[Hypoalphalipoproteinemia and atherosclerosis. Genetic and biochemical profile of 10 families].

The results of lipoprotein studies performed in 67 members of 10 kindreds with familial hypoalphalipoproteinemia are presented. Probands were ten patients referred to the Lipid Clinic of the National Institute of Cardiology for evaluation of their lipid profile, all of whom had history of a definite myocardial infarction occurring before they had reached age 60. Their only plasma lipid abnormality was a reduction of the cholesterol fraction associated with high-density lipoproteins (C-HDL) below the corresponding age-sex specific fifth percentile. We studied 57 other individuals including probands spouses and available first-degree relatives. All participants were clinically examined and their complete coronary risk factor profile was assessed. After a 12 hour fast, plasma samples were obtained for lipid analysis, total cholesterol and trïglycerides were measured by enzymatic methods, C-HDL was determined in the supernatant after plasma precipitation with magnesium chloride: phosphotungstic acid. Low-density lipoprotein cholesterol (C-LDL) was estimated with the formula proposed by DeLong. For every family a pedigree was constructed and statistically analyzed to assess the within-family clustering of low C-HDL levels and the pattern of transmission of the abnormal phenotypes. Mean C-HDL level for propositii was 24.3 mg/dl, the corresponding value for the C-LDL/C-HDL ratio (atherogenic index) was 4.9 and it was elevated above 3.5 (average coronary risk) in 7/10 (70%) of these patients. Obesity, defined by a Quetelet index above 28 in men and 26 in women was present in 4/10 (40%) of the probands, 3/10 (30%) had stable non insulin-dependent diabetes mellitus, prevalence figures for the other coronary risk factors was very low. In addition to probands, the hypoalphalipoproteinemic phenotype was found in 30/57 (52.6%) subjects including spouses (two cases) and first-degree relatives. For these 30 cases the mean C-HDL value was 32 mg/dl. In all ten reported kindred, we clearly observed either horizontal, vertical or both types of within-family transmission of the aberrant phenotype. This finding was considered to be most compatible with the presence of a primary genetic abnormality affecting C-HDL metabolism in all these kindreds in spite of the fact that some of the probands had some conditions like diabetes or obesity that are sometimes associated with secondary reductions of C-HDL. Due to the lack of a reliable biochemical marker, the distinction between primary and secondary hypoalphalipoproteinemia in individual cases is frequently impossible, for this reason the diagnostic assessment depends on family studies.(ABSTRACT TRUNCATED AT 400 WORDS)