Pathophysiology and Natural History Atherosclerosis

Studies were undertaken to determine whether there is an association between elevated levels of intermediate-density lipoproteins (IDL) (Sf 12-60 lipoproteins) and coronary artery disease. Forty-five to sixty-five-year-old men with objectively documented coronary artery disease (n = 58) who were free ofknown risk factors (diabetes, hypertension, obesity, hyperuricemia, and hypercholesterolemia) were compared with similar men who were free of coronary artery disease (n = 52). Smokers could not be excluded. The coronary artery disease group had a higher rate of cigarette smoking (NS, due to large variations); higher concentrations of triglycerides in their plasma (p = .003) and higher levels of very low-density lipoproteins (VLDL) (p = .007), IDL (p = .016), and lowdensity lipoproteins (LDL) (p = .04); as well as somewhat lower levels of high-density lipoprotein (HDL) cholesterol (p = .04). Chi-squared analysis demonstrated a strong association between coronary artery disease and IDL apolipoprotein (apo) B (p = .006), coronary artery disease and IDL triglyceride (p = .032), and coronary artery disease and IDL apo B times IDL triglyceride (p = .006) when the top quintile of the population was compared with the bottom quintile for each of these variables. Stepwise logistic regression analysis resulted in rejection of an association between coronary artery disease and HDL cholesterol, plasma triglyceride, VLDL triglyceride, or LDL triglyceride. However, it did show that coronary artery disease was most strongly associated with smoking and that the second strongest association was with IDL. It was of interest that among those who were free of coronary artery disease, the men who currently smoked had higher levels of IDL apo B and of IDL triglyceride than did the men who never smoked or had not smoked for at least 2 years. However, even among those who never had smoked or had not smoked for at least 2 years, coronary artery disease was associated with increased levels of both IDL apo B and IDL triglyceride. Hence, although current smoking influenced IDL levels, the association between coronary artery disease and elevated IDL levels did not appear to depend on smoking. Since the majority of triglyceride-rich lipoproteins are found in the IDL fraction, these findings may be important in understanding the role of the triglyceriderich lipoproteins in atherosclerosis. Circulation 75, No. 1, 124-130, 1987. THE PRESENT STUDIES were undertaken to determine whether coronary artery disease is associated with an increase in the plasma concentration of intermediate-density lipoprotein (IDL). Initially, IDL was defined ultracentrifugally as the Sf 12-20 fraction and very low-density lipoprotein (VLDL) as the Sf 20-400 From the Department of Medicine, University of Toronto, and the Division of Endocrinology and Metabolism, Toronto General Hospital. Supported by grants from the Heart and Stroke Foundation of Ontario and the Canadian Diabetes Association. Address for correspondence: Dr. George Steiner, Division of Endocrinology and Metabolism, Room EN 11-225, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada. Received May 19, 1986; revision accepted Sept. 11, 1986. 124 fraction. Turnover studies have shown that a one-third larger fraction, the Sf 12-60 fraction, in fact conforms more closely to the kinetic characteristics of the catabolic remnants ofVLDL. l 2Hence, we and others now use the Sf 12-60 limits to define IDL and Sf 60-400 to define VLDL more physiologically.` Three-quarters of the triglyceride-rich lipoprotein particles in the plasma of individuals with mild-to-moderate hypertriglyceridemia are IDL.4 Aortic endothelial cells readily bind VLDL5 and arterial smooth muscle cells can take up remnants of VLDL.6 Other pathophysiologic evidence linking the catabolic remnants of chylomicrons to athCIRCULATION by gest on A ril 5, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-ATHEROSCLEROSIS erogenesis has been reviewed.7 Hence, it is possible that VLDL remnants may be linked to atherogenesis. Patients with type III hyperlipoproteinemia have a marked increase in the incidence of coronary artery disease and in the remnants of triglyceride-rich lipoproteins.8 In 1951, Jones et al.9 had already observed an increase in the concentration of the Sf 12-20 subfraction of lipoproteins in male survivors of myocardial infarction. More recently, Nestel et al. 0 have reported an increase in IDL levels in patients with chronic renal failure, a disorder associated with accelerated atherogenesis. That group has also reported that, at least in women, IDL levels are correlated with the severity of coronary artery disease. " Against this background, we reported a pilot study suggesting that coronary artery disease can be associated with increased levels of IDL.'2 The present study was undertaken to examine this more definitively and to determine whether it was independent of changes in other lipoproteins. During the study, we also observed that smoking can increase the level of IDL.