Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. (AU)

The household economic burden of non-communicable diseases in 18 countries

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. (AU)

Blood pressure control in a registry of clinical practice, PINNACLEBRAZIL REGISTRY

INTRODUCTION: The prevalence of hypertension is estimated to be nearly 50% among Brazilian adults. Achieving an adequate control of this CVD risk factor is challenging but truly relevant on a public health perspective, as this is the top ranking cause of all deaths globally. PURPOSE: We aimed to describe crude and simple metrics of blood pressure management (including its control), as based on current guidelinederived recommendations, after one year of the clinical practice registry METHODS: Patients with documented Hypertension were included by using electronic case report form based on the ACC PINNACLE Registry. The registry has been enrolling patients from general practitioners and specialists. The main goal of the PINNACLE program is to improve the quality of care in "real world" clinical practice. Patients data were evaluated after 01 year of follow-up on regular clinical appointments and the differences on clinical practice were evaluated RESULTS: Currently, PINNACLEBrazil has enrolled 7598 patients, with 87% of diagnosed hypertension. Percentage of patients with a diagnosis of hypertension who had a blood pressure measurement <140/90 mmHg was 47.9%(baseline) and 57.3% (followup). Percentage of patients who had a blood pressure < 140/90 mm Hg, or who had a blood pressure >= 140/90 mm Hg and were prescribed >= 2 antihypertensive medications were 67.1% on baseline and 71.2% after 1 year. CONCLUSION: The preliminary data of PINNACLE Registry in Brazil shows that a significant proportion of hypertensive patients (nearly half) have not presented with adequate control of blood pressure levels and, moreover, a large proportion have not been treated with recommended combination of 02 or more antihypertensive medications to reach targeted BP levels the quality of care was improving after 01 year of registry. (AU)

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group...

Novel approaches in primary cardiovascular disease prevention: the HOPE-3 trial rationale, design, and participants' baseline characteristics

AbstractBACKGROUND:Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels.METHODS:A total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization.RESULTS:Participants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women.CONCLUSIONS:The HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide (HOPE-3 ClinicalTrials.govNCT00468923).

Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of RiskBut Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

Background-—We evaluated lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp-PLA2 inhibitor, in relation to outcomes and the effects ofdarapladib in the STABILITY trial. Methods and Results-—Plasma Lp-PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100)at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp-PLA2activity levels and outcomes. At baseline, the median Lp-PLA2 level was 172.4 lmol/min per liter (interquartile range 143.1–204.2lmol/min per liter). Comparing the highest and lowest Lp-PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) forthe primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) forhospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction afteradjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladibled to a 65% persistent reduction in median Lp-PLA2 activity. There were no associations between on-treatment Lp-PLA2 activityor changes of Lp-PLA2 activity and outcomes, and there were no significant interactions between baseline and on-treatment LpPLA2 activity or changes in Lp-PLA2 activity levels and the effects of darapladib on outcomes...

Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease

Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase therisk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) orplacebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day)or placebo. In the analyses reported here, we compared the 3180 participants assigned tocombined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, andthe second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years...

Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease

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 involvedmainly white persons. It is unclear whether the benefits of statins can be extended toan intermediate-risk, ethnically diverse population without cardiovascular disease. METHODS In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participantsin 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 additionallyin cluded revascularization, heart failure, and resuscitated cardiac arrest. Themedian follow-up was 5.6 years...

Psychosocial factors and obesity in 17 high-, middle- and low-income countries: the Prospective Urban Rural Epidemiologic study.

BACKGROUND/OBJECTIVES: Psychosocial stress has been proposed to contribute to obesity, particularly abdominal, or central obesity, through chronic activation of the neuroendocrine systems. However, these putative relationships are complex and dependent on country and cultural context. We investigated the association between psychosocial factors and general and abdominal obesity in the Prospective Urban Rural Epidemiologic study. SUBJECTS/METHODS: This observational, cross-sectional study enrolled 151 966 individuals aged 35-70 years from 628 urban and rural communities in 17 high-, middle- and low-income countries. Data were collected for 125 290 individuals regarding education, anthropometrics, hypertension/diabetes, tobacco/alcohol use, diet and psychosocial factors (self-perceived stress and depression). RESULTS: After standardization for age, sex, country income and urban/rural location, the proportion with obesity (body mass index ≥30 kg m(-)(2)) increased from 15.7% in 40 831 individuals with no stress to 20.5% in 7720 individuals with permanent stress, with corresponding proportions for ethnicity- and sex-specific central obesity of 48.6% and 53.5%, respectively (P<0.0001 for both). Associations between stress and hypertension/diabetes tended to be inverse. Estimating the total effect of permanent stress with age, sex, physical activity, education and region as confounders, no relationship between stress and obesity persisted (adjusted prevalence ratio (PR) for obesity 1.04 (95% confidence interval: 0.99-1.10)). There was no relationship between ethnicity- and sex-specific central obesity (adjusted PR 1.00 (0.97-1.02)). Stratification by region yielded inconsistent associations. Depression was weakly but independently linked to obesity (PR 1.08 (1.04-1.12)), and very marginally to abdominal obesity (PR 1.01 (1.00-1.03)). CONCLUSIONS: Although individuals with permanent stress tended to be slightly more obese, there was no overall independent effect and no evidence that abdominal obesity or its consequences (hypertension, diabetes) increased with higher levels of stress or depression. This study does not support a causal link between psychosocial factors and abdominal obesity.

The environmental profile of a community's health: a cross-sectional study on tobacco marketing in 16 countries

To examine and compare tobacco marketing in 16 countries while the Framework Convention on Tobacco Control requires parties to implement a comprehensive ban on such marketing.METHODS:Between 2009 and 2012, a kilometre-long walk was completed by trained investigators in 462 communities across 16 countries to collect data on tobacco marketing. We interviewed community members about their exposure to traditional and non-traditional marketing in the previous six months. To examine differences in marketing between urban and rural communities and between high-, middle- and low-income countries, we used multilevel regression models controlling for potential confounders.FINDINGS:Compared with high-income countries, the number of tobacco advertisements observed was 81 times higher in low-income countries (incidence rate ratio, IRR: 80.98; 95% confidence interval, CI: 4.15-1578.42) and the number of tobacco outlets was 2.5 times higher in both low- and lower-middle-income countries (IRR: 2.58; 95% CI: 1.17-5.67 and IRR: 2.52; CI: 1.23-5.17, respectively). Of the 11,842 interviewees, 1184 (10%) reported seeing at least five types of tobacco marketing. Self-reported exposure to at least one type of traditional marketing was 10 times higher in low-income countries than in high-income countries (odds ratio, OR: 9.77; 95% CI: 1.24-76.77). For almost all measures, marketing exposure was significantly lower in the rural communities than in the urban communities.CONCLUSION:Despite global legislation to limit tobacco marketing, it appears ubiquitous. The frequency and type of tobacco marketing varies on the national level by income group and by community type, appearing to be greatest in low-income countries and urban communities.

Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial

AIM:To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation.METHODS AND RESULTS:Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double-blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive either warfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74-1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all-cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex.CONCLUSION:In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women...

Cardiovascular disease burden: evolving knowledge of risk factors in myocardial infarction and stroke through population-based research and perspectives in global prevention

Current knowledge and research perspectives on the top ranking causes of mortality worldwide, i.e., ischemic heart disease and cerebrovascular diseases have developed rapidly. In fact, until recently, the evidence describing the incidence of acute myocardial infarction, the underlying risk factors, and the clinical outcomes of those who have this acute ischemic coronary event has largely been based on studies conducted in developed countries, with limited data for women and usually of low-ethnic diversity. Recent reports by the WHO have provided striking public health information, i.e., the global burden of cardiovascular mortality for the next decades is expected to predominantly occur among developing countries. Therefore, multiethnic population-based research including prospective cohorts and, when appropriate, case-control studies, is warranted. These studies should be specifically designed to ascertain key public health measures, such as geographic variations in non-communicable diseases, diagnosis of traditional and potential newly discovered risk factors, causes of death and disability, and gaps for improvement in healthcare prevention (both primary and secondary) and specific treatments. As an example, a multinational, multiethnic population-based cohort study is the Prospective Urban and Rural Epidemiology study, which is the largest global initiative of nearly 200,000 adults aged 35-70 years, looking at environmental, societal, and biological influences on obesity and chronic health conditions, such as ischemic heart disease, stroke, and cancer among urban and rural communities in low-, middle-, and high-income countries, with national, community, household, and individual-level data. Implementation of population-based strategies is crucial to optimizing limited health system resources while improving care and cardiovascular morbidity and mortality.

Psychosocial factors and obesity in 17 high-, middle- andlow-income countries: the Prospective Urban RuralEpidemiologic study

Psychosocial stress has been proposed to contribute to obesity, particularly abdominal, or centralobesity, through chronic activation of the neuroendocrine systems. However, these putative relationships are complex anddependent on country and cultural context. We investigated the association between psychosocial factors and general andabdominal obesity in the Prospective Urban Rural Epidemiologic study.SUBJECTS/METHODS: This observational, cross-sectional study enrolled 151 966 individuals aged 35–70 years from 628 urban andrural communities in 17 high-, middle- and low-income countries. Data were collected for 125 290 individuals regarding education,anthropometrics, hypertension/diabetes, tobacco/alcohol use, diet and psychosocial factors (self-perceived stress and depression).RESULTS: After standardization for age, sex, country income and urban/rural location, the proportion with obesity (body massindex ⩾ 30 kgm−2) increased from 15.7% in 40 831 individuals with no stress to 20.5% in 7720 individuals with permanent stress,with corresponding proportions for ethnicity- and sex-specific central obesity of 48.6% and 53.5%, respectively (Po0.0001 forboth). Associations between stress and hypertension/diabetes tended to be inverse. Estimating the total effect of permanent stresswith age, sex, physical activity, education and region as confounders, no relationship between stress and obesity persisted(adjusted prevalence ratio (PR) for obesity 1.04 (95% confidence interval: 0.99–1.10)). There was no relationship between ethnicityandsex-specific central obesity (adjusted PR 1.00 (0.97–1.02)). Stratification by region yielded inconsistent associations. Depressionwas weakly but independently linked to obesity (PR 1.08 (1.04–1.12)), and very marginally to abdominal obesity (PR 1.01(1.00–1.03)).