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Background: We aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting., Methods: The PolyPars Study is a two-arm pragmatic cluster-randomised trial nested within the PARS cohort study, including all residents aged over 50 years in the entire district in southern Iran. The 91 villages underwent random allocation into two arms: the control arm, encompassing 45 clusters, was subjected to non-pharmacological intervention (educational training on healthy lifestyle), whereas the intervention arm, comprising 46 clusters, received the non-pharmacological interventions in conjunction with a once-daily polypill tablet. This tablet comprised two antihypertensive agents, a statin and aspirin. The primary outcome was the first occurrence of major cardiovascular events defined as a composite of hospitalisation for acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, non-fatal and fatal stroke, sudden death and heart failure. The Cox regression model, with shared frailty, was used to account for clustering effect., Results: During December 2015-December 2016, a total of 4415 participants aged 50-75 years were recruited (2200 participants in the intervention arm and 2215 participants in the control arm). The overall median of follow-up duration was 4.6 years (interquartile interval 4.4-4.9). The achieved adherence rate to polypill in intervention arm was 86%. In the control group, 176 (8.0%) of 2215 participants developed primary outcome, compared with 88 (4.0%) of 2200 participants in the polypill group. We found substantial reduction in risk of primary outcome both in relative and absolute scales (HR 0.50, 95% CI 0.38 to 0.65; absolute risk reduction 4.0%, 95% CI 2.5% to 5.3%). No difference in serious adverse events was observed between the two groups., Conclusions: The fixed-dose combination therapy using polypill can safely halve the risk of major cardiovascular diseases at the population level., Trial Registration Number: NCT03459560., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fixed-dose combination treatments reduce cardiovascular disease in primary prevention. We aim to explore whether those benefits differ in the presence of CKD., Methods: We conducted an individual participant data meta-analysis in 18,162 participants on the efficacy and safety of treatment for the primary prevention of cardiovascular disease. Combination therapies consisted of at least two BP-lowering drugs and a statin, with or without aspirin versus placebo or minimal care. Here, we examine the differential effect of fixed-dose combination treatment on the risk of developing cardiovascular disease in participants with a low eGFR (<60 ml/min per 1.73 m 2 ; Chronic Kidney Disease Epidemiology Collaboration formula) compared with a normal eGFR (≥60 ml/min per 1.73 m 2 ). The primary composite outcome was time to first occurrence of a combination of cardiovascular death, myocardial infarction, stroke, or arterial revascularization., Results: At baseline, the mean level of eGFR was 76 ml/min per 1.73 m 2 (SD 17). In total, 3315 (18%) participants had low eGFR at baseline. During a median follow-up of 5 years, among participants with normal eGFR, the primary outcome occurred in 232 (3%) participants in the treatment group compared with 339 (5%) in the control group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P < 0.001). In participants with low eGFR, the primary outcome occurred in 64 (4%) participants in the treatment group compared with 130 (8%) in the control group (hazard ratio, 0.49; 95% confidence interval, 0.36 to 0.66; P < 0.001; P for interaction 0.047). The relative risk reduction among participants with low eGFR was larger for combination strategies, including aspirin compared with treatments without aspirin. Apart from dizziness, other side effects did not differ between treatment and control groups, regardless of the stage of their kidney function., Conclusions: A fixed-dose combination treatment strategy is effective and safe at preventing cardiovascular disease, irrespective of eGFR, but relative and absolute risk reductions are larger in individuals with low eGFR., Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023&#95;11&#95;08&#95;CJN0000000000000251.mp3., (Copyright © 2023 by the American Society of Nephrology.)

Background: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking., Methods: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality., Results: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6)., Conclusions: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Environmental exposures account for a growing proportion of global mortality. Large cohort studies are needed to characterize the independent impact of environmental exposures on mortality in low-income settings., Methods: We collected data on individual and environmental risk factors for a multiethnic cohort of 50,045 individuals in a low-income region in Iran. Environmental risk factors included: ambient fine particular matter air pollution; household fuel use and ventilation; proximity to traffic; distance to percutaneous coronary intervention (PCI) center; socioeconomic environment; population density; local land use; and nighttime light exposure. We developed a spatial survival model to estimate the independent associations between these environmental exposures and all-cause and cardiovascular mortality., Findings: Several environmental factors demonstrated associations with mortality after adjusting for individual risk factors. Ambient fine particulate matter air pollution predicted all-cause mortality (per μg/m3, HR 1.20, 95% CI 1.07, 1.36) and cardiovascular mortality (HR 1.17, 95% CI 0.98, 1.39). Biomass fuel use without chimney predicted all-cause mortality (reference = gas, HR 1.23, 95% CI 0.99, 1.53) and cardiovascular mortality (HR 1.36, 95% CI 0.99, 1.87). Kerosene fuel use without chimney predicted all-cause mortality (reference = gas, HR 1.09, 95% CI 0.97, 1.23) and cardiovascular mortality (HR 1.19, 95% CI 1.01, 1.41). Distance to PCI center predicted all-cause mortality (per 10km, HR 1.01, 95% CI 1.004, 1.022) and cardiovascular mortality (HR 1.02, 95% CI 1.004, 1.031). Additionally, proximity to traffic predicted all-cause mortality (HR 1.13, 95% CI 1.01, 1.27). In a separate validation cohort, the multivariable model effectively predicted both all-cause mortality (AUC 0.76) and cardiovascular mortality (AUC 0.81). Population attributable fractions demonstrated a high mortality burden attributable to environmental exposures., Interpretation: Several environmental factors predicted cardiovascular and all-cause mortality, independent of each other and of individual risk factors. Mortality attributable to environmental factors represents a critical opportunity for targeted policies and programs., Competing Interests: The authors have declared that no competing interests exist.

Objective: Prediction models for cardiovascular disease (CVD) mortality come from high-income countries, comprising laboratory measurements, not suitable for resource-limited countries. This study aims to develop and validate a non-laboratory model to predict CVD mortality in a middle-income setting., Study Design and Setting: We used data of population aged 40-80 years from three cohort studies: Tehran Lipid and Glucose Study (n = 5160), Isfahan Cohort Study (n = 4350), and Golestan Cohort Study (n = 45,500). Using Cox proportional hazard models, we developed prediction models for men and women, separately. Cross-validation and bootstrapping procedures were applied. The models' discrimination and calibration were assessed by concordance statistic (C-index) and calibration plot, respectively. We calculated the models' sensitivity, specificity and net benefit fraction in a threshold probability of 5%., Results: The 10-year CVD mortality risks were 5.1% (95%CI: 4.8-5.5) in men and 3.1% (95%CI: 2.9%-3.3%) in women. The optimism-corrected performance of the model was c = 0.774 in men and c = 0.798 in women. The models showed good calibration in both sexes, with a predicted-to-observed ratio of 1.07 in men and 1.09 in women. The sensitivity was 0.76 in men and 0.66 in women. The net benefit fraction was higher in men compared to women (0.46 vs. 0.35)., Conclusion: A low-cost model can discriminate well between low- and high-risk individuals, and can be used for screening in low-middle income countries., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Determining the risk of Cardiovascular Disease (CVD) is a necessity for timely preventive interventions in high-risk groups. However, laboratory testing may be impractical in countries with limited resources. This study aimed at comparison and assessment of the agreement between laboratory-based and non-laboratory-based WHO risk charts models., Methods: This study was performed using the baseline data of 8138 participants in the pars cohort study who had no history of CVD and stroke. The updated 2019 WHO model was used to determine the 10-year fatal and non-fatal CVD risks. In general, there are two types of new WHO risk prediction models for CVD. The scores were determined based on age, sex, smoking status, diabetes, Systolic Blood Pressure (SBP), and total cholesterol for the laboratory-based model and age, sex, smoking status, SBP, and Body Mass Index (BMI) for the non-laboratory-based model. The agreement of these two models was determined via kappa statistics for the classified risk (low: < 10%, moderate: 10-< 20%, high: ≥ 20%). Correlation coefficients (r) and scatter plots was used for correlation between scores., Results: The results revealed very strong correlation coefficients for all sex and age groups (r = 0.84 for males < 60 years old, 0.93 for males ≥ 60 years old, 0.85 for females < 60 years old, and 0.88 for females ≥ 60 years old). In the laboratory-based model, low, moderate, and high risks were 76.10%, 18.17%, and 5.73%, respectively. These measures were respectively obtained as 77.00%, 18.08%, and 4.92% in the non-laboratory-based model. Based on risk classification, the agreement was substantial for males < 60 years old and for both males and females aged ≥ 60 years (kappa values: 0.79 for males < 60 years old, 0.65 for males ≥ 60 years old, and 0.66 for females ≥ 60 years old) and moderate for females < 60 years old (kappa = 0.46)., Conclusions: The non-laboratory-based risk prediction model, which is simple, inexpensive, and non-invasive, classifies individuals almost identically to the laboratory-based model. Therefore, in countries with limited resources, these two models can be used interchangeably., (© 2022. The Author(s).)

Background: Considering the importance of cardiovascular disease (CVD) risk prediction for healthcare systems and the limited information available in the Middle East, we evaluated the SCORE and Globorisk models to predict CVD death in a country of this region., Methods: We included 24 427 participants (11 187 men) aged 40-80 years from four population-based cohorts in Iran. Updating approaches were used to recalibrate the baseline survival and the overall effect of the predictors of the models. We assessed the models' discrimination using C-index and then compared the observed with the predicted risk of death using calibration plots. The sensitivity and specificity of the models were estimated at the risk thresholds of 3%, 5%, 7%, and 10%. An agreement between models was assessed using the intra-class correlation coefficient (ICC). We applied decision analysis to provide perception into the consequences of using the models in general practice; for this reason, the clinical usefulness of the models was assessed using the net benefit (NB) and decision curve analysis. The NB is a sensitivity penalized by a weighted false positive (FP) rate in population level., Results: After 154 522 person-years of follow-up, 437 cardiovascular deaths (280 men) occurred. The 10-year observed risks were 4.2% (95% CI: 3.7%-4.8%) in men and 2.1% (1.8-2%.5%) in women. The c-index for SCORE function was 0.784 (0.756-0.812) in men and 0.780 (0.744-0.815) in women. Corresponding values for Globorisk were 0.793 (0.766- 0.820) and 0.793 (0.757-0.829). The deviation of the calibration slopes from one reflected a need for recalibration; after which, the predicted-to-observed ratio for both models was 1.02 in men and 0.95 in women. Models showed good agreement (ICC 0.93 in men, and 0.89 in women). Decision curve showed that using both models results in the same clinical usefulness at the risk threshold of 5%, in both men and women; however, at the risk threshold of 10%, Globorisk had better clinical usefulness in women (Difference: 8%, 95% CI: 4%-13%)., Conclusion: Original Globorisk and SCORE models overestimate the CVD risk in Iranian populations resulting in a high number of people who need intervention. Recalibration could adopt these models to precisely predict CVD mortality. Globorisk showed better performance clinically, only among high-risk women., (© 2022 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Cardiovascular diseases (CVDs) are the leading cause of death in Iran. A fixed-dose combination therapy (polypill) was proposed as a cost-effective strategy for CVD prevention, especially in lower-resource settings. We conducted the PolyPars trial to assess the effectiveness and safety of polypill for prevention of CVD., Methods: The PolyPars trial is a pragmatic cluster randomized controlled trial nested within the Pars Cohort Study. Participants were randomized to an intervention arm and a control arm. Participants in the control arm received minimal non-pharmacological care, while those in the intervention arm received polypill in addition to minimal care. The polypill comprises hydrochlorothiazide 12.5 mg, aspirin 81 mg, atorvastatin 20 mg, and either enalapril 5 mg or valsartan 40 mg. The primary outcome of the study is defined as the first occurrence of acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, sudden cardiac death, new-onset heart failure, coronary artery revascularization procedures, transient ischemic attack, cerebrovascular accidents (fatal or non-fatal), and hospitalization due to any of the mentioned conditions. The secondary outcomes of the study include adverse events, compliance, non-cardiovascular mortality, changes in blood pressure, fasting blood sugar, and lipids after five years of follow-up., Results: From December 2014 to December 2015, 4415 participants (91 clusters) were recruited. Of those, 2200 were in the polypill arm and 2215 in the minimal care arm. The study is ongoing. This trial was registered with ClinicalTrials.gov number NCT03459560., Conclusion: Polypill may be effective for primary prevention of CVDs in developing countries., (© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: It is unclear which anthropometric obesity indicator best predicts adverse health outcomes. This study aimed to investigate the association of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), and hip-adjusted WC with all-cause and cardiovascular mortality., Methods: 50045 people aged 40-75 (58% women, median BMI: 26.3 kg /m2 ) participated in the population-based Golestan Cohort Study. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for the association of obesity indicators with mortality. We also examined the association of these indicators with intermediate outcomes, including hypertension, blood glucose, dyslipidemia, carotid atherosclerosis, nonalcoholic fatty liver, and visceral abdominal fat., Results: After a median follow-up of 10.9 years (success rate: 99.1%), 6651 deaths (2778 cardiovascular) occurred. Comparing 5th to the 1st quintile, HRs (95% CIs) for all-cause and cardiovascular mortality were 1.12 (1.02-1.22) and 1.59 (1.39-1.83) for BMI, 1.16 (1.07-1.27) and 1.66 (1.44-1.90) for WC, 1.28 (1.17-1.40) and 1.88 (1.63-2.18) for WHtR, 1.44 (1.32-1.58) and 2.04 (1.76-2.36) for WHR, and 1.84 (1.62-2.09) and 2.72 (2.23-3.32) for hip-adjusted WC, respectively. Hip-adjusted WC had the strongest associations with the intermediate outcomes., Conclusion: Indicators of visceral adiposity (e.g., hip-adjusted WC) were much stronger predictors of overall and cardiovascular mortality than were indicators of general adiposity (e.g., BMI). The full-strength effect of visceral adiposity becomes apparent only when both WC, as a risk factor, and hip circumference, as a protective factor, are individually and simultaneously taken into consideration., (© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Little is known about secondary prevention of cardiovascular diseases, using cardio-protective drugs, in the community-level, especially in low- and middle-income countries. We aimed to assess main drug use and its predictors in Northeast of Iran., Methods: This is a cross-sectional analysis on the Golestan Cohort Study data (2004-2008) with 50 045 participants. We assessed drug use in those with a history of ischemic heart disease (IHD) or stroke, recorded by face-to-face interviews. We explored drug use predictors (i.e., age, gender, wealth, education, residency, smoking, body mass index, physical activity, hypertension, and diabetes) through multivariable logistic regression., Results: A total of 3371 (6.7%) participants (56.7 ± 9.0 years, 58.1% female) reported a history of IHD, stroke or both. Median duration since diagnosis was 3.14 years (IQR: 1.25-6.30). Rates of using anti-platelets, statins, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and beta-blockers were 28.8% (95% CI: 27.3-30.3), 5.4 (4.7-6.2), 15.7 (14.5-17.0), and 40.6 (38.9-42.3), respectively. About 43% (41 - 45) of patients did not use any protective drugs. Use of ≥ three drugs was only 7.3% (6.6-8.2). Indicators of ≥1 drug use were: older age (OR for ≥60 vs. <50: 1.37), high wealth score (fifth vs first quintile: 1.60), literacy (1.56), city dwelling (1.32), body mass index (<18.5 and ≥30 vs. 25-29: 0.55 and 1.25, respectively), physical activity (third vs. first tertile: 0.64), hypertension (3.47), and diabetes (1.29); (all P < 0.05)., Conclusion: Drug use after IHD or stroke is low in Northeast of Iran. Comprehensive efforts to promote secondary prevention are urgently needed., (© 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

We investigated the association between dairy product consumption and all-cause, cardiovascular disease (CVD), and cancer mortality in the Golestan Cohort Study, a prospective cohort study launched in January 2004 in Golestan Province, northeastern Iran. A total of 42,403 men and women participated in the study and completed a diet questionnaire at enrollment. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. We documented 3,291 deaths (1,467 from CVD and 859 from cancer) during 11 years of follow-up (2004-2015). The highest quintile of total dairy product consumption (versus the lowest) was associated with 19% lower all-cause mortality risk (hazard ratio (HR) = 0.81, 95% confidence interval (CI): 0.72, 0.91; Ptrend = 0.006) and 28% lower CVD mortality risk (HR = 0.72, 95% CI: 0.60, 0.86; Ptrend = 0.005). High consumption of low-fat dairy food was associated with lower risk of all-cause (HR = 0.83, 95% CI: 0.73, 0.94; Ptrend = 0.002) and CVD (HR = 0.74, 95% CI: 0.61, 0.89; Ptrend = 0.001) mortality. We noted 11% lower all-cause mortality and 16% lower CVD mortality risk with high yogurt intake. Cheese intake was associated with 16% lower all-cause mortality and 26% lower CVD mortality risk. Higher intake of high-fat dairy food and milk was not associated with all-cause or CVD mortality. Neither intake of individual dairy products nor intake of total dairy products was significantly associated with overall cancer mortality. High consumption of dairy products, especially yogurt and cheese, may reduce the risk of overall and CVD mortality., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Dietary protein comes from foods with greatly different compositions that may not relate equally with mortality risk. Few cohort studies from non-Western countries have examined the association between various dietary protein sources and cause-specific mortality. Therefore, the associations between dietary protein sources and all-cause, cardiovascular disease, and cancer mortality were evaluated in the Golestan Cohort Study in Iran., Methods: Among 42,403 men and women who completed a dietary questionnaire at baseline, 3,291 deaths were documented during 11 years of follow up (2004-2015). Cox proportional hazards models estimated age-adjusted and multivariate-adjusted hazard ratios (HRs) and 95% CIs for all-cause and disease-specific mortality in relation to dietary protein sources. Data were analyzed from 2015 to 2016., Results: Comparing the highest versus the lowest quartile, egg consumption was associated with lower all-cause mortality risk (HR=0.88, 95% CI=0.79, 0.97, p trend =0.03). In multivariate analysis, the highest versus the lowest quartile of fish consumption was associated with reduced risk of total cancer (HR=0.79, 95% CI=0.64, 0.98, p trend =0.03) and gastrointestinal cancer (HR=0.75, 95% CI=0.56, 1.00, p trend =0.02) mortality. The highest versus the lowest quintile of legume consumption was associated with reduced total cancer (HR=0.72, 95% CI=0.58, 0.89, p trend =0.004), gastrointestinal cancer (HR=0.76, 95% CI=0.58, 1.01, p trend =0.05), and other cancer (HR=0.66, 95% CI=0.47, 0.93, p trend =0.04) mortality. Significant associations between total red meat and poultry intake and all-cause, cardiovascular disease, or cancer mortality rate were not observed among all participants., Conclusions: These findings support an association of higher fish and legume consumption with lower cancer mortality, and higher egg consumption with lower all-cause mortality., (Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.)

Background: The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013., Methods: GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically., Findings: The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60-80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred., Interpretation: Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts., Funding: Bill & Melinda Gates Foundation., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Background: Cardiovascular diseases (CVD) are becoming major causes of death in developing countries. Risk scoring systems for CVD are needed to prioritize allocation of limited resources. Most of these risk score algorithms have been based on a long array of risk factors including blood markers of lipids. However, risk scoring systems that solely use office-based data, not including laboratory markers, may be advantageous. In the current analysis, we validated the office-based Framingham risk scoring system in Iran., Methods: The study used data from the Golestan Cohort in North-East of Iran. The following risk factors were used in the development of the risk scoring method: sex, age, body mass index, systolic blood pressure, hypertension treatment, current smoking, and diabetes. Cardiovascular risk functions for prediction of 10-year risk of fatal CVDs were developed., Results: A total of 46,674 participants free of CVD at baseline were included. Predictive value of estimated risks was examined. The resulting Area Under the ROC Curve (AUC) was 0.774 (95% CI: 0.762-0.787) in all participants, 0.772 (95% CI: 0.753-0.791) in women, and 0.763 (95% CI: 0.747-0.779) in men. AUC was higher in urban areas (0.790, 95% CI: 0.766-0.815). The predicted and observed risks of fatal CVD were similar in women. However, in men, predicted probabilities were higher than observed., Conclusion: The AUC in the current study is comparable to results of previous studies while lipid profile was replaced by body mass index to develop an office-based scoring system. This scoring algorithm is capable of discriminating individuals at high risk versus low risk of fatal CVD.

Background: High blood pressure is the second most important risk factor of cardiovascular diseases (CVDs) in Iran. It is imperative to estimate the burden of CVDs that can be averted if high blood pressure is controlled at the population level. The aim of the current study was to estimate the avertable CVD mortality in the setting of Golestan Cohort Study (GCS)., Methods: Over 50,000 participants were recruited and followed for a median of 7 years. The exposures of interest in this study were non-optimal systolic blood pressure (SBP) and hypertension measured at baseline. Deaths by cause have been precisely recorded. The Population Attributable Fraction (PAF) of deaths and Years of Life Lost (YLLs) due to CVDs attributable to exposures of interest were calculated., Results: Overall, 223 deaths due to ischemic heart disease (IHD), 207 deaths due to cerebrovascular accidents (CVA), and 460 deaths due to all CVDs could be averted if the SBP of all subjects in the study were optimal. Similarly, 5,560 YLLs due to IHD, 4,771 YLLs due to CVA, and 11,135 YLLs due to CVDs could be prevented if SBP were optimal. In all age groups, the avertable deaths and YLLs were higher due to IHD compared with CVA. Deaths and YLLs attributable to non-optimal SBP in women were less than men., Conclusions: A very large proportion of CVD deaths can be averted if blood pressure is controlled in Iran. Effective interventions in primary and secondary health care setting are mandatory to be implemented as early as possible.

Keywords: Type 2 diabetes; Prediabetes; Ethnicity; Prevalence EN Type 2 diabetes Prediabetes Ethnicity Prevalence 221 224 4 01/24/22 20220101 NES 220101 Dear Editor, We would like to thank the authors of the letter to the editor for their interest in our paper entitled "Nationwide Prevalence of Diabetes and Prediabetes and Associated Risk Factors Among Iranian Adults: Analysis of Data from PERSIAN Cohort Study". In the study by Lord et al. [[7]], although ethnicity was associated with prediabetes among residents of high-prediabetes clusters, they found no association between ethnicity and diabetes status. We did not adjust the model for cardiovascular diseases (CVDs) because CVDs are generally considered to be a consequence of prediabetes and diabetes that occur later in the causal graph and hence are not determinants for prediabetes and diabetes [[13]]. To the best of our knowledge, this is the first study that included major ethnic groups in Iran and provides a direct comparison of diabetes/prediabetes prevalence among different ethnicities. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Background: Summary measures of health are essential in making estimates of health status that are comparable across time and place. They can be used for assessing the performance of health systems, informing effective policy making, and monitoring the progress of nations toward achievement of sustainable development goals. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) as main summary measures of health. We assessed the trends of health status in Iran and 15 neighboring countries using these summary measures. Methods: \Ne used the results of GBD 2015 to present the levels and trends of DALYs, life expectancy (LE), and HALE in Iran and its 15 neighboring countries from 1990 to 2015. For each country, we assessed the ratio of observed levels of DALYs and HALE to those expected based on socio-demographic index (SDI), an indicator composed of measures of total fertility rate, income per capita, and average years of schooling. Results: All-age numbers of DALYs reached over 19 million years in Iran in 2015. The all-age number of DALYs has remained stable during the past two decades in Iran, despite the decreasing trends in all-age and age-standardized rates. The all-cause DALY rates decreased from 47,200 in 1990 to 28,400 per 100,000 in 2015. The share of non-communicable diseases in DALYs increased in Iran (from 42% to 74%) and all of its neighbors between 1990 and 2015; the pattern of change is similar in almost all 16 countries. The DALY rates for NCDs and injuries in Iran were higher than global rates and the average rate in High Middle SDI countries, while those for communicable, maternal, neonatal, and nutritional disorders were much lower in Iran. Among men, cardiovascular diseases ranked first in all countries of the region except for Bahrain. Among women, they ranked first in 13 countries. Life expectancy and HALE show a consistent increase in all countries. Still, there are dissimilarities indicating a generally low LE and HALE in Afghanistan and Pakistan and high expectancy in Qatar, Kuwait, and Saudi Arabia. Iran ranked 11th in terms of LE at birth and 12th in terms of HALE at birth in 1990 which improved to 9th for both metrics in 2015. Turkey and Iran had the highest increase in LE and HALE from 1990 to 2015 while the lowest increase was observed in Armenia, Pakistan, Kuwait, Kazakhstan, Russia, and Iraq. Conclusions: The levels and trends in causes of DALYs, life expectancy, and HALE generally show similarities between the 16 countries, although differences exist. The differences observed between countries can be attributed to a myriad of determinants, including social, cultural, ethnic, religious, political, economic, and environmental factors as well as the performance of the health system. Investigating the differences between countries can inform more effective health policy and resource allocation. Concerted efforts at national and regional levels are required to tackle the emerging burden of non-communicable diseases and injuries in Iran and its neighbors. [ABSTRACT FROM AUTHOR]

Background: The burden of chronic kidney disease (CKD) is increasing globally in particular in fast emerging economies such as Iran. Population-based studies on prevalence of CKD in Iran are scarce. The objective of the current study was to explore the prevalence and determinants of CKD in the setting of Golestan Cohort Study (GCS), the largest prospective cohort in the Middle East. Methods: In this observational study, 11,409 participants enrolled in the second phase of GCS were included. Sex, age, literacy, residence, anthropometric measurements, smoking, opium use, self-reported history of cardiovascular diseases (heart disease and/or stroke), hypertension, diabetes, and lipid profile were the predictors of interest. The outcomes of interest were eGFR and CKD defined as eGFR< 60 ml/min/1.73m2. Results: Mean (SD) of GFR was 70.0 ± 14.7 ml/min/1.73m2 among all participants, 68.2 ± 14.2 among women, and 72.0 ± 15.0 among men. Prevalence of CKD was 23.7% (26.6% in women, 20.6% in men). The prevalence of CKD stages 3a, 3b, 4, and 5 were 20.0%, 3.3%, 0.4% and 0.1%, respectively. Female sex, older age, urban residence, history of CVD, hypertension or diabetes, larger body mass and surrogates of body fat and opium use were all associated with CKD. Opium had a significant positive association with CKD in adjusted model. All anthropometric measurements had positive linear association with CKD. Being literate had inverse association. Sex had significant interaction with anthropometric indices, with higher odds ratios among men compared with women. A significantly high association was observed between the rate of change in waist circumference and systolic blood pressure with risk of CKD. Conclusion: One in four people in this cohort had low eGFR. Obesity and overweight, diabetes, hypertension, and dyslipidemia are major risk factors for CKD. Halting the increase in waist circumference and blood pressure may be as important as reducing the current levels. [ABSTRACT FROM AUTHOR]

Background: Short term randomized trials have shown the effectiveness of a fixed dose combination therapy (known as Polypill) on reducing blood pressure and serum cholesterol but the impact of Polypill on cardiovascular disease risk or mortality has not yet been directly investigated. Previous studies combined the effects of each component assuming a multiplicative joint risk assumption that may have led to overestimating the combined effects. We conducted an updated meta-analysis of randomized trials of anti-hypertensives, statins and aspirin. We used the estimated effect sizes applying a more conservative assumption to estimate the number of ischémie heart disease (IHD) and stroke deaths that could have been averted by Polypill in Iranians aged 55 years or older in 2006. Methods: We searched Medline and reviewed previous meta-analyses to select randomized trials on Angiotensin Converting Enzyme- inhibitors, thiazides, aspirin, and statins. We used a random-effects model to pool relative risks for each component and estimated the joint relative risks using multiplicative and additive assumptions for 4 combinations of Polypill components. We used age- and cause-specific mortality, separately by gender, and estimated the number of preventable deaths from IHD and stroke. Results: Under the additive joint RR assumption, the standard Polypill formulation was estimated to prevent 28500 (95% CI: 21700,34100) IHD deaths and 12700 (95% CI: 8800,15900) stroke deaths. Removing aspirin from the combination decreased preventable IHD deaths by 15% under the additive assumption (5600 deaths) and by 21% under the multiplicative assumption (6800 deaths) and reduced preventable stroke deaths under both additive and multiplicative assumptions by 3% (300 deaths). There was no significant difference between Polypill combinations with anti-hypertensive agents in full-dose or half-dose. Conclusion: Polypill can prevent a large number of IHD and stroke deaths in Iran. The cost-effectiveness, feasibility, and acceptability of this prevention strategy remain to be investigated. [ABSTRACT FROM AUTHOR]

Background: High blood pressure is an important risk factor for all-cause mortality and cardiovascular mortality and morbidity among Iranians. We aimed to estimate its prevalence, correlates, and its rate of awareness, treatment, and control in South of Iran. Methods: The Pars Cohort Study (PCS) was launched in a district of Fars province. All residents between 40 and 75 years old in the district were recruited from 2012 to 2014. Hypertension was defined as either systolic/diastolic blood pressure ≥ 140/90 mm Hg or taking medications. Logistic regression was used to identify the correlates of hypertension and awareness and its treatment and control. A total of 9264 participants were recruited. Of the total participants, 46.2% were men. The mean age was 52.6 years (SD: 9.7). Results: Prevalence of hypertension was 26.9%. Of the total 2489 hypertensives, 49.6% were aware and 55.7% were under treatment. Blood pressure was controlled in 69.2% of treated hypertensives. In the adjusted model, female sex and history of cardiovascular disease (CVD) were positively associated with having hypertension, higher awareness, and better treatment and control. Older age, being overweight or obese, and having a history of diabetes were also positively associated with having hypertension and higher awareness and treatment; however, being overweight or obese was associated with poorer hypertension control. Older age and having a history of diabetes did not show a statistically significant association with control. Conclusion: Being underweight and higher physical activity were inversely associated with having hypertension but were not associated with awareness, treatment, or control. Prevalence of hypertension is high but the rates of awareness, treatment, and control are not adequate. [ABSTRACT FROM AUTHOR]

Background: Opium is one of the most common substances used worldwide with variable epidemiologic features in different regions. This study was performed in southern Iran, to find the epidemiology of opium use and its association with different factors and diseases. Methods: This cross-sectional study was performed on baseline data extracted from Pars Cohort Study performed in Valashahr, a rural area in southern Iran. For any subject, information was collected about demographic factors, some common diseases including heart disease, stroke and hypertension and the state of using opium, other substances and cigarettes. Results: There were 4276 males and 4988 females, with a mean age of 52.6 ± 9.7 years of whom 8.4% reported opium use (17.3% of males and 0.7% of females). In men, the history of stroke and heart disease were significantly more common in opium users (12.6% vs. 8.8%, P = 0.001 and 2.8% vs. 1.5%, P = 0.01, respectively) while the history of hypertension was significantly more common in non-opium users (7.8% vs. 10.3%, P = 0.04). Younger age, male gender, being non-married and positive history of joint pain, cigarette smoking and alcohol consumption were the factors associated with opium use. Conclusion: Opium use is common in non-married men who have a positive history of cigarette smoking and alcohol consumption in the rural population of southern Iran. It is associated with increased risk of heart disease and stroke and decreased risk of hypertension in males. Global interventional and preventive measures are required to control this complicated social problem. [ABSTRACT FROM AUTHOR]