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From the Statistical Consultation and Research Center, Department of Preventive Medicine (W.J.M., H.N.H.), and the Atherosclerosis Research Unit, Division of Cardiology, Department of Medicine (H.N.H.), University of Southern California, Los Angeles, and Donner Laboratory (R.M.K.), Lawrence Berkeley National Laboratory, University of California, Berkeley.
Abstract Accumulating evidence suggests that
triglyceride-rich lipoproteins contribute to
coronary artery disease. Using data from the Monitored
Atherosclerosis Regression Study, an angiographic trial
of middle-aged men and women randomized to lovastatin
or placebo, we investigated relationships between lipoprotein
subclasses and progression of coronary artery
atherosclerosis. Coronary artery lesion
progression was determined by quantitative coronary angiography
in low-grade (<50% diameter stenosis), high-grade
(
50% diameter stenosis), and all coronary artery
lesions in 220 baseline/2-year angiogram pairs. Analytical
ultracentrifugation was used to measure lipoprotein
masses that were statistically evaluated for treatment group
differences and relationships to progression of coronary artery
atherosclerosis. All low density lipoprotein (LDL),
intermediate density lipoprotein (IDL), and very low density
lipoprotein (VLDL) masses were significantly lowered and all high
density lipoprotein (HDL) masses were significantly raised with
lovastatin therapy. The mass of smallest LDL (Svedberg
flotation rate [Sf] 0 to 3), IDL (Sf 12 to
20), all VLDL subclasses (Sf 20 to 60, Sf 60 to
100, and Sf 100 to 400), and peak LDL flotation rate were
significantly related to the progression of coronary artery
lesions, specifically low-grade lesions. Greater baseline levels of
HDL3 were related to a lower likelihood of coronary
artery lesion progression. In multivariate
analyses, small VLDL (Sf 20 to 60) and
HDL3 mass were the most important correlates of
coronary artery lesion progression. These results provide
further evidence for the importance of
triglyceride-rich lipoproteins in the progression of
coronary artery disease. In addition, these results present
new evidence for the possible protective role of HDL3 in
the progression of coronary artery lesions. More specific
information on coronary artery lesion progression may be
obtained through the study of specific apolipoprotein Bcontaining
lipoproteins.
Key Words: triglyceride-rich lipoproteins coronary angiography angiographic trials lipoprotein subclasses coronary artery disease
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