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Coronary artery disease in heterozygous familial hypercholesterolemia

Serum lipids, lipoproteins and Achilles tendon thickness in 52 patients with heterozygous familial hypercholesterolemia (FH) were investigated in order to clarify what are the important factors for the development of coronary artery disease (CAD) in heterozygous FH patients. There were no significant differences in the average concentration of total cholesterol and triglyceride between the patients with and those without CAD. The HDL cholesterol (HDL-C) level was significantly lower in patients with CAD than in those without, and the HDL-C value was within the normal range in most of the patients with heterozygous FH, if not associated with CAD. Although most of the males aged over 50 years had CAD and a decreased level of HDL-C, many of the aged females were without signs of CAD. The HDL-C value of heterozygous FH patients with CAD was significantly lower compared with the age-matched group without CAD. The Achilles tendon was thicker in patients with CAD than in those without CAD, both for males and females, although it was less closely correlated with the incidence of CAD than HDL-C or the atherogenic index. A forecast concerning the development of CAD in heterozygous FH may be possible if we consider multiple parameters, such as HDL-C, atherogenic index, Achilles tendon thickness, etc.

A new isoform of apolipoprotein E — Apo E-5 — Associated with hyperlipidemia and atherosclerosis

Heterogeneity of apolipoprotein E (apo E) was analyzed by isoelectric focusing of apo VLDL in patients with hyperlipidemia and/or atherosclerosis. Six major apo E phenotypes were shown, in agreement with the current genetic model which is composed of 3 major apo E isoproteins, apo E-4, apo E-3 and apo E-2, resulting from three apo E alleles, epsilon 4, epsilon 3 and epsilon 2, at a single genetic locus. We recognized an additional apolipoprotein band, which is located basic to apo E-4 on an isoelectric focusing gel, in 3 patients with hyperlipidemia. The new apolipoprotein component, named apo E-5, was identical with ordinary apo E in apparent molecular weight by SDS-polyacrylamide gel electrophoresis and in its interactions with heparin-Sepharose gel and with anti-apo E antibody. This mutant apo E isoprotein had an isoelectric point more basic by one unit of charge than apo E-4. Two of 3 patients had the phenotype E5/3, and the other the phenotype E5/4. Genetic analysis of the apo E phenotypes in family members of the patients indicated the presence of a new apo E allele (epsilon 5) at the same genetic locus as hitherto known alleles. Since most of the subjects above 50 years old with apo E-5 had ischemic heart disease or cerebral infarction, it was suggested that the mutant apo E-5 may possibly be related to the development of atherosclerosis.

Supravalvular aortic stenosis and coronary ostial stenosis in familial hypercholesterolemia: two-dimensional echocardiographic assessment.

The lesions of the aortic root, which are supravalvular aortic stenosis and coronary ostial stenosis, in familial hypercholesterolemia were studied using two-dimensional echocardiography. The subjects were 25 heterozygotes, six homozygotes and 30 control subjects.The internal diameters of the aortic ring, the sinus of Valsalva and the supravalvular aortic ring were measured. Measurement variation due to body size was avoided by normalizing the latter two values by the diameter of the aortic ring. Four heterozygotes and all homozygotes were judged to have stenosis of the supravalvular aortic ring; none of heterozygotes and four homozygotes had stenosis of the sinus of Valsalva. In three of the four patients with stenosis of both the supravalvular aortic ring and the sinus of Valsalva, a pressure gradient was demonstrated. The degree of supravalvular aortic stenosis correlated with the serum cholesterol level but not with patient age. All homozygotes, even very young ones, had a severe aortic root lesion. In the short-axis view of the aortic root, a lump (raised mass) on the aortic wall indicating atheromatous plaquing was demonstrated in five heterozygotes and all homozygotes. Coronary ostial stenosis was shown in three of the four patients whose plaquing echoes were adjacent to the coronary orifice.We conclude that two-dimensional echocardiography is useful in diagnosing lesions of the aortic root in patients with hypercholesterolemia.

Effect of Atenolol on Serum β2-Microglobulin Level in Hypertensive Diabetic Patients

The effects of atenolol (50 mg once daily) on serum beta 2-microglobulin levels in 11 hypertensive diabetic patients uncomplicated by renal dysfunction were studied. Atenolol significantly decreased serum beta 2-microglobulin levels (micrograms/mL) at four weeks (1.5 +/- 0.13) and at eight weeks (1.4 +/- 0.09) from pretreatment level (1.8 +/- 0.17) (P less than 0.05, respectively), along with statistically significant antihypertensive effects. Blood urea nitrogen, serum creatinine, fasting plasma glucose, HbA1C levels, and body weight remained unchanged. The results suggest that atenolol provides a favorable effect on renal function in hypertensive diabetic patients uncomplicated by renal dysfunction.