Mortality and Morbidity in Adults With Rheumatic Heart Disease.

Importance: Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. Objective: To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Design, Setting, and Participants: Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Results: Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Conclusions and Relevance: Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

Accounting for center-level effects in multicenter randomized controlled trials.

Investigators often conduct randomized controlled trials (RCTs) at multiple centers/sites when determining the effect of a treatment or an intervention. Diversifying recruitment across multiple institutions allows investigators to make recruitment go faster within a shorter timeframe and allows generalizing the study results across diverse populations. Despite having a common study protocol across multiple centers, the eligible participants may be heterogeneous, site policies and practices may vary, and the investigators' experience, training, and expertise may also vary across sites. These factors may contribute to the heterogeneity in effect estimates across centers. As a result, we usually observe some degree of heterogeneity in effect estimates across centers, despite all centers following the same study protocol. During the analysis of such a trial, investigators typically ignore center effects, but some have suggested considering centers as fixed or random effects in the model. It is not clear how considering the effects of centers, either as fixed or random effects, impacts the test of the primary hypothesis. In this article, we first review the practice of accounting for center effects in the analyses of published RCTs and illustrate the extent of heterogeneity observed in a few preexisting multicenter RCTs. To determine the impact of heterogeneity on the test of a primary hypothesis of an RCT, we considered continuous and binary outcomes and the corresponding appropriate model, namely, a simple linear regression model for a continuous outcome and a logistic regression model for the binary outcome. For each model type, we considered three methods: (a) ignore the center effect, (b) account for centers as fixed effects, or (c) account for centers as random effects. Based on simulation studies of these models, we then examine whether considering the center as a fixed or random effect in the model helps to preserve or reduce the type I and type II error rates during the analysis phase of an RCT. Finally, we outline the threshold at which center-level effects are negligible and thus negligible and provide recommendations on when it may be necessary to account for center effects during the analyses of multicenter randomized controlled trials.

Recurrence of new-onset post-operative AF after cardiac surgery: detected by implantable loop recorders: A systematic review and Meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. New-onset post-operative AF may signal an elevated risk of AF and associated outcomes in long-term follow-up. We aimed to estimate the rate of AF recurrence as detected by an implantable loop recorder (ILR) in patients experiencing post-operative AF within 30 days after cardiac surgery. METHODS: We searched MEDLINE, Embase and Cochrane CENTRAL to April 2023 for studies of adults who did not have known AF, experienced new-onset AF within 30 days of cardiac surgery and received an ILR. We pooled individual participant data on timing of AF recurrence using a random-effects model with a frailty model applied to a Cox proportional hazard analysis. RESULTS: From 8671 citations, 8 single-centre prospective cohort studies met eligibility criteria. Data were available from 185 participants in 7 studies, with a median follow-up of 1.7 (IQR: 1.3-2.8) years. All included studies were at a low risk of bias. Pooled AF recurrence rates following 30 post-operative days were 17.8% (95% CI 11.9%-23.2%) at 3 months, 24.4% (17.7%-30.6%) at 6 months, 30.1% (22.8%-36.7%) at 12 months and 35.3% (27.6%-42.2%) at 18 months. CONCLUSIONS: In patients who experience new-onset post-operative AF after cardiac surgery, AF recurrence lasting at least 30 s occurs in approximately 1 in 3 in the first year after surgery. The optimal frequency and modality to use for monitoring for AF recurrence in this population remain uncertain.

Relationship Between Social Support and Clinical Outcomes: An Evaluation of Participant-Nominated Treatment Supporters in the HOPE 4 Intervention.

BACKGROUND: The HOPE 4 trial (Heart Outcomes Prevention and Evaluation 4) investigated the effectiveness of a comprehensive, collaborative model of care, implemented in Colombia and Malaysia, which aimed to reduce cardiovascular disease risk in individuals with hypertension. One component of this intervention was the nomination of a treatment supporter, where participants could select a family member or friend to assist them with their care. The purpose of this study was to investigate the impact of these individuals on participant outcomes, as well as the relationship dynamics between participants and their treatment supporter. METHODS: Participants in the HOPE 4 intervention group with baseline and 12 months of follow-up were included for analysis. They were divided into Every Visit (n=339) and

Evaluation of the potentials of rice varieties and water management practices for reducing human health risks associated with polluted river water irrigated rice in Bangladesh.

The consumption of arsenic and trace-metal-contaminated rice is a human health concern worldwide, particularly in Bangladesh. In this study, the effects of rice varieties and water management practices on the concentrations of arsenic and trace metals in rice grains were investigated to reduce human health risks related to rice consumption. In addition, the performance of risk reduction using the optimum combination of rice variety and water management practices was quantitatively assessed using Monte Carlo simulation, in which non-carcinogenic and carcinogenic risk distributions under the status quo and the optimum combination were compared. The experimental results revealed that Dular and BRRI dhan45 (rice varieties) cultivated under alternate wetting and drying (AWD) and continuous flooding (CF) conditions showed the lowest hazard quotient (HQ) values for copper, cadmium, and arsenic and the lowest target cancer risk (TR) for arsenic. In Dular and BRRI dhan45 (AWD and CF) varieties, the proportion of the population for which HQs exceeded 1.0 (the reference value) tended to decrease (except for arsenic), compared with populations for which the rice varieties and water management practices were not specified. These results suggest that the use of optimum combinations of rice varieties and water management practices could reduce non-carcinogenic and carcinogenic risks associated with arsenic and trace metals uptake via rice grain consumption by the Bangladeshi people.

Social isolation as a risk factor for all-cause mortality: Systematic review and meta-analysis of cohort studies.

BACKGROUND: Although several epidemiological studies have linked social isolation to increased risk of mortality, the magnitude of any effect is unclear, in part because of the use of different measures of social isolation. OBJECTIVE: To examine the association between social isolation and all-cause mortality and investigate whether it differs in various subgroups or populations. DATA SOURCES: We searched for relevant studies in electronic databases: MEDLINE (1946 to December 31, 2021), EMBASE (1974 to December 31, 2021), and PsycINFO (1806 to December 31, 2021). SELECTION CRITERIA: We included both prospective and retrospective cohort studies that examined the association between social isolation and all-cause mortality among adults. DATA COLLECTION AND ANALYSIS: Two reviewers screened and extracted data independently. We contacted study authors to obtain missing information whenever possible. Data were pooled using a random effect model to calculate estimates of the effects of social isolation on all-cause mortality. RESULTS: Data from studies involving 1.30 million individuals were included. The pooled hazard ratio of social isolation for all-cause mortality was 1.33 (95% confidence interval; 1.26-1.41, heterogeneity: Chi² = 112.51, P < 0.00001, I² = 76%). CONCLUSION: Social isolation is associated with increased risk for all-cause mortality. REGISTRATION: PROSPERO (CRD42020152351).

Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study.

BACKGROUND & AIMS: Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and the risk of developing IBD using the Prospective Urban Rural Epidemiology cohort. METHODS: This was a prospective cohort study of 133,137 individuals between the ages of 20 and 80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed up prospectively at least every 3 years. The main outcome was the development of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) were evaluated. Results are presented as adjusted odds ratios (aORs) with 95% CIs. RESULTS: During a median follow-up period of 11.0 years (interquartile range, 9.2-12.2 y), there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was associated significantly with baseline antibiotic (aOR, 2.81; 95% CI, 1.67-4.73; P = .0001) and hormonal medication use (aOR, 4.43; 95% CI, 1.78-11.01; P = .001). Among females, previous or current oral contraceptive use also was associated with IBD development (aOR, 2.17; 95% CI, 1.70-2.77; P < .001). Nonsteroidal anti-inflammatory drug users also were observed to have increased odds of IBD (aOR, 1.80; 95% CI, 1.23-2.64; P = .002), which was driven by long-term use (aOR, 5.58; 95% CI, 2.26-13.80; P < .001). All significant results were consistent in direction for CD and UC with low heterogeneity. CONCLUSIONS: Antibiotics, hormonal medications, oral contraceptives, and long-term nonsteroidal anti-inflammatory drug use were associated with increased odds of incident IBD after adjustment for covariates.

Interaction of Depression and Unhealthy Diets on the Risk of Cardiovascular Diseases and All-Cause Mortality in the Chinese Population: A PURE Cohort Substudy.

This study aimed to identify the interaction of depression and diets on cardiovascular diseases (CVD) incident and death in China and key subpopulations. We included 40,925 participants from the Prospective Urban Rural Epidemiology (PURE)-China cohort which recruited participants aged 35-70 years from 45 urban and 70 rural communities. Depression was measured by the adapted Short-Form (CIDI-SF). The unhealthy diet was considered when the score of Alternative Healthy Eating Index was below the lowest tertile. The primary outcome was a composite outcome of incident CVD and all-cause mortality. Cox frailty models were used to examine the associations. During a median follow-up of 11.9 years (IQR: 9.6-12.6 years), depression significantly increased the risk of the composite outcome (HR = 2.00; 95% CI, 1.16-3.27), major CVD (HR = 1.82; 95% CI, 1.48-2.23), and all-cause mortality (HR = 2.21; 95% CI, 1.51-3.24) for the unhealthy diet group, but not for the healthy diet group. The interaction between depression and diet for the composite outcome was statistically significant (RERI = 1.19; 95% CI, 0.66-1.72; AP = 0.42, 95% CI, 0.27-0.61; SI = 3.30, 95% CI, 1.42-7.66; multiplicative-scale = 1.74 95% CI, 1.27-2.39), even in the subgroup and sensitivity analyses. In addition, the intake of vegetable and polyunsaturated fatty acids contributed most to the interaction of diets and depression. Depressive participants should focus on healthy diets, especially vegetables and polyunsaturated fatty acids, to avoid premature death and CVD.

Hypertension and undiagnosed hypertension among Bangladeshi adults: Identifying prevalence and associated factors using a nationwide survey.

Background: Although undiagnosed hypertension (HTN) is a serious concern worldwide, it is less of an importance in Bangladesh, where there is a dearth of research on the subject. So, we aimed to identify the prevalence and associated factors for diagnosed and undiagnosed HTN. Methods: We analyzed the recent 2017-2018 Bangladesh Demographic and Health Survey data. We included 11,981 participants aged 18 years and above for the analysis. The prevalence rates of both diagnosed and undiagnosed hypertension were computed for all individuals and subgroups. The influence of socio-demographic, household, and community-related variables on HTN and undiagnosed HTN was investigated using multinomial regression analysis. Results: The study finds 1,464 (12.2%) of the 11,981 respondents [6,815 females [56.9 %]; mean age 39.4 years] had diagnosed HTN, whereas 1 898 (15.8%) had undiagnosed HTN. The HTN and undiagnosed HTN were significantly prevalent in the elderly, type 2 diabetic (T2DM), and overweight and obese individuals. In terms of residential regions, people from coastal region had a significantly higher prevalence of both HTN (RRR: 1.37; 95% CI: 1.17-1.62) and undiagnosed HTN (RRR: 1.35; 95% CI: 1.17-1.56) compared to those from the central region of Bangladesh. Conclusions: The high prevalence of undetected hypertension in Bangladesh suggests that screening procedures for the current chronic illness may be inadequate in routine clinical practice. All populations should have access to hypertension screening, but it is especially crucial for the elderly, those with diabetes, those who are overweight or obese, and those from coastal and northern regions of Bangladesh.

INTERBLEED: Design of an International Study of Risk Factors for Gastrointestinal Bleeding and Cardiovascular Events After Gastrointestinal Bleeding.

Background: Bleeding is the most common adverse event in those with cardiovascular (CV) disease receiving antithrombotic therapy, and it most commonly occurs in the gastrointestinal (GI) tract. Clinicians often dismiss bleeding as an adverse event that is reversible with effective antithrombotic therapy, but bleeding is associated with substantial morbidity and mortality, most likely mediated through an increased risk of CV events. Reducing the burden of bleeding requires knowledge of the potentially modifiable risk factors for bleeding and the potentially modifiable risk factors for adverse outcomes after bleeding. Methods: INTERBLEED is an international, multicentre, 2-component, observational study, with an incident case-control study examining the risk factors for GI bleeding, and a prospective cohort study of risk factors for CV events after GI bleeding. Cases either have CV disease and present to the hospital with GI bleeding or develop GI bleeding during hospitalization. Controls have CV disease, but no history of GI bleeding. We use a questionnaire to obtain detailed information on known and potential risk factors for GI bleeding and for CV events and outcomes after bleeding. We obtain CV and anthropometric measurements, perform functional and cognitive assessments, and follow participants at 3 months and 12 months. Results: As of April 1, 2022, the study is ongoing in 10 countries at 31 centres and has recruited 2407 cases and 1478 controls. Conclusions: Knowledge of risk factors for bleeding, and risk factors for CV events and functional decline after bleeding, will help develop strategies to prevent bleeding and subsequent complications.

Contexte: L'hémorragie est l'effet indésirable le plus fréquent chez les patients atteints de maladies cardiovasculaires (CV) qui reçoivent un traitement antithrombotique, et elle survient le plus souvent dans le tractus gastro-intestinal (GI). Les cliniciens considèrent souvent l'hémorragie comme une simple manifestation indésirable réversible par un traitement antithrombotique efficace, mais une morbidité et une mortalité considérables y sont associées, probablement en raison d'un risque accru d'événements CV. Une réduction du fardeau de l'hémorragie nécessite une connaissance des facteurs de risque potentiellement modifiables tant de l'hémorragie que des événements indésirables qui surviennent après l'hémorragie. Méthodologie: INTERBLEED est une étude internationale, observationnelle et multicentrique à deux volets; le premier volet est une étude cas-témoins incidents visant à examiner les facteurs de risque d'hémorragie GI, alors que le second volet est une étude de cohorte prospective visant à examiner les facteurs de risque d'événements CV après une hémorragie GI. Les cas sont des patients atteints de maladies CV qui consultent les services hospitaliers pour une hémorragie GI ou qui présentent une hémorragie GI en cours d'hospitalisation. Les témoins sont des patients atteints de maladies CV, mais sans antécédents d'hémorragie GI. Un questionnaire est utilisé pour obtenir des renseignements détaillés au sujet de facteurs de risque connus et potentiels d'hémorragie GI et d'événements CV et d'autres résultats de santé après une hémorragie. Des mesures cardiovasculaires et anthropométriques ainsi que des évaluations fonctionnelles et cognitives sont réalisées, et les participants sont revus après trois mois et 12 mois. Résultats: En date du 1er avril 2022, l'étude est en cours dans 10 pays et 31 établissements de santé; 2 407 cas et 1 478 témoins ont été recrutés. Conclusions: La connaissance des facteurs de risque d'hémorragie, ainsi que des facteurs de risque d'événements CV et de déclin fonctionnel à la suite d'une hémorragie, aidera à mettre en place des stratégies pour prévenir les hémorragies et les complications qui peuvent en découler.

Modifiable risk factors associated with cardiovascular disease and mortality in China: a PURE substudy.

AIMS: To examine the incidence of cardiovascular disease (CVD) and mortality in China and in key subpopulations, and to estimate the population-level risks attributable to 12 common modifiable risk factors for each outcome. METHODS AND RESULTS: In this prospective cohort of 47 262 middle-aged participants from 115 urban and rural communities in 12 provinces of China, it was examined how CVD incidence and mortality rates varied by sex, by urban-rural area, and by region. In participants without prior CVD, population-attributable fractions (PAFs) for CVD and for death related to 12 common modifiable risk factors were assessed: four metabolic risk factors (hypertension, diabetes, abdominal obesity, and lipids), four behavioural risk factors (tobacco, alcohol, diet quality, and physical activity), education, depression, grip strength, and household air pollution. The mean age of the cohort was 51.1 years. 58.2% were female, 49.2% were from urban areas, and 59.6% were from the eastern region of China. The median follow-up duration was 11.9 years. The CVD was the leading cause of death in China (36%). The rates of CVD and death were 8.35 and 5.33 per 1000 person-years, respectively, with higher rates in men compared with women and in rural compared with urban areas. Death rates were higher in the central and western regions of China compared with the eastern region. The modifiable risk factors studied collectively contributed to 59% of the PAF for CVD and 56% of the PAF for death in China. Metabolic risk factors accounted for the largest proportion of CVD (PAF of 41.7%), and hypertension was the most important risk factor (25.0%), followed by low education (10.2%), high non-high-density lipoprotein cholesterol (7.8%), and abdominal obesity (6.9%). The largest risk factors for death were hypertension (10.8%), low education (10.5%), poor diet (8.3%), tobacco use (7.5%), and household air pollution (6.1%). CONCLUSION: Both CVD and mortality are higher in men compared with women, and in rural compared with urban areas. Large reductions in CVD could potentially be achieved by controlling metabolic risk factors and improving education. Lowering mortality rates will require strategies addressing a broader range of risk factors.

Cardiovascular disease, mortality, and their associations with modifiable risk factors in a multi-national South Asia cohort: a PURE substudy.

AIM: To examine the incidence of cardiovascular disease (CVD), of death, and the comparative effects of 12 common modifiable risk factors for both outcomes in South Asia. METHODS AND RESULTS: Prospective study of 33 583 individuals 35-70 years of age from India, Bangladesh, or Pakistan. Mean follow-up period was 11 years. Age and sex adjusted incidence of a CVD event and mortality rates were calculated for the overall cohort, by urban or rural location, by sex, and by country. For each outcome, mutually adjusted population attributable fractions (PAFs) were calculated in 32 611 individuals without prior CVD to compare risks associated with four metabolic risk factors (hypertension, diabetes, abdominal obesity, high non-HDL cholesterol), four behavioural risk factors (tobacco use, alcohol use, diet quality, physical activity), education, household air pollution, strength, and depression. Hazard ratios were calculated using Cox regression models, and average PAFs were calculated for each risk factor or groups of risk factors. Cardiovascular disease was the most common cause of death (35.5%) in South Asia. Rural areas had a higher incidence of CVD (5.41 vs. 4.73 per 1000 person-years) and a higher mortality rate (10.27 vs. 6.56 per 1000 person-years) compared with urban areas. Males had a higher incidence of CVD (6.42 vs. 3.91 per 1000 person-years) and a higher mortality rate (10.66 vs. 6.85 per 1000 person-years) compared with females. Between countries, CVD incidence was highest in Bangladesh, while the mortality rate was highest in Pakistan. The modifiable risk factors studied contributed to approximately 64% of the PAF for CVD and 69% of the PAF for death. Largest PAFs for CVD were attributable to hypertension (13.1%), high non-HDL cholesterol (11.1%), diabetes (8.9%), low education (7.7%), abdominal obesity (6.9%), and household air pollution (6.1%). Largest PAFs for death were attributable to low education (18.9%), low strength (14.6%), poor diet (6.4%), diabetes (5.8%), tobacco use (5.8%), and hypertension (5.5%). CONCLUSION: In South Asia, both CVD and deaths are highest in rural areas and among men. Reducing CVD and premature mortality in the region will require investment in policies that target a broad range of health determinants.

Risk factors, cardiovascular disease, and mortality in South America: a PURE substudy.

AIMS: In a multinational South American cohort, we examined variations in CVD incidence and mortality rates between subpopulations stratified by country, by sex and by urban or rural location. We also examined the contributions of 12 modifiable risk factors to CVD development and to death. METHODS AND RESULTS: This prospective cohort study included 24 718 participants from 51 urban and 49 rural communities in Argentina, Brazil, Chile, and Colombia. The mean follow-up was 10.3 years. The incidence of CVD and mortality rates were calculated for the overall cohort and in subpopulations. Hazard ratios and population attributable fractions (PAFs) for CVD and for death were examined for 12 common modifiable risk factors, grouped as metabolic (hypertension, diabetes, abdominal obesity, and high non-HDL cholesterol), behavioural (tobacco, alcohol, diet quality, and physical activity), and others (education, household air pollution, strength, and depression). Leading causes of death were CVD (31.1%), cancer (30.6%), and respiratory diseases (8.6%). The incidence of CVD (per 1000 person-years) only modestly varied between countries, with the highest incidence in Brazil (3.86) and the lowest in Argentina (3.07). There was a greater variation in mortality rates (per 1000 person-years) between countries, with the highest in Argentina (5.98) and the lowest in Chile (4.07). Men had a higher incidence of CVD (4.48 vs. 2.60 per 1000 person-years) and a higher mortality rate (6.33 vs. 3.96 per 1000 person-years) compared with women. Deaths were higher in rural compared to urban areas. Approximately 72% of the PAF for CVD and 69% of the PAF for deaths were attributable to 12 modifiable risk factors. For CVD, largest PAFs were due to hypertension (18.7%), abdominal obesity (15.4%), tobacco use (13.5%), low strength (5.6%), and diabetes (5.3%). For death, the largest PAFs were from tobacco use (14.4%), hypertension (12.0%), low education (10.5%), abdominal obesity (9.7%), and diabetes (5.5%). CONCLUSIONS: Cardiovascular disease, cancer, and respiratory diseases account for over two-thirds of deaths in South America. Men have consistently higher CVD and mortality rates than women. A large proportion of CVD and premature deaths could be averted by controlling metabolic risk factors and tobacco use, which are common leading risk factors for both outcomes in the region.

Variations in risks from smoking between high-income, middle-income, and low-income countries: an analysis of data from 179 000 participants from 63 countries.

BACKGROUND: Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. METHODS: We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. FINDINGS: In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65-2·12) than in MICs (1·41, 1·34-1·49) and LICs (1·35, 1·25-1·46; interaction p<0·0001). Similar patterns were observed for each component of the composite outcome in PURE, myocardial infarction in INTERHEART, and stroke in INTERSTROKE. The median levels of tar, nicotine, and carbon monoxide displayed on the cigarette packs from PURE HICs were higher than those on the packs from MICs. In PURE, the proportion of never smokers reporting high second-hand smoke exposure (≥1 times/day) was 6·3% in HICs, 23·2% in MICs, and 14·0% in LICs. The adjusted geometric mean total nicotine equivalent was higher among current smokers in HICs (47·2 µM) than in MICs (31·1 µM) and LICs (25·2 µM; ANCOVA p<0·0001). By contrast, it was higher among never smokers in LICs (18·8 µM) and MICs (11·3 µM) than in HICs (5·0 µM; ANCOVA p=0·0001). INTERPRETATION: The variations in risks from smoking between country income groups are probably related to the higher exposure of tobacco-derived toxicants among smokers in HICs and higher rates of high second-hand smoke exposure among never smokers in MICs and LICs. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Exploring New Models for Cardiovascular Risk Reduction: The Heart Outcomes Prevention and Evaluation 4 (HOPE 4) Canada Pilot Study.

BACKGROUND: There is a gap between evidence and practice in the management of cardiovascular (CV) risk. Previous research indicated benefits from community-based, multi-faceted interventions to screen, diagnose, and manage CV risk in people with hypertension. METHODS: The Heart Outcomes Prevention and Evaluation 4 Canada pilot study (HOPE 4) was a quasi-experimental pre-post interventional study, involving one community each in Hamilton, Ontario and Surrey, British Columbia, Canada. Individuals aged ≥50 years with newly diagnosed or poorly controlled hypertension were included. The intervention was comprised of: (i) simplified diagnostic/treatment algorithms implemented by community health workers (firefighters in British Columbia and community health workers in Ontario) guided by decision support and counselling software; (ii) recommendations for evidence-based CV medications and lifestyle modifications; and (iii) support from family/friends to promote healthy behaviours. The intervention was developed as part of the international Heart Outcomes Prevention and Evaluation 4 Canada pilot study trial and adapted to the Canadian context. The primary outcome was the change in Framingham Risk Score 10-year CV disease risk estimate between baseline and 6 months. RESULTS: Between 2016 and 2017, a total of 193 participants were screened, with 37 enrolled in Surrey, and 19 in Hamilton. Mean age was 69 years (standard deviation 11), with 54% female, 27% diabetic, and 73% with a history of hypertension. An 82% follow-up level had been obtained at 6 months. Compared to baseline, there were significant improvements in the Framingham Risk Score 10-year risk estimate (30.6% vs 24.7%, P < 0.01), and systolic blood pressure (153.1 vs 136.7 mm Hg, P < 0.01). No significant changes in lipids or healthy behaviours were noted. CONCLUSIONS: A comprehensive approach to health care delivery, using a community-based intervention with community health workers, supported by mobile-health technologies, has the potential to significantly reduce cardiovascular risk, but further evaluation is warranted.

CONTEXTE: Il existe un écart entre les données probantes et la pratique en matière de prise en charge du risque cardiovasculaire (CV). Les résultats d'études antérieures montrent que des interventions à volets multiples en milieu communautaire visant à dépister, à diagnostiquer et à prendre en charge le risque CV chez les personnes atteintes d'hypertension peuvent être bénéfiques. MÉTHODOLOGIE: L'étude pilote HOPE4 (Heart Outcomes Prevention and Evaluation 4 Canada) était une étude interventionnelle quasi expérimentale évaluant des patients avant et après certaines interventions, menée au sein de deux communautés canadiennes, l'une située à Hamilton, en Ontario et l'autre à Surrey, en Colombie-Britannique. L'étude réunissait des participants âgés de 50 ans ou plus venant de recevoir un diagnostic d'hypertension ou souffrant d'hypertension mal maîtrisée. Les interventions comprenaient : i) l'utilisation d'algorithmes de diagnostic et de traitement simplifiés par les intervenants en santé du milieu communautaire (pompiers en Colombie-Britannique et agents de santé communautaire en Ontario), à l'aide d'un logiciel d'aide à la décision et de counselling; ii) la formulation de recommandations fondées sur des données probantes concernant la prise de médicaments et l'adoption d'habitudes de vie favorisant la santé CV; et iii) la sollicitation du soutien des membres de la famille et des amis afin de promouvoir l'adoption de comportements favorisant la santé. Ces interventions ont été mises au point dans le cadre de l'étude pilote internationale HOPE4 et adaptées au contexte canadien. Le critère d'évaluation principal était la variation du score de risque de Framingham, qui estime le risque de maladie CV à 10 ans, entre le début et le 6e mois de l'étude. RÉSULTATS: De 2016 à 2017, un nombre total de 193 participants ont été soumis au processus de sélection; 37 patients du centre de Surrey et 19 patients du centre de Hamilton ont été admis à l'étude. L'âge moyen des participants était de 69 ans (écart-type : 11 ans); 54 % d'entre eux étaient des femmes, 27 % étaient atteints de diabète et 73 % avaient des antécédents d'hypertension. Au 6e mois, 82 % des sujets participaient toujours à l'étude. Des améliorations significatives ont été observées comparativement au placebo en ce qui concerne le score de risque de Framingham estimant le risque à 10 ans (30,6 % vs 24,7 %, p < 0,01) et la pression artérielle systolique (153,1 vs 136,7 mmHg, p < 0,01). Aucune variation significative n'a été observée quant à la lipidémie ou aux comportements favorisant la santé. CONCLUSIONS: Une approche exhaustive de la prestation des soins de santé reposant sur des interventions de la part des agents de santé communautaire au moyen de technologies de santé mobiles pourrait aider à réduire significativement le risque CV; une évaluation plus poussée est toutefois nécessaire.

Impact of social isolation on mortality and morbidity in 20 high-income, middle-income and low-income countries in five continents.

OBJECTIVE: To examine the association between social isolation and mortality and incident diseases in middle-aged adults in urban and rural communities from high-income, middle-income and low-income countries. DESIGN: Population-based prospective observational study. SETTING: Urban and rural communities in 20 high income, middle income and low income. PARTICIPANTS: 119 894 community-dwelling middle-aged adults. MAIN OUTCOME MEASURES: Associations of social isolation with mortality, cardiovascular death, non-cardiovascular death and incident diseases. RESULTS: Social isolation was more common in middle-income and high-income countries compared with low-income countries, in urban areas than rural areas, in older individuals and among women, those with less education and the unemployed. It was more frequent among smokers and those with a poorer diet. Social isolation was associated with greater risk of mortality (HR of 1.26, 95% CI: 1.17 to 1.36), incident stroke (HR: 1.23, 95% CI: 1.07 to 1.40), cardiovascular disease (HR: 1.15, 95% CI: 1.05 to 1.25) and pneumonia (HR: 1.22, 95% CI: 1.09 to 1.37), but not cancer. The associations between social isolation and mortality were observed in populations in high-income, middle-income and low-income countries (HR (95% CI): 1.69 (1.32 to 2.17), 1.27 (1.15 to 1.40) and 1.47 (1.25 to 1.73), respectively, interaction p=0.02). The HR associated with social isolation was greater in men than women and in younger than older individuals. Mediation analyses for the association between social isolation and mortality showed that unhealthy behaviours and comorbidities may account for about one-fifth of the association. CONCLUSION: Social isolation is associated with increased risk of mortality in countries at different economic levels. The increasing share of older people in populations in many countries argues for targeted strategies to mitigate its adverse effects.

Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153 152 middle-aged individuals.

AIMS: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine antithrombotic use and clinical outcomes. METHODS AND RESULTS: Baseline ECGs were collected in 153 152 middle-aged participants (ages 35-70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow-up of 7.4 years) were available in one cohort. Cross-sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China, and Southeast Asia (270-360 cases per 100 000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100 000 persons) (P < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs) (P < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received antithrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke [hazard ratio (HR) 2.29; 95% confidence interval (CI) 1.49-3.52] and death (HR 2.97; 95% CI 2.25-3.93); with similar rates in different countries grouped by income level. CONCLUSIONS: Large variations in AF prevalence occur in different regions and countries grouped by income level, but this is only partially explained by traditional AF risk factors. Antithrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.

Arsenic fractionation in sediments and speciation in muscles of fish, Chrysichthys nigrodigitatus from a contaminated tropical Lagoon, Nigeria.

This study assesses arsenic (As) fractionation in sediments and speciation in muscle tissues of Bagrid catfish, Chrysichthys nigrodigitatus from Lagos Lagoon, southwest Nigeria to determine risks to ecological receptors and humans. Residual As was the predominant geochemical fraction (86.2%) in sediments. Arsenite [As (III)] concentrations which ranged from 0.06 to 0.53 mg kg-1 in catfish muscle tissue, accounting for 25.9% of total As was the dominant species. Less toxic dimethylarsinic acid (DMA) which varied between 0.06 and 0.27 mg kg-1 made up to 10.8% of total As in catfish muscle tissue. Estimated human average daily intake (ADI) of As as As (III) and DMA were 1.35 × 10-4 and 0.62 × 10-4 mg kg-1 BW with corresponding hazard quotients (HQs) of 0.45 and 0.21, respectively, indicate no apparent health hazard to adult consumers. The incremental lifetime cancer risks (ILCR) of 0.78 × 10-3 for total As, 0.20 × 10-3 for As (III), and 0.93 × 10-3 for DMA, for adults from the consumption of catfish is slightly higher than the US EPA threshold and indicates moderate carcinogenic risk. Furthermore, 12.5% bioavailable fraction of As in sediment and relatively higher levels of As (III) in fish tissues has ecological and public health implications.