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Digital, 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, Funding Full funding sources are listed at the end of the paper (see Acknowledgments)., Ciencias Médicas y de la Salud

Objective. The main aim of this study was to determine patient satisfaction with nursing care (PSNC) in the medical wards of the UP-Philippine General Hospital (UP-PGH) using a valid and reliable locally developed UP-PGH PSNC questionnaire. Methods. The survey utilized a cross-sectional study design and was conducted in the medical wards of the UP-PGH in 2006. A total of 237 patients were included in the survey.Results. Over a third or 34.3% (95% CI 28%, 40%) and 35% (95% CI 26%, 44%) were highly satisfied with their experience regarding the nurses’ caring attitude and the nurses’ skill/competence respectively. Fewer respondents were highly satisfied with the nurses as information providers, with only 17.2% (95% CI 12%, 22%) saying they were highly satisfied. A little over half or 57.8% (95% CI 52%, 64%) were highly satisfied in the overall evaluation of care.Conclusion. The patients were satisfied with the nursing care provided in two dimensions: The nurse as a caring person and the nurse as a skilled and competent healthcare provider, although only about a third indicated that they were highly satisfied. Nevertheless, 57.8% were highly satisfied in the overallevaluation of care, but these patients may have considered other hospital services and cost. Other factors that might affect patient satisfaction need to be explored and the use of other evaluation tools to augment these findings is recommended.

Aims The International Polycap Study 3 (TIPS-3) trial demonstrated that a polypill containing cholesterol- and multiple blood-pressure-lowering drugs reduces cardiovascular events by 20% compared with placebo in people without cardiovascular disease. The polypill plus aspirin led to a 31% relative risk reduction in cardiovascular disease events compared with double placebo. We report regional variations in costs and affordability of a polypill based on the TIPS-3 trial. Methods and results Countries were categorized using World Bank economic groups: lower-middle-income, upper-middle-income, and high-income countries. Country-specific costs were obtained for hospitalization events, procedures, and non-study medications (2019 US dollars). Polypill price was based on the cheapest equivalent substitute (CES) for each component. For the polypill vs. placebo, the difference in cost over the 4.6 years of the trial was $291 [95% confidence interval (CI): $243–339] per participant in lower-middle-income countries, $1068 (95% CI: $992–1144) in upper-middle-income countries, and $48 (95% CI: −$271 to $367) in high-income countries. Results were similar for the polypill plus aspirin vs. a double placebo. In both cases, the polypill was affordable in all groups using monthly household capacity to pay or a threshold of 4% of the gross national income per capita. Conclusion The use of a polypill (CES) in TIPS-3 increases costs in lower-middle-income countries and upper-middle-income countries but is affordable in countries at various economic levels and is cost neutral (dominant) in high-income countries.

Background Traditional, complementary and alternative medicine (TCAM) is used to treat a broad range of conditions. In low- and middle-income countries (LMICs), TCAM use is particularly common among those with low socio-economic status. To better understand the patterns and impact of TCAM use on the management of non-communicable diseases in these populations, this study examines the prevalence and characteristics of TCAM use for hypertension, its determinants, and its association with hypertension management outcomes and wellbeing among low-income adults in two Southeast Asian countries at different levels of economic and health system development, Malaysia and the Philippines. Methods We analysed cross-sectional data from 946 randomly selected adults diagnosed with hypertension from low-income rural and urban communities in Malaysia (n = 495) and the Philippines (n = 451). We compared the prevalence, characteristics and household expenditure on TCAM use between countries and used multi-level, mixed-effects regression to estimate associations between TCAM use and its determinants, and five hypertension management outcomes and wellbeing. Results The prevalence of TCAM use to manage hypertension was higher in the Philippines than in Malaysia (18.8% vs 8.8%, p Conclusions A small, but significant, proportion of individuals living in low-income communities in Malaysia and the Philippines use TCAM to manage their hypertension, despite a general lack of evidence on efficacy and safety of commonly used TCAM modalities. Recognising that their patients may be using TCAM to manage hypertension will enable health care providers to deliver safer, more patient-centred care.

Digital, Background: Effective treatments for COVID-19 are urgently needed, but conducting randomized trials during the pandemic has been challenging.Methods: The Anti-Coronavirus Therapy (ACT) trials are parallel factorial international trials that aimed to enroll 3500 outpatients and 2500 inpatients with symptomatic COVID-19. The outpatient trial is evaluating colchicine vs usual care, and aspirin vs usual care. The primary outcome for the colchicine randomization is hospitalization or death, and for the aspirin randomization, it is major thrombosis, hospitalization, or death. The inpatient trial is evaluating colchicine vs usual care, and the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily vs usual care. The primary outcome for the colchicine randomization is need for high-flow oxygen, need for mechanical ventilation, or death, and for the rivaroxaban plus aspirin randomization, it is major thrombotic events, need for high-flow oxygen, need for mechanical ventilation, or death. Results: At the completion of enrollment on February 10, 2022, the outpatient trial had enrolled 3917 patients, and the inpatient trial had enrolled 2611 patients. Challenges encountered included lack of preliminary data about the interventions under evaluation, uncertainties related to the expected event rates, delays in regulatory and ethics approvals, and in obtaining study interventions, as well as the changing pattern of the COVID-19 pandemic. Conclusions: The ACT trials will determine the efficacy of antiinflammatory therapy with colchicine, and antithrombotic therapy with aspirin given alone or in combination with rivaroxaban, across the spectrum of mild, moderate, and severe COVID-19. Lessons learned from the conduct of these trials will inform planning of future trials., Contexte : Il est urgent de mettre au point des traitements efficaces contre la COVID-19, mais il n’est pas facile de realiser des essais à repartition aleatoire dans un contexte pandemique.Methodologie : Les essais internationaux factoriels ACT (Anti-Coronavirus Therapy) avaient un objectif d’inscription de 3 500 patients externes et de 2 500 patients hospitalises presentant une COVID-19 symptomatique. L’essai mene auprès de patients externes visait à evaluer la colchicine par rapport aux soins habituels, et l’aspirine par rapport aux soins habituels. Le paramètre d’evaluation principal au terme de la repartition aleatoire des patients etait l’hospitalisation ou le decès dans le groupe traite par la colchicine, et la thrombose majeure, l’hospitalisation ou le decès dans le groupe traite par l’aspirine. L’essai mene auprès de patients hospitalises visant à evaluer la colchicine par rapport aux soins habituels, et un traitement associant le rivaroxaban à 2,5 mg deux fois par jour et l’aspirine à 100 mg une fois par jour par rapport aux soins habituels. Le paramètre d’evaluation principal au terme de la repartition aleatoire des patients etait le recours à l’oxygenotherapie à haut debit ou à la ventilation mecanique ou le decès dans le groupe traite par la colchicine, et la survenue de manifestations thrombotiques majeures, le recours à l’oxyg enotherapie à haut debit ou à la ventilation m ecanique ou le decès dans le groupe traite par l’association rivaroxaban-aspirine. Resultats : À la fin de la periode d’inscription, le 10 fevrier 2022, 3 917 patients externes et 2 611 patients hospitalises formaient la population des essais. Certains aspects se sont reveles problematiques, notamment le manque de donnees preliminaires sur les interventions à evaluer, les incertitudes liees aux taux d´evenements prevus, les retards touchant les approbations reglementaires et ethiques et les interventions de recherche, de même que l’evolution de la pandemie de COVID-19. Conclusions : Les essais ACT d etermineront l’efficacite du traitement anti-inflammatoire par la colchicine et du traitement antithrombotique par l’aspirine, administree seule ou en association avec le rivaroxaban, contre la COVID-19 legère, moderee ou sevère. Les leçons tirees de ces essais orienteront la planification d’essais ulterieurs., Ciencias Médicas y de la Salud

Digital, OBJECTIVE Previous prospective studies on the association of white rice intake with incident diabetes have shown contradictory results but were conducted in single countries and predominantly in Asia. We report on the association of white rice with risk of diabetes in the multinational Prospective Urban Rural Epidemiology (PURE) study. RESEARCH DESIGN AND METHODS Data on 132,373 individuals aged 35–70 years from 21 countries were analyzed. White rice consumption (cooked) was categorized as, Ciencias Médicas y de la Salud

In a meta-analysis, a question always arises. Is it worthwhile to combine estimates from studies of different populations using various formulations of an intervention, evaluating outcomes measured differently? Sometimes even study designs differ. Differences are expected in a meta-analysis. These may be negligible, and a pooled estimate of effect can guide the clinical decision. However, when the differences are large, this estimate may mislead. Effect estimates from study to study differ because of real differences (between-study variability) and because of chance (within-study variability). To combine estimates when there is heterogeneity (between-study differences are large) may not be sensible. Two complementary methods may be used to detect heterogeneity: visual inspection of the forest plot and calculating numerical measures of heterogeneity (I2 and Q). Visual inspection can show effects that are different from the rest. A large I2 (proportion of overall variability attributed to between-study variation) or a small P-value associated with Q may suggest heterogeneity. Large P-values, however, do not mean the absence of heterogeneity. It is more informative to report the confidence interval of the I2. If there is no heterogeneity, a pooled estimate of the true effect may be generated using only within-study variation (fixed-effect model). If there is substantial heterogeneity, reasons should be sought. Subgroup analysis or meta-regression using study-level characteristics may be done. Although more involved and potentially challenging, individual-level data (Individual Participant Data, IPD) may also be used. In the case of unexplained heterogeneity, both within- and between-study variation should be used to generate a pooled estimate (random-effects model). This estimate does not estimate a single true effect but estimates the average of a range of effects of the intervention on populations represented by the studies. If precise enough (narrow confidence interval), this estimate, together with the prediction interval (a measure of uncertainty in the effect one might see in a particular context), can guide clinical and policy decisions.

Digital, OBJECTIVE To evaluate the relation between intake of ultraprocessed food and risk of inflammatory bowel disease (IBD). DESIGN Prospective cohort study. SETTING 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). PARTICIPANTS 116087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years. MAIN OUTCOME MEASURES The main outcome was development of IBD, including Crohn’s disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals. RESULTS Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn’s disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with, Ciencias Médicas y de la Salud

Digital, 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, Ciencias Médicas y de la Salud

Background Cardiovascular disease risk assessment tools help identify individuals likely to benefit from preventative therapies. In this study we compared outcomes using the American College of Cardiology/American Heart Association (ACC/AHA) risk algorithm and the Framingham Risk Score (FRS) tool in the Heart Outcomes Prevention Evaluation (HOPE)-3 study. Methods We compared outcomes using the ACC/AHA algorithm and the FRS with those seen in HOPE-3, which randomized participants to 10 mg rosuvastatin or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; second coprimary outcome additionally included heart failure, cardiac arrest, and revascularization. Results Relative risks using risk scores were similar to those observed in the HOPE-3. Hazards ratios for the first coprimary outcome according to risk categories of ≤ 10%, 10%-20%, and ≥ 20% using the ACC/AHA algorithm were 0.82 (95% confidence interval [CI], 0.53-1.28), 0.72 (95% CI, 0.53-0.96), and 0.72 (95% CI, 0.55-0.93), and absolute risk reduction (ARR) of 0.18%, 1.33%, and 1.85%, respectively, over a median of 5.6 years. Corresponding results using the FRS were 0.69 (95% CI, 0.36-1.35), 0.73 (95% CI, 0.52-1.01), and 0.75 (95% CI, 0.60- 0.94); and ARR of 1.32%, 0.61%, and 1.43%. Hazard ratios for the second coprimary outcome were 0.77 (95% CI, 0.51-1.14), 0.73 (95% CI, 0.56-0.95), and 0.74 (95% CI, 0.58-0.94); and ARR of 0.36%, 1.49%, and 1.85%, using the ACC/AHA algorithm and 0.76 (95% CI, 0.41-1.41), 0.70 (95% CI, 0.52-0.95), and 0.76 (95% CI, 0.62-0.94); and ARR of 1.08%, 0.83%, and 1.56% using the FRS. Conclusions The pragmatic HOPE-3 trial approach identifies in an ethnically diverse primary prevention population individuals at intermediate risk who benefit from statin therapy using simple clinical characteristics without the need for complex, currently used risk assessment tools.

Background Influenza is associated with an increase in the risk of cardiac and other vascular events. Observational data and small randomized trials suggest that influenza vaccination may reduce such adverse vascular events. Research Design and Methods In a randomized controlled trial patients with heart failure are randomized to receive either inactivated influenza vaccine or placebo annually for 3 years. Patients aged ≥18 years with a clinical diagnosis of heart failure and NYHA functional class II, III and IV are eligible. Five thousand patients from 10 countries where influenza vaccination is not common (Asia, the Middle East, and Africa) have been enrolled. The primary outcome is a composite of the following: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalizations for heart failure using standardized criteria. Analyses will be based on comparing event rates between influenza vaccine and control groups and will include time to event, rate comparisons using Poisson methods, and logistic regression. The analysis will be conducted by intention to treat i.e. patients will be analyzed in the group in which they were assigned. Multivariable secondary analyses to assess whether variables such as age, sex, seasonality modify the benefits of vaccination are also planned for the primary outcome. Conclusion This is the largest randomized trial to test if influenza vaccine compared to control reduces adverse vascular events in high risk individuals. Trial registration number Clinicaltrials.gov NCT02762851

Aims To investigate the association of estimated total daily sleep duration and daytime nap duration with deaths and major cardiovascular events. Methods and results We estimated the durations of total daily sleep and daytime naps based on the amount of time in bed and self-reported napping time and examined the associations between them and the composite outcome of deaths and major cardiovascular events in 116 632 participants from seven regions. After a median follow-up of 7.8 years, we recorded 4381 deaths and 4365 major cardiovascular events. It showed both shorter (≤6 h/day) and longer (>8 h/day) estimated total sleep durations were associated with an increased risk of the composite outcome when adjusted for age and sex. After adjustment for demographic characteristics, lifestyle behaviours and health status, a J-shaped association was observed. Compared with sleeping 6–8 h/day, those who slept ≤6 h/day had a non-significant trend for increased risk of the composite outcome [hazard ratio (HR), 1.09; 95% confidence interval, 0.99–1.20]. As estimated sleep duration increased, we also noticed a significant trend for a greater risk of the composite outcome [HR of 1.05 (0.99–1.12), 1.17 (1.09–1.25), and 1.41 (1.30–1.53) for 8–9 h/day, 9–10 h/day, and >10 h/day, P trend < 0.0001, respectively]. The results were similar for each of all-cause mortality and major cardiovascular events. Daytime nap duration was associated with an increased risk of the composite events in those with over 6 h of nocturnal sleep duration, but not in shorter nocturnal sleepers (≤6 h). Conclusion Estimated total sleep duration of 6–8 h per day is associated with the lowest risk of deaths and major cardiovascular events. Daytime napping is associated with increased risks of major cardiovascular events and deaths in those with >6 h of nighttime sleep but not in those sleeping ≤6 h/night.

Digital, Background: Poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries. Methods: We used the Kansas City Cardiomyopathy Questionnaire–12 (KCCQ-12) to record HRQL in 23 291 patients with HF from 40 countries in 8 different world regions in the G-CHF study (Global Congestive Heart Failure). We compared standardized KCCQ-12 summary scores (adjusted for age, sex, and markers of HF severity) among regions (scores range from 0 to 100, with higher score indicating better HRQL). We used multivariable Cox regression with adjustment for 15 variables to assess the association between KCCQ-12 summary scores and the composite of all-cause death, HF hospitalization, and each component over a median follow-up of 1.6 years. Results: The mean age of participants was 65 years; 61% were men; 40% had New York Heart Association class III or IV symptoms; and 46% had left ventricular ejection fraction ≥40%. Average HRQL differed between regions (lowest in Africa [mean± SE, 39.5±0.3], highest in Western Europe [62.5±0.4]). There were 4460 (19%) deaths, 3885 (17%) HF hospitalizations, and 6949 (30%) instances of either event. Lower KCCQ-12 summary score was associated with higher risk of all outcomes; the adjusted hazard ratio (HR) for each 10-unit KCCQ-12 summary score decrement was 1.18 (95% CI, 1.17–1.20) for death. Although this association was observed in all regions, it was less marked in South Asia, South America, and Africa (weakest association in South Asia: HR, 1.08 [95% CI, 1.03–1.14]; strongest association in Eastern Europe: HR, 1.31 [95% CI, 1.21–1.42]; interaction P, Ciencias Medicas y de la Salud

Background/aims:\ud \ud To examine how measuring adherence at 3 weeks by self-report and pill counts compares to measurements at 7 weeks in a pre-randomization run-in period.\ud \ud Methods:\ud \ud Study within a trial of an international parallel group randomized controlled trial (RCT) that compares spironolactone to placebo. Adults receiving dialysis enter an 8-week active run-in period with spironolactone. Adherence was assessed by both self-report and pill counts in a subgroup of participants at both 3 weeks and 7 weeks.\ud \ud Results:\ud \ud 332 participants entered the run-in period of which 166 had complete data. By self-report, 146/166 (94.0%) and 153/166 (92.2%) had at least 80% adherence at 3 and 7 weeks respectively (kappa = 0.27 (95% C.I. 0.16 to 0.38). By pill counts, the mean (SD) adherence was 96.5% (16.1%) and 92.4% (18.2%) at 3 and 7 weeks respectively (r = 0.32) with a mean (SD) difference of 3.1% (17.8%) and a 95% limit of agreement from −31.7% to +37.9%. The proportion of adherent participants by self-report and pill counts at 3 weeks agreed in 87.4% of participants (McNemar's p-value 0.58, kappa 0.11, p = 0.02) and at 7 weeks agreed in 92.2% (McNemar's p-value 0.82, kappa 0.47, p

Digital, 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 119894 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 middleincome and high-income countries compared with lowincome 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, Ciencias Médicas y de la Salud

Digital, Importance Cohort studies report inconsistent associations between fish consumption, a major source of long-chain ω-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown. Objective To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease. Design, Setting, and Participants This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies—147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. This analysis was conducted from January to June 2020. Exposures Fish consumption was recorded using validated food frequency questionnaires. In 1 of the cohorts with vascular disease, a separate qualitative food frequency questionnaire was used to assess intake of individual types of fish. Main Outcomes and Measures Mortality and major CVD events (including myocardial infarction, stroke, congestive heart failure, or sudden death). Results Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] male) were included in the present analysis. During 9.1 years of follow-up in PURE, compared with little or no fish intake (≤50 g/mo), an intake of 350 g/wk or more was not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 0.88-1.05). By contrast, in the 3 cohorts of patients with vascular disease, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/wk (or approximately 2 servings/wk) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher. Fish with higher amounts of ω-3 fatty acids were strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other fish were neutral (collected in 1 cohort of patients with vascular disease). The association between fish intake and each outcome varied by CVD status, with a lower risk found among patients with vascular disease but not in general populations (for major CVD, I2 = 82.6 [P = .02]; for death, I2 = 90.8 [P = .001]). Conclusions and Relevance Findings of this pooled analysis of 4 cohort studies indicated that a minimal fish intake of 175 g (approximately 2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease., Ciencias Médicas y de la Salud

Digital, Aims. Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated. Methods and results. After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64–0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68–1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69–0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69–0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years. Conclusion. The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect, Ciencias Médicas y de la Educación

Digital, Objective Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke. Methods We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension. Results Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (pheterogeneity, Ciencias Médicas y de la Salud

Dietary guidelines recommend limiting red meat intake because it is a major source of medium- and long-chain SFAs and is presumed to increase the risk of cardiovascular disease (CVD). Evidence of an association between unprocessed red meat intake and CVD is inconsistent.The study aimed to assess the association of unprocessed red meat, poultry, and processed meat intake with mortality and major CVD.The Prospective Urban Rural Epidemiology (PURE) Study is a cohort of 134,297 individuals enrolled from 21 low-, middle-, and high-income countries. Food intake was recorded using country-specific validated FFQs. The primary outcomes were total mortality and major CVD. HRs were estimated using multivariable Cox frailty models with random intercepts.In the PURE study, during 9.5 y of follow-up, we recorded 7789 deaths and 6976 CVD events. Higher unprocessed red meat intake (≥250 g/wk vs.50 g/wk) was not significantly associated with total mortality (HR: 0.93; 95% CI: 0.85, 1.02; P-trend = 0.14) or major CVD (HR: 1.01; 95% CI: 0.92, 1.11; P-trend = 0.72). Similarly, no association was observed between poultry intake and health outcomes. Higher intake of processed meat (≥150 g/wk vs. 0 g/wk) was associated with higher risk of total mortality (HR: 1.51; 95% CI: 1.08, 2.10; P-trend = 0.009) and major CVD (HR: 1.46; 95% CI: 1.08, 1.98; P-trend = 0.004).In a large multinational prospective study, we did not find significant associations between unprocessed red meat and poultry intake and mortality or major CVD. Conversely, a higher intake of processed meat was associated with a higher risk of mortality and major CVD.

Summary Background Most studies of long-term exposure to outdoor fine particulate matter (PM2·5) and cardiovascular disease are from high-income countries with relatively low PM2·5 concentrations. It is unclear whether risks are similar in low-income and middle-income countries (LMICs) and how outdoor PM2·5 contributes to the global burden of cardiovascular disease. In our analysis of the Prospective Urban and Rural Epidemiology (PURE) study, we aimed to investigate the association between long-term exposure to PM2·5 concentrations and cardiovascular disease in a large cohort of adults from 21 high-income, middle-income, and low-income countries. Methods In this multinational, prospective cohort study, we studied 157 436 adults aged 35–70 years who were enrolled in the PURE study in countries with ambient PM2·5 estimates, for whom follow-up data were available. Cox proportional hazard frailty models were used to estimate the associations between long-term mean community outdoor PM2·5 concentrations and cardiovascular disease events (fatal and non-fatal), cardiovascular disease mortality, and other non-accidental mortality. Findings Between Jan 1, 2003, and July 14, 2018, 157 436 adults from 747 communities in 21 high-income, middle-income, and low-income countries were enrolled and followed up, of whom 140 020 participants resided in LMICs. During a median follow-up period of 9·3 years (IQR 7·8–10·8; corresponding to 1·4 million person-years), we documented 9996 non-accidental deaths, of which 3219 were attributed to cardiovascular disease. 9152 (5·8%) of 157 436 participants had cardiovascular disease events (fatal and non-fatal incident cardiovascular disease), including 4083 myocardial infarctions and 4139 strokes. Mean 3-year PM2·5 at cohort baseline was 47·5 μg/m3 (range 6–140). In models adjusted for individual, household, and geographical factors, a 10 μg/m3 increase in PM2·5 was associated with increased risk for cardiovascular disease events (hazard ratio 1·05 [95% CI 1·03–1·07]), myocardial infarction (1·03 [1·00–1·05]), stroke (1·07 [1·04–1·10]), and cardiovascular disease mortality (1·03 [1·00–1·05]). Results were similar for LMICs and communities with high PM2·5 concentrations (>35 μg/m3). The population attributable fraction for PM2·5 in the PURE cohort was 13·9% (95% CI 8·8–18·6) for cardiovascular disease events, 8·4% (0·0–15·4) for myocardial infarction, 19·6% (13·0–25·8) for stroke, and 8·3% (0·0–15·2) for cardiovascular disease mortality. We identified no consistent associations between PM2·5 and risk for non-cardiovascular disease deaths. Interpretation Long-term outdoor PM2·5 concentrations were associated with increased risks of cardiovascular disease in adults aged 35–70 years. Air pollution is an important global risk factor for cardiovascular disease and a need exists to reduce air pollution concentrations, especially in LMICs, where air pollution levels are highest. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

Background Chelation therapy is promoted and practiced around the world as a form of alternative medicine in the treatment of atherosclerotic cardiovascular disease. It has been suggested as a safe, relatively inexpensive, non-surgical method of restoring blood flow in atherosclerotic vessels. However, there is currently limited high-quality, adequately-powered research informing evidence-based medicine on the topic, specifically regarding clinical outcomes. Due to this limited evidence, the benefit of chelation therapy remains controversial at present. This is an update of a review first published in 2002. Objectives To assess the effects of ethylene diamine tetra-acetic acid (EDTA) chelation therapy versus placebo or no treatment on clinical outcomes among people with atherosclerotic cardiovascular disease. Search methods For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 6 August 2019. We searched the bibliographies of the studies retrieved by the literature searches for further trials. Selection criteria We included studies if they were randomised controlled trials of EDTA chelation therapy versus placebo or no treatment in participants with atherosclerotic cardiovascular disease. The main outcome measures we considered include all-cause or cause-specific mortality, non-fatal cardiovascular events, direct or indirect measurement of disease severity, and subjective measures of improvement or adverse events. Data collection and analysis Two review authors independently extracted data and assessed trial quality using standard Cochrane procedures. A third author considered any unresolved issues, and we discussed any discrepancies until a consensus was reached. We contacted study authors for additional information. Main results We included five studies with a total of 1993 randomised participants. Three studies enrolled participants with peripheral vascular disease and two studies included participants with coronary artery disease, one of which specifically recruited people who had had a myocardial infarction. The number of participants in each study varied widely (from 10 to 1708 participants), but all studies compared EDTA chelation to a placebo. Risk of bias for the included studies was generally moderate to low, but one study had high risk of bias because the study investigators broke their randomisation code halfway through the study and rolled the placebo participants over to active treatment. Certainty of the evidence, as assessed by GRADE, was generally low to very low, which was mostly due to a paucity of data in each outcome's meta-analysis. This limited our ability to draw any strong conclusions. We also had concerns about one study's risk of bias regarding blinding and outcome assessment that may have biased the results. Two studies with coronary artery disease participants reported no evidence of a difference in all-cause mortality between chelation therapy and placebo (risk ratio (RR) 0.97, 95% CI 0.73 to 1.28; 1792 participants; low-certainty). One study with coronary artery disease participants reported no evidence of a difference in coronary heart disease deaths between chelation therapy and placebo (RR 1.02, 95% CI 0.70 to 1.48; 1708 participants; very low-certainty). Two studies with coronary artery disease participants reported no evidence of a difference in myocardial infarction (RR 0.81, 95% CI 0.57 to 1.14; 1792 participants; moderate-certainty), angina (RR 0.95, 95% CI 0.55 to 1.67; 1792 participants; very low-certainty), and coronary revascularisation (RR 0.46, 95% CI 0.07 to 3.25; 1792 participants). Two studies (one with coronary artery disease participants and one with peripheral vascular disease participants) reported no evidence of a difference in stroke (RR 0.88, 95% CI 0.40 to 1.92; 1867 participants; low-certainty). Ankle-brachial pressure index (ABPI; also known as ankle brachial index) was measured in three studies, all including participants with peripheral vascular disease; two studies found no evidence of a difference in the treatment groups after three months after treatment (mean difference (MD) 0.02, 95% CI -0.03 to 0.06; 181 participants; low-certainty). A third study reported an improvement in ABPI in the EDTA chelation group, but this study was at high risk of bias. Meta-analysis of maximum and pain-free walking distances three months after treatment included participants with peripheral vascular disease and showed no evidence of a difference between the treatment groups (MD -31.46, 95% CI -87.63 to 24.71; 165 participants; 2 studies; low-certainty). Quality of life outcomes were reported by two studies that included participants with coronary artery disease, but we were unable to pool the data due to different methods of reporting and varied criteria. However, there did not appear to be any major differences between the treatment groups. None of the included studies reported on vascular deaths. Overall, there was no evidence of major or minor adverse events associated with EDTA chelation treatment. Authors' conclusions There is currently insufficient evidence to determine the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of people with atherosclerotic cardiovascular disease. More high-quality, randomised controlled trials are needed that assess the effects of chelation therapy on longevity and quality of life among people with atherosclerotic cardiovascular disease.

ObjectivesWe aimed to examine the relationship between access to medicine for cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs) among people at high risk of CVD in high-income countries (HICs), upper and lower middle-income countries (UMICs, LMICs) and low-income countries (LICs) participating in the Prospective Urban Rural Epidemiology (PURE) study.MethodsWe defined high CVD risk as the presence of any of the following: hypertension, coronary artery disease, stroke, smoker, diabetes or age >55 years. Availability and affordability of blood pressure lowering drugs, antiplatelets and statins were obtained from pharmacies. Participants were categorised: group 1—all three drug types were available and affordable, group 2—all three drugs were available but not affordable and group 3—all three drugs were not available. We used multivariable Cox proportional hazard models with nested clustering at country and community levels, adjusting for comorbidities, sociodemographic and economic factors.ResultsOf 163 466 participants, there were 93 200 with high CVD risk from 21 countries (mean age 54.7, 49% female). Of these, 44.9% were from group 1, 29.4% from group 2 and 25.7% from group 3. Compared with participants from group 1, the risk of MACEs was higher among participants in group 2 (HR 1.19, 95% CI 1.07 to 1.31), and among participants from group 3 (HR 1.25, 95% CI 1.08 to 1.50).ConclusionLower availability and affordability of essential CVD medicines were associated with higher risk of MACEs and mortality. Improving access to CVD medicines should be a key part of the strategy to lower CVD globally.

Digital, Objective Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study. Methods The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In the cross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). For the prospective analyses, we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes). Results In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend, Ciencias Médicas y de la Salud

Digital, Background Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. Methods Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. Results The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. Conclusions Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs., Ciencias Médicas y de la Salud

Summary Background Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels. Methods In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs. Findings Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs. Interpretation Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

Dengvaxia, a chimeric yellow fever tetravalent dengue vaccine developed by SanofiPasteur is widely licensed in dengue-endemic countries. In a large cohort study Dengvaxia was found to partially protect children who had prior dengue virus (DENV) infections but sensitized seronegative children to breakthrough DENV disease of enhanced severity. In 2019, the European Medicines Agency and the US FDA issued licenses that reconciled safety issues by restricting vaccine to individuals with prior dengue infections. Using revised Dengvaxia efficacy and safety data we sought to estimate hospitalized and severe dengue cases among the more than 800,000 9 year-old children vaccinated in the Philippines. Despite an overall vaccine efficacy of 69% during 4 years post-vaccination we project there will be more than one thousand vaccinated seronegative and seropositive children hospitalized for severe dengue. Assisting these children through a program of enhanced surveillance leading to improved care deserves widespread support. Clinical responses observed during breakthrough dengue infections in vaccinated individuals counsel prudence in design of vaccine policies. Recommendations concerning continued use of this dengue vaccine are: (1) obtain a better definition of vaccine efficacy and safety through enhanced phase 4 surveillance, (2) obtain a valid, accessible, sensitive, specific and affordable serological test that identifies past wild-type dengue virus infection and (3) clarify safety and efficacy of Dengvaxia in flavivirus immunes. In the absence of an acceptable serological screening test these unresolved ethical issues suggest Dengvaxia be given only to those signing informed consent., Marie Skłodowska-Curie grant agreement No 792494

8 p., BACKGROUND: It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial. METHODS: TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events. RESULTS: The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk. CONCLUSION: Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.

Studies often combine several events, for example, death or myocardial infarction or stroke, into a single study outcome. This is called a composite endpoint. Composite endpoints make doing trials easier by reducing the sample size or follow-up period required to demonstrate the effectiveness of an intervention. However, interpreting the results of composite endpoints can be confusing. To avoid misleading conclusions about the effectiveness of an intervention, it is important for readers of studies reporting a composite endpoint to ascertain that the clinical importance, the frequency of events, and the effect of the intervention on each component of the composite endpoint are similar.

BACKGROUND: Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy. METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo. RESULTS: Between February 2013 and May 2016, we recruited 27,395 participants from 602 centres in 33 countries; 17,598 participants were included in the pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD. CONCLUSIONS: COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy. ispartof: Canadian Journal of Cardiology vol:33 issue:8 pages:1027-1035 ispartof: location:England status: published

ObjectiveTo evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (3.5 g potassium) in adults.DesignInternational prospective cohort study.Setting18 high, middle, and low income countries, sampled from urban and rural communities.Participants103 570 people who provided morning fasting urine samples.Main outcome measuresAssociation of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).ResultsMean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of 3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).ConclusionsThese findings suggest that the simultaneous target of low sodium intake (3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events.

Background. The implementation of the “Sin Tax Law” (RA 10351) in 2013 has increased revenues for healthcare in the Philippines. What changes have taken place in government hospitals since the passage of the law? This qualitative study sought to answer this question by presenting perspectives from patients, doctors, and nurses. Methods. Four focus group discussions (FGDs) and eight semi-structured interviews (SSIs) were conducted among patients, doctors, and nurses in two tertiary government hospitals in Metro Manila, Philippines. Results. Significant changes noted by study participants over the past several years included increased financial assistance for patients as well as improvements in health services and continuity of care. However, their narratives underscored shortcomings in human resources and facilities, raising questions of ‘absorptive capacity’. Conclusion. Given that the Sin Tax Law was the main policy intervention to which the changes reported by study participants can be attributed, the study provides a strong case for a continuation - if not expansion - of the Law, with the recommendation that increased health revenue should also translate to greater support for healthcare workers and enhanced health facilities. As these insights may be overlooked by traditional metrics, the study also recommends that policymakers consider qualitative studies in evaluating the efficacy of health care reforms.

Background: Household air pollution (HAP) from solid fuel use for cooking affects 2.5 billion individuals globally and may contribute substantially to disease burden. However, few prospective studies have assessed the impact of HAP on mortality and cardiorespiratory disease. Objectives: Our goal was to evaluate associations between HAP and mortality, cardiovascular disease (CVD), and respiratory disease in the prospective urban and rural epidemiology (PURE) study. Methods: We studied 91,350 adults 35–70 y of age from 467 urban and rural communities in 11 countries (Bangladesh, Brazil, Chile, China, Colombia, India, Pakistan, Philippines, South Africa, Tanzania, and Zimbabwe). After a median follow-up period of 9.1 y, we recorded 6,595 deaths, 5,472 incident cases of CVD (CVD death or nonfatal myocardial infarction, stroke, or heart failure), and 2,436 incident cases of respiratory disease (respiratory death or nonfatal chronic obstructive pulmonary disease, pulmonary tuberculosis, pneumonia, or lung cancer). We used Cox proportional hazards models adjusted for individual, household, and community-level characteristics to compare events for individuals living in households that used solid fuels for cooking to those using electricity or gas. Results: We found that 41.8% of participants lived in households using solid fuels as their primary cooking fuel. Compared with electricity or gas, solid fuel use was associated with fully adjusted hazard ratios of 1.12 (95% CI: 1.04, 1.21) for all-cause mortality, 1.08 (95% CI: 0.99, 1.17) for fatal or nonfatal CVD, 1.14 (95% CI: 1.00, 1.30) for fatal or nonfatal respiratory disease, and 1.12 (95% CI: 1.06, 1.19) for mortality from any cause or the first incidence of a nonfatal cardiorespiratory outcome. Associations persisted in extensive sensitivity analyses, but small differences were observed across study regions and across individual and household characteristics. Discussion: Use of solid fuels for cooking is a risk factor for mortality and cardiorespiratory disease. Continued efforts to replace solid fuels with cleaner alternatives are needed to reduce premature mortality and morbidity in developing countries. https://doi.org/10.1289/EHP3915

Background: Associations of dairy foods, including whole-fat versus low-fat and specific types of dairy, with metabolic syndrome (MetS), hypertension (HTN) and diabetes mellitus (DM) are not well established, especially in diverse global populations. Methods: The Prospective Urban Rural Epidemiology (PURE) study is a prospective cohort study of individuals aged 35 and 70 years from 21 countries with 9·1 years follow up. Dietary intake of 147,812 individuals was recorded using country specific validated food frequency questionnaires. At baseline, we examined the association of total dairy and types of dairy with the prevalence of MetS and its components. During follow-up, the associations between dairy intake with incident HTN and DM were examined. Findings: In multivariable-adjusted analyses, lower prevalence of MetS was seen with higher intake of total dairy (>=2 servings/d vs zero serving/day; OR 0·76; 95%CI 0·71-0·80, p-trend

Dear Editor,This letter is written in response to an article by Larson et al entitled “Vaccine confidence plummets in the Philippines following dengue vaccine scare: why it matters to pandemic prep...

Background: Cardiovascular diseases (CVDs) are the leading cause of premature mortality in the world and are a growing public health concern in low- and middle-income countries (LMICs), including those in South East Asia. Their management requires coordinated responses by a range of healthcare providers, which should preferably be based on knowledge of the national context. We systematically review evidence on the pathways followed by patients with CVD in Malaysia and the Philippines to understand patient journeys, along with the barriers at each stage. Methods: We searched seven bibliographic databases and grey literature sources to identify material focused on the pathways followed by patients with CVD in Malaysia and the Philippines, and performed a narrative synthesis. Results: The search yielded 25 articles, 3 focused on the Philippines and 22 on Malaysia. Most articles were quantitative analyses that focused on hypertensive patients. Three examined secondary prevention post myocardial infarction, and one each examined acute myocardial infarction, heart failure, and atrial fibrillation. Reported barriers reflected capability (knowledge of behaviours to achieve control or the capacity to conduct these behaviours), intention (attitudes or motivations toward the behaviours to achieve control), and aspects of the health care system (availability, accessibility, affordability and acceptability of services). Conclusions: There are large gaps in our understanding of patient pathways in Malaysia and the Philippines that limit the development of evidence-based strategies to effectively address the CVD burden in South East Asian countries and in LMICs more broadly. Addressing these evidence gaps will require longitudinal mixed-methods studies following patients from initial diagnosis to long-term management.

12 p., Background The measurement of handgrip strength (HGS) has prognostic value with respect to all-cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high-income countries. There is a paucity of information on normative HGS values in non-Caucasian populations from low- or middle-income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions. Methods HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35-70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Results HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25th–75th percentile) 50 kg (43–56 kg) in men 60 years from South East Asia. Reference ranges by ethnicity and body-mass index are also reported. Conclusions Individual HGS measurements should be interpreted using region/ethnic-specific reference ranges.

11 p., BACKGROUND Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease. METHODS In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years. RESULTS The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P=0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P

12 p., BACKGROUND Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. METHODS In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. RESULTS The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes). CONCLUSIONS Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.)

IntroductionUnderstanding explanatory models is important for hypertension, a leading risk factor for cardiovascular disease and stroke. This article aims to determine what adult patients with hypertension in the Philippines attribute their condition to, how these views might be explained and what the implications are for hypertension management.MethodsThis is a qualitative study drawing on 71 semistructured interviews (40 initial and 31 follow-up) and four focus group discussions with patients diagnosed with hypertension. The setting was urban and rural low-income communities in the Philippines.ResultsFour prominent perceived causes were identified—genetics, heat, stress and diet—for what patients refer to as ‘high blood’. We propose a ‘folk physiology’ that rests on local understandings of blood and blood flow, draws from broader cultural notions of illness causation and accounts for a dynamic, non-chronic view of hypertension that in turn informs the health behaviours of those affected.ConclusionsBy understanding that hypertension is frequently seen not as a chronic constant condition but rather as an episodic one triggered by external influences, although in those genetically predisposed to it, it may be possible to address patient’s beliefs and thus adherence to treatment.