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Background: Considerable variability in survival rate after ST-segment elevation myocardial infarction (STEMI) is present and outcomes remain suboptimal, especially in low- and middle-income contraries. This study aimed to investigate predictors of 30- day mortality after STEMI, including reperfusion therapy, in a tertiary hospital in western Iran. Methods: In this registry-based cohort study (2016–2019), we investigated reperfusion therapies – primary percutaneous coronary intervention (PPCI), pharmaco-invasive (thrombolysis followed by angiography/percutaneous coronary intervention), and thrombolysis alone – used in Imam-Ali hospital, the only hospital with a PPCI capability in the Kermanshah Province. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs), using Cox proportional-hazard models, to investigate the potential predictors of 30-day mortality including reperfusion therapy, admission types (direct admission/referral from non-PPCI-capable hospitals), demographic variables, coronary risk factors, vital signs on admission, medical history, and laboratory tests. Results: Data of 2428 STEMI patients (mean age: 60.73; 22.9% female) were available. Reperfusion therapy was performed in 84% of patients (58% PPCI, 10% pharmaco-invasive, 16% thrombolysis alone). Only 17% of the referred patients had received thrombolysis at non-PPCI-capable hospitals. Among patients with thrombolysis, only 38.2% underwent coronary angiography/ percutaneous coronary intervention. The independent predictors of mortality were: no reperfusion therapy (HR: 2.01, 95% CI: 1.36–2.97), referral from non-PPCI-capable hospitals (1.73, 1.22–2.46), age (1.03, 1.01–1.04), glomerular filtration rate (0.97, 0.96–0.97), heart rate>100 bpm (1.94, 1.22–3.08), and systolic blood pressure

AimsTens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.Methods and resultsIn the population-based Golestan Cohort Study—50 045 Iranian participants, 40–75 years, 58% women—we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders—i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4–20) years. During 548 940 person-years—median of 11.3 years, >99% success follow-up—3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49–1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.ConclusionLong-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.

BackgroundMany diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality.MethodsGolestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people—aged 40–75, 28 811 women, 8487 opiate users, 3548 diabetic patients—were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated.ResultsAfter 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00–2.35) in diabetic non-opiate users, 1.63 (1.53–1.74) in non-diabetic opiate users and 2.76 (2.40–3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%–68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%–57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%–42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis.ConclusionsUsing opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary.

Background Coronary artery disease (CAD) is a universal public health challenge, more prominently so in the low- and middle-income countries. In this study, we aimed to determine prevalence and trends of CAD risk factors in patients with documented CAD and to determine their effects on the age of CAD diagnosis. Materials and methods We conducted a registry-based, serial cross-sectional study using the coronary angiography data bank of the Tehran Heart Center. Adult patients who had obstructive (> 50% stenosis) CAD were included in the study. The prevalence and 11-year trends of conventional CAD risk factors were analyzed by sex and age, and their adjusted effects on the age of CAD diagnosis were calculated. Results From January 2005 to December 2015, data for 90,094 patients were included in this analysis. A total of 61,684 (68.5%) were men and 28,410 (31.5%) were women. Men were younger at diagnosis than women, with a mean age of 60.1 in men and 63.2 in women (p Conclusion The major results of this study (lower age of CAD diagnosis in men, lower age of diagnosis associated with most risk factors, and lower prevalence of serum lipids over time) were expected. A prominent finding of this study is confirming opium use was associated with a much younger age of CAD onset, even after adjusting for all other risk factors. In addition to recommendations for control of the traditional risk factors, spreading information about the potential adverse effect of opium use, which has only recently been associated with higher risk of CAD, may be necessary.

Summary Background A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease. Methods The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40–75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle—eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome—occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)—was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov , number NCT01271985 . Findings Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study—3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5–92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55–0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49–0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51–1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33–0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up—ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group. Interpretation Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. Funding Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.

BMI does not reflect the location or amount of body fat. We aimed to investigate the role of general and central obesity measures in the prediction of incident gastrointestinal cancers. In this analysis of the Golestan Cohort Study, we included 47 586 cancer-free individuals followed for 12.3 years (IQR: 10.5-13.2). We investigated the association of obesity measures including BMI, waist circumference and waist-to-hip ratio (WHR) at enrollment and the incidence of esophageal, gastric, colorectal and pancreatic cancers. Cox proportional hazard models were used to estimate the association between covariates and gastrointestinal cancer risk. We observed no significant associations between obesity measures and incidence of the above-mentioned gastrointestinal cancers in men. In women, BMI, waist circumference and WHR were associated with significant reductions in the risk of esophageal squamous cell carcinoma (ESCC): hazard ratio (HR): 0.67 [95% confidence interval (CI): 0.56-0.81], HR: 0.71 (95% CI: 0.60-0.84) and HR: 0.80 (95% CI: 0.68- 0.94), respectively. In addition, WHR was associated with significantly increased risks for colorectal cancer (HR: 1.39, 95% CI: 1.08-1.78) and gastric cancer (HR: 1.24, 95% CI: 1.01-1.51) in women. In this study, statistically significant associations between obesity measures and incident esophageal, gastric and colorectal cancers were seen in women.

OBJECTIVES Coronary artery disease is becoming a major health concern in the young population. Male and female patients may experience different journeys after coronary artery disease events. We aimed to evaluate risk factors and compare outcomes between young male and female patients undergoing coronary artery bypass graft surgery (CABG). METHODS In this registry-based large sample size study, patients undergoing isolated CABG at a young age (premature isolated CABG) between 2007 and 2016 were included and followed up until 2020. Premature was defined as women and men younger than 55 years old. The main end points of the study were 7-year all-cause mortality and 7-year major adverse cardiovascular and cerebrovascular events (MACCEs). RESULTS Of a total of 24 428 patients who underwent CABG, 7217 patients (men-to-women ratio ≈4:1) with premature isolated CABG were included. The median follow-up duration was 78.5 months (75.2–81.6 months). The prevalence rates of diabetes mellitus, hypertension, dyslipidaemia and obesity were significantly higher in women than in men (58.3% vs 28.6%, 64.2% vs 38.5%, 69.7% vs 55.3% and 44.7 vs 23.9, respectively; all Ps < 0.05). The risk factor burden (mean of the risk factor count per year) was also higher among the female population. Diabetes mellitus was the common mortality predictor between men and women. In the subgroup analysis (interaction analysis in the adjusted model), hypertensive females had a higher rate of MACCE and a higher rate of mortality than hypertensive males; however, this difference was not significant in the non-hypertensive population. Opium addiction was a strong predictor of MACCE and all-cause mortality among men. Female patients had a higher rate of 7-year MACCE (hazard ratio, 1.33; 95% confidence interval, 1.16–1.51) and a higher rate of 7-year all-cause mortality (hazard ratio, 1.23; 95% confidence interval, 0.98–1.53). CONCLUSIONS The risk factor profile and predictors of outcomes were different between our female and male patients. Women carried a higher risk of events and mortality after CABG at a young age.

Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Findings In 2019, 273 center dot 9 million (95% uncertainty interval 258 center dot 5 to 290 center dot 9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 center dot 72% (4 center dot 46 to 5 center dot 01). 228 center dot 2 million (213 center dot 6 to 244 center dot 7; 83 center dot 29% [82 center dot 15 to 84 center dot 42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global agestandardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 center dot 21% [-1 center dot 26 to -1 center dot 16]), similar progress was not observed for chewing tobacco (0 center dot 46% [0 center dot 13 to 0 center dot 79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 center dot 94% [-1 center dot 72 to -0 center dot 14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Summary Background Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings In 2019, 273 & middot;9 million (95% uncertainty interval 258 & middot;5 to 290 & middot;9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 & middot;72% (4 & middot;46 to 5 & middot;01). 228 & middot;2 million (213 & middot;6 to 244 & middot;7; 83 & middot;29% [82 & middot;15 to 84 & middot;42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 & middot;21% [-1 & middot;26 to -1 & middot;16]), similar progress was not observed for chewing tobacco (0 & middot;46% [0 & middot;13 to 0 & middot;79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 & middot;94% [-1 & middot;72 to -0 & middot;14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. For complete list of authors see http://dx.doi.org/10.1016/S2468-2667(21)00065-7

BACKGROUND: Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality. METHODS: Golestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people—aged 40–75, 28 811 women, 8487 opiate users, 3548 diabetic patients—were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated. RESULTS: After 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00–2.35) in diabetic non-opiate users, 1.63 (1.53–1.74) in non-diabetic opiate users and 2.76 (2.40–3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%–68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%–57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%–42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis. CONCLUSIONS: Using opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases., Central Illustration, Highlights • The burden of CVD, in number of DALYs and deaths, continues to increase globally. • CVD burden attributable to modifiable risk factors continues to increase globally. • Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.

Background Whether pre-diabetes in the absence of hypertension (HTN) or dyslipidemia (DLP) is a risk factor for occurrence of major adverse cardiovascular events (MACE) is not fully established. We investigated the effect of impaired fasting glucose (IFG) alone and in combination with HTN, DLP or both on subsequent occurrence of MACE as well as individual MACE components. Methods This longitudinal population-based study included 11,374 inhabitants of Northeastern Iran. The participants were free of any cardiovascular disease at baseline and were followed yearly from 2010 to 2017. Cox proportional hazard models were fitted to measure the hazard of IFG alone or in combination with HTN and DLP on occurrence of MACE as the primary endpoint. Results Four hundred thirty-seven MACE were recorded during 6.2 ± 0.1 years follow up. IFG alone compared to normal fasting glucose (NFG) was not associated with an increase in occurrence of MACE (HR, 0.87; 95% CI, 0.19–4.02; p, 0.854). However, combination of IFG and HTN (HR, 2.88; 95% CI, 2.04–4.07; p, 0.000) or HTN + DLP (HR, 2.98; 95% CI, 1.89–4.71; p, 0.000) significantly increased the risk for MACE. Moreover, IFG + DM with or without HTN, DLP, or both was also associated with an increase in the incidence of MACE. Conclusion IFG, per se, does not appear to increase hazard of MACE. However, IFG with HTN or HTN + DLP conferred a significant hazard for MACE in an incremental manner. Moreover, IFG without HTN, adjusted for DLP, can be associated with an increase in the risk for CVD- death.

Background Whether pre-diabetes in the absence of hypertension (HTN) or dyslipidemia (DLP) is a risk factor for occurrence of major adverse cardiovascular events (MACE) is not fully established. We investigated the effect of impaired fasting glucose (IFG) alone and in combination with HTN, DLP or both on subsequent occurrence of MACE as well as individual MACE components. Methods This longitudinal population-based study included 9,831 inhabitants of Northeastern Iran. The participants were free of any cardiovascular disease at baseline and were followed yearly from 2010 to 2017. Cox proportional hazard models were fitted to measure the hazard of IFG alone or in combination with HTN and DLP on occurrence of MACE as the primary endpoint. Results 297 MACE were recorded during 6.2±0.1 years follow up. IFG alone compared to normal fasting glucose (NFG) was not associated with increased in occurrence of MACE (HR, 1.05; 95% CI, 0.59-1.86; p, 0.8). However, combination of IFG and HTN (HR, 2.75; 95% CI, 1.93-3.90; p, 0.001) or HTN + DLP (HR, 2.85; 95% CI, 1.79-4.54; p, 0.001) significantly increased the hazard of MACE. In contrast, IFG with DLP at baseline did not increase the hazard of MACE compared to normoglycemic- normolipemic individuals (p,0.2). The results also indicated IFG with HTN, DLP, or HTN+DLP were associated with significant higher HRs for some individual components of MACE. Conclusion IFG, per se, does not appear to increase hazard of MACE. However, IFG with HTN or HTN + DLP conferred a significant hazard for MACE in an incremental manner.

Background Whether pre-diabetes in the absence of hypertension (HTN) or dyslipidemia (DLP) is a risk factor for occurrence of major adverse cardiovascular events (MACE) is not fully established. We investigated the effect of impaired fasting glucose (IFG) alone and in combination with HTN, DLP or both on subsequent occurrence of MACE as well as individual MACE components. Methods This longitudinal population-based study included 9,831 inhabitants of Northeastern Iran. The participants were free of any cardiovascular disease at baseline and were followed yearly from 2010 to 2017. Cox proportional hazard models were fitted to measure the hazard of IFG alone or in combination with HTN and DLP on occurrence of MACE as the primary endpoint. Results 297 MACE were recorded during 6.2±0.1 years follow up. IFG alone compared to normal fasting glucose (NFG) was not associated with increased in occurrence of MACE (HR, 1.05; 95% CI, 0.59-1.86; p, 0.8). However, combination of IFG and HTN (HR, 2.75; 95% CI, 1.93-3.90; p, 0.001) or HTN + DLP (HR, 2.85; 95% CI, 1.79-4.54; p, 0.001) significantly increased the hazard of MACE. In contrast, IFG with DLP at baseline did not increase the hazard of MACE compared to normoglycemic- normolipemic individuals (p,0.2). The results also indicated IFG with HTN, DLP, or HTN+DLP were associated with significant higher HRs for some individual components of MACE. Conclusion IFG, per se, does not appear to increase hazard of MACE. However, IFG with HTN or HTN + DLP conferred a significant hazard for MACE in an incremental manner.

Background: A fixed-dose combination therapy ("polypill" strategy) has been proposed as an approach to reduce the burden of cardiovascular disease (CVD), especially in lower resource settings. We conducted the PolyIran Study to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide and either enalapril or valsartan, for primary and secondary prevention of CVD. Methods: The study population comprised of rural participants of the Golestan Cohort Study aged 50 years or older. Considering villages as clusters, the study participants were cluster randomized to a package of non-pharmacological preventive interventions either alone (minimal care arm) or together with a once daily polypill (polypill arm). Participants were followed for 60 months. The primary outcome was occurrence of major cardiovascular events (MCVE), which was compared between the two arms using Cox regression models with shared frailty. Findings: Overall, 6838 individuals were enrolled in the study, including 3417 (in 116 clusters) in the minimal care arm and 3421 (in 120 clusters) in the polypill arm. Median (interquartile range) adherence to polypill tablets was 80.5% (48.5%-92.2%). During the follow up, 202 and 301 participants in the polypill and minimal care arms, respectively, had one or more MCVE (adjusted hazard ratio [HR]=0.66; 95% confidence interval [CI]: 0.55-0.80). Polypill was effective for both primary and secondary prevention of CVD. When restricted to participants with high adherence, the risk of MCVE was further reduced (adjusted HR=0.43; 95%CI: 0.33-0.55). Overall, the frequency of adverse events was comparable between the two arms. Interpretation: Using polypill was effective in preventing MCVE. Medication adherence was high, and rates of adverse events were low. The polypill strategy may be considered as an additional effective component in controlling CVDs, especially in low resources settings. Trial Registration: Cllinicaltrials.gov identifier: NCT01271985. Funding Statement: The study was supported by and Alborz Darou, Barakat Foundation, and Tehran University of Medical Sciences. Golestan Cohort study was supported by Cancer Research UK (grant number: C20/A5860), Tehran University of Medical Sciences (grant number: 81/15), and the International Agency for Research on Cancer. Declaration of Interests: The authors disclose no conflicts. Ethics Approval Statement: The protocol of the PolyIran Study was reviewed and approved by Institutional Review Board (IRB) of Digestive Diseases Research Institute and Tehran University of Medical Sciences.

ObjectivesTo examine the causes of premature mortality (DesignProspective.SettingThe Golestan Cohort Study in northeastern Iran.Participants50 045 people aged 40 or more participated in this population-based study from baseline (2004–2008) to August 2017, with over 99% success follow-up rate.Main outcome measuresThe top causes of premature death, HR and their 95% CI and population attributable fraction (PAF) for risk factors.ResultsAfter 444 168 person-years of follow-up (median of 10 years), 6347 deaths were reported, of which 4018 (63.3%) occurred prematurely. Ischaemic heart disease (IHD) accounted for 33.9% of premature death, followed by stroke (14.0%), road injuries (4.7%), stomach cancer (4.6%) and oesophageal cancer (4.6%). Significant risk/protective factors were: wealth score (HR for highest vs lowest quintile: 0.57, PAF for lowest four quintiles vs top quintile: 28%), physical activity (highest vs lowest tertile: 0.67, lowest two tertiles vs top tertile: 22%), hypertension (1.50, 19%), opium use (1.69, 14%), education (middle school or higher vs illiterate: 0.84, illiterate or primary vs middle school or higher: 13%), tobacco use (1.38, 11%), diabetes (2.39, 8%) and vegetable/fruit consumption (highest vs lowest tertile: 0.87, lowest two tertiles vs top tertile: 8%). Collectively, these factors accounted for 76% of PAF in men and 69% in women.ConclusionIHD and stroke are the leading causes of premature mortality in the Golestan Cohort Study. Enhancing socioeconomic status and physical activity, reducing opium and tobacco use, increasing vegetable/fruit consumption and controlling hypertension and diabetes are recommended to reduce premature deaths.

PURPOSE The efficacy of alternative delivery models for a cardiac rehabilitation program (CRP) in low- and middle-income countries is not well documented. This study compared the traditional hospital-based CRP with a hybrid CRP in western Iran. METHODS This observational study was conducted with postcoronary surgery patients in Imam-Ali Hospital in Kermanshah, Iran. Both program models included 2 phases: (1) a common preliminary phase (2-4 weeks) involving exercise training and a plan to control cardiac risk factors; and (2) a complementary phase (8 weeks) consisting of group educational classes and exercise training conducted 3 times a week in the hospital or once a week accompanied by phone calls in the hybrid program. Changes in exercise capacity, blood pressure, lipids, resting heart rate, body mass index, waist circumference, smoking, depression, anxiety, and quality of life as well as differences in attendance at hospital sessions were investigated. RESULTS From a total of 887 patients, 780 (87.9%) completed the programs. There was no association between course completion and type of CRP. Mean age of patients completing the programs was 55.6 ± 8.7 years and 23.8% were female. The hospital-based (n = 585) and hybrid (n = 195) programs resulted in a significant increase in exercise capacity (P < .001 for both). Additional improvements in other outcomes were noted and attendance rates were similar in both CRPs. CONCLUSIONS A well-designed hybrid CRP can be a viable alternative for hospital-based CRP in low- and middle-income countries where there are no appropriate health facilities in remote areas.

PURPOSE: Determinants of outpatient cardiac rehabilitation (CR) use in low- and middle-income countries are not well-known. This study analyzed CR use after coronary bypass surgery by gender and geography and effects of systematic referral, program model, and insurance types on CR participation in the west of Iran. METHODS: This observational study was conducted in Imam-Ali University Hospital in Kermanshah (KSH), the only CR center in the region (2002-2012). There were 2 CR programs: hospital-based and hybrid (combination of home-based and intermittent hospital-based sessions). Patients were divided into groups who lived inside and outside KSH (O-KSH). Referral, participation, and completion rates and program selection were compared by geography, gender, and insurance types. The effects of systematic referral (as of June 2011) were also analyzed. RESULTS: Of 4735 patients, 44.6% were referred for, 18.7% enrolled in, and 16.5% completed CR. In KSH compared with O-KSH, referral rates were 58.0% versus 30.7% and participation rates were 27.0% versus 10.2%, respectively (P < .001, in both cases). Participation rate in women was lower than that in men (15.6% vs 20.0%, respectively; P = .001). Systematic referral increased participation, especially in women and O-KSH (P < .001, in both cases). The O-KSH patients and those with unfavorable insurance mostly selected the hybrid program (P < .001, in both cases). Among participants, completion rates based on gender and geography were similar. CONCLUSIONS: Referral and participation rates of coronary bypass surgery patients in CR were low in the west of Iran, especially in women and O-KSH. Systematic referral along with the hybrid program increased them significantly.