Search

Objective: To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults.Methods: Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours. Using compositional data analysis Cox regression, we investigated how reallocating time between movement behaviours was associated with CVD incidence.Results: In leave-one-participant-out analysis, our machine-learning method classified free-living movement behaviours with mean accuracy 88% (95% CI 87% to 89%) and Cohen's kappa 0.80 (95% CI 0.79 to 0.82). Among 87 498 UK Biobank participants, there were 4105 incident CVD events. Reallocating time from any behaviour to MVPA, or reallocating time from sedentary behaviour to any behaviour, was associated with lower CVD risk. For an average individual, reallocating 20 min/day to MVPA from all other behaviours proportionally was associated with 9% (95% CI 7% to 10%) lower risk, while reallocating 1 hour/day to sedentary behaviour from all other behaviours proportionally was associated with 5% (95% CI 3% to 7%) higher risk.Conclusion: Machine-learning methods classified movement behaviours accurately in free-living accelerometer data. Reallocating time from other behaviours to MVPA, and from sedentary behaviour to other behaviours, was associated with lower risk of incident CVD, and should be promoted by interventions and guidelines. [ABSTRACT FROM AUTHOR]

Objective: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics.Methods: We conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists' Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up.Results: There were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken ≥12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was -11.1 (-11.3 to -10.8)/-5.6 (-5.7 to -5.4) mm Hg; between active treatment and placebo was -5.1 (-5.3 to -5.0)/-2.3 (-2.4 to -2.2) mm Hg; and between active and control arms for drug comparison trials was -1.4 (-1.5 to -1.3)/-0.6 (-0.7 to -0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use.Conclusion: These findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions. [ABSTRACT FROM AUTHOR]

Objective: To investigate sex differences in prevalence, treatment and control of major cardiovascular risk factors in England.Methods: Data from the Health Survey for England 2012-2017 on non-institutionalised English adults (aged ≥16 years) were used to investigate sex differences in prevalence, treatment and control of major cardiovascular risk factors: body mass index, smoking, systolic blood pressure and hypertension, diabetes, and cholesterol and dyslipidaemia. Physical activity and diet were not assessed in this study.Results: Overall, 49 415 adults (51% women) were included. Sex differences persisted in prevalence of cardiovascular risk factors, with smoking, hypertension, overweight and dyslipidaemia remaining more common in men than in women in 2017. The proportion of individuals with neither hypertension, dyslipidaemia, diabetes nor smoking increased from 32% to 36% in women and from 28% to 29% in men between 2012 and 2017. Treatment and control of hypertension and diabetes improved over time and were comparable in both sexes in 2017 (66% and 51% for treatment and control of hypertension and 73% and 20% for treatment and control of diabetes). However, women were less likely than men to have treated and controlled dyslipidaemia (21% vs 28% for treatment and 15% vs 24% for control, for women versus men in 2017).Conclusions: Important sex differences persist in cardiovascular risk factors in England, with an overall higher number of risk factors in men than in women. A combination of public health policy and individually tailored interventions is required to further reduce the burden of cardiovascular disease in England. [ABSTRACT FROM AUTHOR]

Background and Objective: Hypertensive disorders of pregnancy (HDPs) affect 5%-10% of pregnancies and have been associated with excess maternal cardiovascular disease (CVD) risk. The primary aim of this study was to reliably estimate absolute and relative risks of CVD after HDP.Methods: A retrospective cohort of women who had singleton pregnancies in New South Wales, Australia, between 2002 and 2016 and identified using linked population health administrative databases. The primary exposure was new-onset HDP (pre-eclampsia/eclampsia and gestational hypertension), and the endpoint was hospitalisation or death due to ischaemic or hypertensive heart disease, or stroke. Kaplan-Meier analysis estimated risks among mothers following their first birth, and multivariable time-dependent Cox regression estimated the association between HDP and CVD.Results: Among 528 106 women, 10.3% experienced HDP in their first pregnancy. The 10-year estimated risk of CVD was 2.1 per 1000 if no HDP and 5.5 per 1000 following HDP. Adjusting for demographics, gestational diabetes, small for gestational age and preterm birth, we found that there was an interaction between smoking and HDP, and a larger effect of early-onset (<34 weeks) HDP, compared with late-onset HDP. The HR for women with early-onset HDP who did not smoke was 4.90 (95% CI 3.00 to 7.80) and the HR for those who did smoke was 23.5 (95% CI 13.5 to 40.5), each compared with women without HDP who did not smoke.Conclusion: In this nationally representative Australian cohort, HDP, especially early onset, conferred a clear increase in the risk of CVD, with amplification by smoking. Targeted preventive health, during and after pregnancy, could prevent a substantial burden of CVD among childbearing women. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate whether digital home monitoring with centralised specialist support for remote management of heart failure (HF) is more effective in improving medical therapy and patients' quality of life than digital home monitoring alone.Methods: In a two-armed partially blinded parallel randomised controlled trial, seven sites in the UK recruited a total of 202 high-risk patients with HF (71.3 years SD 11.1; left ventricular ejection fraction 32.9% SD 15.4). Participants in both study arms were given a tablet computer, Bluetooth-enabled blood pressure monitor and weighing scales for health monitoring. Participants randomised to intervention received additional regular feedback to support self-management and their primary care doctors received instructions on blood investigations and pharmacological treatment. The primary outcome was the use of guideline-recommended medical therapy for chronic HF and major comorbidities, measured as a composite opportunity score (total number of recommended treatment given divided by the total number of opportunities the treatment should have been given, with a score 1 indicating 100% adherence to recommendations). Co-primary outcome was change in physical score of Minnesota Living with Heart Failure questionnaire.Results: 101 patients were randomised to 'enhanced self-management' and 101 to 'supported medical management'. At the end of follow-up, the opportunity score was 0.54 (95% CI 0.46 to 0.62) in the control arm and 0.61 (95% CI 0.52 to 0.70) in the intervention arm (p=0.25). Physical well-being of participants also did not differ significantly between the groups (17.4 (12.4) mean (SD) for control arm vs 16.5 (12.1) in treatment arm; p for change=0.84).Conclusions: Central provision of tailored specialist management in a multi-morbid HF population was feasible. However, there was no strong evidence for improvement in use of evidence-based treatment nor health-related quality of life.Trial Registration Number: ISRCTN86212709. [ABSTRACT FROM AUTHOR]

Introduction Diet is an important modifiable risk factor for many chronic diseases. Measurement of dietary intake usually relies on self-report, subject to multiple biases. There is a need to understand gender differences in the self-report of dietary intake and the implications of any differences in targeting nutrition interventions. Literature in this area is limited and it is currently unknown whether self-report dietary assessment methods are equally accurate for women and men. The aim of this systematic review is to determine whether there are differences by gender in reporting energy intake compared with a reference measure of total energy expenditure. Methods and analysis A comprehensive search of published original research studies will be performed in MEDLINE, Scopus, Web of Science, EMBASE, CINAHL and Cochrane library. Original research studies will be included if they were conducted in free-living/unhospitalised adults and included a measure for both women and men of (a) self-reported energy intake and (b) total energy expenditure by doubly labelled water. One author will conduct the electronic database searches, two authors will independently screen studies, conduct a quality appraisal of the included studies using standardised tools and extract data. If further information is needed, then study authors will be contacted. If appropriate, a random-effects meta-analysis will be conducted, with inverse probability weighting, to quantify differences in the mean difference in agreement between reported energy intake and measured energy expenditure between women and men, by selfreport assessment method. Subgroup analyses will be conducted by participant factors, geographical factors and study quality. Ethics and dissemination All data used will be from published primary research studies or deidentified results provided at the discretion of any study authors that we contact. We will submit our findings to a peer-reviewed scientific journal and will disseminate results through presentations at international scientific conferences. [ABSTRACT FROM AUTHOR]

Introduction End-stage kidney disease (ESKD) is a major public health problem affecting more than 2 million people worldwide. It is one of the most severe chronic non-communicable diseases. Haemodialysis (HD) is the most common therapeutic option but is also associated with a risk of cardiovascular events, hospitalisation and suboptimal quality of life. Over the past decades, haemodiafiltration (HDF) has become available. Although high-dose HDF has shown some promising survival advantage compared to conventional HD, the evidence remains controversial. A Cochrane systematic review found, in low-quality trials, with various convective forms of dialysis, a reduction in cardiovascular, but not all-cause mortality and the effects on non-fatal cardiovascular events and hospitalisation were uncertain. In contrast, an individual patient data analysis suggested that high-dose HDF reduced both all-cause and cardiovascular mortality compared to HD. In view of these discrepant results, a definitive trial is required to determine whether high-dose HDF is preferable to high-flux HD. The comparison of high-dose HDF with high-flux HD (CONVINCE) study will assess the benefits and harms of high-dose HDF versus a conventional high-flux HD in adults with ESKD. Methods and analysis This international, prospective, open label, randomised controlled trial aims to recruit 1800 ESKD adults treated with HD in nine European countries. Patients will be randomised 1:1 to high-dose HDF versus continuation of conventional high-flux HD. The primary outcome will be all-cause mortality at 3 years’ follow-up. Secondary outcomes will include cause-specific mortality, cardiovascular events, all-cause and infection-related hospitalisations, patient-reported outcomes (eg, health-related quality of life) and cost-effectiveness. Ethics and dissemination The CONVINCE study will address the question of benefits and harms of high-dose HDF compared to high-flux HD for kidney replacement therapy in patients with ESKD with a focus on survival, patient perspectives and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether sex differences exist in the management of patients with a history of coronary heart disease (CHD) in primary care.Methods: General practice records of patients aged ≥18 years with a history of CHD in a large general practice dataset in Australia, MedicineInsight, were analysed. Sex-specific, age-standardised proportions of patients prescribed with recommended medications; assessed for cardiovascular risk factors; and achieved treatment targets according to the General Practice Management Plan were reported.Results: Records of 130 926 patients (47% women) from 438 sites were available from 2014 to 2018. Women were less likely to be prescribed with recommended medications (prescribed ≥3 medications: women 44%, men 61%; p<0.001). Younger patients, especially women aged <45 years, were substantially underprescribed (aged <45 years prescribed ≥3 medications: women 2%, men 8%; p<0.001). Lower proportions of women were assessed for cardiovascular risk factors (blood test for lipids: women 70%-76%, men 77%-81%; p<0.001). Body size was not commonly assessed (body mass index: women 59%, men 62%; p<0.001; waist: women 23%, men 25%; p<0.001). Higher proportions of women than men achieved targets for most risk factors (achieved ≥4 targets in patients assessed for all risk factors: women 82%, men 76%).Conclusion: Gaps in preventative management including prescription of indicated medications and risk factor monitoring have been reported from the late 1990s and this large-scale general practice data analysis indicate they still persist. Moreover, the gap is larger in women compared to men. We need new ways to address these gaps and the sex inequity. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to help readers choose an appropriate observational study design for measuring an association between an exposure and disease incidence. We discuss cohort studies, sub-samples from cohorts (case-cohort and nested case-control designs), and population-based or hospital-based case-control studies. Appropriate study design is the foundation of a scientifically valid observational study. Mistakes in design are often irremediable. Key steps are understanding the scientific aims of the study and what is required to achieve them. Some designs will not yield the information required to realise the aims. The choice of design also depends on the availability of source populations and resources. Choosing an appropriate design requires balancing the pros and cons of various designs in view of study aims and practical constraints. We compare various cohort and case-control designs to estimate the effect of an exposure on disease incidence and mention how certain design features can reduce threats to study validity. [ABSTRACT FROM AUTHOR]

Introduction Previous research from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) and others has shown that pharmacological blood pressure (BP)- lowering substantially reduces the risk of major cardiovascular events, including ischaemic heart disease, heart failure and stroke. In this new phase, the aim is to conduct individual patient-level data (IPD) meta-analyses involving eligible BP-lowering randomised controlled trials (RCTs) to address uncertainties relating to efficacy and safety of BP-lowering treatment. Methods and analysis RCTs investigating the effect of pharmacological BP-lowering, with a minimum of 1000 patient-years of follow-up in each trial arm, are eligible. Our systematic review identified 100 potentially eligible trials. We requested their investigators/sponsors to contribute baseline, follow-up and outcomes data. As of June 2018, the collaboration has obtained data from 49 trials (n=315 046 participants), with additional data currently in the process of being transferred from four RCTs (n=34 642 participants). In addition, data harmonisation has commenced. Scientific activities of the collaboration are overseen by the Steering Committee with input from all collaborators. Detailed protocols for individual meta-analyses will be developed and registered on public platforms. Ethics and dissemination Ethics approval has been obtained for this new and extended phase of the BPLTTC, the largest collaboration of de-identified IPD from RCTs. It offers an efficient and ethical manner of re-purposing existing data to answer clinically important questions relating to BP treatment as well as methodological questions relating to IPD meta-analyses. Among the immediate impacts will include reliable quantification of effects of treatment modifiers, such as baseline BP, age and prior disease, on both vascular and non-vascular outcomes. Analyses will further assess the impact of BPlowering on important, but less well understood, outcomes, such as new-onset diabetes and renal disease. Findings will be published in peer-reviewed medical journals on behalf of the collaboration. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a stronger risk factor for cardiovascular disease in women than men. We assessed whether there are sex differences in the effects of 43 established and novel risk factors and the risk of incident AF.Methods: Data were used from the Scottish Heart Health Extended Cohort, a prospective cohort study with over 20 years of follow-up for AF incidence. Cox regression models were used to obtain the adjusted sex-specific HRs and 95% CIs, and the women-to-men ratio of HRs (RHRs), of incident AF associated with personal characteristics, smoking, physical measurements, diabetes mellitus, lipid, inflammatory, cardiac, and diet- and renal-related markers.Results: Overall, 15 737 participants (52% women) were included. There were sex differences in the relationship between a 1 SD increase in body mass index (BMI), NT-pro-BNP, uric acid, and cystatin-C and the risk of AF. The HRs were 1.17 (95% CI 1.08 to 1.27) in women and 1.36 (95% CI 1.24 to 1.49) in men for BMI (RHR 0.86, 95% CI 0.77 to 0.97); 1.84 (95% CI 1.62 to 2.09) in women and 1.54 (95% CI 1.40 to 1.68) in men for NT-pro-BNP (RHR 1.22, 95% CI1.05 to 1.42); 1.27 (95% CI 1.14 to 1.41) in women and 1.10 (95% CI 1.00 to 1.20) in men for uric acid (RHR 1.17, 95% CI 1.01 to 1.35); and 1.22 (95% CI 1.13 to 1.32) in women and 1.07 (95% CI 0.96 to 1.18) in men for cystatin-C (RHR 1.16, 95% CI 1.05 to1.27).Conclusion: Higher BMI is a stronger risk factor for AF in men whereas elevated NT-pro-BNP, uric acid and cystatin-C were more strongly associated with the risk of AF in women. [ABSTRACT FROM AUTHOR]

Objectives To investigate the sex-specific association between smoking and lung cancer. Design Systematic review and meta-analysis. Data sources We searched PubMed and EMBASE from 1 January 1999 to 15 April 2016 for cohort studies. Cohort studies before 1 January 1999 were retrieved from a previous meta-analysis. Individual participant data from three sources were also available to supplement analyses of published literature. Eligibility criteria for selecting studies Cohort studies reporting the sex-specific relative risk (RR) of lung cancer associated with smoking. Results Data from 29 studies representing 99 cohort studies, 7 million individuals and >50 000 incident lung cancer cases were included. The sex-specific RRs and their ratio comparing women with men were pooled using random-effects meta-analysis with inverse-variance weighting. The pooled multiple-adjusted lung cancer RR was 6.99 (95% Confidence Interval (CI) 5.09 to 9.59) in women and 7.33 (95% CI 4.90 to 10.96) in men. The pooled ratio of the RRs was 0.92 (95% CI 0.72 to 1.16; I2=89%; p<0.001), with no evidence of publication bias or differences across major pre-defined participant and study subtypes. The women-to-men ratio of RRs was 0.99 (95% CI 0.65 to 1.52), 1.11 (95% CI 0.75 to 1.64) and 0.94 (95% CI 0.69 to 1.30), for light, moderate and heavy smoking, respectively. Conclusions Smoking yields similar risks of lung cancer in women compared with men. However, these data may underestimate the true risks of lung cancer among women, as the smoking epidemic has not yet reached full maturity in women. Continued efforts to measure the sex-specific association of smoking and lung cancer are required. [ABSTRACT FROM AUTHOR]

Objectives To characterise sex differences in macronutrient intakes and adherence to dietary recommendations in the UK Biobank population. Design Cross-sectional population-based study. Setting UK Biobank Resource. Participants 210 106 (52.5% women) individuals with data on dietary behaviour. Main outcome measures Women-to-men mean differences in nutrient intake in grams and as a percentage of energy and women-to-men ORs in non-adherence, adjusting for age, socioeconomic status and ethnicity. Results There were sex differences in energy intake and distribution. Men had greater intakes of energy and were less likely to have energy intakes above the estimated average requirement compared with women. Small, but significant, sex differences were found in the intakes of all macronutrients. For all macronutrients, men had greater absolute intakes while women had greater intakes as a percentage of energy. Women were more likely to have intakes that exceeded recommendations for total fat, saturated fat and total sugar. Men were less likely to achieve the minimum recommended intakes for protein, polyunsaturated fat and total carbohydrate. Over 95% of men and women were non-adherent to fibre recommendations. Sex differences in dietary intakes were moderated by age and to some extent by socioeconomic status. Conclusions There are significant sex differences in adherence to dietary recommendations, particularly for sugar. However, given the increased focus on food groups and dietary patterns for nutritional policy, these differences alone may not be sufficient for policy and health promotion. Future studies that are able to explore the sex differences in intakes of different food groups that are risk factors for diet-related diseases are warranted to improve the current understanding of the differential impact of diet on health in women and men. [ABSTRACT FROM AUTHOR]

Objective To assess the relationship between risk factor clusters and cardiovascular disease (CVD) incidence in Asian and Caucasian populations and to estimate the burden of CVD attributable to each cluster. Setting Asia Pacific Cohort Studies Collaboration. Participants Individual participant data from 34 population-based cohorts, involving 314 024 participants without a history of CVD at baseline. Outcome measures Clusters were 11 possible combinations of four individual risk factors (current smoking, overweight, blood pressure (BP) and total cholesterol). Cox regression models were used to obtain adjusted HRs and 95% CIs for CVD associated with individual risk factors and risk factor clusters. Populationattributable fractions (PAFs) were calculated. Results During a mean follow-up of 7 years, 6203 CVD events were recorded. The ranking of HRs and PAFs was similar for Australia and New Zealand (ANZ) and Asia; clusters including BP consistently showed the highest HRs and PAFs. The BP-smoking cluster had the highest HR for people with two risk factors: 4.13 (3.56 to 4.80) for Asia and 3.07 (2.23 to 4.23) for ANZ. Corresponding PAFs were 24% and 11%, respectively. For individuals with three risk factors, the BP-smoking-cholesterol cluster had the highest HR (4.67 (3.92 to 5.57) for Asia and 3.49 (2.69 to 4.53) for ANZ). Corresponding PAFs were 13% and 10%. Conclusions Risk factor clusters act similarly on CVD risk in Asian and Caucasian populations. Clusters including elevated BP were associated with the highest excess risk of CVD. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether there are sex differences in risk factor management of patients with established coronary heart disease (CHD), and to assess demographic variations of any potential sex differences.Methods: Patients with CHD were recruited from Europe, Asia, and the Middle East between 2012-2013. Adherence to guideline-recommended treatment and lifestyle targets was assessed and summarised as a Cardiovascular Health Index Score (CHIS). Age-adjusted regression models were used to estimate odds ratios for women versus men in risk factor management.Results: 10 112 patients (29% women) were included. Compared with men, women were less likely to achieve targets for total cholesterol (OR 0.50, 95% CI 0.43 to 0.59), low-density lipoprotein cholesterol (OR 0.57, 95% CI 0.51 to 0.64), and glucose (OR 0.78, 95% CI 0.70 to 0.87), or to be physically active (OR 0.74, 95% CI 0.68 to 0.81) or non-obese (OR 0.82, 95% CI 0.74 to 0.90). In contrast, women had better control of blood pressure (OR 1.31, 95% CI 1.20 to 1.44) and were more likely to be a non-smoker (OR 1.93, 95% CI 1.67 to 2.22) than men. Overall, women were less likely than men to achieve all treatment targets (OR 0.75, 95% CI 0.60 to 0.93) or obtain an adequate CHIS (OR 0.81, 95% CI 0.73 to 0.91), but no significant differences were found for all lifestyle targets (OR 0.93, 95% CI 0.84 to 1.02). Sex disparities in reaching treatment targets were smaller in Europe than in Asia and the Middle East. Women in Asia were more likely than men to reach lifestyle targets, with opposing results in Europe and the Middle East.Conclusions: Risk factor management for the secondary prevention of CHD was generally worse in women than in men. The magnitude and direction of the sex differences varied by region. [ABSTRACT FROM AUTHOR]

Graphs and tables are indispensable aids to quantitative research. When developing a clinical prediction rule that is based on a cardiovascular risk score, there are many visual displays that can assist in developing the underlying statistical model, testing the assumptions made in this model, evaluating and presenting the resultant score. All too often, researchers in this field follow formulaic recipes without exploring the issues of model selection and data presentation in a meaningful and thoughtful way. Some ideas on how to use visual displays to make wise decisions and present results that will both inform and attract the reader are given. Ideas are developed, and results tested, using subsets of the data that were used to develop the ASSIGN cardiovascular risk score, as used in Scotland. [ABSTRACT FROM AUTHOR]

Objective: Investigation of variations in provider performance and its determinants may help inform strategies for improving patient outcomes.Methods: We used the National Heart Failure Audit comprising 68 772 patients with heart failure with reduced left ventricular ejection fraction (HFREF), admitted to 185 hospitals in England and Wales (2007-2013). We investigated hospital adherence to three recommended key performance measures (KPMs) for inhospital care (ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) on discharge, β-blockers on discharge and referral to specialist follow-up) individually and as a composite performance score. Hierarchical regression models were used to investigate hospital-level variation.Results: Hospital-level variation in adherence to composite KPM ranged from 50% to 97% (median 79%), but after adjustments for patient characteristics and year of admission, only 8% (95% CI 7% to 10%) of this variation was attributable to variations in hospital features. Similarly, hospital prescription rates for ACE-I/ARB and β-blocker showed low adjusted hospital-attributable variations (7% CI 6% to 9% and 6% CI 5% to 8%, for ACE-I/ARB and β-blocker, respectively). Referral to specialist follow-up, however, showed larger variations (median 81%; range; 20%, 100%) with 26% of this being attributable to hospital-level differences (CI 22% to 31%).Conclusion: Only a small proportion of hospital variation in medication prescription after discharge was attributable to hospital-level features. This suggests that differences in hospital practices are not a major determinant of observed variations in prescription of investigated medications and outcomes. Future healthcare delivery efforts should consider evaluation and improvement of more ambitious KPMs. [ABSTRACT FROM AUTHOR]

Background and Purpose: Limited data exist on health-related quality of life (HRQoL) after intracerebral haemorrhage (ICH). We aimed to determine baseline factors associated with HRQoL among participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2).Methods: The INTERACT studies were randomised controlled trials of early intensive blood pressure (BP) lowering in patients with ICH (<6 hours) and elevated systolic BP (150-220 mm Hg). HRQoL was determined using the European Quality of Life Scale (EQ-5D) at 90 days, completed by patients or proxy responders. Binary logistic regression analyses were performed to identify factors associated with poor overall HRQoL.Results: 2756 patients were included. Demographic, clinical and radiological factors associated with lower EQ-5D utility score were age, randomisation outside of China, antithrombotic use, high baseline National Institutes of Health Stroke Scale (NIHSS) score, larger ICH, presence of intraventricular extension and use of proxy responders. High (≥14) NIHSS score, larger ICH and proxy responders were associated with low scores in all five dimensions of the EQ-5D. The NIHSS score had a strong association with poor HRQoL (p<0.001). Female gender and antithrombotic use were associated with decreased scores in dimensions of pain/discomfort and usual activity, respectively.Conclusions: Poor HRQoL was associated with age, comorbidities, proxy source of assessment, clinical severity and ICH characteristics. The strongest association was with initial clinical severity defined by high NIHSS score.Trial Registration Numbers: NCT00226096 and NCT00716079; Post-results. [ABSTRACT FROM AUTHOR]

Objective: Experimental evidence has shown potential cardioprotective actions of phosphodiesterase type-5 inhibitors (PDE5is). We investigated whether PDE5i use in patients with type 2 diabetes, with high-attendant cardiovascular risk, was associated with altered mortality in a retrospective cohort study.Research Design and Methods: Between January 2007 and May 2015, 5956 men aged 40-89 years diagnosed with type 2 diabetes before 2007 were identified from anonymised electronic health records of 42 general practices in Cheshire, UK, and were followed for 7.5 years. HRs from multivariable survival (accelerated failure time, Weibull) models were used to describe the association between on-demand PDE5i use and all-cause mortality.DC1SM110.1136/heartjnl-2015-309223.supp1Supplementary appendix RESULTS: Compared with non-users, men who are prescribed PDE5is (n=1359) experienced lower percentage of deaths during follow-up (19.1% vs 23.8%) and lower risk of all-cause mortality (unadjusted HR=0.69 (95% CI: 0.64 to 0.79); p<0.001)). The reduction in risk of mortality (HR=0.54 (0.36 to 0.80); p=0.002) remained after adjusting for age, estimated glomerular filtration rate, smoking status, prior cerebrovascular accident (CVA) hypertension, prior myocardial infarction (MI), systolic blood pressure, use of statin, metformin, aspirin and β-blocker medication. PDE5i users had lower rates of incident MI (incidence rate ratio (0.62 (0.49 to 0.80), p<0.0001) with lower mortality (25.7% vs 40.1% deaths; age-adjusted HR=0.60 (0.54 to 0.69); p=0.001) compared with non-users within this subgroup.Conclusion: In a population of men with type 2 diabetes, use of PDE5is was associated with lower risk of overall mortality and mortality in those with a history of acute MI. [ABSTRACT FROM AUTHOR]

Objective: Type I and II diabetes are associated with a greater relative risk of cardiovascular diseases (CVD) in women than in men. Sex differences in adiposity storage may explain these findings. Methods: A cross-sectional study of 480 813 participants from the UK Biobank without history of CVD was conducted to assess whether the difference in body size in people with and without diabetes was greater in women than in men. Age-adjusted linear regression analyses were used to obtain the mean difference in women minus men in the difference in body size measures, separately for type I and II diabetes. Results: Body size was higher in individuals with diabetes than in individuals without diabetes, particularly in type II diabetes. Differences in body size between individuals with and without type II diabetes were more extreme in women than in men; compared to those without type II diabetes, body mass index and waist circumference were 1.94 (95% CI 1.82 to 2.07) and 4.84 (4.53 to 5.16) higher in women than in men, respectively. In type I diabetes, body size differed to a similar extent between those with and without diabetes in women as in men. This pattern was observed across all prespecified subgroups. Conclusions: Differences in body size associated with diabetes were significantly greater in women than in men in type II diabetes but not in type I diabetes. Prospective studies can determine whether sex differences in body size associated with diabetes underpin some of the excess risk for CVD in women with type II diabetes. [ABSTRACT FROM AUTHOR]

Objectives: In general populations, the adverse effects of smoking on coronary risk have been demonstrated to be greater in women than in men; whether this is true for individuals with diabetes is unclear. Design: Cohort study. Setting: 20 countries worldwide participating in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial. Participants: 11 140 patients with type 2 diabetes aged ≥55 years and in cardiovascular risk at the time of randomisation. Primary and secondary outcome measures: Major cardiovascular events (death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction (MI)), all cardiovascular events (major cardiovascular event or peripheral arterial disease or transient ischaemic attack), and all-cause mortality. Secondary outcome measures were major coronary events (fatal and non-fatal MI), major cerebrovascular events (fatal and non-fatal stroke), nephropathy (new or worsening renal disease), and all cancer. Results: At baseline, 6466 (56% women) participants were never-smokers, 1550 (28% women) were daily smokers and 3124 (21% women) were former smokers. Median follow-up time was 5 years. In Cox regression models after multiple adjustments, compared with never smoking, daily smoking was associated with increased risk of all primary and secondary outcomes with the exception of major cerebrovascular disease. Only for major coronary events was there any evidence of a stronger effect in women than in men (ratio of the adjusted HRs women:men; 1.64 (0.83 to 3.26) p=0.08). [ABSTRACT FROM AUTHOR]

Objective To determine if the dietary supplements, glucosamine and/or chondroitin, result in reduced joint space narrowing (JSN) and pain among people with symptomatic knee osteoarthritis. Methods A double-blind randomised placebo-controlled clinical trial with 2-year follow-up. 605 participants, aged 45-75 years, reporting chronic knee pain and with evidence of medial tibio-femoral compartment narrowing (but retaining >2 mm medial joint space width) were randomised to once daily: glucosamine sulfate 1500 mg (n=152), chondroitin sulfate 800 mg (n=151), both dietary supplements (n=151) or matching placebo capsules (n=151). JSN (mm) over 2 years was measured from digitised knee radiographs. Maximum knee pain (0-10) was self-reported in a participant diary for 7 days every 2 months over 1 year. Results After adjusting for factors associated with structural disease progression (gender, body mass index (BMI), baseline structural disease severity and Heberden's nodes), allocation to the dietary supplement combination (glucosamine-chondroitin) resulted in a statistically significant (p=0.046) reduction of 2-year JSN compared to placebo: mean difference 0.10 mm (95% CI 0.002 mm to 0.20 mm); no significant structural effect for the single treatment allocations was detected. All four allocation groups demonstrated reduced knee pain over the first year, but no significant between-group differences (p=0.93) were detected. 34 (6%) participants reported possibly-related adverse medical events over the 2-year follow-up period. Conclusions Allocation to the glucosamine-chondroitin combination resulted in a statistically significant reduction in JSN at 2 years. While all allocation groups demonstrated reduced knee pain over the study period, none of the treatment allocation groups demonstrated significant symptomatic benefit above placebo. [ABSTRACT FROM AUTHOR]

Objectives: In Western countries, lower socioeconomic status is associated with a higher risk of cardiovascular disease (CVD) and premature mortality. These associations may plausibly differ in Asian populations, but data are scarce and direct comparisons between the two regions are lacking. We, thus, aimed to compare such associations between Asian and Western populations in a large collaborative study, using the highest level of education attained as our measure of social status. Setting: Cohort studies in general populations conducted in Asia or Australasia. Participants: 303 036 people (71% from Asia) from 24 studies in the Asia Pacific Cohort Studies Collaboration. Studies had to have a prospective cohort study design, have accumulated at least 5000 person-years of follow-up, recorded date of birth (or age), sex and blood pressure at baseline and date of, or age at, death during follow-up. Outcome measures: We used Cox regression models to estimate relationships between educational attainment and CVD (fatal or non-fatal), as well as all-cause, cardiovascular and cancer mortality. Results: During more than two million person-years of follow-up, 11 065 deaths (3655 from CVD and 4313 from cancer) and 1809 CVD non-fatal events were recorded. Adjusting for classical CVD risk factors and alcohol drinking, hazard ratios (95% CIs) for primary relative to tertiary education in Asia (Australasia) were 1.81 (1.38, 2.36) (1.10 (0.99, 1.22)) for all-cause mortality, 2.47(1.47, 4.17) (1.24 (1.02, 1.51)) for CVD mortality, 1.66 (1.00, 2.78) (1.01 (0.87, 1.17)) for cancer mortality and 2.09 (1.34, 3.26) (1.23 (1.04, 1.46)) for all CVD. Conclusions: Lower educational attainment is associated with a higher risk of CVD or premature mortality in Asia, to a degree exceeding that in the Western populations of Australasia. [ABSTRACT FROM AUTHOR]

Background We aimed to investigate the relationship between potentially modifiable risk factors in middle age and disability after 13 years using the Framingham Offspring Study (FOS). We further aimed to develop a disability risk algorithm to estimate the risk of future disability for those aged 45–65 years. Methods FOS is a longitudinal study. We used examination 5 (1991–1995; ‘baseline’) and examination 8 (2005–2008; ‘follow-up’). We included participants aged between 45–65 years at ‘baseline’ with complete predictor and outcome measures (n=2031; mean age 53.9 years). Predictors considered were body mass index, smoking, hypertension, diabetes and dyslipidaemia. We used multinomial logistic regression to identify predictors of disability or death. We assessed external validity using Australian data. Results By examination 8, 156 participants had disability and 198 had died. Disability was associated with smoking (OR (95% CI) 1.81 (1.18 to 2.78)); obesity (2.95 (1.83 to 4.77)); diabetes 1.96 (1.11 to 3.45) and being female (OR 1.67 (1.13 to 2.45). The model performed moderately well in predicting disability and death in an Australian population. Based on our algorithm, a 45-year-old man/woman with the combined risk factors of obesity, diabetes and smoking has similar likelihood of surviving free of disability to a 65-year-old man/woman without any of the same risk factors. Conclusions and relevance The derived risk algorithm allows, for the first time, quantification of the substantial combined impact on future disability of key modifiable risk factors in mid-life. Here we demonstrated the combined impact of obesity, diabetes and smoking to be similar to 20 years of aging. [ABSTRACT FROM AUTHOR]

Objectives: Headaches are a common medical problem, yet few studies, particularly trials, have evaluated therapies that might prevent or control headaches. We, thus, investigated the effects on the occurrence of headaches of three levels of dietary sodium intake and two diet patterns (the Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits, vegetables and low-fat dairy products with reduced saturated and total fat) and a control diet (typical of Western consumption patterns)). Design: Randomised multicentre clinical trial. Setting: Post hoc analyses of the DASH-Sodium trial in the USA. Participants: In a multicentre feeding study with three 30 day periods, 390 participants were randomised to the DASH or control diet. On their assigned diet, participants ate food with high sodium during one period, intermediate sodium during another period and low sodium during another period, in random order. Outcome measures: Occurrence and severity of headache were ascertained from self-administered questionnaires, completed at the end of each feeding period. Results: The occurrence of headaches was similar in DASH versus control, at high (OR (95% CI)=0.65 (0.37 to 1.12); p=0.12), intermediate (0.57 (0.29 to 1.12); p=0.10) and low (0.64 (0.36 to 1.13); p=0.12) sodium levels. By contrast, there was a lower risk of headache on the low, compared with high, sodium level, both on the control (0.69 (0.49 to 0.99); p=0.05) and DASH (0.69 (0.49 to 0.98); p=0.04) diets. Conclusions: A reduced sodium intake was associated with a significantly lower risk of headache, while dietary patterns had no effect on the risk of headaches in adults. Reduced dietary sodium intake offers a novel approach to prevent headaches. [ABSTRACT FROM AUTHOR]

Objectives: Several studies have shown that smoking may confer a greater excess risk for chronic diseases in women compared with men. The reasons for this excess risk of smoking in women are unclear, yet sex differences in smoking habits may play a role. We, thus, characterised sex differences in smoking habits in a contemporary Western population. Design: Cross-sectional population-based study. Setting: UK Biobank Resource. Participants: 499 797 (54% women) individuals with data on smoking habits. Main outcome measures: Women-to-men prevalence ratios in smoking status, and the womenminus- men mean difference in age at smoking initiation, number of cigarettes smoked daily and age at smoking cessation in 5-year birth cohort bands. Results: The women-to-men ever-smoking ratio ranged from 0.57 in the oldest to 0.87 in the youngest birth cohort. In the oldest cohort, born 1935-1939, women started smoking 1.9 years (95% CI 1.7 to 2.1) later than did men, but in those born after 1959 there was no difference in the age at initiation. The oldest women smoked 5.3 (95% CI 4.7 to 5.9) cigarettes per day fewer than did the oldest men, compared with 2.0 (95% CI 1.7 to 2.3) fewer cigarettes smoked per day in the youngest, born 1965-1969. Among quitters, women born before 1945 were, on average, 1.5 years older than their male contemporaries, but this differential was 1 year or less among people born after 1949. Conclusions: Differences in smoking behaviour between women and men have decreased over time. Even past differentials are unlikely to explain the increased susceptibility to smoking-related chronic disease in women compared with men that has previously been observed. Future studies are required to determine whether sex differences in the physiological and biological effects of smoking are responsible for the differential impact of smoking on health in women and men. [ABSTRACT FROM AUTHOR]

Introduction: The scientific evidence base in support of salt reduction is strong but the data required to translate these insights into reduced population salt intake are mostly absent. The aim of this research project is to develop the evidence base required to formulate and implement a national salt reduction programme for India. Methods and analysis: The research will comprise three components: a stakeholder analysis involving government, industry, consumers and civil society organisations; a population survey using an age-stratified and sex-stratified random samples drawn from urban (slum and non-slum) and rural areas of North and South India; and a systematic quantitative evaluation of the nutritional components of processed and restaurant foods. The stakeholder interviews will be analysed using qualitative methods to summarise the main themes and define the broad range of factors influencing the food environment in India. The population survey will estimate the mean daily salt consumption through the collection of 24 h urine samples with concurrent dietary surveys identifying the main sources of dietary sodium/salt. The survey of foods will record the nutritional composition of the chief elements of food supply. The findings from this research will be synthesised and proposals fora national salt reduction strategy for India will be developed in collaboration with key stakeholders. Ethics and dissemination: This study has been approved by the Human Research Ethics Committees of the University of Sydney and the Centre for Chronic Disease Control in New Delhi, and also by the Indian Health Ministry's Screening Committee. The project began fieldworkin February 2014 and will report the main results in 2016. The findings will be targeted primarily at public health policymakers and advocates, but will be disseminated widely through other mechanisms including conference presentations and peer-reviewed publications, as well as to the participating communities. [ABSTRACT FROM AUTHOR]

Background That socioeconomic deprivation has shown a correlation with disease-specific mortality in Western societies is well documented. However, it is unclear whether these findings are also apparent in Asian societies. Accordingly, we conducted the first systematic review and meta-analysis of studies from Asia that have reported on the association between socioeconomic position and adult mortality risk. Methods Relevant studies were identified through an electronic search of databases. Studies were included if they had published quantitative estimates of the association between socioeconomic status (SES) and mortality in a general population-based sample. The pooled multiple-adjusted relative risks for mortality in the lowest SES group relative to the highest SES group were studied. Random effects meta-analyses were computed. Results A total of 29 cohort studies from 10 Asian countries were identified, comprising 1 370 023 individuals and 71 818 total deaths. The three markers of SES most widely used (education, income, occupation) were inversely related to mortality outcomes under consideration (all-causes, cardiovascular disease, cancer). For instance, the pooled relative risks of low education compared with high education were: 1.40 (95% CI 1.29 to 1.52) for all-cause mortality, 1.66 (1.23 to 2.25) for cardiovascular mortality and 1.16 (1.07 to 1.27) for cancer mortality. There was some evidence that the age of cohort members at study induction, the gross national product of the country from which the cohort was drawn and geographical region modified the association between SES and mortality. Conclusions Concordant with findings from Western societies, socioeconomic disadvantage is associated with total and cause-specific mortality in Asia. [ABSTRACT FROM AUTHOR]

Objective: The gold standard method for measuring population sodium intake is based on a 24 h urine collection carried out in a random population sample. However, because participant burden is high, response rates are typically low with less than one in four agreeing to provide specimens. At this low level of response it is possible that simply asking for volunteers would produce the same results. Setting: Lithgow, New South Wales, Australia. Participants: We randomly selected 2152 adults and obtained usable 24 h urine samples from 306 (response rate 16%). Specimens were also collected from a further 113 volunteers. Estimated salt consumption and the costs for each strategy were compared. Results: The characteristics of the 'random' and 'volunteer' samples were moderately different in mean age 58 (SD 14.6 vs 49(17.7) years, respectively; p<0.001) as well as self-reported alcohol use, tobacco use, history of hypertension and prescription drug use (all p<0.04). Overall crude mean 24 h urinary salt excretion was 8.9(3.6) g/day in the random sample vs 8.5(3.3) g/day for the volunteers (p=0.42). Corresponding age-adjusted and sex-adjusted estimates were 9.2(3.3) and 8.8(3.4) g/day (p=0.29). Estimates for men 10.3(3.8) vs 9.6(3.3) g/day; (p=0.26) and women 7.6(3) vs 7.9(3.2) g/day; (p=0.43) were also similar for the two samples, as was salt excretion across age groups (p=0.72). The cost of obtaining each 24 h urine sample was two times greater for the random compared to volunteer samples ($A62 vs $A31). Conclusions: The estimated salt consumption derived from the two samples was comparable and was not substantively different to estimates obtained from other surveys. In countries where salt is pervasive and cannot easily be avoided, estimates of consumption obtained from volunteer samples may be valid and less costly. [ABSTRACT FROM AUTHOR]

Prediction models are increasingly used to complement clinical reasoning and decision making in modern medicine in general, and in the cardiovascular domain in particular. Developed models first and foremost need to provide accurate and (internally and externally) validated estimates of probabilities of specific health conditions or outcomes in targeted patients. The adoption of such models must guide physician's decision making and an individual's behaviour, and consequently improve individual outcomes and the cost-effectiveness of care. In a series of two articles we review the consecutive steps generally advocated for risk prediction model research. This first article focuses on the different aspects of model development studies, from design to reporting, how to estimate a model's predictive performance and the potential optimism in these estimates using internal validation techniques, and how to quantify the added or incremental value of new predictors or biomarkers (of whatever type) to existing predictors. Each step is illustrated with empirical examples from the cardiovascular field. INSET: Box 1 Guide on the main design and analysis issues for…. [ABSTRACT FROM AUTHOR]

Prediction models are increasingly used to complement clinical reasoning and decision making in modern medicine in general, and in the cardiovascular domain in particular. Developed models first and foremost need to provide accurate and (internally and externally) validated estimates of probabilities of specific health conditions or outcomes in targeted patients. The adoption of such models must guide physician's decision making and an individual's behaviour, and consequently improve individual outcomes and the cost-effectiveness of care. In a series of two articles we review the consecutive steps generally advocated for risk prediction model research. This first article focuses on the different aspects of model development studies, from design to reporting, how to estimate a model's predictive performance and the potential optimism in these estimates using internal validation techniques, and how to quantify the added or incremental value of new predictors or biomarkers (of whatever type) to existing predictors. Each step is illustrated with empirical examples from the cardiovascular field. INSET: Box 1 Guide on the main design and analysis issues for…. [ABSTRACT FROM AUTHOR]

Objective: To improve equity in cardiovascular disease prevention by developing a cardiovascular risk score including social deprivation and family history. Design: The ASSIGN score was derived from cardiovascular outcomes in the Scottish Heart Health Extended Cohort (SHHEC). It was tested against the Framingham cardiovascular risk score in the same database. Setting: Random-sample, risk-factor population surveys across Scotland 1984–87 and North Glasgow 1989, 1992 and 1995. Participants: 6540 men and 6757 women aged 30–74, initially free of cardiovascular disease, ranked for social deprivation by residence postcode using the Scottish Index of Multiple Deprivation (SIMD) and followed for cardiovascular mortality and morbidity through 2005. Results: Classic risk factors, including cigarette dosage, plus deprivation and family history but not obesity, were significant factors in constructing ASSIGN scores far each sex. ASSIGN scores, lower on average, correlated closely with Framingham values far 10-year cardiovascular risk. Discrimination of risk in the SHHEC population was significantly, but marginally, improved overall by ASSIGN. However, the social gradient in cardiovascular event rates was inadequately reflected by the Framingham score, leaving a large social disparity in future victims not identified as high risk. ASSIGN classified more people with social deprivation and positive family history as high risk, anticipated more of their events, and abolished this gradient. Conclusion: Conventional cardiovascular scores fail to target social gradients in disease. By including unattributed risk from deprivation, ASSIGN shifts preventive treatment towards the socially deprived. Family history is valuable not least as an approach to ethnic susceptibility. ASSIGN merits further evaluation for clinical use. [ABSTRACT FROM AUTHOR]

Objectives To determine the benefits and risks of a non-steroidal anti-inflammatory drug (NSAID) as prophylaxis for ectopic bone formation in patients undergoing total hip replacement (or revision) surgery. Design Double blind randomised placebo controlled clinical trial, stratified by treatment site and surgery (primary or revision). Setting 20 orthopaedic surgery centres in Australia and New Zealand. Participants 902 patients undergoing elective primary or revision total hip replacement surgery. Intervention 14 days treatment with ibuprofen (1200 mg daily) or matching placebo started within 24 hours of surgery. Main outcome measures Changes in self reported hip pain and physical function 6 to 12 months after surgery (Western Ontario and McMaster University Arthritis index). Results There were no significant differences between the groups for improvements in hip pain (mean difference - 0.1, 95% confidence interval - 0.4 to 0.2, P = 0.6) or physical function ( - 0.1, - 0.4 to 0.2, P = 0.5), despite a decreased risk of ectopic bone formation (relative risk 0.69, 0.56 to 0.83) associated with ibuprofen. There was a significantly increased risk of major bleeding complications in the ibuprofen group during the admission period (2.09, 1.00 to 4.39). Conclusions These data do not support the use of routine prophylaxis with NSAIDs in patients undergoing total hip replacement surgery. Trial registration NCT00145730. [ABSTRACT FROM AUTHOR]

Objective Declining mean systolic and diastolic blood pressures were observed in most populations of the World Health Organization MONICA (monitoring trends and determinants in cardiovascular disease) project from the mid-1980s to mid-1990s. We tested whether pooled results would show mean change associated with decline in high readings only, resulting from better antihypertensive medication, or with similar falls in low, middle, and high readings, implying other causes. Design Independent, random sample, cross sectional population surveys, each end of the MONICA decade. Setting 38 populations in 21 countries across four continents. Participants Design target in each survey of 200 participants in each 10 year age and sex group from age 35 to 64 Main outcome measures Changes in the population in mean systolic and diastolic blood pressure, and in low, middle, and high readings--the 20th, 50, and 80th centiles--and the differences between these changes. Results Individual populations differed considerably, but pooling the 38 population results gave mean changes in systolic blood pressure of -2.2 mm Hg in men, -3.3 mm Hg in women, and in diastolic blood pressure of -1.4 mm Hg in men and -2.2 mm Hg in women (overall average -2.26 mm Hg, population median -1.55 mm Hg). Antihypertensive medication, associated with high readings, rose by 0.5% to 11.4%. However, average falls in low and middle blood pressure readings were so similar to those in high readings and in the mean that no effect from improving treatment of hypertension was detected. Results in contrasted subgroups were consistent. Conclusions Blood pressure fell across 38 MONICA populations at all levels of readings, with no differential fall in high readings attributable to better control of hypertension. Despite the importance of medication to individuals, in that decade other determinants of blood pressure lowering must have been more pervasive and powerful in whole populations. [ABSTRACT FROM AUTHOR]