Hyperlipidemias: Zannad F

Zannad F, Agabiti-Rosei E. · Inserm, CIC 9501 et U684, CHU Nancy, France. · J Hypertens. · Pubmed #18815513 No free full text.

Abstract: In addition to the prevention and treatment of macro- and microvascular complications, management goals for patients with type 2 diabetes include reducing the risk of cardiovascular events with a view to improving quality of life. A number of epidemiological and observational cohort studies have been published in Italy and France in an effort to determine the patient profile of individuals with type 2 diabetes in these countries and to gather data on current clinical practice and prescribing patterns. The results of the studies confirm that cardiovascular risk factors, such as hypertension and elevated cholesterol, commonly occur in patients with type 2 diabetes and that these co-morbid conditions are not well controlled. As a consequence, both macro- and microvascular complications are prevalent in this patient population. It is clear that the management of type 2 diabetes in France and Italy is suboptimal. In both primary and specialist care, treatment guidelines need to be reinforced and a more aggressive approach needs to be adopted in the treatment of modifiable cardiovascular risk factors and in particular hypertension. Collectively, the available data highlight the importance of managing global cardiovascular risk within the context of diabetes care. Greater adherence to therapeutic targets recommended in guidelines will ensure that greater proportions of patients attain these treatment goals thereby reducing diabetes-related morbidity and mortality.

Guerci B, Kearney-Schwartz A, Böhme P, Zannad F, Drouin P. · Service de Diabétologie, Maladies Métaboliques et Maladies de la Nutrition, Hôpital Jeanne d'Arc, CHU de Nancy, B.P. 303, 54201 Toul Cedex. · Diabetes Metab. · Pubmed #11547216 links to  free full text

Abstract: Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.

Simon T, Boutouyrie P, Gompel A, Christin-Maitre S, Laurent S, Thuillez C, Zannad F, Bernaud C, Jaillon P, Anonymous00318. · Department of Pharmacology, Paris VI University, Saint Antoine University Hospital AP-HP, Paris, France. · Fundam Clin Pharmacol. · Pubmed #14748765 No free full text.

Abstract: Carotid intima-media thickness (IMT) measurement is a noninvasive method used for quantification of early stage of atherosclerosis. Data suggest that the combination of statin and hormone replacement therapy (HRT) might be useful in reducing the early progression of atherosclerosis in postmenopausal women. The main aim of the study is to compare the effects of 12-month therapy with atorvastatin (80 mg/day), HRT (oral 17beta-estradiol 1 or 2 mg/day, plus cyclic dydrogesterone 10 mg) alone and their combination vs. placebo on the progression of carotid IMT by using a high-definition echotracking device. The secondary objectives are to assess the effects of the treatments vs. placebo on arterial stiffness, lipid profile and C-reactive protein. The CASHMERE trial is an European randomized study with a 2 x 2-factorial design, double blinded for atorvastatin and prospective randomized, open blinded endpoint evaluation (PROBE) method applied to HRT. The investigators can adjust the dose of estradiol at any time during follow-up if necessary. A total of 800 postmenopausal women with mild hypercholesterolemia and with no previous history of cardiovascular disease will be included and followed up by their physicians [general practitioners (GPs) or gynecologists] for 1 year. The CASHMERE trial is the first randomized clinical trial to examine the effects of a statin alone or combined with HRT on the structure and the function of carotid artery as early markers of atherosclerosis in postmenopausal women with mild hypercholesterolemia. The results are expected for 2007.

Rajagopalan S, Zannad F, Radauceanu A, Glazer R, Jia Y, Prescott MF, Kariisa M, Pitt B. · Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA. · Am J Cardiol. · Pubmed #17631074 No free full text.

Abstract: Angiotensin receptor blockers have been hypothesized to have synergistic effects with statins. We evaluated the effects of valsartan alone or combined with simvastatin on blood pressure (BP) and indexes of inflammation and oxidant stress in hypertensive patients with hyperlipidemia. In this double-blind trial, 404 patients were randomized to 12 weeks valsartan 160 mg (V) or valsartan 160 mg plus simvastatin 20 mg (V/S20) or 80 mg (V/S80). Twenty-four-hour mean ambulatory BP and biochemical marker measurements were recorded at baseline and study end. There were no statistically significant between-treatment differences for least-square mean reductions from baseline in systolic BP (V, -9.22; V/S20, -9.25; V/S80, -9.58 mm Hg; p <0.0001 for all within-treatment changes vs baseline). Plasma high-sensitivity C-reactive protein decreased with the combinations but not with V alone (least-square mean median change from baseline, -0.16, -0.20, -0.70 mg/L; p = 0.0001 for V/S80 vs baseline; p = 0.045 for V/S20 vs baseline; p = 0.0023 for V/S80 vs V/S20; p = 0.0045 for V/S80 vs V). Monocyte chemoattractant protein-1 was reduced by V, with no evidence for additional lowering with V/S combinations. In conclusion, addition of simvastatin to valsartan did not incrementally lower BP. However, V/S80 was superior to V and V/S20 in reducing high-sensitivity C-reactive protein.