Individual and Combined Effects of Environmental Risk Factors for Esophageal Cancer Based on Results From the Golestan Cohort Study.

BACKGROUND & AIMS: Northeast Iran has one of the highest reported rates of esophageal squamous cell carcinoma (ESCC) worldwide. Decades of investigations in this region have identified some local habits and environmental exposures that increase risk. We analyzed data from the Golestan Cohort Study to determine the individual and combined effects of the major environmental risk factors of ESCC. METHODS: We performed a population-based cohort of 50,045 individuals, 40 to 75 years old, from urban and rural areas across Northeast Iran. Detailed data on demographics, diet, lifestyle, socioeconomic status, temperature of drinking beverages, and different exposures were collected using validated methods, questionnaires, and physical examinations, from 2004 through 2008. Participants were followed from the date of enrollment to the date of first diagnosis of esophageal cancer, date of death from other causes, or date of last follow-up, through December 31, 2017. Proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between different exposures and ESCC. RESULTS: During an average 10 years of follow-up, 317 participants developed ESCC. Opium smoking (HR 1.85; 95% CI 1.18-2.90), drinking hot tea (≥60°C) (HR 1.60; 95% CI 1.15-2.22), low intake of fruits (HR 1.48; 95% CI 1.07-2.05) and vegetables (HR 1.62; 95% CI 1.03-2.56), excessive tooth loss (HR 1.66; 95% CI 1.04-2.64), drinking unpiped water (HR 2.04; 95% CI 1.09-3.81), and exposure to indoor air pollution (HR 1.57; 95% CI 1.08-2.29) were significantly associated with increased risk of ESCC, in a dose-dependent manner. Combined exposure to these risk factors was associated with a stepwise increase in the risk of developing ESCC, reaching a more than 7-fold increase in risk in the highest category. Approximately 75% of the ESCC cases in this region can be attributed to a combination of the identified exposures. CONCLUSIONS: Analysis of data from the Golestan Cohort Study in Iran identified multiple risk factors for ESCC in this population. Our findings support the hypothesis that the high rates of ESCC are due to a combination of factors, including thermal injury (from hot tea), exposure to polycyclic aromatic hydrocarbons (from opium and indoor air pollution), and nutrient-deficient diets. We also associated ESCC risk with exposure to unpiped water and tooth loss.

Household Fuel Use and Cardiovascular Disease Mortality: Golestan Cohort Study.

BACKGROUND: Household air pollution is the third largest risk factor for global disease burden, but direct links with cardiovascular disease mortality are limited. This study aimed to evaluate the relationship between household fuel use and cardiovascular disease mortality. METHODS AND RESULTS: The Golestan Cohort Study in northeastern Iran enrolled 50 045 individuals 40 to 75 years of age between 2004 and 2008 and collected data on lifetime household fuel use and other baseline exposures. Participants were followed up through 2012 with a 99% successful follow-up rate. Cox proportional hazards models were fitted to calculate hazard ratios for associations between pehen (local dung), wood, kerosene/diesel, or natural gas burning for cooking and heating and all-cause and cause-specific mortality, with adjustment for lifetime exposure to each of these fuels and potential confounders. A total of 3073 participants (6%) died during follow-up; 78% of these deaths were attributable to noncommunicable diseases, including cardiovascular, oncological, and respiratory illnesses. Adjusted 10-year hazard ratios from kerosene/diesel burning were 1.06 (95% confidence interval, 1.02-1.10) and 1.11 (95% confidence interval, 1.06-1.17) for all-cause and cardiovascular mortality, respectively. Subtype-specific analyses revealed a significant increase in ischemic heart disease (10-year hazard ratio, 1.14; 95% confidence interval, 1.06-1.21) and a trend toward cerebrovascular accident (10-year hazard ratio, 1.08; 95% confidence interval, 0.99-1.17) mortality. Stratification by sex revealed a potential signal for increased risk for all-cause and cardiovascular disease mortality among women compared with men, with similar risk for ischemic heart disease mortality. CONCLUSIONS: Household exposure to high-pollution fuels was associated with increased risk for all-cause and cardiovascular disease mortality. Replicating these results worldwide would support efforts to reduce such exposures.

Mortality from respiratory diseases associated with opium use: a population-based cohort study.

BACKGROUND: Recent studies have suggested that opium use may increase mortality from cancer and cardiovascular diseases. However, no comprehensive study of opium use and mortality from respiratory diseases has been published. We aimed to study the association between opium use and mortality from respiratory disease using prospectively collected data. METHODS: We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50 045 adults were enrolled from 2004 to 2008, and followed annually until June 2015, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest. RESULTS: During the follow-up period, 331 deaths from respiratory disease were reported (85 due to respiratory malignancies and 246 due to non-malignant aetiologies). Opium use was associated with an increased risk of death from any respiratory disease (adjusted HR 95% CI 3.13 (2.42 to 4.04)). The association was dose-dependent with a HR of 3.84 (2.61 to 5.67) for the highest quintile of cumulative opium use versus never use (Ptrend<0.001). The HRs (95% CI) for the associations between opium use and malignant and non-malignant causes of respiratory mortality were 1.96 (1.18 to 3.25) and 3.71 (2.76 to 4.96), respectively. CONCLUSIONS: Long-term opium use is associated with increased mortality from both malignant and non-malignant respiratory diseases.

Hazards of cigarettes, smokeless tobacco and waterpipe in a Middle Eastern Population: a Cohort Study of 50†000 individuals from Iran.

BACKGROUND: There is limited information about the hazards of cigarettes, smokeless tobacco and waterpipe in the Middle East. The aim of this study was to determine the association between different types of tobacco use and earlier death in the Golestan Cohort Study. METHODS: The Study includes 50 045 adults (aged 40-75 years) from north eastern Iran. The baseline questionnaire (2004-2008) assessed information about use of cigarettes, chewing tobacco (nass) and waterpipe. To assess the use of each type of tobacco compared with never tobacco users, we used Cox regression models adjusted for age, socioeconomic status, area of residence, education and other tobacco used, and stratified by sex, ethnicity and opium use. RESULTS: 17% of participants reported a history of cigarette smoking, 7.5% chewing tobacco (nass) and 1.1% smoking waterpipe, and these figures declined in the later birth cohorts. During a median follow-up of 8 years, 4524 deaths occurred (mean age 64.8+9.9 years). Current (HR=1.44; 95% CI 1.28 to 1.61) and former (HR=1.35; 95% CI 1.16 to 1.56) cigarette smokers had higher overall mortality relative to never tobacco users. The highest cigarette-associated risk was for cancer death among current heavy smokers (HR=2.32; 95% CI 1.66 to 3.24). Current nass chewing was associated with overall mortality (HR=1.16; 95% CI 1.01 to 1.34), and there was a 61% higher risk of cancer death in people chewing nass more than five times a day. We observed an association between the cumulative lifetime waterpipe use (waterpipe-years≥28) and both overall (HR=1.66; 95% CI 1.11 to 2.47), and cancer mortality (HR=2.82; 95% CI 1.30 to 6.11). CONCLUSIONS: Regular use of cigarettes, smokeless tobacco and waterpipe were associated with the risk of earlier death (particularly from cancer) in our cohort.

Prediagnostic serum levels of inflammatory biomarkers are correlated with future development of lung and esophageal cancer.

This study tests the hypothesis that prediagnostic serum levels of 20 cancer-associated inflammatory biomarkers correlate directly with future development of head and neck, esophageal, and lung cancers in a high-risk prospective cohort. This is a nested case-control pilot study of subjects enrolled in the Golestan Cohort Study, an ongoing epidemiologic project assessing cancer trends in Golestan, Iran. We measured a panel of 20 21 cytokines, chemokines, and inflammatory molecules using Luminex technology in serum samples collected 2 or more years before cancer diagnosis in 78 aerodigestive cancer cases and 81 controls. Data was analyzed using Wilcoxon rank sum test, odds ratios, receiver operating characteristic areas of discrimination, and multivariate analysis. Biomarkers were profoundly and globally elevated in future esophageal and lung cancer patients compared to controls. Odds ratios were significant for association between several biomarkers and future development of esophageal cancer, including interleukin-1Rα (IL-1Ra; 35.9), interferon α2 (IFN-a2; 34.0), fibroblast growth factor-2 (FGF-2; 17.4), and granulocyte/macrophage colony-stimulating factor (GM-CSF; 17.4). The same pattern was observed among future lung cancer cases for G-CSF (27.7), GM-CSF (13.3), and tumor necrosis factor-α (TNF-a; 8.6). By contrast, the majority of biomarkers studied showed no significant correlation with future head and neck cancer development. This study provides the first direct evidence that multiple inflammatory biomarkers are coordinately elevated in future lung and esophageal cancer patients 2 or more years before cancer diagnosis.

Impact of body size and physical activity during adolescence and adult life on overall and cause-specific mortality in a large cohort study from Iran.

We conducted this study to examine life-course body size and physical activity in relation to total and cause-specific mortality, which has not previously been studied in the low and middle-income countries in Asia. The Golestan Cohort Study is a population-based cohort in northeastern Iran in which 50,045 people above the age of 40 have been followed since 2004. Participants were shown a validated pictogram to assess body size at ages 15, 30, and the time of recruitment. Information on occupational physical activity at these ages was also collected. Subjects were followed up annually, and cause of death was determined. Cox regression models were adjusted for age at cohort start, smoking, socioeconomic status, ethnicity, place of residence, education, and opium use. Models for body size were also adjusted for physical activity at the same age, and vice versa. During a total of 252,740 person-years of follow-up (mean follow-up duration 5.1 ± 1.3 years) through December 2011, 2,529 of the cohort participants died. Larger body sizes at ages 15 or 30 in both sexes were associated with increased overall mortality. Cancer mortality was more strongly associated with adolescent obesity, and cardiovascular mortality with early adulthood body size. Weight gain between these ages was associated with cardiovascular mortality. Obese adolescents who lost weight still had increased mortality from all medical causes in both sexes. Physical activity during adolescence and early adulthood had no association with mortality, but at cohort baseline higher levels of activity were associated with reduced mortality. Mortality in this Middle-Eastern population was associated with obesity both during adolescence and early adult life.

Opium use and risk of mortality from digestive diseases: a prospective cohort study.

OBJECTIVES: Opium use, particularly in low doses, is a common practice among adults in northeastern Iran. We aimed to investigate the association between opium use and subsequent mortality from disorders of the digestive tract. METHODS: We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50,045 adults were enrolled during a 4-year period (2004-2008) and followed annually until December 2012, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest. RESULTS: In all, 8,487 (17%) participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 474 deaths from digestive diseases were reported (387 due to gastrointestinal cancers and 87 due to nonmalignant etiologies). Opium use was associated with an increased risk of death from any digestive disease (adjusted hazard ratio (HR)=1.55, 95% confidence interval (CI)=1.24-1.93). The association was dose dependent, with a HR of 2.21 (1.57-3.31) for the highest quintile of cumulative opium use vs. no use (Ptrend=0.037). The HRs (95% CI) for the associations between opium use and malignant and nonmalignant causes of digestive mortality were 1.38 (1.07-1.76) and 2.60 (1.57-4.31), respectively. Increased risks were seen both for smoking opium and for ingestion of opium. CONCLUSIONS: Long-term opium use, even in low doses, is associated with increased risk of death from both malignant and nonmalignant digestive diseases.

Long-term opiate use and risk of cardiovascular mortality: results from the Golestan Cohort Study.

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.

p16INK4a hypermethylation and p53, p16 and MDM2 protein expression in esophageal squamous cell carcinoma.

BACKGROUND: Tumor suppressor genes p53 and p16INK4a and the proto-oncogene MDM2 are considered to be essential G1 cell cycle regulatory genes whose loss of function is associated with ESCC carcinogenesis. We assessed the aberrant methylation of the p16 gene and its impact on p16INK4a protein expression and correlations with p53 and MDM2 protein expressions in patients with ESCC in the Golestan province of northeastern Iran in which ESCC has the highest incidence of cancer, well above the world average. METHODS: Cancerous tissues and the adjacent normal tissue obtained from 50 ESCC patients were assessed with Methylation-Specific-PCR to examine the methylation status of p16. The expression of p16, p53 and MDM2 proteins was detected by immunohistochemical staining. RESULTS: Abnormal expression of p16 and p53, but not MDM2, was significantly higher in the tumoral tissue. p53 was concomitantly accumulated in ESCC tumor along with MDM2 overexpression and p16 negative expression. Aberrant methylation of the p16INK4a gene was detected in 31/50 (62%) of esophageal tumor samples, while two of the adjacent normal mucosa were methylated (P < 0.001). p16INK4a aberrant methylation was significantly associated with decreased p16 protein expression (P = 0.033), as well as the overexpression of p53 (P = 0.020). CONCLUSIONS: p16 hypermethylation is the principal mechanism of p16 protein underexpression and plays an important role in ESCC development. It is associated with p53 protein overexpression and may influence the accumulation of abnormally expressed proteins in p53-MDM2 and p16-Rb pathways, suggesting a possible cross-talk of the involved pathways in ESCC development.

Development of a low-cost real-time reverse transcriptase-polymerase chain reaction technique for the detection and quantification of hepatitis C viral load.

BACKGROUND: It is necessary to develop a highly specific and sensitive assay to quantify the exact amount of hepatitis C virus (HCV) RNA in blood of patients with hepatitis C. For this reason, a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay for quantification of HCV RNA in human plasma was developed. METHODS: A pair of primers as well as hybridization probes were selected. A real-time RT-PCR was set up and optimized. To establish the sensitivity of the assay, a serial dilution of HCV standards and reference sera, including the six major HCV genotypes, was used. The performance of the assay was evaluated with 191 known HCV-RNA positive and 100 negative samples. RESULTS: The real-time assay had a sensitivity of 50 IU/mL, with a dynamic range of detection between 10(3) and 10(6) IU/mL. The coefficients of variation of threshold cycle values in intra- and inter-day-runs were <1.77% and 3.40%, respectively. Measurement of HCV-RNA positive samples yielded reproducible data with 100% specificity. CONCLUSIONS: The high sensitivity, simplicity, reproducibility, wide dynamic range, and low cost of this real-time HCV RNA quantification makes this method especially suitable for monitoring viral load during therapy and tailoring of treatment schedules accordingly.

Epidemiology of uninvestigated gastrointestinal symptoms in adolescents: a population-based study applying the Rome II questionnaire.

OBJECTIVES: : Gastrointestinal (GI) disorders in early life contribute to a lower quality of life and more persistent GI symptoms during the rest of life. Epidemiologic data on adolescence GI disorders are scarce. We aimed to perform a population-based study to assess the prevalence of GI symptoms in adolescents and their relation to sex, age, and socioeconomic status. MATERIALS AND METHODS: : A multistage random sample of Tehran middle and high school students (ages 14-19 years) was selected. A validated Persian version of the Rome II questionnaire was used to measure the frequency of different GI disorders as well as demographic socioeconomic variables. RESULTS: : A total of 1436 participants were enrolled in the study, 736 (51.3%) of whom were men. Mean (SD) age was 16.9 (1.8) years. The frequency of at least 1 GI symptom was 32.4%. The 4 most prevalent GI symptoms were bloating (16.9%), heartburn (4.9%), incontinence (4.3%), and irritable bowel syndrome (4.1%). Bloating, irritable bowel syndrome, and proctalgia fugax were significantly more common in girls (P < 0.05). Incontinence was significantly more prevalent in lower socioeconomic status levels (P = 0.01). In logistic regression, age was a risk factor for abdominal bloating and dysphagea and a protective factor for incontinence. CONCLUSIONS: : Our study indicates that GI symptoms are common among adolescents. Girls are more prone to these disorders. Special psychological and medical interventions are necessary for high-risk groups.

Magnetic resonance imaging signal reduction may precede volume loss in the pituitary gland of transfusion-dependent beta-thalassemic patients.

BACKGROUND: Pituitary iron overload in patients with transfusion-dependent beta-thalassemia may lead to delayed puberty. Magnetic resonance imaging (MRI) has the potential to estimate tissue iron concentration by detecting its paramagnetic effect and hypophyseal damage by measuring its dimensions indirectly. PURPOSE: To investigate the association of pituitary MRI findings and pubertal status in thalassemic patients as well as to demonstrate any priority in appearance of them. MATERIAL AND METHODS: Twenty-seven beta-thalassemic patients, aged 15-25 years, were divided into 13 with (group A) and 14 without hypogonadism (group B), matched by age, gender, duration of transfusion, and chelation therapy. Thirty-eight age- and sex-adjusted healthy control individuals were also included (group C). All participants underwent pituitary MRI using a 1.5 T unit. Pituitary-to-fat signal intensity ratios (SIR) were calculated from coronal T2-weighted images. Estimated pituitary volumes were measured using pituitary height, width, and length on T1-weighted images. RESULTS: The mean values of pituitary-to-fat SIRs were significantly lower in group A as compared with group B (P <0.001), and likewise group B had statistically lower values than group C (P=0.03). The pituitary height and volume were significantly decreased in group A compared to group B (P = 0.006 and P = 0.002, respectively), while these differences did not demonstrate statistically significance between groups B and C. CONCLUSION: Pituitary MRI findings such as signal intensity reduction and decrease in volume can be useful markers in estimating pituitary dysfunction in beta-thalassemic patients. Compared to healthy controls, lower values of pituitary-to-fat SIRs in thalassemic patients experiencing normal puberty, without marked decrease in volume, indicate that signal reduction may precede volume loss and could be expected first on MRI.

Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study.

BACKGROUND: Evidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence. METHODS: This study was done in a population-based cohort of 50 045 individuals aged 40-75 years from northeast Iran. Data on participant demographics, diet, lifestyle, opium use, and different exposures were collected upon enrolment using validated questionnaires. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between opium use and different cancer types. FINDINGS: During a median 10 years of follow-up, 1833 participants were diagnosed with cancer. Use of opium was associated with an increased risk of developing all cancers combined (HR 1·40, 95% CI 1·24-1·58), gastrointestinal cancers (1·31, 1·11-1·55), and respiratory cancers (2·28, 1·58-3·30) in a dose-dependent manner (ptrend<0·001). For site-specific cancers, use of opium was associated with an increased risk of developing oesophageal (1·38, 1·06-1·80), gastric (1·36, 1·03-1·79), lung (2·21, 1·44-3·39), bladder (2·86, 1·47-5·55), and laryngeal (2·53, 1·21-5·29) cancers in a dose-dependent manner (ptrend<0·05). Only high-dose opium use was associated with pancreatic cancer (2·66, 1·23-5·74). Ingestion of opium (but not smoking opium) was associated with brain (2·15, 1·00-4·63) and liver (2·46, 1·23-4·95) cancers in a dose-dependent manner (prend<0·01). We observed consistent associations among ever and never tobacco users, men and women, and individuals with lower and higher socioeconomic status. INTERPRETATION: Opium users have a significantly higher risk of developing cancers in different organs of the respiratory, digestive, and urinary systems and the CNS. The results of this analysis show that regular use of opiates might increase the risk of a range of cancer types. FUNDING: World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, US National Cancer Institute, International Agency for Research on Cancer.

Limited evidence of physical therapy on balance after stroke: A systematic review and meta-analysis.

BACKGROUND: Stroke results in balance disorders and these directly affect autonomy and quality of life. The purpose of this systematic review and meta-analysis was to determine the efficacy of physical therapy (PT) on balance and postural control after stroke. METHODS: We included all randomized controlled trials assessing the efficacy of PT on balance and postural control in adult patients after stroke without language restriction. Medline, Embase/Scopus, Cochrane Central Register of Controlled Trials, PEDro, Pascal, and Francis databases were searched until January 2019. Primary outcomes were balance (Berg Balance scale and Postural Assessment Scale for Stroke) and postural control with postural deviation or stability measurement in sitting or standing static evaluation. A pair of independent reviewers selected studies, extracted data, and assessed risk of bias. Meta-analyses with subgroups (categories of PT, time post-stroke, and lesion location) and meta-regression (duration of PT) were conducted. RESULTS: A total of 145 studies (n = 5912) were selected from the 13,123 records identified. For balance, evidence was found in favor of the efficacy of functional task-training alone (standardized mean difference 0.39, 95% confidence interval [0.09; 0.68], heterogeneity I2 = 63%) or associated with musculoskeletal intervention and/or cardiopulmonary intervention (0.37, [0.19; 0.55], I2 = 48%), electrostimulation (0.91, [0.49; 1.34], I2 = 52%) immediately after intervention, compared to sham treatment or usual care (ST/UC). For postural deviation eyes open, assistive devices were more effective than no treatment (-0.21, [-0.37; -0.05], I2 = 0%) immediately after intervention; for postural stability eyes open, functional task-training and sensory interventions were more effective than ST/UC (0.97, [0.35; 1.59], I2 = 65% and 0.80, [0.46; 1.13], I2 = 37% respectively) immediately after intervention. CONCLUSIONS: Functional task-training associated with musculoskeletal intervention and/or cardiopulmonary intervention and sensory interventions seem to be immediately effective in improving balance and postural stability, respectively. The heterogeneity of PT and the weak methodological quality of studies limited the interpretation and the confidence in findings.

Epidemiology of upper gastrointestinal cancers in Iran: a sub site analysis of 761 cases.

AIM: To define the sub site distribution of upper gastrointestinal cancers in three provinces of Iran. METHODS: The study was carried out in three provinces in Iran: Ardabil, Golestan, and Tehran. In Arbabil and Golestan, the data was collected from the sole referral center for gastrointestinal cancers and the local cancer registry. For Tehran province, data from two major private hospitals were used. All gastric and esophageal cancer patients diagnosed during the period from September 2000 and April 2002 were included in the study. RESULTS: A total of 761 patients with upper gastrointestinal cancers were identified, 314 from Ardabil, 261 from Golestan, and 186 from Tehran. In Tehran, the relative rate of cancer increased from the upper esophagus to the distal stomach. In Golestan, the reverse pattern was observed. In Ardabil, the mid portion (distal esophagus and proximal stomach) was involved most frequently. CONCLUSION: There were considerable variations in the sub site of upper gastrointestinal cancers in the three provinces studied. We cannot provide any explanation for this variation. Further research aimed at explaining the discrepancies in sub site distribution of upper gastrointestinal cancers may help identify important risk factors.

The Combined Effects of Healthy Lifestyle Behaviors on All-Cause Mortality: The Golestan Cohort Study.

BACKGROUND: Most studies that have evaluated the association between combined lifestyle factors and mortality outcomes have been conducted in populations of developed countries. OBJECTIVES: The aim of this study was to examine the association between combined lifestyle scores and risk of all-cause and cause-specific mortality for the first time among Iranian adults. METHODS: The study population included 50,045 Iranians, 40 - 75 years of age, who were enrolled in the Golestan Cohort Study, between 2004 and 2008. The lifestyle risk factors used in this study included cigarette smoking, physical inactivity, and Alternative Healthy Eating Index. The lifestyle score ranged from zero (non-healthy) to 3 (most healthy) points. From the study baseline up to analysis, a total of 4691 mortality cases were recorded. Participants with chronic diseases at baseline, outlier reports of calorie intake, missing data, and body mass index of less than 18.5 were excluded from the analyses. Cox regression models were fitted to establish the association between combined lifestyle scores and mortality outcomes. RESULTS: After implementing the exclusion criteria, data from 40,708 participants were included in analyses. During 8.08 years of follow-up, 3,039 cases of all-cause mortality were recorded. The adjusted hazard ratio of a healthy lifestyle score, compared with non-healthy lifestyle score, was 0.68 (95% CI: 0.54, 0.86) for all-cause mortality, 0.53 (95% CI: 0.37, 0.77) for cardiovascular mortality, and 0.82 (95% CI: 0.53, 1.26) for mortality due to cancer. When we excluded the first two years of follow up from the analysis, the protective association between healthy lifestyle score and cardiovascular death did not change much 0.55 (95% CI: 0.36, 0.84), but the inverse association with all-cause mortality became weaker 0.72 (95% CI: 0.55, 0.94), and the association with cancer mortality was non-significant 0.92 (95% CI: 0.58, 1.48). In the gender-stratified analysis, we found an inverse strong association between adherence to healthy lifestyle and mortality from all causes and cardiovascular disease in either gender, but no significant relationship was seen with mortality from cancer in men or women. Stratified analysis of BMI status revealed an inverse significant association between adherence to healthy lifestyle and mortality from all causes, cardiovascular disease and cancer among non-obese participants. CONCLUSION: We found evidence indicating that adherence to a healthy lifestyle, compared to non-healthy lifestyle, was associated with decreased risk of all-cause mortality and mortality from cardiovascular diseases in Iranian adults.

Cardiovascular disease mortality and years of life lost attributable to non-optimal systolic blood pressure and hypertension in northeastern Iran.

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.

Heart Disease Is Associated With Anthropometric Indices and Change in Body Size Perception Over the Life Course: The Golestan Cohort Study.

BACKGROUND: Cardiovascular disease and obesity are now becoming leading causes of morbidity and mortality in low- and middle-income countries. OBJECTIVES: We investigated the relationship between prevalent heart disease (HD) and current anthropometric indices and body size perception over time from adolescence to adulthood in Iran. METHODS: We present a cross-sectional analysis of baseline data from a prospective study of adults in Golestan Province, Iran. Demographics, cardiac history, and current anthropometric indices-body mass index, waist circumference, and waist to hip ratio-were recorded. Body size perception for ages 15 years, 30 years, and at the time of interview was assessed via pictograms. Associations of these factors and temporal change in perceived body size with HD were evaluated using multivariable logistic regression models. RESULTS: Complete data were available for 50,044 participants; 6.1% of which reported having HD. Higher body mass index, waist circumference, and waist to hip ratio were associated with HD (p < 0.001). Men had a U-shaped relationship between HD and body size perception at younger ages. For change in body size perception, men and women demonstrated a U-shaped relationship with prevalent HD from adolescence to early adulthood, but a J-shaped pattern from early to late adulthood. CONCLUSIONS: HD was associated with anthropometric indices and change in body size perception over time for men and women in Iran. Due to the increasing prevalence of overweight and obesity in low- and middle-income countries, interventions focused on decreasing the cumulative burden of risk factors throughout the life course may be an important component of cardiovascular risk reduction.

Gastroesophageal Reflux Disease and overall and Cause-specific Mortality: A Prospective Study of 50000 Individuals.

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.