[Recommendations of the French National Health Authority for management of high blood pressure in clinical practice]. / Les recommandations de la Haute Autorité de Santé sur la prise en charge de l'HTA à l'épreuve des faits.

UNLABELLED: The new recommendations of the French national authority for health (or Haute Autorité de Santé: HAS) concerning management of high blood pressure (HBP) deserve to be compared with real clinical practices in a large population. MATERIAL AND METHODS: [corrected] EPIMIL is a prospective epidemiological study designed to assess the prevalence of the metabolic syndrome and the risk factors in a 2045 French male military personnel coming from Paris area. The different recommendations of the HAS have been applied to these subjects, and the aim of this work is to compare these theoretical objectives to what is done in real practice. RESULTS: Among these 2045 subjects aged of mean 38,6 +/- 8,8 years, 78 (4%) are known and treated for HPB. Although half of them present more than two associated risk factors, the means of systolic blood pressure and diastolic blood pressure stay at high levels. The blood pressure (BP) targets established at 140/90 mmHg are only reached by 33 patients (42%). Among the 1967 subjects considered to have normal BP, the BP considered as optimal (120/80 mmHg) is only found in 695 subjects (35.3%) and 428 (21.7%) do present ignored or neglected HBP, in spite of the presence of important associated risk factors. Then, the cardiovascular risk stratification into levels, as recommended by the HAS, shows that for these subjects considered to have normal BP, risk is finally low for 6%, moderate for 12%, and high for 3.5%. COMMENTS: In a selected and in theory regularly followed population, the recommendations of the HAS are insufficiently applied, as well for detection or treatment of HBP. Then, information of both medical personnel and also the interested parties should be necessary, in order to see these recommendations applied in real practice.

Epidemiology of the metabolic syndrome in 2045 French military personnel (EPIMIL study).

CONTEXT: The Metabolic syndrome is considered to be an important public health problem, but few epidemiological studies have defined the present situation in France. EPIMIL is a prospective epidemiological study that began on February 1, 2003. SUBJECTS AND METHODS: This study was designed to identify the clinical and laboratory parameters of metabolic syndrome and cardiovascular risk factors in a population of 2045 male military personnel based in the Paris region. The initial 1-year cross-sectional study will be followed by a 10-year follow-up and patient care. RESULTS: The 2045 subjects included 185 (9%) presented at least 3 of the 5 NCEP ATP III criteria defining metabolic syndrome. They were significantly older (42.2 +/- 8.5 yrs) than the other subjects (37.3 +/- 8.7 yrs, P<0.001), had a higher BMI (29.5 +/- 3.4 vs 24.8 +/- 2.9 kg/m2, P<0.001) and a greater body weight at age 20 (75.4 +/- 11 vs 70.4 +/- 8.5 kg, P<0.01). Smoking, little physical activity and family histories of diabetes and arterial hypertension were more frequent in these men. While levels of the cholesterol and CRP us were higher, Lp(a) and homocysteine concentrations were normal. Plasma insulin and BMI (r = 0.456 P<0.0001) and plasma insulin and waist circumference (r = 0.446 P<0.0001) were well correlated. Lastly, plasma insulin, free fatty acids and cardiovascular risk increased steadily with the increase in the number of metabolic syndrome criteria. CONCLUSIONS: These results in a large and particularly uniform population of men show the prevalence of metabolic syndrome in adult men, and demonstrate its link with insulin resistance. Men with several risk factors require specific care, particularly for hypertension and dyslipidemia; the effectiveness of this care will be evaluated during the follow-up period.

[Is mild hyperhomocysteinemia an additional risk factor of the metabolic syndrome?]. / L'hyperhomocystéinémie est-elle un facteur de risque supplémentaire du syndrome métabolique?

INTRODUCTION: Metabolic syndrome is a cardiovascular risk factors cluster and hyperhomocysteinemia an obvious independant risk factor. OBJECTIVE: To ascertain if hyperhomocysteinemia is associated with the metabolic syndrome. METHODS: "Epimil" is a prospective epidemiologic survey, which began by a cross-sectionnal study of cardiovascular risk factors in a French population, which then will be followed for ten years for supervision and intervention. Initial data collection, blood pressure measurement, ECG and blood samples (biology and DNA) have been performed. For the metabolic syndrome, we used the criterias of the third report of the national cholesterol education program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (NCEP ATP III). RESULTS: Out of 2045 men aged from 20 to 58 years (37.7+/-8.7 years), 185 (9%) have metabolic syndrome (at least three criterias), 587 (29%) a blood homocysteine>or=12 micromol/L and 202 (10%)>or=15 micromol/L. Homocysteinemia is 10.97+/-5.01 micromol/L for the whole population and doesn't differ with (11.4+/-6 micromol/L) or without (10.9+/-5 micromol/L) the metabolic syndrome, as does its values distribution. It's not correlate with the body mass index, waist and hip measurements, nor with glycemia, HbA1c, insulin resistance and cardiovascular risk markers (CRPus, microalbuminuria). It weakly correlates with systolic and diastolic blood pressure, creatinine clearance, tobacco use, cholesterolemia, triglycerides and free fatty acids but not with HDL and LDL fractions, nor lipoprotein (a). Among this population, it slightly contributes to the ten years vascular risk evaluated according to Framingham equations or Score system. CONCLUSIONS: Homocysteinemia and the prevalence of hyperhomocysteinemia don't differ with or without the metabolic syndrome and doesn't correlate its main criterias.

Comparison of the efficacy of simvastatin and standard fibrate therapy in the treatment of primary hypercholesterolemia and combined hyperlipidemia.

Five multicenter, randomized, double-blind, placebo-controlled studies were conducted in France to compare the efficacy and safety of once-daily simvastatin treatment (10-40 mg/day) with conventional therapy with gemfibrozil 900 mg/day, ciprofibrate 100 mg/day, bezafibrate 400 mg/day, and fenofibrate 300 or 400 mg/day in a total of 800 patients with hypercholesterolemia. Simvastatin was associated with statistically significantly greater (p < or = 0.01) mean percent reductions in plasma low-density lipoprotein (LDL) cholesterol compared with each of the five fibrate regimens, even when administered at its recommended starting dose of 10 mg/day. Furthermore, approximately 90% of patients treated once daily with simvastatin experienced an at least 20% decrease in plasma LDL cholesterol compared with only 36 to 68% of patients treated with the individual fibrate agents (p < or = 0.05). The effectiveness of simvastatin in reducing LDL cholesterol did not differ as a function of the baseline plasma concentrations of total cholesterol or triglycerides. In contrast, the effectiveness of fibrate therapy in lowering plasma LDL cholesterol levels was significantly diminished (p < or = 0.05) among patients with triglyceride concentrations > 1.7 mmol/l. Plasma high-density lipoprotein (HDL) cholesterol levels were increased by approximately 10% after treatment with simvastatin or the fibrates. Although fibrate therapy was more effective overall in lowering plasma triglyceride levels, the effectiveness of simvastatin in reducing plasma triglyceride levels was generally 2- to 4-fold greater in patients with hypercholesterolemia associated with triglyceride levels > or = 2.3 mmol/l than in those with hypercholesterolemia associated with triglyceride levels < 2.3 mmol/l. The results of these studies confirm the superiority of simvastatin to standard fibrate therapy in reducing plasma levels of total and LDL cholesterol. They further indicate that once-daily treatment with simvastatin is effective in patients with isolated hypercholesterolemia or hypercholesterolemia associated with elevated triglyceride levels.

[Comparison of the efficacy between simvastatin and gemfibrozil in primary hypercholesterolemia]. / Comparaison de l'efficacité de la simvastatine et du gemfibrozil dans l'hypercholestérolémie primaire. Groupe d'Etude Français.

The efficacy on plasma lipids, apo A1 and B of a HMG Co A Reductase inhibitor, simvastatin, and a fibrate derivative, gemfibrozil, were compared in 136 hypercholesterolemic patients. The study was randomized, double-blinded and the active drug was given after a 4 week period of placebo. Gemfibrozil (n = 69) was given at 900 mg q.p.m. during the entire study. The primary dose of simvastatin was 10 mg q.p.m. during the first 6-weeks of treatment. At the end of this period, the dose was doubled if the cholesterol level was above 2 g/l (5,16 mmol/l). The same modification was carried out 12 weeks after the beginning active drug treatment with the same criteria. The baselines of total cholesterol were 3.24 +/- 0.69 g/l (8.38 +/- 1.78 mmol/l) 3.21 +/- 0.72 g/l (8.31 +/- 1.87 mmol/l) for patients with simvastatin and those with gemfibrozil respectively. So, at the end of active treatment, 64% of patients in the simvastatin group (n = 67) received 40 mg q.p.m. After 18 weeks of treatment, 89% of patients treated with Simvastatin and 37% with gemfibrozil had more than 20% reduction in LDL cholesterol. Simvastatin was more efficient on total cholesterol, LDL-C and apo B. The increase of HDL-C is similar in both groups of patients. In contrast, the level of triglycerides was further decreased by gemfibrozil. The tolerance was good in the two groups of patients and no difference in the frequency of side effects was observed.

Permanent administration of d-fenfluramine in rats: paradoxical effects.

In order to test the hypothesis of Levitzky that d-fenfluramine (d-F) acts by modifying the ponderal set-point, we compared the effects of a permanent infusion of d-F on food intake and body weight (BW). The effect on the weight persisted as long as the infusion; the clear-cut anorectic effect lasted only a few days. This paradox is compatible with the set-point hypothesis. In rats rendered overweight by insulin treatment, the d-F-induced decrease in BW was approximately four times smaller than in controls. In rats rendered overweight by a cafeteria diet, the decrease in BW was twice as large in permanently cafeteria fed rats as in cafeteria, then, ad lib fed rats. In rats rendered underweight by a restricted chow diet and then returned to an ad lib feeding, the final BW depended only on the doses of d-F (0.6 or 12 mg/kg BW/day), whatever the weight at the beginning of infusion. Thus, the underweight paradigm fits well with the set-point hypothesis; the overweight paradigm fits only partially.

Comparative effects of several simple carbohydrates on erythrocyte insulin receptors in obese subjects.

The effects of simple carbohydrates on erythrocyte insulin receptors, plasma insulin and plasma glucose were studied during four hypocaloric, hyperproteic, diets. One diet contained no carbohydrate; the other three contained 36 g of either glucose, galactose or fructose. These diets were given for a 14-day period to groups of moderately obese subjects. The hypocaloric carbohydrate-free diet produced a decrease in plasma insulin and glucose concentrations concomitant with an increase in the number of insulin receptors. A similar increase in insulin receptor number was found when the diet was supplemented with glucose or galactose, but not with fructose. The presence of fructose in the diet prevented any increase in insulin receptor number.

Stress and sucrose hyperphagia: role of endogenous opiates.

Two experimental situations induce hyperphagia in the rat: the cafeteria model and the tail-pinching model. In non-deprived rats which are offered for one hour a choice of 3 liquid cafeteria items in addition to ordinary chow and water, mild tail-pinching results in a preferential sucrose hyperphagia; naltrexone (2.5 mg/kg IP) suppresses this stress-induced hyperphagia; beta-endorphin (3 micrograms ICV) has the same effect. This apparent discrepancy is discussed: the antagonist may suppress the hyperphagia because it suppresses the reward provoked by the sucrose, the agonist because it makes it unnecessary.

Effects of an overfeeding regimen--the affective component of the sweet sensation.

In some isolated parts of North Africa, there persists an ancient Berber custom of imposing an overfeeding regimen on young girls before marriage, to achieve an obesity which is regarded as aesthetically pleasing. We have studied the effect of such a regimen, lasting 12--16 weeks, on blood lipids and on the affective reactions to sweet tastes in nine subjects. It is known that the pleasantness of alimentary cues i.e., the feeding behaviour, depends on the subject's nutritional state. Only three subjects gained weight (by 3,5 and 8 kg), in spite of the strong pressure to overeat. No change in plasma lipid concentrations were observed. Nevertheless, at the end of the regimen every subject showed a highly significant decrease in the rated pleasantness of sweet stimuli when they were tested fasting. However, the reduction in sweet pleasantness induced by ingestion of a 200 ml load of 1.4 M glucose solution was not changed by the overfeeding. Thus, pressure to overfeed can reduce hunger, as seen in the attractiveness of sweet foods in fasted subjects, without modifying glucose-induced satiety.

Energy and nitrogen balances in 24 severely burned patients receiving 4 isocaloric diets of about 10 MJ/m2/day (2392 Kcalories/m2/day).

Twenty-four subjects with burns ranging from 25-70 per cent received for 12 days exclusively per os a series of 4 isocaloric diets of about 4000 Kcal--'normal', or hyperproteic, or hyperlipidic, or hyperglucidic according to a randomized schedule. Oxygen consumptions were measured at the end of each diet and nitrogen balance was determined every day. Though patients were not massively overfed there remained a positive energy gap. The nitrogen balance was found to be equilibrated on the whole but clearly positive with the hyperproteic diet and clearly negative with the hyperlipidic-normoproteic diet. Thus there is no rationale for the huge energy overfeeding classically used.

Effects of slimming and composition of diets on VO2 and thyroid hormones in healthy subjects.

Oxygen consumption and plasma thyroid hormone concentrations are modified by both low- and high-calorie diets. It has been suggested that the trigger may be changes in weight ("adipostatic" hypothesis involving the difference between the actual weight and the "set point") or changes in amount of carbohydrate in the diet ("carbohydrate" hypothesis). Two experiments were performed in order to test both hypotheses. Fourteen young healthy volunteers were studied: 1) at their spontaneous stable weight; 2) while losing weight rapidly on a calorically restricted diet; 3) and then at their stable new weight when consuming a refeeding diet. The calorie restricted diet resulted in decrease of VO2, and T3, and an increase of rT3; the refeeding diet resulted in values of VO2, T3, and rT3 intermediate between those of the spontaneous diet and those of the restricted diet. Another group of nine subjects were studied at their spontaneous caloric and proteic levels, comparing a diet containing only protein and carbohydrate with a diet containing only protein and fat. During the low carbohydrate diet rT3 increased and T3 decreased but they remained unchanged during the carbohydrate-rich diet. Thus neither the adipostatic hypothesis nor the carbohydrate hypothesis is sufficient alone to explain the observed changes in serum T3 and rT3.

Effects of a high protein very-low-energy diet on ambulatory subjects with special reference to nitrogen balance.

Forty young healthy ambulatory volunteers were given a very-low-energy diet (2.34 MJ, 560 kcal) containing 70 g of proteins of good biological value, 36 g carbohydrates, 2 g potassium, 0.5 g sodium, polyvitamins and 21 water. The nitrogen balance reached equilibrium on the 8th day. No risk factors were found. These results were compared with 4000 cases collected over 12 years. The latter were given a protein diet with neither salt nor carbohydrates. The addition of salts and carbohydrates resulted only in an increase of the subjects' comfort. The analysis of deaths occurring in the U.S.A. after protein diets lead to the conclusion that these very probably linked to the duration of the protein diet, the poor biological value of proteins provided, the insufficiency in potassium intake. The conditions for a safe use of a very-low-energy diet, are a large intake of proteins of good biological value, a large intake of potassium and probably small intake of carbohydrates and sodium.