Lipoprotein-associated phospholipase A2 activity is increased in patients with definite familial hypercholesterolemia compared with other forms of hypercholesterolemia.

BACKGROUND AND AIM: Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a key role in atherosclerosis development. It is considered a marker of increased risk of cardiovascular disease (CVD) and plaque vulnerability. Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol and a higher prevalence of early CVD. Our aim was to evaluate the differences in Lp-PLA2 activity in a population of hypercholesterolemic patients with and without definite FH. METHODS AND RESULTS: Hypercholesterolemic patients were consecutively recruited. Definite FH was defined according to Dutch Lipid Clinic Network criteria ≥8. All patients underwent routine clinical examination and biological assessments and Lp-PLA2 activity was measured in blood samples. Among 469 patients, 118 had a definite diagnosis of FH. Lp-PLA2 activity was significantly higher in definite FH patients compared to non-definite FH patients (206.5 ± 54.5 vs. 180.8 ± 48.4 nmol/min/mL, p < 0.0001). Lp-PLA2 positively correlated with total cholesterol, LDL-C and apolipoprotein B and negatively with HDL-C and apolipoprotein A-1. In multivariate analysis, definite FH diagnosis, LDL-C, HDL-C and statin treatment remained correlates of Lp-PLA2 independently of systolic blood pressure. CONCLUSIONS: Lp-PLA2 activity was higher in definite FH than in non-definite FH patients independently of LDL-C levels and statin treatment. These results highlight the particular phenotype of FH subjects among hypercholesterolemic patients. As increased Lp-PLA2 activity suggests, FH patients exhibit higher arterial inflammation that may contribute to their high cardiovascular risk. Our results reinforce the potential beneficial role of statins pleiotropic effects and the need for proper identification and treatment of FH patients.

Psychological predictors of the combined adoption of physical exercise and dietary change among adults with hypercholesterolemia.

BACKGROUND: Although combined changes in eating habits and physical activity are pivotal to hypercholesterolemia management and the prevention of cardiovascular disease, little is known about the factors influencing the adoption of both behaviors by adults with hypercholesterolemia. The goal of this study was to identify psychological factors that predict a combined adoption of dietary modification and physical activity among adults with hypercholesterolemia. METHODS: We recruited a sample of 1100 adults with hypercholesterolemia (56.9% male, mean age=56.5 years) through a nationally representative online panel. Participants reported their physical activity using the International Physical Activity Questionnaire (IPAQ) and their eating habits using a Food-Frequency Questionnaire (FFQ). We assessed a comprehensive set of psychological variables, including hypercholesterolemia knowledge and perception, patient's cardiovascular history, doctor-patient relationship, social-cognitive beliefs, and personality traits. Based on IPAQ and FFQ scores, we classified participants into four groups (dietary modification plus physical exercise, dietary modification, physical exercise, passive). RESULTS: Our analysis showed that subjective hypercholesterolemia knowledge, beliefs about the effects of hypercholesterolemia, external locus of control (other people and chance), nutrition and physical exercise self-efficacy, and trait self-control significantly influenced the simultaneous adoption of physical exercise and dietary modification. CONCLUSIONS: This study highlights the importance of psychological factors in predicting the combined adoption of physical exercise and dietary modification among adults with hypercholesterolemia. Addressing these factors could help improve hypercholesterolemia prevention strategies.

Cardiovascular risk and lifestyle habits of consumers of a phytosterol-enriched yogurt in a real-life setting.

BACKGROUND: Data on the characteristics of consumers of phytosterol-enriched products and modalities of consumption are rare. An observational study evaluating the lifestyle characteristics and cardiovascular risk (CVR) profile of phytosterol-enriched yogurt consumers was performed in France. METHODS: Subjects were recruited from general practitioners via electronic medical records. Data were obtained from 358 consumers and 422 nonconsumers with 519 subject questionnaires (243 consumers, 276 nonconsumers; 67% response). RESULTS: Consumers had more cardiovascular risk factors than nonconsumers (2.0 ± 1.5 versus 1.6 ± 1.4; P < 0.001) and a higher 10-year SCORE cardiovascular risk (1.8 ± 2.0% versus 1.6 ± 2.2%; P = 0.008); they were older (P = 0.030) and had a higher incidence of hypercholesterolaemia (P < 0.001) and family or personal history of heart disease (P = 0.023/P = 0.026, respectively). Among consumers not on cholesterol-lowering medication, 99% were eligible for lifestyle interventions and 56% were eligible for lipid-lowering drug according to European guidelines. Consumers had a healthier lifestyle, with a higher (fruit/vegetable - saturated fatty acid) score than nonconsumers (P = 0.035), focused more on low-intensity leisure activity (P = 0.023), spent more time travelling by foot or bicycle (P = 0.012) and were more likely to act to reduce CVR. Phytosterol-enriched yogurt intake conformed to recommendations in two-thirds of consumers and was mainly consumed because of concerns over cholesterol levels and CVR. CONCLUSIONS: The higher cardiovascular disease risk profile of phytosterol-enriched yogurt consumers corresponds to a population for whom European guidelines recommend lifestyle changes to manage cholesterol. The coherence of the data in terms of risk factors, adherence to lifestyle recommendations and the consumption of phytosterol-enriched yogurt conforming to recommendations reflects a health-conscious consumer population.

Physiopathology of necrobiotic xanthogranuloma with monoclonal gammopathy.

RATIONALE: Xanthomatosis associated with monoclonal gammopathy includes hyperlipidaemic xanthoma (HX), normolipidaemic xanthoma (NX) and necrobiotic xanthogranuloma (NXG). All three pathologies are characterized by skin or visceral lesions related to cholesterol accumulation, monoclonal immunoglobulin (MIg) and hypocomplementemia. The pathophysiology underlying NXG remains unknown although the involvement of MIg is suspected. OBJECTIVE: To provide further insights into the pathophysiology of NXG, we evaluated the plasma lipid phenotype, mechanisms involved in cellular cholesterol accumulation and role of MIg in an analysis of blood and plasma markers of inflammation in 16 patients with xanthomatosis [NXG (n = 8) and NX (n = 8)] associated with monoclonal IgG relative to the relevant controls. RESULTS: The lipid profile of patients with NXG was characterized by a low HDL-C phenotype and an abnormal distribution of HDL particles. Sera from patients with NXG induced cholesterol accumulation in human macrophages. This accumulation was due in part to a significant reduction in the HDL capacity to promote cholesterol efflux from macrophages, which was not found in the case of NX. The MIg of NXG and NX patients was tested positively by ELISA to recognize a large spectrum of lipoproteins. High plasma levels of pro-inflammatory cytokines (TNFα and IL-6), soluble cytokine receptors (sIL-6R, sTNFRI and sTNFRII), adhesion molecules (VCAM-1 and ICAM-1) and chemokines (MCP-1, IL-8 and MIP-1α) were observed in both patients with NXG and NX, revealing a specific xanthoma inflammatory signature which was inversely correlated with plasma levels of anti-inflammatory HDL. However, patients with NXG were distinguished by elevated levels of IL-15 and a marked increase in the rate of intermediate CD14++CD16+ monocytes. CONCLUSION: This study revealed that NXG is characterized by impaired macrophage lipid homeostasis associated with a systemic inflammatory profile that may result from the interaction of MIg and lipoproteins.

Discontinuation of statin therapy due to muscular side effects: a survey in real life.

BACKGROUNDS AND AIMS: To assess the burden of statin related muscular symptom in real life. METHODS AND RESULTS: We conducted a wide survey on 10,409 French subjects. Among these, 2850 (27%) had hypercholesterolemia and 1074 were treated with statins. Muscular symptoms were reported by 104 (10%) statin treated patients and led to discontinuation in 30% of the symptomatic patients. The main prescribed statins were low doses rosuvastatin, atorvastatin and simvastatin. Pains were the most commonly described symptoms (87%) but many patients also reported stiffness (62%), cramps (67%), weakness or a loss of strength during exertion (55%). Pain was localized in 70% but mostly described as affecting several muscular groups. Approximately 38% of patients reported that their symptoms prevented even moderate exertion during everyday activities, while 42% of patients suffered major disruption to their everyday life. CONCLUSION: Muscular symptoms associated with average dosage statin therapy are more frequent than in clinical trials and have a greater impact on patients' life than usually thought.

Serum levels of adhesion molecules ICAM-1 and VCAM-1 and tissue inhibitor of metalloproteinases, TIMP-1, are elevated in patients with autoimmune thyroid disorders: relevance to vascular inflammation.

Serum levels of ICAM-1 (Inter Cellular Adhesion Molecule-1), VCAM-1 (Vascular cell Adhesion Molecule-1-I), TIMP-1 (tissue inhibitor of metalloproteinases 1) and MMP-9 (Metalloproteinase 9) are well established markers of inflammation. The physiopathological link between inflammation, atherosclerosis and autoimmunity is well demonstrated. However, serum levels of these biomarkers in patients with autoimmune-mediated dysthyroidism, including their evolution after improvement of the thyroid disorder have not been assessed. So, we evaluated the circulating levels of these markers in autoimmune and in non-autoimmune-mediated dysthyroid patients, and their evolution after treatment of thyroid disease. We conducted a prospective study to evaluate these markers before and after treatment in hyperthyroid patients (n = 33; 28 patients with autoimmune disease), hypothyroid patients (n = 38; 33 patients with autoimmune disease) and euthyroid subjects (n = 33). At baseline, serum levels of ICAM-1, VCAM-1 and TIMP-1 were significantly elevated in patients with hyperthyroidism as compared to euthyroid and hypothyroid patients (respectively p = 0.0005 and p < 0.0001). In multivariate analysis, the differences remained significant for VCAM-1 and TIMP-1. Median levels of ICAM-1, VCAM-1 and TIMP-1 were significantly higher in patients with autoimmune-mediated dysthyroidism compared to euthyroid patients (respectively p < 0.0001 and p = 0.002). In hyperthyroid patients, ICAM-1, VCAM-1 and TIMP-1 concentrations fell significantly after they had become euthyroid (respectively p = 0.0006; p < 0.0001 and p = 0.0009), although VCAM-1 values remained higher than those observed in the control group (p = 0.005). We found that autoimmune-mediated dysthyroidism were associated with increased peripheral blood concentrations of VCAM-1, ICAM-1 and TIMP-1. Whether these biological abnormalities translate into increase intima remodelling and atherosclerosis remains to be studied.

The THEMA study: a sociodemographic survey of hypercholesterolaemic individuals.

BACKGROUND: Hypercholesterolaemia is estimated to affect 20% of the population, although little sociodemographic information is available on affected individuals. The present study aimed to gather relevant information and investigate social determinants of dietary compliance. METHODS: A telephone survey was carried out on a representative population sample. Quotas were applied for gender, geography and degree of urbanisation. Individuals were eligible if they were hypercholesterolaemic, and were being followed by a doctor. Sociodemographic, socioeconomic and health data were collected, as well as information about the individuals' perception of the disease, their relationship and beliefs surrounding food, and their food behaviour (shopping, cooking, eating-out, deviation from prescribed diet). The association between compliance with diet and medication was investigated. RESULTS: Overall, 802 individuals were included, representing 8% of those contacted, as opposed to the expected 20%. Mean (SD) age was 60 (14.2) years, with 51% of individuals living as a couple; 48% had a good level of physical activity; 44% considered that the hypercholesterolaemia was inherited; 31% felt that the disease was normal beyond the age of 45 years. The functional and convivial aspects of eating were of more importance than that of health maintenance. Cheese was particularly likely to be eaten in dietary lapses. Of a subgroup of 729 individuals, 476 (65%) took medication; of these 476 individuals, 51% complied with dietary recommendations (P < 0.05). CONCLUSIONS: The key factors associated with dietary compliance in hypercholesterolaemic individuals were identified: age, sex, the perceptions of hypercholesterolaemia, and the sociocultural aspects of food. By contrast to general assumptions, both dietary and medicinal measures are practised fairly well by a large proportion of these individuals.

[Hypercholesterolemia, from screening to treatment: Who, why and how to manage]. / Hypercholestérolémie, du dépistage au traitement : quelle prise en charge, pour qui et pour quel bénéfice.

Hypercholesterolemia refers to dyslipidemia with an increased circulating cholesterol levels. This is the most common dyslipidemia and is associated with an increased risk of developing atheromatous cardiovascular diseases. One of the major challenges in primary prevention is to define the threshold for therapeutic intervention that allow to obtain a significant clinical benefit without unnecessarily expose the patient to potential side effects of lipid-lowering treatments. It is also important to recall to screen patient for heterozygous familial hypercholesterolemia, a common genetic disease of lipid metabolism responsible for particularly severe and early coronary disease. In this article, the issues of hypercholesterolemia screening, the definition of therapeutic targets and expected benefits as well as the modalities of therapeutic management (by also addressing the problem of statin intolerance) will be addressed.

[Adherence to national guidelines for lipid management in a department of endocrinology]. / Prise en charge des patients dyslipidémiques : analyse des écarts entre le référentiel et la pratique dans un centre hospitalier.

OBJECTIVES: National guidelines for lipid management have been updated in March 2005 by the French Health Products Safety Agency (Afssaps). The objective of this study was to assess clinical practices based on these recommendations in a department of endocrinology specialized in the management of dyslipidemic patients. MATERIALS AND METHODS: A sample of patients was independently selected among those referred to our outpatient clinic for assessment of hyperlipidemia. We analyzed retrospectively whether the management of dyslipidemia in these patients was consistent with national guidelines. RESULTS: We included 62 patients. At admission, 61% of patients had a lipid-lowering treatment that was consistent with the guidelines and a LDL-cholesterol value below the target level. At discharge, the lipid-lowering treatment was modified in 27% of patients. The changes were consistent with Afssaps guidelines in 79% of patients. Cases of non-compliance with the guidelines were explained by a lower threshold of LDL-cholesterol target in patients with carotid plaques and no changes because LDL-cholesterol was just above the LDL-cholesterol target. CONCLUSION: Lipid management was consistent with Afssaps guidelines in a majority of patients. However, this study emphasized unresolved problems in lipid management, such as the question of integrating arterial status in the therapeutic decision.

Abdominal obesity is associated with ineffective control of cardiovascular risk factors in primary care in France.

AIM: Insufficient control of cardiovascular risk factors is observed in primary care. The goal of the present study was to evaluate the association of abdominal obesity with achievement of treatment targets for HbA(1c), LDL cholesterol, triglycerides, HDL cholesterol and blood pressure in primary care. METHODS: In this cross-sectional observational epidemiological study, primary-care practitioners completed a questionnaire covering demographic and socioeconomic data, medical history, drug treatment, and clinical and biological characteristics for 3351 patients (1630 men and 1721 women). Therapeutic targets were HbA(1c) <7%, LDL cholesterol <1.6g/L, triglycerides <1.5 g/L and SBP/DBP <140/90 mmHg. Multivariate analyses were performed to assess the relationship between waist circumference and a lack of cardiovascular risk-factor control. RESULTS: The patients' mean ages were 58+/-14 years and 55+/-16 years for men and women, respectively. A large waist circumference was positively and significantly (P<0.0001 for all) associated with diabetes, hypercholesterolaemia, hypertriglyceridaemia, low HDL cholesterol and hypertension. The prevalence of patients not achieving therapeutic targets increased across waist-circumference quartiles. For treated patients, the odds ratios (95% CI) (adjusted for age, gender, education, smoking status and medical specialty) for not achieving treatment targets were 17.6 (2.2-142) for triglycerides, 2.8 (1.3-6.1) for HbA(1c) and 1.4 (0.9-2.0) for blood pressure on comparisons with extreme quartiles of waist-circumference distribution. CONCLUSION: In primary care, a lack of control of triglycerides, HbA(1c) and, to a lesser extent, blood pressure increases with waist circumference independently of confounders. This suggests that abdominal obesity is associated of poor results in the treatment of diabetes and hypertriglyceridaemia.

Effects of a low-calorie diet associated with weight loss on lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in healthy obese women.

INTRODUCTION: Platelet-activating factor acetylhydrolase (PAF-AH or Lp-PLA(2)) is a Ca(2+)-independent phospholipase A(2) primarily associated in plasma with low density lipoproteins (LDL), especially with small dense LDL (sdLDL) particles. Increased plasma Lp-PLA(2) levels have been associated with increased cardiovascular risk in large clinical trials. AIM: To assess the effects of weight loss on Lp-PLA(2) activity and to examine the association of Lp-PLA(2) activity changes with the alterations of sdLDL, the primary carrier of Lp-PLA(2) in plasma. METHODS: Twenty-eight obese, non-diabetic women participated in a weight reduction program. Anthropometric parameters were assessed and parameters of glucose metabolism, lipid profile, Lp-PLA(2) activity, and LDL phenotype (using a 3% polyacrylamide gel-tube electrophoresis method), were determined at baseline and after 4months of weight loss. RESULTS: A 10% diet-induced weight loss resulted in significant improvement in most parameters of lipid and glucose metabolism. Moreover, Lp-PLA(2) activity was significantly reduced (-10.2%, p<0.01). Mean LDL particle diameter did not change after the weight loss program. The cholesterol levels of very low-density lipoprotein (VLDL) and large-buoyant LDL particles were significantly reduced, but neither the cholesterol levels of sdLDL particles nor the % proportion of the sdLDL-cholesterol over the total LDL-cholesterol were changed after the intervention program. Interestingly, the changes in Lp-PLA(2) activity were correlated with the changes of VLDL-cholesterol (r=0.39, p<0.05), but not with the changes of anthropometric or other lipid variables. CONCLUSIONS: A low-calorie diet associated with weight loss in obese women resulted in the significant reduction of the plasma levels of Lp-PLA(2), the potentially new predictor for incident atherosclerotic disease.

[Contribution of NMR to the assessment of dyslipidemia-related cardiovascular risk]. / Apport de la RMN dans l'évaluation du risque cardiovasculaire lié aux dyslipidémies.

Serum level of cholesterol bound to low density lipoproteins (LDL-cholesterol) is the basic parameter used to assess lipid-related cardiovascular risk. This parameter however underestimates the number of small dense LDLs that are especially atherogenic. A new analytic proposal is based on the determination of lipoproteinic profiles obtained by NMR (Liposcience, Raleigh, NC, United-States [Am J Cardiol 90 (2002) 22i-29i]; collaboration with M.J. Chapman, Inserm U551), that allows to quantify the number of atherogenic apo B-100-containing particles. This analysis is rapid, reproducible and does not require a previous separation of lipoproteins by ultracentrifugation. NMR signals come from the terminal methyl groups of lipids located in the envelope and the core of lipoproteins. Each lipoprotein subclass produces a specific NMR signal, so that analysis of the contribution of each signal to the global signal gives the concentration of particles subclasses (nanomole per litre or micromole per litre), concentration in mass of lipid subclasses (milligram per decilitre of cholesterol or triglycerides), together with mean diameters (nanometre) of very low density lipoproteins (VLDLs), low density lipoproteins (LDLs) and high density lipoproteins (HDLs). These particles sizes [Circulation 113 (2006) 113: 1556-1563] are not totally superimposable with those obtained with more classical methodologies, especially polyacrymaide gel electrophoresis of ultracentrifugally isolated lipoproteins, especially for LDLs [Clin Chem 52 (2006) 1722-1727]. Standardization of methodologies is thus required before generalising their use in clinical biology; the NMR technology especially requires complementary studies for its application to populations with extreme lipid values, such as IIa homozygous hypercholesterolemic subjects.

[Familial hypercholesterolemia: A largely underestimated cardiovascular risk]. / Hypercholestérolémie familiale : un risque cardiovasculaire largement sous-estimé.

BACKGROUND: Familial hypercholesterolemia is a monogenic autosomal dominant dyslipidemia characterized by a permanent and isolated increase of cholesterol carried by low-density lipoproteins. The prevalence of its heterozygous form is estimated between 1/500 and 1/250, and in the absence of specific treatment, this form is responsible for an increase by a factor of 13 of the risk of premature coronary artery disease compared to patients non-affected by the disease. OBJECTIVES: To perform an inventory of the knowledge of heterozygous familial hypercholesterolemia in France for physicians involved in the management of the disease. METHODS: A survey was conducted (by phone and internet) among a representative sample of 495 physicians (cardiologists, endocrinologists/diabetologists, gynecologists, general practitioners) who, in parallel, completed 579 patient records. RESULTS: Thirty-two percent (95% CI [27.8; 36.2]) of physicians reported the difference between polygenic hypercholesterolemia and familial hypercholesterolemia. The presence of tendinous xanthomas, a key element of diagnosis, was spontaneously mentioned by 44% (95% CI [34; 54.2]) of cardiologists. Six percent (95% CI [2.2; 12.6]) of them gave a correct estimate of the prevalence of familial hypercholesterolemia. The likelihood of transmission of heterozygous familial hypercholesterolemia, when one parent is affected, was known for 59% (95% CI [48.7; 68.7]) of surveyed cardiologists. A cascade screening was performed systematically by 4% (95% CI [1.1; 9.9]) of them. Eighteen percent (95% CI [11; 26.9]) of cardiologists gave an accurate estimation of cardiovascular risk of heterozygous familial hypercholesterolemia. Fifty-seven percent (95% CI [46.7; 66.8]) of cardiologists admitted being misinformed about the heterozygous familial hypercholesterolemia and 83% (95% CI [74.1; 89.7]) expressed a need for information about this disease. CONCLUSION: The lack of knowledge of heterozygous familial hypercholesterolemia and its associated cardiovascular risk is probably the cause of a diagnostic default leading to inappropriate management of this disease.

Screening for liver disease using non-invasive biomarkers (FibroTest, SteatoTest and NashTest) in patients with hyperlipidaemia.

BACKGROUND: Mortality related to complications of cirrhosis is increasing in patients with insulin-resistance factors. Hyperlipidaemic patients have multiple risk factors of insulin resistance. It is impossible to perform liver biopsy in such a large number of hyperlipidaemic patients to identify patients with advanced liver fibrosis or with steatohepatitis (non-alcoholic steatohepatitis, NASH). AIMS: To use the non-invasive biomarkers, FibroTest (FT), SteatoTest and NashTest, and to assess the prevalence of advanced liver disease in a large population of hyperlipidaemic patients. METHODS: A consecutive cohort of hyperlipidaemic patients was followed prospectively in a lipid centre and the sera were analysed retrospectively. RESULTS: A total of 2834 subjects were included: 1909 hyperlipidaemic patients and 925 blood donors (BD). Advanced fibrosis was identified by FT in 53/1909 (2.8%) hyperlipidaemic patients vs. 0/925 BD (0%) (P < 0.0001); advanced steatosis in 569/1893 hyperlipidaemic patients (30.1%) vs. 8/164 (4.9%) BD (P < 0.0001) and NASH in 132/1893 (7%) vs. 0/164 (0%), respectively (P < 0.0001). There was a highly significant and linear association between the number of metabolic syndrome factors and liver disease prevalence - the highest being for type 2 diabetics: advanced steatosis 66%, NASH 24% and advanced fibrosis 6%. CONCLUSIONS The prevalence of fibrosis, steatosis and NASH in hyperlipidaemic patients appears to be high (3%, 30% and 7%, respectively). Biomarkers could be useful for screening of advanced fibrosis and NASH in patients with several metabolic syndrome factors, to prevent liver mortality.

[Subclinical hypothyroidism: a cardiovascular risk factor?]. / L'hypothyroidie infracinique: facteur de risque cardiovasculaire?

Although patent hypothyroidism is clearly associated with increased cardiovascular risk, the relationship between infraclinical hypothyroidism and cardiovascular disease remains controversial though probable. This relationship is mediated by the traditional risk factors (lipids, hypertension), by changes in parameters of inflammation and haemostasis, and by a direct effect of thyroid hormones on the vessel wall. The authors review the epidemiological evidence and the mechanisms underlying the association between infraclinical hypothyroidism and cardiovascular risk and the therapeutic implications of this association.

[Prevalence of sleep apnea in men with metabolic syndrome and controlled hypertension]. / Prévalence et déterminants du syndrome d'apnée du sommeil chez des hommes ayant un syndrome métabolique et une hypertension artérielle contrôlée.

BACKGROUND: Abdominal obesity and high blood pressure (HBP) are known to be associated with sleep apnea syndrome (SAS). Resistant hypertension commonly leads physicians to prescribe a sleep record because the prevalence of SAS is high in patients with resistant hypertension. Data on the prevalence of SAS in patients with treated and controlled hypertension are lacking. Moreover, while the metabolic syndrome (MS) and insulin resistance frequently occur in association with SAS, few studies have evaluated the prevalence of SAS in patients with MS. Epworth sleepiness scale (ESS) is often proposed to identify patients at high risk for sleep disorders and for which a sleep record should be prescribed. The reliability of this test to identify SAS has not been studied in patients with MS. OBJECTIVES: (i) To assess the prevalence of SAS in men with MS, (ii) to study the relationship between controlled hypertension and SAS in patients with MS, (iii) to assess the reliability of the ESS to diagnose SAS in patients with MS. METHODS: Among 135 men hospitalized for MS, the 125 who had no history of SAS were systematically evaluated by a nocturnal polygraphy was systematically performed in the 125 men without known SAS at the admission. An excessive daytime sleepiness was assessed by the ESS. Results of analyses in patients with controlled HBP (<130/85 mmHg with antihypertensive drug(s), n=41) were compared with those in patients with normotension (<130/85 mmHg without treatment, n=32). RESULTS: The prevalence of SAS (apnea-hypopnea index (AHI) >or=15/h) in men with MS was 44% in the whole population, 28.1% in the subgroup of patients with normotension and 61.0% in patients with treated and controlled HBP. A severe SAS (AHI >or=30/h) was respectively present in 6.3% and 34.1% of patients with normotension and controlled HTA (p<0.01). Compared with patients without SAS, those with SAS displayed higher blood pressure and BMI. Logistic regression analysis showed that controlled HTA was a determinant of SAS which persisted after adjustment for BMI. As suggested by the ROC curve, the ESS is not a good tool to identify patients with SAS. With a threshold of 11/24 the positive and negative values of this scale were of 0.20 and 0.47. CONCLUSION: The prevalence of SAS is high in men with MS. The ESS does not identify patients who should undergo a nocturnal record. Because a severe SAS is found in nearly one third of patients with MS and controlled HBP, we suggest that a nocturnal record should be systematically proposed to these patients irrespective of the degree of daytime sleepiness assessed by questionnaires.

[New insights and perspectives in the management of dyslipidemia]. / Avancées récentes et perspectives dans le traitement des dyslipidémies athérogènes.

PURPOSE: Recent end point trials of lipid-lowering drugs have shown that patients at very high-risk for coronary disease benefit from treatments that lowers low density lipoprotein cholesterol (LDL cholesterol) plasma levels< or =70 mg/dl and that patients with at least 2 risk factors benefit from LDL cholesterol levels< or =100 mg/dl. Epidemiologic studies have shown that the concentration of high density lipoprotein cholesterol (HDL cholesterol) is a strong, independent, inverse predictor of coronary disease risk. Innovative pharmacological approaches to raise low HDL cholesterol levels are currently of considerable interest, especially for patients with type 2 diabetes or metabolic syndrome. RESULTS: Rosuvastatin has shown superior efficacy in lowering LDL cholesterol, although evidence of clinical benefit is actually lacking. Ezetimibe is a lipid-lowering drug that inhibits absorption of dietary and biliary cholesterol. Its co-administration with statin has given very interesting results. Niacin is the most effective of currently available options for raising HDL cholesterol, although tolerability can be an issue, with serious side effects such as loss of glucose control and liver toxicity. Flushing may occur in 80% of treated patients. Two CETP inhibitors have shown therapeutical efficacy to raise HDL cholesterol, but clinical benefit remains uncertain.

[Graves' disease and autoimmune thrombocytopenic purpura: distinct outcomes of the two diseases]. / Maladie de Basedow et purpura thrombopénique auto-immun: l'évolution n'est pas toujours parallèle.

The association of idiopathic thrombocytopenic purpura and Graves' disease is rare. Hence, little is known about the outcomes of these two diseases when associated. We report two cases of idiopathic thrombocytopenic purpura associated with Graves' disease, in which the two diseases had distinct outcomes. Thus, the hypothesis of cross-reaction between antithyroid antibodies and platelet epitopes, which has been proposed to explain the association, seems unlikely.

Lessons from france: the cardiovascular prevention clinic in the la pitié-salpêtrière hospital in paris.

Cardiovascular disease is the principal cause of morbidity and mortality in the Netherlands. In this background, various initiatives have been launched to reduce the frequency of cardiovascular disease. One of those is the creation of clinical units with a special focus on prevention of cardiovascular disease. Hitherto, the prevention programmes of these clinics have been heterogeneous and therefore difficult to compare with respect to results. Similar developments in creating clinical initiatives concerning prevention of cardiovascular disease are found across Europe. With this in mind, lessons could be learned from each other's experiences. In our contribution, we would like to present the Cardiovascular Prevention Clinic in the Pitié- Salpêtrière Hospital in Paris, France, as an interesting example of a well-acknowledged cardiovascular prevention clinic that combines both daily clinical care and cardiovascular science. (Neth Heart J 2007;15:22-6.).

Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose-tolerant obese subjects during weight loss.

OBJECTIVE: To investigate the mRNA expression of adiponectin, AdipoR1 and AdipoR2, the two recently cloned adiponectin receptors and peroxisome proliferator activated receptor (PPAR)gamma2 in adipose tissue of obese individuals before and during a very low calorie diet (VLCD) inducing weight loss. METHODS: Twenty-three non-diabetic obese subjects with normal (NGT, n = 11) or impaired glucose tolerance (IGT, n = 12) (age, 47 +/- 3 years; body mass index, 39.3 +/- 1.3 kg/m2) were studied before and after a 3-week 3.9 MJ diet daily without exercise. mRNA levels of nine IGT and six NGT subjects were measured by real-time PCR in s.c. abdominal adipose tissue. RESULTS: Metabolic parameters and insulin sensitivity were improved by VLCD in the IGT group, but minimally affected in the NGT group. VLCD increased expression of AdipoR1 in the IGT (P = 0.02), but not in the NGT group. Adiponectin, AdipoR2 and PPARgamma2 mRNA levels did not change during VLCD in any group. In the IGT, but not in the NGT group, AdipoR1 and AdipoR2 expressions were positively related to that of PPARgamma2 and, after VLCD, AdipoR1 and AdipoR2 expressions were positively related to each other and to that of adiponectin. CONCLUSION: In the NGT group, the 3-week VLCD inducing weight loss did not modify metabolic parameters, insulin sensitivity and the expression of the adiponectin system in adipose tissue. By contrast, in the IGT group, AdipoR1 expression increased and we found a coordinate regulation of the expression of adiponectin and its receptors. These modifications could participate, through adiponectin action on adipocytes, to the improved metabolic parameters observed in IGT subjects.