Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension

Objectives: Previous studies have demonstrated that high dose allopurinol is able to regress Left Ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well- controlled blood pressure but without established cardiovascular disease.Methods: We conducted a mechanistic proof-of-concept randomised, placebo controlled, double-blind trial of allopurinol (600mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress. Results: 72 patients were randomised into the trial. Mean baseline urate was 362.2 ± 96.7umol/L. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared to placebo (LV mass -0.37 ± 6.08 g vs -3.75 ± 3.89 g; p=0.012). Oxidative stress markers (Thiobarbituric acid reactive substances) were significantly higher in the allopurinol group vs placebo (0.26 ± 0.85uM vs -0.34 ± 0.83uM; p=0.007). Other markers of vascular function were not significantly different between the two groups.Conclusions: Treatment with high dose allopurinol in normo-uricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be due to an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.<br/

Efficacy of noninvasive cardiac imaging tests in diagnosis and management of stable coronary artery disease

Ify R Mordi,1,2 Athar A Badar,2 R John Irving,2 Jonathan R Weir-McCall,1 J Graeme Houston,1 Chim C Lang1,2 1Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK; 2Department of Cardiology, Ninewells Hospital and Medical School, Dundee, UK Abstract: The aim of this review was to discuss the current literature regarding the utility of noninvasive imaging in diagnosis and management of stable coronary artery disease (CAD) including recent data from large randomized trials assessing diagnosis and prognosis. Current guidelines recommend revascularization in patients with refractory angina and in those with potential prognostic benefit. Appropriate risk stratification through noninvasive assessment is important in ensuring patients are not exposed to unnecessary invasive coronary angiograms. The past 20&nbsp;years have seen an unprecedented expansion in noninvasive imaging modalities for the assessment of stable CAD, with cardiovascular magnetic resonance and computed tomography complementing established techniques such as myocardial perfusion imaging, echocardiography and exercise electrocardiogram. In this review, we examine the current state-of-the-art in noninvasive imaging to provide an up-to-date analysis of current investigation and management options. Keywords: angina, noninvasive imaging, SPECT, stress echo, cardiovascular magnetic resonance, CT coronary angiograph

China’s dilemma in climate change mitigation : the energy problem

The vulnerability of China to the adverse impacts of rising global warming is outlined, including projected impacts on coastlines, agriculture, water supply, land degradation, and public health, since these are important reasons why China, partly for reasons of national security, is increasingly addressing the climate change problem in national and international discussions. This paper then profiles China’s greenhouse gas (GHG) emissions and illustrates how the pressure from the international community, especially that from the US, would impel China to make more substantial contribution to global climate effort. After examining China’s coal-dominated energy mix, we review the current approaches undertaken by China to combat climate change. They are essentially programs that aim to increase energy efficiency and deploy alternative energies, thus reducing energy costs and bringing about ancillary climate benefits. China’s active participation in the Clean Development Mechanism (CDM) is then discussed. We show that it appears to be impossible, with current or currently developing technologies such as Carbon Capture and Storage (CCS), to produce the 80% reductions in GHG emissions which scientists recommend over the next four decades. What other measures might be feasible for China to make more substantial contributions to global climate-change-mitigation efforts? China’s dilemma is the need to sustain a developing economy which depends crucially on GHG-emitting processes. It appears to be impossible to do this without some radical restructuring of economic activity, since it seems that it cannot be done by some combination of greater energy-efficiency and substituting fossil fuels by renewables or nuclear power. An alternative over the longer term is to promote relocalization of production and exchange using local and regional renewable resources. There are many towns and cities in the world in which groups are planning and beginning to implement such changes. In fact, China is almost uniquely well-qualified to take this approach, and indeed, could become a leader in such innovations and such technologies. In the longer term, it is very much in China’s national interest to follow this path

A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes:the MET-REMODEL trial

Aim We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes. Methods and results We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference −1.37 (95% confidence interval: −2.63 to −0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study. Conclusion Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials

A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes:The DAPA-LVH Trial

AIM: We tested the hypothesis that dapagliflozin may regress left ventricular hypertrophy (LVH) in people with type 2 diabetes (T2D). METHODS AND RESULTS: We randomly assigned 66 people (mean age 67 ± 7 years, 38 males) with T2D, LVH, and controlled blood pressure (BP) to receive dapagliflozin 10 mg once daily or placebo for 12 months. Primary endpoint was change in absolute left ventricular mass (LVM), assessed by cardiac magnetic resonance imaging. In the intention-to-treat analysis, dapagliflozin significantly reduced LVM compared with placebo with an absolute mean change of −2.82g [95% confidence interval (CI): −5.13 to −0.51, P = 0.018]. Additional sensitivity analysis adjusting for baseline LVM, baseline BP, weight, and systolic BP change showed the LVM change to remain statistically significant (mean change −2.92g; 95% CI: −5.45 to −0.38, P = 0.025). Dapagliflozin significantly reduced pre-specified secondary endpoints including ambulatory 24-h systolic BP (P = 0.012), nocturnal systolic BP (P = 0.017), body weight (P < 0.001), visceral adipose tissue (VAT) (P < 0.001), subcutaneous adipose tissue (SCAT) (P = 0.001), insulin resistance, Homeostatic Model Assessment of Insulin Resistance (P = 0.017), and high-sensitivity C-reactive protein (hsCRP) (P = 0.049). CONCLUSION: Dapagliflozin treatment significantly reduced LVM in people with T2D and LVH. This reduction in LVM was accompanied by reductions in systolic BP, body weight, visceral and SCAT, insulin resistance, and hsCRP. The regression of LVM suggests dapagliflozin can initiate reverse remodelling and changes in left ventricular structure that may partly contribute to the cardio-protective effects of dapagliflozin. CLINICALTRIALS.GOV IDENTIFIER: NCT0295681

Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source : Design of the NAVIGATE ESUS randomized trial

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Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design

Background Heart failure (HF) and diabetes (DM) are a lethal combination. The current armamentarium of anti-diabetic agents has been shown to be less efficacious and sometimes even harmful in diabetic patients with concomitant cardiovascular disease, especially HF. Sodium glucose linked co-transporter type 2 (SGLT2) inhibitors are a new class of anti-diabetic agent that has shown potentially beneficial cardiovascular effects such as pre-load and after load reduction through osmotic diuresis, blood pressure reduction, reduced arterial stiffness and weight loss. This has been supported by the recently published EMPA-REG trial which showed a striking 38 and 35 % reduction in cardiovascular death and HF hospitalisation respectively. Methods The REFORM trial is a novel, phase IV randomised, double blind, placebo controlled clinical trial that has been ongoing since March 2015. It is designed specifically to test the safety and efficacy of the SLGT2 inhibitor, dapagliflozin, on diabetic patients with known HF. We utilise cardiac-MRI, cardio-pulmonary exercise testing, body composition analysis and other tests to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard of care over a 1 year observation period. The primary outcome is to detect the change in left ventricular (LV) end systolic and LV end diastolic volumes. The secondary outcome measures include LV ejection fraction, LV mass index, exercise tolerance, fluid status, quality of life measures and others. Conclusions This trial will be able to determine if SGLT2 inhibitor therapy produces potentially beneficial effects in patients with DM and HF, thereby replacing current medications as the drug of choice when treating patients with both DM and HF

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe