G. Turpin

Cysteine is a cardiovascular risk factor in hyperlipidemic patients.

Several studies have reported that moderate hyperhomocysteinemia is related to an increased risk for atherosclerosis, but few data are available with regard to any other thiol compound having a potential vascular toxicity. Therefore, we measured both total cysteine and homocysteine plasma levels in patients with hyperlipidemia (242 males and 147 females, 41-65 years old). Homocysteine was higher in males than in females, 13.2+/-4.1 versus 11.1+/-3.4 micromol/l (P<0.0001). The mean cysteine level was 243.3+/-45.7 micromol/l in the whole study population. The subjects were split in two groups, symptomatic patients with cardiovascular disease (n = 106) and asymptomatic subjects (n = 283). Blood pressure, smoking status, total cholesterol, LDL-cholesterol and triglycerides did not statistically differ between groups, but the mean HDL-cholesterol level was lower in symptomatic patients (1.24+/-0.38 versus 1.42+/-0.41, P<0.0001). Cysteine levels were higher in patients with cardiovascular disease than in asymptomatic patients, respectively 254.7+/-47.7 versus 239.1+/-44.3 micromol/l (P = 0.003). A similar result was found for homocysteine, respectively 13.1+/-4.3 versus 12.2+/-3.9 micromol/l (P = 0.05). To analyse whether cysteine levels were related to atherosclerosis independently of age, adjusted levels were compared between asymptomatic patients with normal carotid arteries (n = 176), carotid atherosclerosis (n = 107) and symptomatic patients (n = 106). Age adjusted cysteine levels differed significantly between groups (P = 0.027) while the P-value was of borderline significance for homocysteine (P = 0.09). Odds ratios for having symptomatic cardiovascular disease were 1.81 (95% CI, 1.02-3.21) and 2.05 (95% CI, 1.16-3.60) for the mid and highest tertiles of cysteine using the lowest as the reference. After adjustment in a multivariate model including age, sex, and creatinine, the odds ratio for disease remained significant between the highest tertile versus the lowest (OR = 1.89). Adjusted odds ratios were found to be weaker when homocysteine tertiles were compared. Our data suggest that plasma total cysteine is a risk factor for atherosclerosis in hyperlipidemic patients.

Chronic hyperprolactinemia and plasma lipids in women

SummaryPlasma total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) were studied in 15 hyperprolactinemic women who had a prolactin (PRL) adenoma, in comparison to 15 age-matched control women. In the hyperprolactinemic group, plasma lipids were also correlated to age, excess body weight (EBW), plasma PRL, and estradiol-17β (E2). Plasma TC, TG, and LDL-C were similar in both hyperprolactinemic and control women, while plasma HDL-C was significantly lower (P<0.01) in the hyperprolactinemic group. The correlation study showed a significant negative correlation between HDL-C and EBW (r=−0.64;P<0.02) and a slightly significant positive correlation between TG and PRL (r=0.54;P<0.05). The direct effect of PRL on plasma lipids is difficult to establish since many factors influencing lipid metabolism are altered during hyperprolactinemia.

A study of the structural heterogeneity of low-density lipoproteins in two patients homozygous for familial hypercholesterolaemia, one of phenotype E2/2

Abstract The structural heterogeneity of the low‐density lipoproteins (d 1·019—1·063 g ml‐1) in two female patients homozygous for familial hypercholesterolaemia, one of phenotype E2/2, has been evaluated using a new ultracentrifugal density gradient procedure. The mass distribution, chemical composition, particle size and heterogeneity, hydrated density and apolipoprotein content of 16 LDL subfractions were determined. By gradient gel electrophoresis, the lighter LDL subfractions (d 1·016—1·037 g ml‐1) displayed a single particle species which progressively diminished in size from 24·8 to 22·0 nm with increase in density. By contrast, subfractions of higher density (d> 1·037 g ml‐1) exhibited two LDL particle species of distinct size; one component decreased in size from 21·8 to 20·4 nm with increase in density, while the second maintained an essentially constant diameter (between 22·5 and 23·5 nm) across these LDL subfractions. Immunoblotting with anti‐apo‐B100 of LDL subspecies separated by gradient gel electrophoresis showed all particles to contain apo‐B100. However, dot‐blots and immunoblotting with a monoclonal antibody to lipo‐protein (a) (Lp(a)) revealed that the LDL particle subspecies of greatest diameter (22·5—23·5 nm) present in the denser subfractions (d> 1·037 g ml‐1) also contained the Lp(a) antigen. These findings, taken together with the high plasma Lp(a) levels (> 60 mg dl‐1) in our patients, raise the possibility that Lp(a) may contribute in a significant manner to the atherogenic process in homozygous familial hypercholesterolaemia.

Étude clinique, biologique et génétique de la forme réguliére de la xanthomatose tendineuse hypercholestérol-émique familiale

Abstract The authors give a report of their experience of 250 cases of familial hypercholesterolaemic tendinous xanthomatosis, which constitutes the largest number of cases hitherto investigated. They emphasize the remarkable homogeneity and reproducibility of the clinical, extravascular and vascular as well as biological manifestations of this disease. It appears to be a special form of serious essential hypercholesterolaemia, or Type II hyperlipidaemia, intermediate between the “hyper-serious” form of Type II or cutaneo-tendinous xanthomatosis, which is presumed to be homozygotic, and the more common form of minor essential hypercholesterolaemia. The cardio-vascular prognosis of this disease is serious, although the attacks, especially coronary and cerebrovascular, occur most often in adults, leading to an often dramatic shortening of life, which is somewhat less severe in women than in men. The homogeneity of the clinical and biological aspects of this syndrome perhaps do not persist in such an absolute manner on genetic transmission, which is not rigorously univocal. But in all cases a dominant genetic determination, either monogenic or polygenic, is implicated.

Etude clinique, biologique, génétique et thérapeutique de la xanthomatose tubereuse pure A propos de 20 observations

Abstract On the basis of 20 cases of pure xanthoma tuberosum multiplex and data collected from the literature, the authors outline the clinical, biological, genetic and therapeutic characteristics of this affection. Clinically, the emphasis is on the exclusiveness of tuberous xanthomas (with the exception of borderline cases which involve a single small tendinous xanthoma), the fact that they are as persistent as the biological anomalies, and the importance and early occurrence of atheromatous complications. The characteristic biological feature is the truly intermediate position of the chemical as well as the electrophoretic lipid pattern between that of essential hypercholesteraemia and that of endogenous hyperglyceridaemia. This leads the author to a rejection of typological rigidity, which might preclude a comparison (so desirable in this context) of different electrophoretic patterns, specifically type III and type II + IV. The condition involves truly mixed hyperlipidaemia - both hypercholesteraemia and hyperglyceridaemia — which produces a pattern quite different from type II or essential hyperlipaemia. Genetically, it seems likely that pure xanthoma tuberosum multiplex, as expressive of mixed hyperlipidaemia, is a homologue of cutaneotendinous xanthoma as expressive of essential hypercholesteraemia, that is to say: a homozygous cumulate form of a minor defect, generally transmitted as an autosomal dominant. The above criteria, together with the excellent therapeutic response to a combination of dietetic measures (glucide restriction or total caloric restriction, and substitution of unsaturated fatty acids) and medication with aryloxybutyrate derivatives, characterize pure xanthoma tuberosum multiplex as a distinct pathological entity which is the prototype or reference model of mixed hyperlipidaemia.

Formes cutaneo-tendineuses de xanthomatose hypercholesterolemique etude clinique, biologique et genetique de 11 cas

Abstract In the light of personal observations studied and followed up in our Centre, a clinical and biological physiognomy might be ascribed to homozygotic forms of familial hypercholesterolaemic tendinous xanthomatosis (XTHF): The early appearance of cutaneous and tendinous xanthomas, the exceptional spread of cutaneous xanthomatosis, largely taking precedence over tendinous localisations, the unusual precocity and severity of the cardiovascular symptoms, point, after clinical examination, to a bilateral inheritance of a hypercholesterolaemic abnormality. The biological balance, revealing a considerable increase of the cholesterol in blood (about double the rate in the usual forms of XTHF) and the absence of an important or permanent hyperglyceridaemia, will support this diagnosis, confirmed by genetic research.