Associations of the glycaemic index and the glycaemic load with risk of type 2 diabetes in 127 594 people from 20 countries (PURE): a prospective cohort study.

BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets. METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs). FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030). INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes. FUNDING: Full funding sources are listed at the end of the Article.

Clinical features, socioeconomic status, management, short and long-term outcomes of patients with acute myocardial infarction: Phase I results of PEACE MENA registry.

BACKGROUND: The Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa (PEACE MENA) is a prospective registry program in Arabian countries that involves in patients with acute myocardial infarction (AMI) or acute heart failure (AHF). METHODS: This prospective, multi-center, multi-country study is the first report of the baseline characteristics and outcomes of inpatients with AMI who were enrolled during the first 14-month recruitment phase. We report the clinical characteristics, socioeconomic, educational levels, and management, in-hospital, one month and one-year outcomes. RESULTS: Between April 2019 and June 2020, 1377 patients with AMI were enrolled (79.1% males) from 16 Arabian countries. The mean age (± SD) was 58 ± 12 years. Almost half of the population had a net income < $500/month, and 40% had limited education. Nearly half of the cohort had a history of diabetes mellitus, hypertension, or hypercholesterolemia; 53% had STEMI, and almost half (49.7%) underwent a primary percutaneous intervention (PCI) (lowest 4.5% and highest 100%). Thrombolytics were used by 36.2%. (Lowest 6.45% and highest (90.9%). No reperfusion occurred in 13.8% of patients (lowest was 0% and highest 72.7%).Primary PCI was performed less frequently in the lower income group vs. high income group (26.3% vs. 54.7%; P<0.001). Recurrent ischemia occurred more frequently in the low-income group (10.9% vs. 7%; P = 0.018). Re-admission occurred in 9% at 1 month and 30% at 1 year, whereas 1-month mortality was 0.7% and 1-year mortality 4.7%. CONCLUSION: In the MENA region, patients with AMI present at a young age and have a high burden of cardiac risk factors. Most of the patients in the registry have a low income and low educational status. There is heterogeneity among key performance indicators of AMI management among various Arabian countries.

Morbidity and mortality of acute heart failure patients stratified by mitral regurgitation in the Arabian Gulf: Observations from the Gulf acute heart failure registry (Gulf CARE).

This study aimed to evaluate the clinical outcomes of patients with acute heart failure (AHF) stratified by mitral regurgitation (MR) in the Arabian Gulf. Patients from the Gulf CARE registry were identified from 47 hospitals in seven Arabian Gulf countries (Yemen, Oman, Kuwait, Qatar, Bahrain, the United Arab Emirates, and Saudi Arabia) from February to November 2012. The cohort was stratified into two groups based on the presence of MR. Univariable and multivariable statistical analyses were performed. The population cohort included 5005 consecutive patients presenting with AHF, of whom 1491 (29.8 %) had concomitant MR. The mean age of patients with AHF and concomitant MR was 59.2 ± 14.9 years, and 63.1 % (n = 2886) were male. A total of 58.6 % (n = 2683) had heart failure (HF) with reduced ejection fraction (EF) (HFrEF), 21.0 % (n = 961) had HF with mildly reduced EF (HFmrEF), and 20.4 % (n = 932) had HF with preserved EF (HFpEF). Patients with MR had a lower haemoglobin (Hb) level (12.4 vs. 12.7 g/dL; p < 0.001), and a higher prevalence of left atrial enlargement (80.2 % vs. 55.1 %; p < 0.001), cardiogenic shock (9.7 % vs. 7.3 %; p = 0.006) and atrial fibrillation (7.6 % vs. 5.6 %; p = 0.006), and HFrEF (71.0 % vs. 52.6 %; P < 0.001). Multivariable analysis demonstrated that MR was independently associated with increased all-cause mortality at 1-year and 3-month HF rehospitalization [1-year all-cause mortality, adjusted odds ratio (aOR), 1.40; 95 % confidence interval (Cl): 1.13-1.74; p = 0.002; 3-month HF rehospitalization, aOR, 1.26; 95 % Cl: 1.06-1.49; p = 0.009]. In an Arabian Gulf cohort with AHF, concomitant MR was associated with an increased risk of 1-year mortality and 3-months HF rehospitalization.

Physicians' perceptions and beliefs on the current dyslipidemia management practices within Saudi Arabia.

Background: Limited reports addressing physicians' understanding of the various low-density lipoprotein cholesterol (LDL-C) targets/statin intensity required for treating the various dyslipidemia patient populations in Saudi Arabia are available. Therefore, the current study assessed the perceptions and beliefs of practicing clinicians in Saudi Arabia regarding the current practice for management of dyslipidemia and potential perceived barriers to adherence to lipid guidelines encountered in their regular clinical practice. Knowledge of different clinical practices and beliefs could have a positive impact on improving the quality of future care provided by physicians. Methods: A survey questionnaire was designed to assess physicians' familiarity, usage, and adherence to seven different international guidelines and used to evaluate the management of dyslipidemia, practice of patient treatment, and perceived obstacles to adhering to lipid guidelines related to specific patients, doctors, and practice issues. Results: A total of 467 physicians were recruited for the study: (1) 57.2% were primary care physicians (PCPs) and (2) 42.8% were specialists. About 90.8% of them followed lipid guidelines of which the most common set were based on those by the American College of Cardiology/American Heart Association. The most utilized risk assessment tool was the atherosclerotic cardiovascular disease (ASCVD) risk calculator. About 60% of the physicians set an LDL-C target for their patients based on a combination of patients' risk factors and lipid profiles. In all, 42.1% of the physicians chose not to change existing therapy among patients with dyslipidemia to attain a non-high-density lipoprotein goal with controlled LDL-C level. Atorvastatin accounted for the greatest percentage of primary and secondary prevention choices (71.9% and 69.6%, respectively). Rosuvastatin was mostly preferred by physicians for patients with familial hypercholesterolemia. About two-thirds of the physicians (77.9%) prescribed statins to diabetic patients aged 40-75 years. Statin intolerance was encountered by 62.9% of the physicians in ≤ 10% of patients by 62.9%. Therapeutic strategies included switching to an alternative statin (40.1%) followed by reducing the statin dose (35.3%). Ezetimibe was prescribed by most physicians (77.9%) as an add-on to statin if the LDL-C target was not achieved. Fibrate was most preferred by physicians (62.7%) for hypertriglyceremia treatment followed by statins (28.7% of the physicians). Sixty-six percent reported not using proprotein convertase subtilisin/kexin type 9 serine protease inhibitors in their clinical practice due to unavailability at their institute (51.8%), high costs (26.3%), and/or lack of knowledge (20.6%). Perceived barriers to guideline adherence identified by physicians were lack of familiarity and knowledge of the guidelines, patient non-adherence, medication costs, and lack of timely follow-up appointments and educational tools. Multiple similarities and differences were observed after comparisons were made between specialists and PCPs in terms of guideline preference, clinical practice, and perceived barriers. Conclusion: Different perceptions and attitudes among physicians in Saudi Arabia were found due to variable recommendations by international lipid guidelines. Perceived barriers that included the patient, physician, and practice were identified by physicians at multiple levels. Multiple challenges and different action gaps were observed when comparing specialists to PCPs. It is recommended that standardized practices be followed by clinicians in Saudi Arabia, and actions to address the outlined barriers are essential for optimizing health outcomes and ASCVD prevention.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

AIM: To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. BACKGROUND: The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. OBJECTIVE: Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. METHODS: The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipidlowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. RESULTS: Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. CONCLUSION: The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.

Diet, cardiovascular disease, and mortality in 80 countries.

AIMS: To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries. METHODS AND RESULTS: A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0-6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of ≤1 points, a diet score of ≥5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63-0.77)], CVD (HR 0.82; 0.75-0.91), myocardial infarction (HR 0.86; 0.75-0.99), and stroke (HR 0.81; 0.71-0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66-0.81), CVD (HR 0.79; 0.72-0.87), myocardial infarction (HR 0.85; 0.71-0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73-1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65-0.80] and stroke (OR 0.57; 0.50-0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison). CONCLUSION: A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.

Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Characteristics and predictors of out-of-hospital cardiac arrest in young adults hospitalized with acute coronary syndrome: A retrospective cohort study of 30,000 patients in the Gulf region.

INTRODUCTION: The characteristics of young adults with out-of-hospital cardiac arrest (OHCA) due to acute coronary syndrome (ACS) has not been well described. The mean age of gulf citizens in ACS registries is 10-15 years younger than their western counterparts, which provided us with a unique opportunity to investigate the characteristics and predictors of OHCA in young adults presenting with ACS. METHODOLOGY: This was a retrospective cohort study using data from 7 prospective ACS registries in the Gulf region. In brief, all registries included consecutive adults who were admitted with ACS. OHCA was defined as cardiac arrest upon presentation (i.e., before admission to the hospital). We described the characteristics of young adults (< 50 years) who had OHCA and performed multivariate logistic regression analysis to assess independent predictors of OHCA. RESULTS: A total of 31,620 ACS patients were included in the study. There were 611 (1.93%) OHCA cases in the whole cohort [188/10,848 (1.73%) in young adults vs 423/20,772 (2.04%) in older adults, p = 0.06]. Young adults were predominantly males presenting with ST-elevation myocardial infarction (STEMI) [182/188 (96.8%) and 172/188 (91.49%), respectively]. OHCA was the sentinel event of coronary artery disease (CAD) in 70% of young adults. STEMI, male sex, and non-smoking status were found to be independent predictors of OHCA [OR = 5.862 (95% CI 2.623-13.096), OR: 4.515 (95% CI 1.085-18.786), and OR = 2.27 (95% CI 1.335-3.86), respectively]. CONCLUSION: We observed a lower prevalence of OHCA in ACS patients in our region as compared to previous literature from other regions. Moreover, OHCA was the sentinel event of CAD in the majority of young adults, who were predominantly males with STEMIs. These findings should help risk-stratify patients with ACS and inform further research into the characteristics of OHCA in young adults.

Clinical Features, Socioeconomic Status, Management, and Outcomes of Acute Heart Failure: PEACE MENA Registry Phase I Results.

INTRODUCTION: PEACE MENA (Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa) is a prospective registry in Arab countries for in-patients with acute myocardial infarction (AMI) or acute heart failure (AHF). Here, we report the baseline characteristics and outcomes of in-patients with AHF who were enrolled during the first 14 months of the recruitment phase. METHODS: A prospective, multi-centre, multi-country study including patients hospitalized with AHF was conducted. Clinical characteristics, echocardiogram, BNP (B-type natriuretic peptide), socioeconomic status, management, 1-month, and 1-year outcomes are reported. RESULTS: Between April 2019 and June 2020, a total of 1258 adults with AHF from 16 Arab countries were recruited. Their mean age was 63.3 (±15) years, 56.8% were men, 65% had monthly income ≤US$ 500, and 56% had limited education. Furthermore, 55% had diabetes mellitus, 67% had hypertension; 55% had HFrEF (heart failure with reduced ejection fraction), and 19% had HFpEF (heart failure with preserved ejection fraction). At 1 year, 3.6% had a heart failure-related device (0-22%) and 7.3% used an angiotensin receptor neprilysin inhibitor (0-43%). Mortality was 4.4% per 1 month and 11.77% per 1-year post-discharge. Compared with higher-income patients, lower-income patients had a higher 1-year total heart failure hospitalization rate (45.6 vs 29.9%, p=0.001), and the 1-year mortality difference was not statistically significant (13.2 vs 8.8%, p=0.059). CONCLUSION: Most of the patients with AHF in Arab countries had a high burden of cardiac risk factors, low income, and low education status with great heterogeneity in key performance indicators of AHF management among Arab countries.

Ultra-processed foods and mortality: analysis from the Prospective Urban and Rural Epidemiology study.

BACKGROUND: Higher intake of ultra-processed foods (UPFs) has been associated with increased risk of CVD and mortality in observational studies from Western countries but data from non-Western countries are limited. OBJECTIVES: We aimed to assess the association between consumption of UPFs and risk of mortality and major CVD in a cohort from multiple world regions. DESIGN: This analysis includes 138,076 participants without a history of CVD between the ages of 35 and 70 y living on 5 continents, with a median follow-up of 10.2 y. We used country-specific validated food-frequency questionnaires to determine individuals' food intake. We classified foods and beverages based on the NOVA classification into UPFs. The primary outcome was total mortality (CV and non-CV mortality) and secondary outcomes were incident major cardiovascular events. We calculated hazard ratios using multivariable Cox frailty models and evaluated the association of UPFs with total mortality, CV mortality, non-CV mortality, and major CVD events. RESULTS: In this study, 9227 deaths and 7934 major cardiovascular events were recorded during the follow-up period. We found a diet high in UPFs (≥2 servings/d compared with 0 intake) was associated with higher risk of mortality (HR: 1.28; 95% CI: 1.15, 1.42; P-trend < 0.001), CV mortality (HR: 1.17; 95% CI: 0.98, 1.41; P-trend = 0.04), and non-CV mortality (HR: 1.32; 95% CI 1.17, 1.50; P-trend < 0.001). We did not find a significant association between UPF intake and risk of major CVD. CONCLUSIONS: A diet with a high intake of UPFs was associated with a higher risk of mortality in a diverse multinational study. Globally, limiting the consumption of UPFs should be encouraged.

Urbanization and physical activity in the global Prospective Urban and Rural Epidemiology study.

Urbanization may influence physical activity (PA) levels, although little evidence is available for low- and middle- income countries where urbanization is occurring fastest. We evaluated associations between urbanization and total PA, as well as work-, leisure-, home-, and transport-specific PA, for 138,206 adults living in 698 communities across 22 countries within the Prospective Urban and Rural Epidemiology (PURE) study. The 1-week long-form International PA Questionnaire was administered at baseline (2003-2015). We used satellite-derived population density and impervious surface area estimates to quantify baseline urbanization levels for study communities, as well as change measures for 5- and 10-years prior to PA surveys. We used generalized linear mixed effects models to examine associations between urbanization measures and PA levels, controlling for individual, household and community factors. Higher community baseline levels of population density (- 12.4% per IQR, 95% CI - 16.0, - 8.7) and impervious surface area (- 29.2% per IQR, 95% CI - 37.5, - 19.7), as well as the rate of change in 5-year population density (- 17.2% per IQR, 95% CI - 25.7, - 7.7), were associated with lower total PA levels. Important differences in the associations between urbanization and PA were observed between PA domains, country-income levels, urban/rural status, and sex. These findings provide new information on the complex associations between urbanization and PA.

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

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

Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective cohort study.

BACKGROUND: The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development. METHODS: We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries. FINDINGS: During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; pinteraction=0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; pinteraction=0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; pinteraction=0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; pinteraction=0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; pinteraction <0·0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2·95; 2·25-3·87; pinteraction <0·0001), but not of cardiovascular diseases or mortality. INTERPRETATION: The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Care of patients with ST-elevation myocardial infarction: an international analysis of quality indicators in the acute coronary syndrome STEMI Registry of the EURObservational Research Programme and ACVC and EAPCI Associations of the European Society of Cardiology in 11 462 patients.

AIMS: To use quality indicators to study the management of ST-segment elevation myocardial infarction (STEMI) in different regions. METHODS AND RESULTS: Prospective cohort study of STEMI within 24 h of symptom onset (11 462 patients, 196 centres, 26 European Society of Cardiology members, and 3 affiliated countries). The median delay between arrival at a percutaneous cardiovascular intervention (PCI) centre and primary PCI was 40 min (interquartile range 20-74) with 65.8% receiving PCI within guideline recommendation of 60 min. A third of patients (33.2%) required transfer from their initial hospital to one that could perform emergency PCI for whom only 27.2% were treated within the quality indicator recommendation of 120 min. Radial access was used in 56.6% of all primary PCI, but with large geographic variation, from 76.4 to 9.1%. Statins were prescribed at discharge to 98.7% of patients, with little geographic variation. Of patients with a history of heart failure or a documented left ventricular ejection fraction ≤40%, 84.0% were discharged on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and 88.7% were discharged on beta-blockers. CONCLUSION: Care for STEMI shows wide geographic variation in the receipt of timely primary PCI, and is in contrast with the more uniform delivery of guideline-recommended pharmacotherapies at time of hospital discharge.

Influenza vaccine to reduce adverse vascular events in patients with heart failure: a multinational randomised, double-blind, placebo-controlled trial.

BACKGROUND: Influenza increases the risk of cardiovascular events and deaths. We aimed to see whether influenza vaccination reduces death and vascular events in patients with heart failure. METHODS: We did a pragmatic, randomised, double-blind, placebo-controlled trial in 30 centres (mostly hospitals affliated with universities or a research institute) in ten countries in Asia, the Middle East, and Africa (7 in India, 4 in Philippines, 4 in Nigeria, 6 in China, 1 in Zambia, 2 in Mozambique, 3 in Saudi Arabia, 1 in Kenya, 1 in Uganda, and 1 in Zambia). Participants (aged ≥18 years; 52·1% female; not disaggregated by race or ethnicity) with heart failure (New York Heart Association class II, III, or IV) were randomly assigned (1:1) by a centralised web-based system with block randomisation stratified by site, to receive 0·5 ml intramuscularly once a year for up to 3 years of either inactivated standard dose influenza vaccine or placebo (saline). We excluded people who had received influenza vaccine in 2 of the previous 3 years, and those likely to require valve repair or replacement. Those who administered assigned treatments were not masked and had no further role in the study. Investigators, study coordinators, outcome adjudicators, and participants were masked to group assignment. The first of two co-primary outcomes was a first-event composite for cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, and the second was a recurrent-events composite for cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. Outcomes were assessed every 6 months in the intention-to-treat population. Secondary outcomes were all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, hospitalisation for heart failure, and pneumonia, both overall and during periods of peak influenza exposure. This study is registered with ClinicalTrials.gov, NCT02762851. FINDINGS: Between June 2, 2015, and Nov 21, 2021, we enrolled 5129 participants and randomly assigned (1:1) 2560 (50·0%) to influenza vaccine and 2569 (50·0%) to placebo. The first co-primary outcome occurred in 380 (14·8%) of 2560 participants in the vaccine group and 410 (16·0%) of 2569 participants in the placebo group (hazard ratio [HR] 0·93 [95% CI 0·81-1·07]; p=0·30). The second co-primary outcome occurred in 754 (29·5%) of 2560 participants in the vaccine group and 819 (31·9%) of 2569 participants in the placebo group; HR 0·92 [95% CI 0·84-1·02]; p=0·12). The secondary outcomes of all-cause hospitalisations (HR 0·84 [95% CI 0·74-0·97]; p=0·013) and pneumonia (HR 0·58 [0·42-0·80]; p=0·0006) were significantly reduced in the vaccine group compared with in the placebo group but there was no significant difference between groups for all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. In a prespecified analysis, in which events were limited to periods of peak influenza circulation, the first co-primary outcome, and the secondary outcomes of all-cause death, cardiovasular death, and pneumonia were significantly lower in the vaccinated group than in the placebo group, whereas the second co-primary outcome and the secondary outcomes of non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, and hospitalisation for heart failure were not significantly lower. INTERPRETATION: Although the prespecified co-primary outcomes during the entire period of observation were not statistically significant, the reduction during the peak influenza circulating period suggests that there is likely to be a clinical benefit of giving influenza vaccine, given the clear reduction in pneumonia, a moderate reduction in hospitalisations, and a reduction in cardiovascular events and deaths during periods of peak circulation of influenza. Taken in conjunction with previous trials and the observational studies, the collective data suggest benefit. FUNDING: UK Joint Global Health Trials Scheme and Canadian Institutes for Health Research Foundation.

Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. METHODS: In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men). INTERPRETATION: Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women. FUNDING: Funding sources are listed at the end of the Article.

Association of Sitting Time With Mortality and Cardiovascular Events in High-Income, Middle-Income, and Low-Income Countries.

Importance: High amounts of sitting time are associated with increased risks of cardiovascular disease (CVD) and mortality in high-income countries, but it is unknown whether risks also increase in low- and middle-income countries. Objective: To investigate the association of sitting time with mortality and major CVD in countries at different economic levels using data from the Prospective Urban Rural Epidemiology study. Design, Setting, and Participants: This population-based cohort study included participants aged 35 to 70 years recruited from January 1, 2003, and followed up until August 31, 2021, in 21 high-income, middle-income, and low-income countries with a median follow-up of 11.1 years. Exposures: Daily sitting time measured using the International Physical Activity Questionnaire. Main Outcomes and Measures: The composite of all-cause mortality and major CVD (defined as cardiovascular death, myocardial infarction, stroke, or heart failure). Results: Of 105 677 participants, 61 925 (58.6%) were women, and the mean (SD) age was 50.4 (9.6) years. During a median follow-up of 11.1 (IQR, 8.6-12.2) years, 6233 deaths and 5696 major cardiovascular events (2349 myocardial infarctions, 2966 strokes, 671 heart failure, and 1792 cardiovascular deaths) were documented. Compared with the reference group (<4 hours per day of sitting), higher sitting time (≥8 hours per day) was associated with an increased risk of the composite outcome (hazard ratio [HR], 1.19; 95% CI, 1.11-1.28; Pfor trend < .001), all-cause mortality (HR, 1.20; 95% CI, 1.10-1.31; Pfor trend < .001), and major CVD (HR, 1.21; 95% CI, 1.10-1.34; Pfor trend < .001). When stratified by country income levels, the association of sitting time with the composite outcome was stronger in low-income and lower-middle-income countries (≥8 hours per day: HR, 1.29; 95% CI, 1.16-1.44) compared with high-income and upper-middle-income countries (HR, 1.08; 95% CI, 0.98-1.19; P for interaction = .02). Compared with those who reported sitting time less than 4 hours per day and high physical activity level, participants who sat for 8 or more hours per day experienced a 17% to 50% higher associated risk of the composite outcome across physical activity levels; and the risk was attenuated along with increased physical activity levels. Conclusions and Relevance: High amounts of sitting time were associated with increased risk of all-cause mortality and CVD in economically diverse settings, especially in low-income and lower-middle-income countries. Reducing sedentary time along with increasing physical activity might be an important strategy for easing the global burden of premature deaths and CVD.

Medications for blood pressure, blood glucose, lipids, and anti-thrombotic medications: relationship with cardiovascular disease and death in adults from 21 high-, middle-, and low-income countries with an elevated body mass index.

AIMS: Elevated body mass index (BMI) is an important cause of cardiovascular disease (CVD). The population-level impact of pharmacologic strategies to mitigate the risk of CVD conferred by the metabolic consequences of an elevated BMI is not well described. METHODS AND RESULTS: We conducted an analysis of 145 986 participants (mean age 50 years, 58% women) from 21 high-, middle-, and low-income countries in the Prospective Urban and Rural Epidemiology study who had no history of cancer, ischaemic heart disease, heart failure, or stroke. We evaluated whether the hazards of CVD (myocardial infarction, stroke, heart failure, or cardiovascular death) differed among those taking a cardiovascular medication (n = 29 174; including blood pressure-lowering, blood glucose-lowering, cholesterol-lowering, or anti-thrombotic medications) vs. those not taking a cardiovascular medication (n = 116 812) during 10.2 years of follow-up. Cox proportional hazard models with the community as a shared frailty were constructed by adjusting age, sex, education, geographic region, physical activity, tobacco, and alcohol use. We observed 7928 (5.4%) CVD events and 9863 (6.8%) deaths. Cardiovascular medication use was associated with different hazards of CVD (interaction P < 0.0001) and death (interaction P = 0.0020) as compared with no cardiovascular medication use. Among those not taking a cardiovascular medication, as compared with those with BMI 20 to <25 kg/m2, the hazard ratio (HR) [95% confidence interval (95% CI)] for CVD were, respectively, 1.14 (1.06-1.23); 1.45 (1.30-1.61); and 1.53 (1.28-1.82) among those with BMI 25 to <30 kg/m2; 30 to <35 kg/m2; and ≥35 kg/m2. However, among those taking a cardiovascular medication, the HR (95% CI) for CVD were, respectively, 0.79 (0.72-0.87); 0.90 (0.79-1.01); and 1.14 (0.98-1.33). Among those not taking a cardiovascular medication, the respective HR (95% CI) for death were 0.93 (0.87-1.00); 1.03 (0.93-1.15); and 1.44 (1.24-1.67) among those with BMI 25 to <30 kg/m2; 30 to <35 kg/m2; and ≥35 kg/m2. However, among those taking a cardiovascular medication, the respective HR (95% CI) for death were 0.77 (0.69-0.84); 0.88 (0.78-0.99); and 1.12 (0.96-1.30). Blood pressure-lowering medications accounted for the largest population attributable benefit of cardiovascular medications. CONCLUSION: To the extent that CVD risk among those with an elevated BMI is related to hypertension, diabetes, and an elevated thrombotic milieu, targeting these pathways pharmacologically may represent an important complementary means of reducing the CVD burden caused by an elevated BMI.

Variations in the financial impact of the COVID-19 pandemic across 5 continents: A cross-sectional, individual level analysis.

BACKGROUND: COVID-19 has caused profound socio-economic changes worldwide. However, internationally comparative data regarding the financial impact on individuals is sparse. Therefore, we conducted a survey of the financial impact of the pandemic on individuals, using an international cohort that has been well-characterized prior to the pandemic. METHODS: Between August 2020 and September 2021, we surveyed 24,506 community-dwelling participants from the Prospective Urban-Rural Epidemiology (PURE) study across high (HIC), upper middle (UMIC)-and lower middle (LMIC)-income countries. We collected information regarding the impact of the pandemic on their self-reported personal finances and sources of income. FINDINGS: Overall, 32.4% of participants had suffered an adverse financial impact, defined as job loss, inability to meet financial obligations or essential needs, or using savings to meet financial obligations. 8.4% of participants had lost a job (temporarily or permanently); 14.6% of participants were unable to meet financial obligations or essential needs at the time of the survey and 16.3% were using their savings to meet financial obligations. Participants with a post-secondary education were least likely to be adversely impacted (19.6%), compared with 33.4% of those with secondary education and 33.5% of those with pre-secondary education. Similarly, those in the highest wealth tertile were least likely to be financially impacted (26.7%), compared with 32.5% in the middle tertile and 30.4% in the bottom tertile participants. Compared with HICs, financial impact was greater in UMIC [odds ratio of 2.09 (1.88-2.33)] and greatest in LMIC [odds ratio of 16.88 (14.69-19.39)]. HIC participants with the lowest educational attainment suffered less financial impact (15.1% of participants affected) than those with the highest education in UMIC (22.0% of participants affected). Similarly, participants with the lowest education in UMIC experienced less financial impact (28.3%) than those with the highest education in LMIC (45.9%). A similar gradient was seen across country income categories when compared by pre-pandemic wealth status. INTERPRETATION: The financial impact of the pandemic differs more between HIC, UMIC, and LMIC than between socio-economic categories within a country income level. The most disadvantaged socio-economic subgroups in HIC had a lower financial impact from the pandemic than the most advantaged subgroup in UMIC, with a similar disparity seen between UMIC and LMIC. Continued high levels of infection will exacerbate financial inequity between countries and hinder progress towards the sustainable development goals, emphasising the importance of effective measures to control COVID-19 and, especially, ensuring high vaccine coverage in all countries. FUNDING: Funding for this study was provided by the Canadian Institutes of Health Research and the International Development Research Centre.

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

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