Association of PPAR‐γ2 and β3‐AR Polymorphisms With Postmenopausal Hypertension

The aim of this study was to test the association of peroxisome proliferator‐activated receptor (PPAR‐γ2) (Pro12Ala, C1431T) and β3‐AR (Trp64Arg) polymorphisms with metabolic, nutritional, and blood pressure parameters in 271 postmenopausal women (151 hypertensive and 120 normotensive controls). The TaqMan genotyping assay and restriction fragment length polymorphism methods were used to determine the distributions of selected alleles and genotype frequencies. Nutritional status was determined by a bioimpedance method and dietary habits were assessed via 7‐day dietary recall. The distribution of selected genotypes and allele frequencies did not differ between hypertensive women and normal controls after analysis by chi‐square test. The postmenopausal hypertensive women were older and had higher body fat mass, serum glucose, and triglyceride levels. The cluster analysis showed that the hypertensive group with Pro12Pro genotype had highest pulse pressure and mean arterial pressure values when compared with Pro12Ala patients. In the logistic regression analysis, blood glucose (Pro12Ala polymorphism) and energy intake (C1431Tand T1431T polymorphisms) determined hypertension.     

Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol

Aims/hypothesis Studies suggest that in addition to blood glucose concentrations, thiazolidinediones such as rosiglitazone improve some cardiovascular (CV) risk factors and surrogate markers, that are abnormal in type 2 diabetes. However, fluid retention might lead to cardiac failure in a minority of people. The aim of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study is to evaluate the long-term impact of these effects on CV outcomes, as well as on long-term glycaemic control, in people with type 2 diabetes.Materials and methods RECORD is a 6-year, randomised, open-label study in type 2 diabetic patients with inadequate blood glucose control (HbA₁c 7.1–9.0%) on metformin or sulphonylurea alone. The study is being performed in 327 centres in Europe and Australasia. After a 4-week run-in, participants were randomised by current treatment stratum to add-on rosiglitazone, metformin or sulphonylurea, with dose titration to a target HbA₁c of 7.0%. If confirmed HbA₁c rises to 8.5%, either a third glucose-lowering drug is added (rosiglitazone-treated group) or insulin is started (non-rosiglitazone group). The same criterion for failure of triple oral drug therapy in the rosiglitazone-treated group is used for starting insulin in this group. The primary endpoint is the time to first CV hospitalisation or death, blindly adjudicated by a central endpoints committee. The study aim is to evaluate non-inferiority of the rosiglitazone group vs the non-rosiglitazone group with respect to CV outcomes. Safety, tolerability and study conduct are monitored by an independent board. All CV endpoint and safety data are held and analysed by a clinical trials organisation, and are not available to the study investigators while data collection is open.Results Over a 2-year period a total of 7,428 people were screened in 25 countries. Of these, 4,458 were randomised; 2,228 on background metformin, 2,230 on background sulphonylurea. Approximately half of the participants are male (52%) and almost all are Caucasian (99%).Conclusions/interpretation The RECORD study should provide robust data on the extent to which rosiglitazone, in combination with metformin or sulphonylurea therapy, affects CV outcomes and progression of diabetes in the long term.     

Renal specific secondary hypertension

Chronic kidney disease (CKD) is now understood to affect over 5% of all adult patients and it conveys a risk of reduced survival in those affected. At least 80% of those patients with stages 3-5 CKD (i.e. GFR <60 ml/min) suffer with hypertension, and in most the major cause is due to pertubation of an important renal endocrine system, the renin-angiotensin-aldosterone (RAA) axis. In this article the epidemiology of renal-related hypertension and its importance in pre-disposing to the increased cardiovascular risk in renal disease are discussed. Hypertension is known to be a major cause of progressive loss of renal function in CKD, particularly because of activation of the RAA, and hence the case for blockade of this system with ACE inhibitors and Angiotensin receptor blockers is highlighted.     

Higher Cholesterol Level Predicts Cardiovascular Event and Inversely Associates With Mortality in Hemodialysis Patients: 10‐Year Outcomes of the Q‐Cohort Study

The prevalence of atherosclerotic diseases is higher in hemodialysis patients. The aim of the current study was to investigate associations between cholesterol level and the incidences of cardiovascular disease (CVD) and mortality in hemodialysis patients. A total of 3517 participants undergoing maintenance hemodialysis were followed up for 10 years. Total cholesterol (TC) level was divided into quartile in baseline data. The multivariate analyses were calculated by a Cox proportional hazards model. The incidences of ischemic heart disease (IHD), peripheral artery disease (PAD), and CVD were significantly positively associated with higher cholesterol levels after adjustment for confounding factors (P < 0.01, P = 0.04, and P < 0.01, respectively). Furthermore, the incidences of cancer‐associated mortality and all‐cause mortality were significantly positively associated with lower cholesterol levels after adjustment for confounding factors (both P < 0.01). The lowest TC level at all‐cause mortality risk was 179 mg/dL. From these results, higher TC predicts IHD, PAD, and CVD events, and lower TC predicts cancer‐associated mortality and all‐cause mortality in patients undergoing maintenance hemodialysis.     

DIABETIC NEPHROPATHY ‐ WHO CARES?

Diabetic nephropathy has become the most common single cause of Established Renal Failure (ERF) in the United States of America (USA) and Europe. In the United Kingdom (UK) diabetic nephropathy is seen in 18% of new patients requiring dialysis (1). In the USA 7.3% of all adults and 17.8% of those over 65 years have diabetes mellitus (2). Furthermore diabetic nephropathy is the cause of ERF in up to 45% of patients on dialysis (3). Recently compiled data by the World Health Organisation (WHO) shows that approximately 150 million people worldwide have diabetes and predict that this number may well have doubled to 300 million by 2025 (4). These figures are clearly daunting and renal units must prepare themselves for the rising number of patients with diabetes needing renal replacement therapy (RRT) in the future. Renal specialist nurses do not always have a major role to play in the prevention of diabetic nephropathy. Their remit must be to try and delay the progression to ERF and perhaps more importantly to concentrate their efforts on their ERF patient population with diabetes that have co‐existing diabetes related pathologies. This article will attempt to discuss how renal nurses can best expand/extend their skills and knowledge to provide effective care for this patient group, and explore whether developing new and innovative roles or just new ways of working is the way forward.     

IFN‐γ mediates early B‐cell loss in experimental African trypanosomosis

African trypanosomes infect humans and animals throughout the African continent. These parasites maintain chronic infections by various immune evasion strategies. While antigenic variation of their surface coat is the most studied strategy linked to evading the host humoral response, African trypanosomes also induce impaired B‐cell lymphopoiesis, the destruction of the splenic B‐cell compartment and abrogation of protective memory responses. Here we investigate the mechanism of follicular B‐cell destruction. We show that during infection follicular B cells undergo apoptosis, correlating to enhanced Fas death receptor surface expression. Investigation of various type 1 cytokine knockout mice indicates a crucial role of IFN‐γ in the early onset of FoB cell destruction. Indeed, both IFN‐γ^?/? and IFN‐γR^?/? mice are protected from trypanosomosis‐associated FoB cell depletion, exhibiting an inhibition of B‐cell apoptosis as well as a reduced activation of FoB cells during the first week post‐infection. The data presented herein offer new insights into B‐cell dysfunctioning during experimental African trypanosome infections.