Hyperapobetalipoproteinemia (HyperapoB), defined as an elevated plasma level of the major apoprotin (B) of low density (beta) lipoproteins (LDL), in the presence of a normal level of LDL cholesterol, has been previously found in at least 50% of patients with coronary artery disease (CAD). Our goals here are to determine if HyperapoB explains a significant proportion of CAD, after other risk factors for CAD are considered, and to understand better the biochemical basis of HyperapoB.
Our specific aims are to determine: 1) if an elevated plasma LDL-B protein level per se predicts the presence of arteriographically defined CAD in 200 index cases (100 men, 100 women) undergoing coronary arteriography, after the influence of other risk factors are considered. These factors are plasma levels of total cholesterol; triglyceride; cholesterol in very low density (prebeta) VLDL (d less than 1.006 g/ml), intermediate density lipoproteins (IDL, d 1.006-1.019 gm/ml), LDL (d 1.019-1.063 g/ml), total high density (alpha) lipoproteins (HDL), and HDL subfractions (HDL2 (d 1.063-1.12 g/ml) and HDL3 (d 1.12-1.21 g/ml); apoA I; and Lp(a) lipoprotein. LDL B will be measured by radial immunodiffusion (RID) in both plasma and the d greater than 1.019 g/ml untracentrifugal infranate. Blood pressure, obesity, diabetes, cigarette smoking, and family history of CAD will also be assessed. There will be two control groups: those index cases without CAD; and the spouses (n = 160) of the index cases. Univariate and multivariate analyses and a model of risk factor interaction will be used to determine if plasma LDL B level strongly and independently predicts CAD; 2) if the expression of HyperboB persists with time and is due to the presence of a smaller, denser fraction of LDL enriched in B protein and depleted in cholesterol. The index cases and spouses will be restudied (Visit 2), and a subset (36 index cases [12 hypertriglyceridemic HyperaboB; 12 normotriglyceridemic HyperaboB and 12 normal] and their spouses) will return for a third visit. The composition of LDL (cholesterol/B protein) and the sizes of the LDL fractions( determined by gradient gel electrophoresis) will be determined at Visits 1, 2 and 3. At Visit 3, LDL and its fractions will be characterized further by density gradient ultracentrifugation, chemical composition, gravimetric analysis and polyacrylamide gel electrophoresis. These studies may explain a significant proportion of the risk of CAD that is currently poorly understood and improve our understanding of HyperaboB.
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