Abstract-Two or more antihypertensive agents are increasingly used to control blood pressure (BP) in hypertensive patients. However, it is unclear whether fixed-dose combinations (FDCs) of 2 antihypertensive agents in a single tablet provide greater benefits than the corresponding free-drug components given separately. A meta-analysis was performed to assess compliance, persistence, BP control, and safety associated with FDCs in comparison with their free-drug components. Fifteen included studies (nϭ32331) reported on Ն1 of the evaluated outcomes. In 3 cohort studies and 2 trials reporting on drug compliance (nϭ17 999), the use of FDCs was associated with significantly better compliance (odds ratio: Pϭ0.19). In 9 trials (nϭ1671) with BP data, use of an FDC was associated with nonsignificant changes in systolic and diastolic BPs of 4.1 mm Hg (95% CI: Ϫ9.8 to 1.5; Pϭ0.15) and 3.1 mm Hg (95% CI: Ϫ7.1 to 0.9; Pϭ0.13), respectively. In these BP-lowering comparisons, there was heterogeneity associated with differences in study design but no publication bias. In conclusion, compared with free-drug combinations, FDCs of antihypertensive agents are associated with a significant improvement in compliance and with nonsignificant beneficial trends in BP and adverse effects. (Hypertension. 2010;55:399-407.)

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Background The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure. MethodsWe did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg). The primary outcome was a major cardiovascular event (defined as a composite of fatal and non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital), analysed as per intention to treat.Findings Data for 344 716 participants from 48 randomised clinical trials were available for this analysis. Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/89 mm Hg in participants without previous cardiovascular disease (n=186 988). There was substantial spread in participants' blood pressure at baseline, with 31 239 (19•8%) of participants with previous cardiovascular disease and 14 928 (8•0%) of individuals without previous cardiovascular disease having a systolic blood pressure of less than 130 mm Hg. The relative effects of blood pressure-lowering treatment were proportional to the intensity of systolic blood pressure reduction. After a median 4•15 years' follow-up (Q1-Q3 2•97-4•96), 42 324 participants (12•3%) had at least one major cardiovascular event. In participants without previous cardiovascular disease at baseline, the incidence rate for developing a major cardiovascular event per 1000 person-years was 31•9 (95% CI 31•3-32•5) in the comparator group and 25•9 (25•4-26•4) in the intervention group. In participants with previous cardiovascular disease at baseline, the corresponding rates were 39•7 (95% CI 39•0-40•5) and 36•0 (95% CI 35•3-36•7), in the comparator and intervention groups, respectively. Haz...

We immunohistochemically examined 12 core proteins involved in the chromatin remodeling machinery using a tissue microarray composed of 150 lung adenocarcinoma (AD) and 150 squamous cell carcinoma (SCC) cases. Most of the proteins showed nuclear staining, whereas some also showed cytoplasmic or membranous staining. When the expression patterns of all tested antigens were considered, proteins with nuclear staining clustered into two major groups. Nuclear signals of BRM, Ini-1, retinoblastoma, mSin3A, HDAC1, and HAT1 clustered together, whereas nuclear signals of BRG1, BAF155, HDAC2, BAF170, and RbAP48 formed a second cluster. Additionally, two thirds of the cases on the lung tissue array had follow-up information, and survival analysis was performed for each of the tested proteins. Positive nuclear BRM (N-BRM) staining correlated with a favorable prognosis in SCC and AD patients with a 5 year-survival of 53.5% compared with 32.3% for those whose tumors were negative for N-BRM (P ‫؍‬ 0.015). Furthermore, patients whose tumors stained positive for both N-BRM and nuclear BRG1 had a 5 year-survival of 72% compared with 33.6% (P ‫؍‬ 0.013) for those whose tumors were positive for either or negative for both markers. In contrast, membranous BRM (M-BRM) staining correlated with a poorer prognosis in AD patients with a 5 year-survival of 16.7% compared with those without M-BRM staining (38.1%; P ‫؍‬ 0.016). These results support the notion that BRM and BRG1 participate in two distinct chromosome remodeling complexes that are functionally complementary and that the nuclear presence of BRM, its coexpression with nuclear BRG1, and the altered cellular localization of BRM (M-BRM) are useful markers for nonsmall cell lung cancer prognosis.

Pfizer, Servier Research Group, and Leo Laboratories.

Mini gastric bypass is being explored by many bariatric surgeons as a standalone bariatric procedure. Several surgeons from different parts of the world have now published their extensive experience with this procedure. It appears to be an effective bariatric procedure with acceptable weight loss, co-morbidity resolution, and complication rates in the short and medium term. Its proponents claim that it is safer and easier than the gold standard Roux-en-Y gastric bypass. However, concerns with regard to symptomatic gastric or oesophageal biliary reflux requiring revisional surgery and long-term risk of gastric and oesophageal cancers persist. This paper reviews the published experience to date with this procedure and examines the surrounding controversy.

OBJECTIVE -The purpose of this study was to determine the baseline predictors of newonset diabetes (NOD) in hypertensive patients and to develop a risk score to identify those at high risk of NOD. RESEARCH DESIGN AND METHODS -Among 19,257 hypertensive patients in theAnglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) who were randomly assigned to receive one of two antihypertensive regimens (atenolol Ϯ thiazide or amlodipine Ϯ perindopril), 14,120 were at risk of developing diabetes at baseline. Of these, 1,366 (9.7%) subsequently developed NOD during median follow-up of 5.5 years. A multivariate Cox model was developed to identify the independent predictors of NOD and individual risk scores.RESULTS -NOD was significantly associated with an increase in baseline fasting plasma glucose (FPG), BMI, serum triglycerides, and systolic blood pressure. In contrast, amlodipine Ϯ perindopril in comparison with atenolol Ϯ thiazide treatment (hazard ratio 0.66 [95% CI 0.59 -0.74]), high HDL cholesterol, alcohol use, and age Ͼ55 years were found to be significantly protective factors. FPG was the most powerful predictor with risk increasing by 5.8 times (95% CI 5.23-6.43) for each millimole per liter rise Ͼ5 mmol/l. The risk of NOD increased steadily with increasing quartile of risk score, with a 19-fold increase (95% CI 14.3-25.4) among those in the highest compared with those in the lowest quartile. The model showed excellent internal validity and discriminative ability.CONCLUSIONS -Baseline FPG Ͼ5 mmol/l, BMI, and use of an atenolol Ϯ diuretic regimen were among the major determinants of NOD in hypertensive patients. The model developed from these data allows accurate prediction of NOD among hypertensive subjects. Diabetes Care 31:982-988, 2008O bservational data suggest that hypertension is a risk factor for type 2 diabetes (1); hence, the two conditions frequently coexist. The increased propensity of the hypertensive population to develop diabetes is variably affected by different classes of antihypertensive medication. Recently, results of a network meta-analysis, using data from 22 clinical trials comprising 143,153 participants who did not have diabetes at randomization, suggested that the association between antihypertensive agents and incident diabetes is lowest for angiotensinogen receptor blockers and ACE inhibitors followed by calcium channel blockers and placebo, with ␤-blockers and diuretics increasing risk (2). The diabetogenicity of ␤-blockers and diuretics is consistent with their adverse impact on blood glucose levels, which has been reported for several decades (3-5). In contrast with the adverse effects of diuretics (3,6,7) and ␤-blockers (8) on the incidence of new-onset diabetes (NOD) in randomized trials, the bulk of trial evidence suggests that drugs that block the renin-angiotensin system exert a protective role against the development of NOD (2,9,10). These differential effects have influenced recommendations for antihypertensive drug sequencing contained in British g...

Legacy effects of those originally assigned atorvastatin may contribute to long-term benefits on all-cause mortality. An explanation for long-term benefits on non-CV deaths has not been established.