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Controversy exists regarding the association of dietary advanced glycation end products (dAGEs) with the risk of disease outcomes and mortality. We aimed to examine, prospectively, the association between dAGEs intake and the risk of overall and cause-specific mortality in the Golestan Cohort Study. The cohort was conducted between 2004 and 2008 in Golestan Province (Iran) recruiting 50,045 participants aged 40-75 years. Assessment of dietary intake over the last year was performed at baseline using a 116-item food frequency questionnaire. The dAGEs values for each individual were calculated based on published databases of AGE values of various food items. The main outcome was overall mortality at the time of follow-up (13.5 years). Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cause-specific mortality were estimated according to the dAGEs quintiles. During 656, 532 person-years of follow-up, 5406 deaths in men and 4722 deaths in women were reported. Participants at the highest quintile of dAGE had a lower risk of overall mortality (HR: 0.89, 95% CI: 0.84, 0.95), CVD mortality (HR: 0.89, 95% CI: 0.84, 0.95), and death from other causes (HR: 0.89, 95% CI: 0.84, 0.95) compared to those in the first quintile after adjusting for confounders. We found no association of dAGEs with risk of mortality from cancer (all), respiratory and infectious diseases, and injuries. Our findings do not confirm a positive association between dAGEs and the risk of mortality in Iranian adults. There is still no agreement among studies investigating dAGEs and their health-related aspects. So, further high-quality studies are required to clarify this association.

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.

Aims: Individuals with non-alcoholic steatohepatitis or elevated liver enzymes have increased cardiovascular mortality but are often excluded from prevention trials. We investigated the effectiveness of fixed-dose combination therapy for the prevention of major cardiovascular events (MCVE) among individuals with and without presumed non-alcoholic steatohepatitis (pNASH)., Methods and Results: Two thousand four hundred participants over 50 were randomized into the intervention and control groups. Consent was obtained post-randomization. Consenting participants in the intervention group were given a pill containing aspirin, atorvastatin, hydrochlorothiazide, and valsartan (polypill). Participants were followed for 5 years. Presumed non-alcoholic steatohepatitis was diagnosed by ultrasonography and elevated liver enzymes. The primary outcome was MCVE. ClinicalTrials.gov: NCT01245608. Among the originally randomized population, 138 of 1249 in the intervention group (11.0%) and 137 of 1017 controls (13.5%) had MCVE during the 5-year follow-up [unadjusted risk ratio (RR) 0.83, 95% confidence interval (CI) 0.66-1.03]. Of the 1508 participants who consented to additional measurements and treatment, 63 of 787 (8.0%) intervention group participants and 86 of 721 (11.9%) controls had MCVE (adjusted RR 0.61, 95% CI 0.44-0.83). Although the adjusted relative risk of MCVE in participants with pNASH (0.35, 95% CI 0.17-0.74) was under half that for participants without pNASH (0.73, 95% CI 0.49-1.00), the difference did not reach statistical significance. There was no change in liver enzymes in participants taking polypill but among those with pNASH, there was a significant decrease after 60 months of follow-up (intragroup -12.0 IU/L, 95% CI -14.2 to -9.6)., Conclusion: Among patients consenting to receive fixed-dose combination therapy, polypill is safe and effective for the prevention of MCVE, even among participants with fatty liver and increased liver enzymes., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Tens 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 Results: In 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., Conclusion: Long-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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

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; p interaction =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., (Copyright © 2019 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

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: Previous studies have found associations between oral health and mortality, but the majority of previous studies have been conducted in high-income countries., Methods: We used data from the Golestan Cohort Study, a study of 50 045 people aged 40 to 75 years in north eastern Iran, recruited from January 2004 to June 2008. Tooth loss and decayed, missing and filled teeth (DMFT) were assessed by trained physicians. Frequency of tooth brushing and use of dentures were self-reported. Cause-specific mortality was ascertained through March 2014. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations between the oral health variables, overall mortality and cause-specific mortality., Results: Participants with the greatest tooth loss had increased overall mortality (HR 1.43; 95% CI: 1.28, 1.61) compared with those with the least tooth loss; similar estimates were observed for DMFT score. For cause-specific mortality, an increased risk of death was found for tooth loss and mortality from cardiovascular disease (HR 1.33; 95% CI: 1.13, 1.56), cancer (HR 1.30; 95% CI: 1.03, 1.65) and injuries (HR 1.99; 95% CI: 1.28, 3.09). The associations between oral health and injury mortality were strongly attenuated after exclusion of participants with comorbid conditions at baseline. No statistical interaction was found between denture use and tooth loss or DMFT on mortality., Conclusions: Poor oral health appears to predict overall and cause-specific mortality in populations in economic transition. Investigation of the underlying mechanisms might provide an important contribution to reducing mortality., (Published by Oxford University Press on behalf of the International Epidemiological Association 2017. This work is written by US Government employees and is in the public domain in the United States.)

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 complexity of treatment regimens, costs and pill burden decrease the medication adherence and contribute to shortfall in cardiovascular preventive drug coverage. The polypill, a fixed dose combination pill of established drugs, is expected to increase adherence and reduce the costs whilst preventing major cardiovascular events (MCVE)., Design and Methods: The PolyIran trial is a pragmatic cluster randomized trial nested within the Golestan Cohort Study (GCS). Subjects were randomized to either non-pharmacological preventive interventions alone (minimal care arm) or together with a polypill (polypill arm) comprising hydrochlorothiazide, aspirin, atorvastatin and either enalapril or valsartan. This study benefits from the infrastructure of the primary health care system in Iran and the interventions are delivered by the local auxiliary health workers (Behvarz) to the participants. The primary outcome of the study is the occurrence of first MCVE within five years defined as non-fatal and fatal myocardial infarction, unstable angina, sudden death, heart failure, coronary artery revascularization procedures, and non-fatal and fatal stroke., Trial Status: From February 2011 to April 2013, 8410 individuals (236 clusters) attended the eligibility assessment. Of those, 3421 in the polypill arm and 3417 in the minimal care arm were eligible. The study is ongoing., Conclusion: The infrastructure of GCS and the primary health care system in Iran enabled the conduct of this pragmatic large-scale trial. If the polypill strategy proves effective, it may be implemented to prevent cardiovascular disease in developing countries., (© The European Society of Cardiology 2014.)

Background: Cardiovascular disease (CVD) is among the most common causes of mortality in all populations. Nonalcoholic steatohepatitis is a common finding in patients with CVD. Prevention of CVD in individual patients typically requires periodic clinical evaluation, as well as diagnosis and management of risk factors such as hypertension and hyperlipidemia. However, this is resource consuming and hard to implement, especially in developing countries. We designed a study to investigate the effects of a simpler strategy: a fixed-dose combination pill consisting of aspirin, valsartan, atorvastatin and hydrochlorthiazide (PolyPill) in an unselected group of persons aged over 50 years., Design: The PolyIran-Liver study was performed in Gonbad city as an open label pragmatic randomized controlled trial nested within the Golestan Cohort Study. We randomly selected 2,400 cohort study participants aged above 50 years, randomly assigned them to intervention or usual care and invited them to participate in an additional measurement study (if they met the eligibility criteria) to measure liver related outcomes. Those agreeing and randomized to the intervention arm were offered a daily single dose of PolyPill. We will follow participants for 5 years. The primary outcome is major cardiovascular events, secondary outcomes include all-cause mortality and liver related outcomes: liver stiffness and liver enzyme levels. Cardiovascular outcomes and mortality will be determined from the cohort study and liver-related outcomes in those consenting to follow up. Analysis will be by allocated group., Trial Status: Between October and December 2011, 1,320 intervention and 1,080 control participants were invited to participate in the additional measurement study. For all these participants, the major cardiovascular events will be determined using blind assessment of outcomes through the cohort study. In the intervention and control arms, 875 (66%) and 721 (67%) respectively, met the eligibility criteria and agreed to participate in the additional measurement study. Liver related outcomes will be measured in these participants. Of the 1,320 participants randomized to the intervention, 787 (60%) accepted the PolyPill., Conclusion: The PolyIran-liver urban study will provide us with important information on the effectiveness of PolyPill on major cardiovascular events, all-cause mortality and liver related outcomes. (ClinicalTrials.gov ID: NCT01245608).

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]

Introduction: Individuals with nonalcoholic steatohepatitis or elevated liver enzymes have increased cardiovascular mortality but are often excluded from prevention trials. We investigated the effectiveness of fixed-dose combination therapy in prevention of major cardiovascular events (MCVE) among individuals with and without presumed nonalcoholic steatohepatitis (pNASH). Methods: 2400 Participants over 50 were randomized into intervention and control. Consent was taken post randomization. Participants in the intervention group were given a combination pill containing aspirin, atorvastatin, hydrochlorothiazide, and valsartan (Polypill). Participants were followed for 5 years. pNASH was diagnosed by ultrasonography and elevated liver enzymes. The primary outcome was MCVE. Clinical Trials. gov ID: NCT01245608. Results: 892 participants did not consent or meet enrollment criteria and 1508 entered the study. During 5-years of follow-up, 63/787 (8. 0%) intervention group participants and 86/721 (11. 9%) controls had MCVE (adjusted RR 0. 61, 95%CI 0. 44 to 0. 83). Although the adjusted relative risk of MCVE in participants with pNASH (0. 35, 95%CI 0. 17 to 0. 74) was under half that for participants without pNASH (0. 73, 95%CI 0. 49 to 1. 00), the difference did not reach statistical significance. Outcomes were also evaluated for the pre-consent population. 138/1249 in the intervention group (11. 0%) and 137/1017 controls (13. 5%) had MCVE during the 5-year follow-up (unadjusted RR 0. 83, 95%CI 0. 66-1. 03). Participants with pNASH in the intervention group had a significant decrease in liver enzyme levels after 60 months of follow-up (intragroup -12. 0 IU/L, 95%CI -14. 2 to -9. 6). Conclusion: Fixed-dose combination therapy is safe and effective for prevention of MCVE even among participants with fatty liver and increased liver enzymes. [ABSTRACT FROM AUTHOR]

BACKGROUND Only a few studies in Western countries have investigated the association between gastroesophageal reflux disease (GERD) and mortality at the general population level and they have shown mixed results. This study investigated the association between GERD symptoms and overall and cause-specific mortality in a large prospective population-based study in Golestan Province, Iran. METHODS Baseline data on frequency, onset time, and patient-perceived severity of GERD symptoms were available for 50001 participants in the Golestan Cohort Study (GCS). We identified 3107 deaths (including 1146 circulatory and 470 cancer-related) with an average follow-up of 6.4 years and calculated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for multiple potential confounders. RESULTS Severe daily symptoms (defined as symptoms interfering with daily work or causing nighttime awakenings on a daily bases, reported by 4.3% of participants) were associated with cancer mortality (HR 1.48, 95% CI: 1.04-2.05). This increase was too small to noticeably affect overall mortality. Mortality was not associated with onset time or frequency of GERD and was not increased with mild to moderate symptoms. CONCLUSION We have observed an association with GERD and increased cancer mortality in a small group of individuals that had severe symptoms. Most patients with mild to moderate GERD can be re-assured that their symptoms are not associated with increased mortality. [ABSTRACT FROM AUTHOR]