lesion subsets. METHODS AND RESULTS: Two hundred seventy
subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295
mg/dL (4.91 to 7.63 mmol/L) and total triglyceride < 500 mg/dL (5.65
mmol/L) were randomized to low-fat, low-cholesterol diet and either
lovastatin 80 mg/d or placebo. Logistic regression was used to model the
association between risk factors and coronary lesion progression in
mild/moderate (< 50% S) and severe (> or = 50% S) lesions in 220
angiogram pairs analyzed by computer quantitative coronary angiography. In
the placebo group, risk factors (P < .05) for the progression of
mild/moderate lesions were triglycerides and TC/high-density lipoprotein
cholesterol (HDL-C). Risk factors for the progression of severe lesions
were HDL-C (negative), low-density lipoprotein cholesterol (LDL-C)/HDL-C,
and TC/HDL-C. TC/HDL-C was the predominant risk factor for both
mild/moderate and severe lesions in the multivariate analysis. In the
lovastatin group, with aggressive lowering of LDL-C and TC below 85 mg/dL
and 156 mg/dL, respectively, risk factors for mild/moderate lesions
included triglycerides and very-low-density lipoprotein-LDL- associated
apolipoprotein C-III (apo C-III-heparin precipitate), a marker of
triglyceride-rich lipoprotein particles. Apo C-III-heparin precipitate was
the predominant risk factor in the multivariate analysis. Risk factors for
severe lesions were LDL-C, LDL-C/HDL-C, TC/HDL-C, and apo B; LDL-C/HDL-C
was the predominant risk factor. CONCLUSIONS: These results indicate that
triglyceride-rich lipoproteins and cholesterol-rich lipoproteins have a
differential effect on mild/moderate and severe lesion progression,
respectively. These results add to the growing evidence of the importance
of triglyceride- rich lipoproteins as a risk factor for coronary artery
disease and the need for treatment in the progression of atherosclerosis.
ARTICLES
Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin
Atherosclerosis Research Institute, University of Southern California School of Medicine, Los Angeles 90033.
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J. Hasler-Rapacz, M. F. Prescott, J. Von Linden-Reed, J. M. Rapacz Jr, Z. Hu, and J. Rapacz Elevated Concentrations of Plasma Lipids and Apolipoproteins B, C-III, and E Are Associated With the Progression of Coronary Artery Disease in Familial Hypercholesterolemic Swine Arterioscler Thromb Vasc Biol, May 1, 1995; 15(5): 583 - 592. [Abstract] [Full Text]
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