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Oxidative stress has been increasingly linked to the high incidence of cardiovascular events in patients with chronic kidney disease (CKD), especially as traditional cardiovascular risk factors seem to not be able to account for the huge cardiovascular morbidity and mortality in this population group. Oxidative stress is increased in patients with renal impairment as a result of increased oxidant activity and reduced antioxidant capacity, and this is increased in a graded manner with increasing renal dysfunction. Inflammation, which is also present in CKD, further amplifies the oxidant generation process. The two clinical sequelae of oxidative stress are endothelial dysfunction and left ventricular hypertrophy, which have adverse cardiovascular consequences. With our new understanding of oxidative stress, it is now important to assess treatment options that reduce it in the hope that they reverse endothelial dysfunction and left ventricular hypertrophy and the clinical sequelae of these abnormalities.

Aims/hypothesis Low 25-hydroxyvitamin D levels predict future cardiovascular events and are common in patients with type 2 diabetes. We compared the effect of 100,000 and 200,000 IU doses of vitamin D 3 on endothelial function, blood pressure and markers of glycaemic control in patients with type 2 diabetes. Methods This was a randomised, parallel group, placebo-controlled trial. Patients with type 2 diabetes and baseline 25-hydroxyvitamin D levels <100 nmol/l were enrolled from community and hospital-based diabetes clinics. Participants were assessed in a university department of clinical pharmacology and received a single oral dose of placebo or vitamin D 3 (100,000 IU or 200,000 IU) at baseline, randomly allocated via numbered bottles prepared offsite; participants and investigators were both blinded to treatment allocation. Endothelial function, office blood pressure, B-type natriuretic peptide, insulin resistance and glycosylated haemoglobin were measured at baseline, and at 8 and 16 weeks. Results We randomised 61 participants to the three groups (placebo 22, 100,000 IU vitamin D 3 19, 200,000 IU vitamin D 3 20). There was no significant difference in the primary outcome of endothelial function at 8 weeks (placebo 5.2%, n  = 22; 100,000 IU 4.3%, n  = 19; 200,000 IU 4.9%, n  = 17) or at 16 weeks. Insulin resistance and glycosylated haemoglobin did not improve with either dose of vitamin D 3 . On covariate analysis, systolic blood pressure was significantly lower in both treatment arms than in the placebo group at 8 weeks (placebo 146.4 mmHg, 100,000 IU 141.4 mmHg [ p  = 0.04 vs placebo], 200,000 IU 136.8 mmHg [ p  = 0.03 vs placebo]). B-type natriuretic peptide levels were significantly lower in the 200,000 IU group by 16 weeks (placebo 34 pg/ml, 200,000 IU 21 pg/ml, p  = 0.02). No significant excess of adverse effects was noted in the treatment arms. Conclusions/interpretation High-dose vitamin D 3 improved systolic blood pressure and B-type natriuretic peptide levels, but not endothelial function, insulin resistance or glycosylated haemoglobin in patients with type 2 diabetes. Trial registration ISRCTN50587697 ( www.controlled-trials.com ) Funding Diabetes UK, grant number 06/0003429. M. D. Witham is funded by a Scottish Government NES/CSO Clinician Scientist Award.

This paper presents a life cycle assessment (LCA) of the International Energy Agency (IEA) 15 MW Reference Wind Turbine (RWT), on floating platforms, deployed in commercial-scale arrays at multiple locations around Scotland in the ScotWind leasing round. Site-specific energy production and vessel operations are provided by a dedicated offshore wind farm operations and maintenance (O&M) model, COMPASS, allowing service operation vessel (SOV) O&M impacts to be assessed with increased confidence. For climate change, the median global warming impact varied from 17.4 to 26.3 gCO2eq/kWh across the four sites within a 95% confidence interval using an uncertainty assessment of both foreground and background data. As is common with other offshore renewable energy systems, materials and manufacture account for 71% to 79% of global warming impact, while O&M comprise between 9% and 16% of the global warming impacts. High-voltage direct current (HVDC) export cables, floating platforms, and composite blades are significant contributors to the environmental impacts of these arrays (by mass and material choice), while the contributions from ballast, vessel transportation emissions, and power-train components are lower. The results suggest that material efficiencies, circularity, and decarbonizing material supply inventories should be a priority for the Scottish floating wind sector, followed by minimizing vessel operations and the decarbonization of vessel propulsion, while avoiding burden shifting to other impact categories.

Vitamin K insufficiency is common and linked to an increased risk of cardiovascular disease and osteoporotic fractures. The aim of this study was to examine whether daily supplementation with oral vitamin K could improve vascular health and physical function in older people with established vascular disease. A double blind, randomised, placebo-controlled trial. Participants aged ≤ 70 years with a history of vascular disease were randomised to receive 6 months of daily oral 100mcg vitamin K2 (MK7 subtype) or matching placebo with outcomes measured at 0, 3 and 6 months. The primary outcome was between-group difference in endothelial function assessed using flow-mediated dilatation of the brachial artery at 6 months. Secondary outcomes included carotid-radial pulse wave velocity, augmentation index, blood pressure, carotid intima-media thickness, C-reactive protein, B-type natriuretic peptide, cholesterol and desphospho-uncarboxylated matrix Gla protein levels. Handgrip strength and the Short Physical Performance Battery assessed physical function, while postural sway was measured using a 3-dimensional force platform. 80 participants were randomised, mean age 77 (SD 5) years; 44/80 were male. Vitamin K levels rose in the intervention arm compared to placebo (+48 pg/ml vs −6 pg/ml, p=0.03) at 6 months. Desphospho-uncarboxylated Matrix Gla protein levels fell in the intervention group compared to placebo at 6 months (−130 [SD 117] pmol/L vs +13 [SD 180] pmol/L, p<0.001). No change was seen in endothelial function (between group difference −0.3% [95%CI −1.3 to 0.8], p=0.62). A modest, non-significant improvement in pulse wave velocity was seen in the vitamin K group (−0.8m/s [95%CI −1.8 to 0.3], p=0.15) while all other vascular and physical function outcomes unchanged. Six months of vitamin K2 supplementation did not improve markers of vascular health or physical function in older patients with vascular disease.

Objective: To investigate patients' adherence to statin treatment prescribed following their first myocardial infarction (MI) and to estimate the effect of adherence to statins on recurrence of MI and all cause mortality. Design: Cohort study using a record linkage database. Setting: Tayside, Scotland, UK. Patients: Patients who experienced their first MI between January 1990 and November 1995. Main outcome measures: Percentage of statin use and adherence to statins by patients after an MI and the relative risk of hospitalisation for recurrent MI. The effect of adherence on all cause mortality was also examined. The covariates used were age, sex, socioeconomic deprivation, serum cholesterol concentration, diabetes mellitus, cardiovascular drug use, and other hospitalisations. Results: Of 5590 patients who experienced an incident MI, 717 (12.8%) experienced at least one further MI. Only 7.7% of patients used statins after an MI during the study period. Compared with those not taking statins, those who had 80% or better adherence to statin treatment had an adjusted relative risk of recurrent MI of 0.19 (95% confidence interval (CI) 0.08 to 0.47) and all cause mortality of 0.47 (95% CI 0.22 to 0.99). There was no significant reduction in either end point for those who were less than 80% adherent to statins. Conclusions: Despite the infrequent use of statin during the study period, good adherence to statin treatment was associated with lower risk of recurrent MI.

Background:Regular physical activity is vital for maintaining the health and independence of older people. Few objective data exist on the effect of weather on physical activity levels in this group. The objective of this study was to evaluate the effect of weather using an objective measure of physical activity.Methods:This was a retrospective study of 127 participants, >65 years old, who were enrolled in a previous randomised controlled trial. The main outcome was daily activity counts measured using the RT3 triaxial accelerometer over 1-week periods. These were correlated with local weather data including daily maximum temperature, sunshine, precipitation and wind speed that were obtained from the metrological office.Results:The mean age of the subjects was 78.6 years; 90/127 were female; and 720 usable daily counts were obtained for the 127 participants. The mean daily counts showed a striking seasonal variation, with maximum activity in June and minimum in February (137 557 vs 65 010 counts per day, p<0.001). Day length, mean maximum temperature and mean daily sunshine were able to explain 72.9% of the monthly variance in daily activity levels. Daily counts showed moderate correlation with day length (r = 0.358, p<0.001), maximum temperature (r = 0.345, p<0.001), duration of sunshine (r = 0.313, p<0.001) and rain (r = −0.098, p = 0.008) but not with wind speed (r = 0.093, p = 0.12). Multivariate analysis showed that day length, sunshine duration and maximum temperature were independent predictors of daily activity (adjusted R2 = 0.16).Conclusions:Physical activity levels among older people are much higher in summer than in winter. Day length, sunshine duration and maximum temperature have a significant influence on physical activity levels.

Objectives: To examine whether the favourable effects on endothelial function, vascular angiotensin converting enzyme (ACE) activity, cardiac remodelling, autonomic function, and QT intervals of spironolactone in combination with ACE inhibitor also occur in patients with New York Heart Association class I–II congestive heart failure (CHF) taking optimal treatment (including β blockers). Methods: Double blind, crossover study comparing 12.5–50 mg/24 hours spironolactone (three months) with placebo in 43 patients with class I–II CHF taking ACE inhibitors and β blockers. Results: Acetylcholine induced vasodilatation improved with spironolactone (p  =  0.044). Vascular ACE activity fell (p  =  0.006). QTc and QTd fell (mean (SD) QTc 473 (43.1) ms with placebo, 455 (35.4) ms with spironolactone, p  =  0.002; QTd 84.5 (41.3) ms with placebo, 72.1 (32.3) ms with spironolactone, p  =  0.037). β-Type natriuretic peptide (BNP) and procollagen III N-terminal peptide (PIIINP) concentrations were also reduced by spironolactone (mean (SD) BNP 48.5 (29.6) pg/ml with placebo, 36.8 (28.5) pg/ml with spironolactone, p  =  0.039; PIIINP 3.767 (1.157) μg/ml with placebo, 3.156 (1.123) μg/ml with spironolactone, p  =  0.000). Conclusions: Spironolactone improves vascular function (endothelial function, vascular ACE activity) and other markers of prognosis (BNP, collagen markers, and QT interval length) in asymptomatic or mild CHF when added to optimal treatment including β blockade. This gives support to the hypothesis that the prognostic benefit seen in RALES (randomised aldactone evaluation study) and EPHESUS (eplerenone postacute myocardial infarction heart failure efficacy and survival study) may also occur in patients with milder CHF already taking standard optimal treatment.

Aims/hypothesis Aldosterone antagonism improves endothelial function (and reduces deaths) in chronic heart failure. It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension. We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes, focussing on blood pressure, endothelial function, glycaemic control and key hormones. Methods We performed a randomised, placebo-controlled, double-blind, crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension, comparing spironolactone versus placebo. Patients had their endothelial function assessed by standard forearm venous occlusion plethysmography. Results There was no significant improvement in endothelium-dependent vasodilatation in response to acetylcholine, despite highly significant reductions in systolic and diastolic blood pressure. However, spironolactone significantly worsened glycaemic control, plasma angiotensin II and cortisol. Conclusions/interpretation Spironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on standard treatment, but does not improve vascular endothelial function in this group. We speculate that any tendency for the spironolactone-induced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol. Trials Registry no.: ISRCTN 76558770

Patients with type 2 diabetes mellitus are at greater cardiovascular risk than the general population. Although it is widely acknowledged that diabetes is a risk factor for coronary artery disease, the increased prevalence of potentially lethal left ventricular abnormalities in this population is less well appreciated. We carried out an echocardiographic study of 500 subjects with type 2 diabetes mellitus to assess the prevalence of left ventricular hypertrophy (LVH) and left ventricular systolic dysfunction (LVSD). We also assessed whether abnormalities in diastolic filling parameters were present. Of the 371 patients in whom left ventricular mass could be successfully assessed, 264 had LVH (71%). Left ventricular systolic dysfunction was much less common, being present in 16/385 patients (4.2%). Long axis contraction was abnormal in 29/429 patients (6.8%). Diastolic filling abnormalities were present in 178/435 (41%) of patients who could be classified using the selected criteria. We conclude that left ventricular abnormalities are common in type 2 diabetic patients. As medical therapy is available for both LVH and LVSD and has been demonstrated to reduce cardiovascular death, these left ventricular abnormalities could be ideal targets for screening, followed by selective therapeutic intervention.

Objective: To study whether the effect of allopurinol on improvement of endothelial dysfunction in chronic heart failure (CHF) translates into improved exercise capacity and to examine whether allopurinol also improves B-type natriuretic peptide (BNP), the other important prognostic marker of CHF. Design: Randomised, double blind, placebo controlled crossover trial. Setting: Teaching hospital. Patients: 50 patients with CHF (New York Heart Association functional classes II and III) were recruited. Interventions: 50 patients with CHF were randomly assigned to three months’ treatment with allopurinol (300 mg/day) or placebo. At two and three months into treatment, they underwent a modified Bruce exercise protocol and a six minute walk test. Blood was taken for BNP and haemoglobin analysis. Results: Neither exercise test was altered by allopurinol. However, plasma BNP concentrations fell significantly (p  =  0.035) with allopurinol (11.9 pmol/l) versus placebo (14.4 pmol/l). Haemoglobin concentrations also fell highly significantly with allopurinol (p  =  0.001). Conclusions: An important negative finding is that despite high hopes for it, allopurinol had no effect on exercise capacity in CHF. On the other hand, allopurinol did reduce BNP, which is the best available surrogate marker for prognosis in CHF.