The effect of perindopril on postural instability in older people with a history of falls-a randomised controlled trial.

Design: double-blind, parallel group, placebo-controlled randomised trial. Methods: we recruited people aged >65 years with at least one fall in the previous year. Participants received 4 mg perindopril or placebo daily for 15 weeks. The primary outcome was the between-group difference in force-plate measured anteroposterior (AP) sway at 15 weeks. Secondary outcomes included other measures of postural sway, limits of stability during maximal forward, right and left leaning, blood pressure, muscle strength, 6-min walk distance and falls. The primary outcome was assessed using two-way ANOVA, adjusted for baseline factors. Results: we randomised 80 participants. Mean age was 78.0 (SD 7.4) years; 60 (75%) were female. About 77/80 (96%) completed the trial. At 15 weeks there were no significant between-group differences in AP sway with eyes open (mean difference 0 mm, 95% CI -8 to 7 mm, P = 0.91) or eyes closed (mean difference 2 mm, 95% CI -7 to 12 mm, P = 0.59); no differences in other measures of postural stability, muscle strength or function. About 16/40 (42%) of patients in each group had orthostatic hypotension at follow-up. The median number (IQR) of falls was 1 (0,4) in the perindopril versus 1 (0,2) in the placebo group (P = 0.24). Conclusions: perindopril did not improve postural sway in older people at risk of falls. Clinical Trials Registration: ISRCTN58995463.

Metformin and its effects on myocardial dimension and left ventricular hypertrophy in normotensive patients with coronary heart disease (the MET-REMODEL study): rationale and design of the MET-REMODEL study.

Left ventricular hypertrophy (LVH) is a common and independent risk factor for cardiovascular events in patients with coronary artery disease (CAD). Controlling blood pressure is the standard approach to the management of LVH, but this is only partially effective as LVH also persists in normotensive patients. Apart from blood pressure (BP), other main risk factors associated with LVH are insulin resistance (IR) and central obesity. The diabetic medication, Metformin, reduces IR and aids weight loss and may therefore regress LVH. The MET REMODEL study will investigate the ability of Metformin to regress LVH in 64 patients with CAD. The MET-REMODEL trial is a single-center, phase IV, double blind, randomized, placebo-controlled trial to investigate the efficacy of Metformin in regression of the independent cardiac risk factor of LVH in patients with CAD who are insulin resistant. A minimum of 64 adults with a history of CAD with LVH and IR will be randomized into two groups to receive, either Metformin XL or placebo. The primary endpoint of this trial is to investigate any change in left ventricular mass index. Secondary endpoints include changes to insulin resistance measured using fasting insulin resistance index (FIRI), obesity, LV size, and function and improvement in endothelial function. A positive result will assist clinicians to identify a new mechanism for LVH regression by administering Metformin XL. This may also lead to investigating the mortality benefit of Metformin in patients with CAD and LVH.

Allopurinol treatment reduces arterial wave reflection in stroke survivors.

The importance of xanthine oxidase and its products is being increasingly recognized in cardiovascular medicine. Patients who have had a stroke are at high risk of future cardiovascular events and this risk is higher in those with high urate levels. The aim of this pilot study was to see if inhibiting xanthine oxidase altered arterial wave reflection, determined from the augmentation index (AIx). In a double-blind study, 30 patients with high urate (> or = 0.38 mmol/L) were randomized to 300 mg allopurinol or placebo for 8 weeks. AIx measurements were made before and after treatment using the validated SphygmoCor pulse waveform analysis system. For patients treated with allopurinol, there was a reduction in AIx from 26.08 +/- 3.31% to 20.15 +/- 2.23% compared with an increase in the placebo group from 23.57 +/- 3.13% to 27.64 +/- 3.44% (P = 0.031, ANOVA). The vascular benefits of allopurinol are rapidly emerging. We have demonstrated that allopurinol has beneficial effects on AIx, a validated measure of vascular function. A further larger study is warranted to look at whether a therapeutic intervention with allopurinol will impact positively on mortality and morbidity in stroke survivors.

The association between serum urate levels and arterial stiffness/endothelial function in stroke survivors.

There is increasing evidence that serum uric acid is an independent marker of cardiovascular risk. We have shown previously that high urate is associated with cardiac death in stroke survivors independently of conventional risk factors. We sought to determine in stroke survivors the association between high urate levels and arterial stiffness and endothelial function. One hundred and twenty stroke survivors were recruited. We assessed pulse wave velocity of the carotid artery using an echotracking ultrasound system. Endothelial function was assessed by measuring forearm skin blood flow responses, using laser Doppler imaging, to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Patients with high serum urate (0.42-0.71 mmol/l) had a greater pulse wave velocity (P<0.02) and a lower ACh response (P=0.001) than patients with lower urate (0.12-0.28 mmol/l). Pulse wave velocity significantly correlated with serum urate (r=-0.358, P<0.001), HDL cholesterol (r=-0.22, P=0.02), and male gender (r=0.26, P=0.005). The ACh response significantly correlated with serum urate (r=-0.30, P=0.001), male gender (r=-0.45, P<0.001), HDL cholesterol (r=0.42, P<0.001), and triglycerides (r=-0.24, P=0.01). Stepwise multiple regression showed that serum urate was significantly associated with pulse wave velocity (beta=0.35, P<0.001), independently of other risk variables. For the ACh response the significant determinants were male gender (beta=-0.38, P<0.001) and HDL cholesterol (beta=0.23, P=0.018). We have shown for the first time that elevated serum urate is associated with increased arterial stiffness in stroke survivors, independently of other risk factors. A therapeutic intervention trial of lowering of serum urate is required to see whether this will impact positively on mortality and morbidity in patients with high-risk of strokes.