Pathophysiology and Natural History Thrombosis

Although the serum lipoprotein fraction Lp(a) has been associated with coronary artery atherosclerosis, its relationship to narrowing of saphenous vein grafts has not previously been elucidated. We therefore measured serum Lp(a) levels in 167 symptomatic patients undergoing cardiac catheterization who had had coronary artery bypass surgery 0.7 to 14.3 years earlier. Lp(a), total cholesterol, and total triglyceride levels were compared with the degree of saphenous vein graft stenosis to test for any association. Serum Lp(a) levels were significantly associated with the degree of stenosis of saphenous vein grafts (r = .24, p = .002). Mean Lp(a) levels (mg/dl) in the 135 patients with stenosis were almost double (32.0 + 32.7 mean ± SD) those in the 32 patients with no graft stenosis (16.7 ± 22.6; p = .002). Graft stenosis was not associated with previous myocardial infarction, hypertension, obesity, diabetes, or smoking. Serum cholesterol levels (mg/dl) were slightly higher in the stenosis group (251.3 ± 69) than in the no-stenosis group (231.8 ± 48.8), but the difference was of borderline significance (p = .06). A stepwise increase in mean Lp(a) was found in groups of patients with increasing vein graft stenosis. At a serum Lp(a) level of 31.6 mg/dl or above, 92% of the patients demonstrated vein graft stenosis. Thus, patients with elevated Lp(a) levels have an increased risk of developing saphenous vein graft stenosis after coronary bypass surgery. Circulation 77, No. 6, 1238-1244, 1988. AORTOCORONARY BYPASS with saphenous veins is currently the most widely used procedure for revascularizing the myocardium.'-' However, the clinical outlook for such patients has been somewhat dampened by recent reports of long-term patency that indicate that at 10 years or more after surgery, only about 60% of grafts remain patent,3'4 and that nearly one-half of the patent grafts show angiographic evidence of atherosclerosis.4 Several studies have reported an association between elevated serum cholesterol levels and atherosclerosis of vein grafts as determined at autopsy.5 6 Recently, plasma low-density lipoprotein (LDL) levels have been shown to be elevated and plasma high-density lipoprotein (HDL) levels reduced in patients with stenotic grafts more than 10 years after From the Departments of Brain and Vascular Research, Biostatistics and Epidemiology, Cardiology, and Cardiothoracic Surgery. The Cleveland Clinic Foundation, Cleveland, and the Department of Medical Biochemistry, Karl Franzens University of Graz, Graz, Austria. Supported in part by Public Health Service NIH grant HL-29582 and by an institutional grant. Address for correspondence: Henry F. Hoff, Ph.D., Research Institute (FF4), The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44106. Received August 10, 1987; revision accepted March 3, 1988. bypass surgery compared with levels in those with no demonstratable graft stenosis.` In this same study, graft stenosis correlated more closely with apolipoprotein B (apo B), the protein portion of LDL, than with LDL cholesterol. A number of clinical studies have demonstrated a link between stenosis due to atherosclerosis of native coronary arteries and serum Lp(a),'s a lipoprotein fraction originally discovered by Berg, 10 whose chemical properties are similar to those of LDL. "Such an association has also been shown to exist for stenosis in carotid16 17 and in cerebral arteries. 8 However, to date no study has demonstrated an association between serum Lp(a) levels and stenosis of saphenous vein grafts (SVGs). We therefore initiated a cross-sectional study of a group of symptomatic patients undergoing angiograms who had undergone bypass surgery 0.7 to 14.3 years earlier.