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A Mediterranean dietary pattern is widely recommended for the prevention of chronic disease. We sought to define the most likely effects of the Mediterranean diet on vascular disease and mortality. We searched MEDLINE, EMBASE and the Cochrane Central Register without language restriction for randomized controlled trials comparing Mediterranean to control diets. Data on study design, patient characteristics, interventions, follow-up duration, outcomes and adverse events were sought. Individual study relative risks (RR) were pooled to create summary estimates. Six studies with a total of 10950 participants were included. Effects on major vascular events (n = 477), death (n = 693) and vascular deaths (n = 315) were reported for 3, 5 and 4 studies respectively. For one large study (n = 1000) there were serious concerns about the integrity of the data. When data for all studies were combined there was evidence of protection against major vascular events (RR 0.63, 95% confidence interval 0.53-0.75), coronary events (0.65, 0.50-0.85), stroke (0.65, 0.48-0.88) and heart failure (0.30, 0.17-0.56) but not for all-cause mortality (1.00, 0.86-1.15) or cardiovascular mortality (0.90, 0.72-1.11). After the study of concern was excluded the benefit for vascular events (0.69, 0.55-0.86) and stroke (0.66, 0.48-0.92) persisted but apparently positive findings for coronary events (0.73, 0.51-1.05) and heart failure (0.25, 0.05-1.17) disappeared. The Mediterranean diet may protect against vascular disease. However, both the quantity and quality of the available evidence is limited and highly variable. Results must be interpreted with caution.

Following an acute myocardial infarction (MI), patients with persistently elevated biomarkers of inflammation, in particular C-reactive protein (CRP), are at significantly increased risk of further cardiovascular events. Colchicine is a unique anti-inflammatory medication that has shown promise in reducing such events in patients with stable coronary heart disease. The current study tested the ability of low dose colchicine to reduce CRP levels at 30 days after an acute MI, a key marker of future outcome, and its safety and tolerability in this setting. We conducted a randomized, double-blind, trial of low-dose colchicine (0.5 mg daily) or matching placebo in 237 patients admitted with an acute MI. The primary end-point was the proportion of patients with a residual high sensitivity CRP level ≥2 mg/L after 30 days of treatment, a threshold associated with a worse prognosis. At 30-day follow-up, 44% of patients treated with colchicine had a CRP level ≥2 mg/L compared to 50% of those randomized to placebo (P = .35) and the median CRP in patients randomized to colchicine was 1.6 mg/L (interquartile range [IQR] 0.7–3.5) compared to 2.0 mg/L (IQR 0.9–4.0) in patients randomized to placebo (P = .11). The median absolute reduction in CRP levels was −4.3 mg/L (IQR −1.1 to −14.1) among colchicine treated patients and −3.3 mg/L (IQR −0.9 to −14.4, P = .44) in placebo treated patients. The relative reduction was a fall of 78% compared to a fall of 64% (P = .09). Low dose colchicine was well tolerated and did not reduce compliance with other secondary preventative medications at 30-days. Treatment with low dose colchicine was safe and well tolerated, but was not associated with a significantly increased likelihood of achieving a CRP level <2 mg/L or lower absolute levels of CRP 30 days after an acute MI.

Recent hypertension guidelines have reversed previous recommendations for lower blood pressure targets in high-risk patients, such as those with cardiovascular disease, renal disease, or diabetes. This change represents uncertainty about whether more intensive blood pressure-lowering strategies are associated with greater reductions in risk of major cardiovascular and renal events. We aimed to assess the efficacy and safety of intensive blood pressure-lowering strategies. For this updated systematic review and meta-analysis, we systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between Jan 1, 1950, and Nov 3, 2015. We included randomised controlled trials with at least 6 months' follow-up that randomly assigned participants to more intensive versus less intensive blood pressure-lowering treatment, with different blood pressure targets or different blood pressure changes from baseline. We did not use any age or language restrictions. We did a meta-analysis of blood pressure reductions on relative risk (RR) of major cardiovascular events (myocardial infarction, stroke, heart failure, or cardiovascular death, separately and combined), and non-vascular and all-cause mortality, end-stage kidney disease, and adverse events, as well as albuminuria and progression of retinopathy in trials done in patients with diabetes. We identified 19 trials including 44 989 participants, in whom 2496 major cardiovascular events were recorded during a mean 3·8 years of follow-up (range 1·0–8·4 years). Our meta-analysis showed that after randomisation, patients in the more intensive blood pressure-lowering treatment group had mean blood pressure levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group. Intensive blood pressure-lowering treatment achieved RR reductions for major cardiovascular events (14% [95% CI 4–22]), myocardial infarction (13% [0–24]), stroke (22% [10–32]), albuminuria (10% [3–16]), and retinopathy progression (19% [0–34]). However, more intensive treatment had no clear effects on heart failure (15% [95% CI −11 to 34]), cardiovascular death (9% [–11 to 26]), total mortality (9% [–3 to 19]), or end-stage kidney disease (10% [–6 to 23]). The reduction in major cardiovascular events was consistent across patient groups, and additional blood pressure lowering had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes. Serious adverse events associated with blood pressure lowering were only reported by six trials and had an event rate of 1·2% per year in intensive blood pressure-lowering group participants, compared with 0·9% in the less intensive treatment group (RR 1·35 [95% CI 0·93–1·97]). Severe hypotension was more frequent in the more intensive treatment regimen (RR 2·68 [1·21–5·89], p=0·015), but the absolute excess was small (0·3% vs 0·1% per person-year for the duration of follow-up). Intensive blood pressure lowering provided greater vascular protection than standard regimens. In high-risk patients, there are additional benefits from more intensive blood pressure lowering, including for those with systolic blood pressure below 140 mmHg. The net absolute benefits of intensive blood pressure lowering in high-risk individuals are large. National Health and Medical Research Council of Australia.

Background A healthy diet is an important component of secondary prevention of coronary heart disease (CHD). The TEXT ME study was a randomised clinical trial of people with CHD that were randomised into standard care or a text-message programme in addition to standard care. This analysis aimed to: 1) assess the effects of the intervention onadherence to the dietary guideline recommendations; 2) assess the consistency of effect across sub-groups; and 3) assess whether adherence to the dietary guideline recommendations mediated the improvements in objective clinical outcomes. Methods Dietary data were collected using a self-report questionnaire to evaluate adherence to eight dietary guideline recommendations in Australia, including consumption of vegetables, fruits, fish, type of fat used for cooking and in spreads, takeaway food, salt and standard alcohol drinks. The primary outcome of this analysis was the proportion of patients adhering to ≥ 4 dietary guideline recommendations concomitantly and each recommendation was assessed individually as secondary outcomes. Data were analysed using log-binomial regression for categorical variables and analysis of covariance for continuous variables. Results Among 710 patients, 54% were adhering to ≥ 4 dietary guideline recommendations (intervention 53% vs control 56%, p  = 0.376) at baseline. At six months, the intervention group had a significantly higher proportion of patients adhering to ≥ 4 recommendations (314, 93%) compared to the control group (264, 75%, RR 1.23, 95% CI 1.15–1.31, p  < 0.001). In addition, the intervention patients reported consuming higher amounts of vegetables, fruits, and fish per week; less takeaway foods per week; and greater salt intake control. The intervention had a similar effect in all sub-groups tested. There were significant mediational effects of the increase in adherence to the recommendations for the association between the intervention and LDL-cholesterol ( p  < 0.001) and body mass index (BMI) at six months follow-up ( p  = 0.005). Conclusion A lifestyle-focused text-message programme improved adherence to the dietary guideline recommendations, and specifically improved self-reported consumption of vegetables, fruits, fish, takeaway foods and salt intake. Importantly, these improvements partially mediated improvements in LDL-cholesterol and BMI. This simple and scalable text-messaging intervention could be used as a strategy to improve diet in people with CHD. Trial registration Australia and New Zealand Clinical Trials Registry ACTRN12611000161921 . Registered on 10 February 2011.

An elevated preoperative white blood cell count has been associated with a worse outcome after coronary artery bypass grafting (CABG). Leukocyte subtypes, and particularly the neutrophil-lymphocyte (N/L) ratio, may however, convey superior prognostic information. We hypothesized that the N/L ratio would predict the outcome of patients undergoing surgical revascularization. Baseline clinical details were obtained prospectively in 1938 patients undergoing CABG. The differential leukocyte was measured before surgery, and patients were followed-up 3.6 years later. The primary end point was all-cause mortality. The preoperative N/L ratio was a powerful univariable predictor of mortality (hazard ratio [HR] 1.13 per unit, P < .001). In a backward conditional model, including all study variables, it remained a strong predictor (HR 1.09 per unit, P = .004). In a further model, including the European system for cardiac operative risk evaluation, the N/L ratio remained an independent predictor (HR 1.08 per unit, P = .008). Likewise, it was an independent predictor of cardiovascular mortality and predicted death in the subgroup of patients with a normal white blood cell count. This excess hazard was concentrated in patients with an N/L ratio in the upper quartile (>3.36). An elevated N/L ratio is associated with a poorer survival after CABG. This prognostic utility is independent of other recognized risk factors.

Community pharmacists have regular interactions with people living with type 2 diabetes to supply medications, and have a potential role in supporting other primary care professionals in the screening, management, monitoring and facilitation of timely referral of microvascular complications. This study aimed to investigate the contemporary and future roles of community pharmacists in diabetes-related microvascular complication management. This study involved an online Australian nation-wide survey of pharmacists administered Qualtrics® and distributed through social media platforms, state and national pharmacy organisations, and major banner groups. Descriptive analyses were undertaken using SPSS. Among 77 valid responses, 72% of pharmacists already provided blood pressure and blood glucose monitoring services for the management of type 2 diabetes. Only 14% reported providing specific microvascular complication services. Over 80% identified a need for a comprehensive microvascular complication monitoring and referral service, and agreed it is feasible and within the scope of practice of a pharmacist. Almost all respondents agreed that they would implement and provide a monitoring and referral service if provided with appropriate training and resources. Potential barriers to service implementation were competing demands and lack of remuneration and awareness among consumers and health professionals. Type 2 diabetes services in Australian community pharmacies do not currently focus on microvascular complication management. There appears to be strong support for implementing a novel screening, monitoring and referral service community pharmacy to facilitate timely access to care. Successful implementation would require additional pharmacist training, and identification of efficient pathways for service integration and remuneration.

ObjectiveCardiovascular complications are important causes of morbidity and mortality in elective non-cardiac surgery. Although difficult to diagnose, perioperative myocardial infarction (MI) remains prognostically important. High-sensitivity troponin T (hs-TnT) assays allow detection of very minor damage to cardiac muscle. These assays are yet to be fully evaluated in the perioperative setting. Our aim was to determine the incidence and predictors of myocardial necrosis in patients at high cardiovascular risk undergoing elective non-cardiac surgery using hs-TnT.DesignProspective observational cohort study.Patients352 consecutive patients undergoing elective major non-cardiac surgery prescribed antiplatelet therapy for primary or secondary cardiovascular event prevention.Main outcome measureThe incidence of elevated preoperative hs-TnT (≥14 ng/litre), hs-TnT-defined perioperative myocardial necrosis (≥ 14ng/litre and 50% increase from preoperative level), and perioperative MI were determined in relation to patient and surgical factors.ResultsPreoperative hs-TnT was elevated in 31% and postoperative myocardial necrosis occurred in 22% of patients. Predictors of elevated baseline hs-TnT included age (OR 1.10, p<0.001), male gender (OR 2.91, p<0.001), diabetes requiring insulin therapy (OR 4.85, p=0.004) and chronic kidney disease (OR 3.60, p<0.001). Independent predictors of perioperative myocardial necrosis were age (OR 1.07, p<0.001), intraoperative hypotension (OR 3.67, p=0.001) and orthopaedic surgery (OR 2.46, p=0.005). Only 2% of patients suffered clinically apparent MI. Elevated preoperative hs-TnT did not predict perioperative myocardial necrosis or MI.ConclusionsPerioperative myocardial damage occurs frequently in patients undergoing elective non-cardiac surgery, although the majority of events are clinically undetected. Age and intraoperative hypotension are independent predictors of myocardial necrosis in this setting.

ObjectiveRenal dysfunction predicts an increased risk of both early and long-term mortality after cardiac surgery. Cystatin C enables glomerular filtration rate (GFR) to be estimated accurately and may be superior in this regard to creatinine-based estimates. We hypothesised, therefore, that cystatin C and derived estimates of GFR would independently predict long-term survival after cardiac surgery and would be superior in this respect to traditional estimates of GFR. The current study tests this hypothesis in a large and well-characterised cohort of patients.DesignA prospective cohort study.SettingRegional cardiothoracic centre in Northeast Scotland.Participants1010 patients undergoing non-emergent cardiac surgery between 2004 and 2007. Serum creatinine and cystatin C levels were measured preoperatively and demographic and clinical variables were recorded.Primary outcome measureAll-cause mortality, established from the National Records of Scotland.ResultsThe median duration of follow-up after surgery was 9.7 years (IQR 8.9–10.6 years), during which 297 participants died. Preoperative creatinine and cystatin C levels and estimates of GFR derived from these were all strong predictors of death using Cox regression and remained independently predictive after adjustment for the logistic European System for Cardiac Operative Risk Evaluation, a well-validated clinical risk score and a range of other clinical predictors. Cystatin C-based measures were superior to creatinine-based estimates of GFR.ConclusionsCystatin C and creatinine derived eGFR are powerful and independent predictors of long-term mortality following cardiac surgery. Estimates of GFR derived from cystatin C convey superior prognostic information to conventional creatinine-based estimates, but the observed differences are modest.

BackgroundHypertension is a major cause of premature death worldwide, controlled by only one in five adults. Two trials (Australia and USA) found a single quadpill containing a quarter dosage of four classes of medication effective in reducing blood pressure (BP) among participants with hypertension. By pooling these trials, we can estimate the overall benefit of the quadpill and its heterogeneity across subgroups and two important barriers for BP control: clinician medication inertia and participant medication adherence.MethodsIn a prespecified pooled individual participant data analysis of two QUARTET randomised, multicentre, double-blinded trials in people with hypertension using ≤1medication, quadpill (irbesartan (37.5 mg) (Australia)/candesartan (2 mg) (USA)), amlodipine (1.25 mg), indapamide (0.625 mg), bisoprolol (2.5 mg) unattended office systolic BP (SBP) at 12 weeks was compared with initial monotherapy (irbesartan (150 mg) (Australia), candesartan (8 mg) (USA)). Heterogeneity was assessed using an interaction term in the mixed cox model. Adherence, ≥80% pill count and treatment inertia were estimated.ResultsIn 653 participants (Australia, 591 (91%); USA, 62 (9%)) a significant drop in mean SBP (6.5 mm Hg (95% CI 4.8 to 8.8; p<0·001)) and diastolic BP (5.6 mm Hg (95% CI 4.5 to 6.9; p<0.001)) in favour of the quadpill was found, with less need for uptitration (p<0.001) and less treatment inertia (non-significant: p=0.303). Adherence was high for both treatment arms (over 80%). Compared with monotherapy, the quadpill effect varied by ethnicity (SBP reduced by White (6.9 mm Hg; 95% CI 4.7 to 9.2), Hispanic (3.3 mm Hg; 95% CI 4.0 to 10.6), Asian (12.3 mm Hg; 95% CI 6.2 to 18.5) and Black/other (1.4 mm Hg; 95% CI −9.0 to 6.3), interaction p=0.032).ConclusionThis prospective individual participant data pooled analysis provides further evidence that the quadpill strategy is superior to initial monotherapy by virtue of improved BP-lowering, less need for uptitration and being associated with less treatment inertia.

IntroductionPoor adherence to risk factor control and life-saving medications is a key factor affecting long-term patient prognosis. Evidence indicates that sex plays a significant role in the uptake of both pharmacological and non-pharmacological interventions, ultimately influencing long-term outcomes. This study aimed to quantify sex differences in risk factor management and medication adherence following acute coronary syndrome (ACS).MethodsThis is a secondary analysis of the TEXTMEDS randomised clinical trial - a single-blind, multicentre randomised controlled trial of patients post-ACS. We compared sex differences in achieving clinical and lifestyle targets for secondary prevention, namely blood pressure control (<140/90 mm Hg), low-density lipoprotein cholesterol (LDL-C) (<1.8 mmol/L), healthy body mass index (BMI) (<25 kg/m²), regular physical activity (Global Physical Activity Questionnaire score ≥600), smoking status and adherence to cardioprotective medications (aspirin, beta blockers, ACE/angiotensin receptor blockers, statins, antiplatelets), using adjusted logistic regression models. Medication adherence was defined as taking ≥80% of prescribed doses in the month prior to follow-up, across all five drug classes, unless contraindicated.ResultsOf 1379 patients (mean age 58.5±10.7 years; 1095 (79.4%) male), females were less likely than men to achieve LDL-C targets (adjusted OR (aOR): 0.61, 95% CI 0.45 to 0.82) and engage in regular physical activity (aOR: 0.61, CI 0.47 to 0.80), but more likely to achieve a healthy BMI (aOR: 1.47, CI 1.04 to 2.06). Female patients are less likely to adhere to their medication compared with male counterparts (aOR: 0.68, CI 0.50 to 0.92). However, this association weakened and lost statistical significance after further adjustment for socio-economic factors (aOR: 0.71, CI 0.50 to 1.03). There were no significant interactions between sociodemographic or clinical factors and sex in relation to overall medication adherence (P-interactions >0.05).ConclusionThis study reveals that female patients are less likely to achieve LDL-C targets and engage in physical activity but more likely to maintain a healthy BMI. Although females showed lower medication adherence, this association weakened after adjusting for socio-economic factors. These findings highlight the importance of sex-sensitive strategies focusing on risk factor control and medication adherence for improving cardiovascular health outcomes.Trial registration numberACTRN12613000793718.