Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Towards hepatitis C virus elimination in Iran: A blueprint for comprehensive strategies.

The hepatitis C virus (HCV) continues to pose a significant public health challenge in Iran, mirroring a worldwide concern. This situation calls for a cohesive strategy that aligns with the World Health Organization's (WHO) goals for HCV elimination by 2030. Central to this strategy is targeting high-risk groups, notably people who inject drugs and prisoners, with prevention, screening and treatment. The deployment of point-of-care testing and treatments in prisons and harm reduction facilities is vital. The adoption of cost-effective generic direct-acting antivirals represents a major step forward. Furthermore, innovative educational initiatives for healthcare providers and awareness campaigns for the public are critical. Additionally, tackling stigma, ensuring treatment affordability and upholding strict surveillance and data management, coupled with ongoing policy reviews, are vital components. This comprehensive and integrated approach is designed to drive Iran towards eliminating HCV and can serve as a blueprint for other countries with similar challenges.

Dental health and lung cancer risk in the Golestan Cohort Study.

BACKGROUND: Poor oral health has been linked to various systemic diseases, including multiple cancer types, but studies of its association with lung cancer have been inconclusive. METHODS: We examined the relationship between dental status and lung cancer incidence and mortality in the Golestan Cohort Study, a large, prospective cohort of 50,045 adults in northeastern Iran. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between three dental health measures (i.e., number of missing teeth; the sum of decayed, missing, or filled teeth (DMFT); and toothbrushing frequency) and lung cancer incidence or mortality with adjustment for multiple potential confounders, including cigarette smoking and opium use. We created tertiles of the number of lost teeth/DMFT score in excess of the loess adjusted, age- and sex-specific predicted numbers, with subjects with the expected number of lost teeth/DMFT or fewer as the reference group. RESULTS: During a median follow-up of 14 years, there were 119 incident lung cancer cases and 98 lung cancer deaths. Higher DMFT scores were associated with a progressively increased risk of lung cancer (linear trend, p = 0.011). Compared with individuals with the expected DMFT score or less, the HRs were 1.27 (95% CI: 0.73, 2.22), 2.15 (95% CI: 1.34, 3.43), and 1.52 (95% CI: 0.81, 2.84) for the first to the third tertiles of DMFT, respectively. The highest tertile of tooth loss also had an increased risk of lung cancer, with a HR of 1.68 (95% CI: 1.04, 2.70) compared with subjects with the expected number of lost teeth or fewer (linear trend, p = 0.043). The results were similar for lung cancer mortality and did not change substantially when the analysis was restricted to never users of cigarettes or opium. We found no associations between toothbrushing frequency and lung cancer incidence or mortality. CONCLUSION: Poor dental health indicated by tooth loss or DMFT, but not lack of toothbrushing, was associated with increased lung cancer incidence and mortality in this rural Middle Eastern population.

Validity and reproducibility of the PERSIAN Cohort food frequency questionnaire: assessment of major dietary patterns.

BACKGROUND: Dietary patterns, encompassing an overall view of individuals' dietary intake, are suggested as a suitable means of assessing nutrition's role in chronic disease development. The aim of this study was to evaluate the validity and reproducibility of a food frequency questionnaire (FFQ) designed for use in the Prospective Epidemiological Research Studies in IrAN (PERSIAN), by comparing major dietary patterns assessed by the FFQ with a reference method. METHODS: Study participants included men and women who enrolled in the PERSIAN Cohort Study at seven of the eighteen centers. These centers were chosen to include dietary variations observed among the different Iranian ethnic populations. Two FFQ were completed for each participant over a one-year study period (FFQ1 upon enrollment and FFQ2 at the end of the study), with 24 interviewer-administered 24-hour dietary recalls (24 h) being completed monthly in between. Spearman correlation coefficients (SCC) were used comparing FFQs 1 and 2 to the 24 h to assess validity, while FFQ1 was compared to FFQ2 to assess reproducibility of the questionnaire. RESULTS: Three major dietary patterns-Healthy, Low Protein/High Carb and Unhealthy-were identified, accounting for 70% of variance in the study population. Corrected SCC ranged from 0.31 to 0.61 in the validity and from 0.34 to 0.57 in reproducibility analyses, with the first two patterns, which accounted for over 50% of population variance, correlated at above 0.5 in both parameters, showing acceptable findings. CONCLUSIONS: The PERSIAN Cohort FFQ is suitable for identification of major dietary patterns in the populations it is used for, in order to assess diet-disease relationships.

The Factor Structure and Generalizability of the Iranian Socioeconomic Status (SES) Questionnaire Administered in a Nationally Divergent Population.

Background: Measuring socioeconomic status (SES) as an independent variable is challenging, especially in epidemiological and social studies. This issue is more critical in large-scale studies on the national level. The present study aimed to extensively evaluate the validity and reliability of the Iranian SES questionnaire. Methods: This psychometric, cross-sectional study was conducted on 3000 households, selected via random cluster sampling from various areas in East Azerbaijan province and Tehran, Iran. Moreover, 250 students from Tabriz University of Medical Sciences were selected as interviewers to collect data from 40 districts in Iran. The construct validity and internal consistency of the SES questionnaire were assessed using exploratory and confirmatory factor analyses and the Cronbach's alpha. Data analysis was performed in SPSS and AMOS. Results: The complete Iranian version of the SES questionnaire consists of 5 factors. The Cronbach's alpha was calculated to be 0.79, 0.94, 0.66, 0.69, and 0.48 for the occupation, self-evaluation of economic capacity, house and furniture, wealth, and health expenditure, respectively. In addition, the confirmatory factor analysis results indicated the data's compatibility with the 5-factor model (comparative fit index = 0.96; goodness of fit index = 0.95; incremental fit index = 0.96; root mean square error of approximation = 0.05). Conclusion: According to the results, the confirmed validity and reliability of the tool indicated that the Iranian version of the SES questionnaire could be utilized with the same structure on an extensive level and could be applicable for measuring the SES in a broader range of populations.

Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high-incidence area: Golestan Cohort Study.

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.

Population attributable proportion and number of cancer cases attributed to potentially modifiable risk factors in Iran in 2020.

In the current study, we aimed to calculate the fraction of cancer attributable to modifiable risk factors in Iran in 2020. Population attributable fractions (PAFs) were calculated for established cancer risk factors using three data sources: the national cancer incidence reports, relative risks extracted from global and national meta-analyses, and exposure prevalence from national/subnational population-based surveys. In addition to overall cancers, the PAFs were estimated separately for each cancer site among men and women. Overall, 32.6% of cancers in 2020 in Iran were attributable to known risk factors. The PAF in men (40.2%) was twice as high as in women (21.1%). Cigarette smoking (15.4%), being overweight (5.0%), opium use (3.9%) and H. pylori infection (3.8%) were the leading causes of cancers. For men, the highest PAFs belonged to cigarette smoking (26.3%), opium use (6.8%) and being overweight (3.1%), while for women, the highest PAFs belonged to being overweight (7.2%), H. pylori infection (2.7%) and cigarette smoking (2.7%). Among Iranian men and women, the PAFs of waterpipe smoking were 2% and 0.9%, respectively. A third of incident cancers in Iran are due to modifiable exposures, mainly cigarette smoking, being overweight, and H. pylori infection. Opium consumption and waterpipe smoking collectively accounted for 8.8% of cancer occurrence in men and 1.3% in women in Iran. These emerging risk factors should be taken into consideration in future PAF studies.

Opium use and risk of lung cancer: A multicenter case-control study in Iran.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.

Association Between Incident Type 2 Diabetes and Opium Use: Mediation by Body Mass and Adiposity.

Opiates can affect glucose metabolism and obesity, but no large prospective study (to our knowledge) has investigated the association between long-term opium use, body mass index (BMI; weight (kg)/height (m)2), and incident type 2 diabetes mellitus (T2DM). We analyzed prospective data from 50,045 Golestan Cohort Study participants in Iran (enrollment: 2004-2008). After excluding participants with preexisting diseases, including diabetes, we used adjusted Poisson regression models to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2DM in opium users compared with nonusers, using mediation analysis to assess the BMI-mediated association of opium use with incident T2DM. Of 40,083 included participants (mean age = 51.4 (standard deviation, 8.8) years; 56% female), 16% were opium users (median duration of use, 10 (interquartile range), 4-20) years). During follow-up (until January 2020), 5,342 incident T2DM cases were recorded, including 8.5% of opium users and 14.2% of nonusers. Opium use was associated with an overall decrease in incident T2DM (IRR = 0.83, 95% CI: 0.75, 0.92), with a significant dose-response association. Most (84.3%) of this association was mediated by low BMI or waist circumference, and opium use did not have a direct association with incident T2DM (IRR = 0.97, 95% CI: 0.87, 1.08). Long-term opium use was associated with lower incidence of T2DM, which was mediated by low body mass and adiposity.

Smoke exposure associated with higher urinary benzene biomarker muconic acid (MUCA) in Golestan Cohort Study participants.

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS).Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model.Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 h) of MUCA.Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants.

Polypharmacy and pattern of medication use among patients with gastroesophageal reflux disease: results from Pars Cohort study.

BACKGROUND: Gastroesophageal Reflux Disease (GERD) is a common chronic condition. Its chronic nature may affect the pattern of medication use. This study aimed to investigate the prevalence, associated factors, and patterns of polypharmacy and medication use among GERD patients in southwestern Iran. METHODS: We used data from the Pars Cohort Study. We classified drugs using the Anatomical Therapeutic Chemical classification system. The Lexicomp® database was used to assess potential drug-drug interactions. Multivariable Poisson regression was applied. Adjusted prevalence ratio (PR) and its 95% confidence interval (CI) were estimated. RESULTS: A total of 9262 participants were included. Among 2,325 patients with GERD, age-standardized prevalence of polypharmacy was 9.5% (95% CI: 7.5%, 11.6%) in males, and 19.3% (95% CI: 17.2%, 21.4%) in females. The PR of experiencing Polypharmacy by GERD patients compared to non-GERD patients was 1.82 (95% CI: 1.61, 2.05%). Multimorbidity (PR: 3.33; CI: 2.66, 4.15), gender (PR: 1.68; CI: 1.30, 2.18), and metabolic syndrome (PR: 1.77; CI: 1.45, 2.15) were associated with polypharmacy among GERD patients. Drugs for acid-related disorders were the most common used drugs among men, women and elders. We found that 13.9%, 4.2%, and 1.1% of GERD patients had type C, D and X drug interactions, respectively. CONCLUSION: GERD is correlated with a higher prevalence of polypharmacy. Among GERD patients, females, those with multi-morbidities, and those with metabolic syndrome may be affected more by polypharmacy. Considering the fairly high rate of interactions identified, a review of the medication list is essential when approaching GERD patients, and physicians must check for medications that may worsen GERD.

Prevalence and determinants of opioid use disorder among long-term opiate users in Golestan Cohort Study.

BACKGROUND: Number of opiate users worldwide has doubled over the past decade, but not all of them are diagnosed with opioid use disorder. We aimed to identify the prevalence and risk factors for OUD after ten years of follow-up. METHODS: Among 8,500 chronic opiate users at Golestan Cohort Study baseline (2004-2008), we recalled a random sample of 451 subjects in 2017. We used three questionnaires: a questionnaire about current opiate use including type and route of use, the drug use disorder section of the Composite International Diagnostic Interview lifetime version, and the validated Kessler10 questionnaire. We defined opioid use disorder and its severity based on the DSM-5 criteria and used a cutoff of 12 on Kessler10 questionnaire to define psychological distress. RESULTS: Mean age was 61.2 ± 6.6 years (84.7% males) and 58% were diagnosed with opioid use disorder. Starting opiate use at an early age and living in underprivileged conditions were risk factors of opioid use disorder. Individuals with opioid use disorder were twice likely to have psychological distress (OR = 2.25; 95%CI: 1.44-3.52) than the users without it. In multivariate regression, former and current opiate dose and oral use of opiates were independently associated with opioid use disorder. Each ten gram per week increase in opiate dose during the study period almost tripled the odds of opioid use disorder (OR = 3.18; 95%CI: 1.79-5.63). CONCLUSIONS: Chronic opiate use led to clinical opioid use disorder in more than half of the users, and this disorder was associated with psychological distress, increasing its physical and mental burden in high-risk groups.

Higher intakes of fiber, total vegetables, and fruits may attenuate the risk of all-cause and cause-specific mortality: findings from a large prospective cohort study.

BACKGROUND: Although studies have reported an inverse association between fruits, vegetables, and fiber consumption and all-cause and cause-specific mortality, the issue remains incompletely defined in the Middle Eastern population. AIMS: The current study aimed to investigate the association between dietary fiber, fruit, and vegetable intake and all-cause and cause-specific mortality. METHODS: A total of 48632 participants (mean age = 52years), 57.5% (n = 27974) women and 42.5% (n = 20658) men, were recruited from an ongoing large-scale prospective cohort study (the Golestan Cohort Study (GCS)), in the north of Iran. Using a validated semi-quantitative 116-item food questionnaire, dietary intakes were collected. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) of all-cause and cause-specific mortality were reported. RESULTS: After approximately 14 years of follow-up, 10,774 deaths were recorded. In the fully adjusted model, compared to those in the lowest quintile of intake, those in the second and third quintiles of dietary fiber intake had a 7%-10% reduction in risk of all-cause mortality, and a 15%-17% reduction in the risk of mortality from other causes. Increasing consumption of fruits was also associated with a decreased risk of mortality for all-cause mortality by 9%-11%, and all cancer by 15-20%. Further, those in the third and fourth quintiles of vegetables intake had 11%-12% lower risk for CVD mortality. DISCUSSION: The results from the GCS further support the current recommendations on following a healthy diet containing proper amounts of fiber, vegetables, and fruits, as health-protective dietary items. CONCLUSIONS: Higher intake of dietary fiber, fruits, and vegetables has the potential to reduce both overall and cause-specific mortality rates. However, additional cohort studies with larger sample size and long-term follow-up durations are required to establish these findings.

Polypill for prevention of cardiovascular diseases with focus on non-alcoholic steatohepatitis: the PolyIran-Liver trial.

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 association between dietary acid load and odds of non-alcoholic fatty liver disease: A case-control study.

Background: Data on the association between dietary acid load and non-alcoholic fatty liver disease (NAFLD) are scarce and controversial. Aim: This study aimed to assess the association between dietary acid-base loads and odds of NAFLD. Methods: In the current study, 196 cases of NAFLD (proven by a gastroenterologist using Fibroscan) and 803 age-matched controls were enrolled from the same clinic. Dietary intakes of patients with NAFLD and controls without hepatic steatosis were evaluated using a validated food frequency questionnaire. Dietary acid load was estimated using the validated potential renal acid load (PRAL) algorithm. Multivariable logistic regression model was used to estimate the odds of NAFLD across quintiles of PRAL. Results: The mean ± SD age of the study population (43% male) was 43.28 ± 14.02 years. The mean ± SD of PRAL was -1.90 ± 7.12 for all participants. After adjustment for all known confounders, subjects in the third quintile of PRAL (nearly with neutral PRAL) had a 54% lower odds of NAFLD compared with those in the lowest quintiles of the PRAL [(OR: 0.46; 95%CI: 0.24-0.89), (P = 0.021)]. However, the odds of NAFLD in the highest quintiles of PRAL was not different in comparison to the lowest quintiles (OR: 0.90; 95%CI: 0.41-1.57). Conclusion: In conclusion, our results have shown a modest U shaped relationship between PRAL and NAFLD. Further studies with acid-base biomarkers are needed to confirm the role of dietary acid load in the development of NAFLD and its potential mechanisms.

Meat consumption and risk of esophageal and gastric cancer in the Golestan Cohort Study, Iran.

Red meat and processed meat are associated with some gastrointestinal cancers. Our study aims to investigate the association of different meat types with esophageal and gastric cancer (EC, GC) in a high-risk population. The Golestan Cohort Study (GCS) is a population-based cohort of 50 045 individuals aged 40 to 75 from northeast Iran. Detailed data on different exposures were collected using validated questionnaires. We considered quintiles of meat consumption, using grams and density (g/1000 kcal/day). We calculated intake of red, processed, organ and white meat, as well as total red meat, including the first three. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between meat types and cancer. During 12 years of follow-up, out of 49 585 participants (57.4% women), 369 developed EC (48.2% women) and 368 developed GC (27.5% women), including 309 esophageal squamous cell, 20 esophageal adenocarcinomas, 216 cardia and 95 non-cardia GC. No association was found for EC except for red meat among females (HR for one quintile increase 1.13, 95% CI = 1.00-1.27). The risk of GC increased for intake of total red meat (HR 1.08, 95% CI = 1.00-1.17) and red meat separately (HR 1.09, 95% CI = 1.00-1.18). The HR for red meat and non-cardia GC was 1.23 (95% CI = 1.02-1.48). No associations were observed for other types of meat. In conclusion, in this high-risk population red meat intake is associated with GC, but not EC, suggesting a substantial role of this modifiable factor in determining the burden of GC.

Comparing the risk of cardiovascular diseases and all-cause mortality in four lifestyles with a combination of high/low physical activity and healthy/unhealthy diet: a prospective cohort study.

BACKGROUND: In this study, we assessed the risk of cardiovascular diseases (CVDs) and all-cause mortality in subjects having an only physical activity or a healthy diet or both compared to those having none of these healthy behaviors in the Golestan Cohort Study (GCS). METHODS: A total of 50,045 participants aged ≥ 40 years were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a median of 13.9 years. Four lifestyles were compared: healthy diet and active (HDA), healthy diet but inactive (HDI), unhealthy diet but active (UDA), and unhealthy diet and inactive (UDI), with UDI being considered as the reference group. Diet quality was assessed by the Dietary Approaches to Stop Hypertension diet score, which was calculated based on a validated food frequency questionnaire. The primary outcomes were death from any cause and CVDs. Adjusted Cox models were used to estimate the hazards ratio (HR) and 95% confidence intervals (CI) for overall and CVDs mortality. RESULTS: During 467,401 person-years of follow-up, 6,256 overall deaths and 2,043 confirmed CVDs deaths were reported. After adjustment for potential confounders, there was a significant lower risk for all-cause mortality in participants with both healthy behaviors (HR = 0.79, 95% CI = 0.73 to 0.86) or only one healthy behavior [HDI: HR = 0.84, 95% CI = 0.78 to 0.90)] and [UDI: HR = 0.91, 95% CI = 0.85 to 0.97] compared to those with both unhealthy behaviors. For CVDs mortality, the HDA lifestyle (HR = 0.74, 95%CI = 0.65 to 0.86), as well as the UDA lifestyle (HR = 0.83, 95%CI = 0.74 to 0.94) indicated a significant lower risk compared to the UDI lifestyle. The HDI lifestyle was not more effective than UDI. CONCLUSION: The greatest reduction in all-cause and CVDs mortality was related to the HDA. For all-cause mortality, both HDI and UDA lifestyles were associated with a decreased risk in comparison to UDI, but for CVDs mortality, only UDA but not HDI decreased the risk.

Dietary acid load and mortality from all causes, CVD and cancer: results from the Golestan Cohort Study.

Given the limited studies and controversial results on association between dietary acid load and mortality from CVD and cancers, we aimed to investigate this association in a large population cohort study in Middle East, with a wide range of dietary acid load. The study was conducted on the platform of the Golestan Cohort Study (GCS), which enrolled 50 045 participants in 2004-2008. Dietary intake was assessed using a validated FFQ. Dietary potential renal acid load (PRAL) score was calculated from nutrient intake. Death and its causes were identified and confirmed by two or three physicians. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95 % CI for total and cause-specific mortalities. Then, the associations were modelled using restricted cubic splines. PRAL range was -57·36 to +53·81 mEq/d for men and -76·70 to +49·08 for women. During 555 142 person-years of follow-up, we documented 6830 deaths, including 3070 cardiovascular deaths, 1502 cancer deaths and 2258 deaths from other causes. For overall deaths, in final model after adjustment for confounders, participants in the first and fifth quintiles of PRAL had a higher risk of mortality compared with the second quintile of PRAL (HR: 1·08; 95 % CI1·01, 1·16 and HR: 1·07; 95 % CI 1·01, 1·15, respectively); Pfor trend < 0·05). Participants in the first and fifth quintiles of PRAL had a 12 % higher risk of CVD mortality compared with the Q2 of PRAL (HR: 1·12; 95 % CI 1·01-1·25 and HR: 1·12; 95 % CI 1·01, 1·26, respectively; Pfor trend < 0·05). We found that all-cause and CVD mortality rates were higher in the lowest and highest PRAL values, in an approximately U-shaped relation (P-values for the overall association and the non-linear association of energy-adjusted PRAL with total mortality were < 0·001 and < 0·001, and with CVD mortality were 0·008 and 0·003, respectively). Our results highlight unfavourable associations of high acidity and alkalinity of diet with the increased total and CVD mortality risk. It may be important to consider a balanced acid-base diet as a protective strategy to prevent pre-mature death, especially from CVD.

Associations between exploratory dietary patterns and incident type 2 diabetes: a federated meta-analysis of individual participant data from 25 cohort studies.

PURPOSE: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world. METHODS: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis. RESULTS: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRRpooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I2 = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRRpooled per 1 SD = 1.057, 95% CI 1.027-1.088). CONCLUSION: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed.

Population-based pattern of medication use and prevalence of polypharmacy among patients with cardiovascular diseases: results of the Pars cohort study from Iran.

BACKGROUND: Polypharmacy in patients with cardiovascular diseases (CVDs) has been linked to several adverse outcomes. This study aimed to investigate the pattern of medication use and prevalence of polypharmacy among CVDs patients in Iran. METHOD: We used the baseline data of the Pars cohort study (PCS). The participants were asked to bring their medication bags; then, the medications were classified using the Anatomical Therapeutic Chemical classification. Polypharmacy was defined as using five or more medications concurrently. Poisson regression modeling was applied. The adjusted prevalence ratios (PR) and its 95% confidence interval (CI) were estimated. RESULTS: Totally, 9262 participants were enrolled in the PCS, of whom 961 had CVDs. The prevalence of polypharmacy in participants with and without CVDs was 38.9% and 7.1%, respectively. The highest prevalence of polypharmacy (51.5%) was among obese patients. Abnormal waist-hip ratio (PR: 2.79; 95% CI 1.57-4.94), high socioeconomic status (PR: 1.65; 95% CI 1.07-2.54), tobacco-smoking (PR: 1.35; 95% CI 1.00-1.81), patients with more than three co-morbidities (PR: 1.41; 95% CI 1.30-1.53), high physical activity (PR: 0.66; 95% CI 0.45-0.95), use of opiate ever (PR: 0.46; 95% CI 0.26-0.82), and healthy overweight subjects (PR: 0.22; 95% CI 0.12-0.39) were associated with polypharmacy. Cardiovascular drugs (76.1%), drugs acting on blood and blood-forming organs (50.4%), and alimentary tract and metabolism drugs (33.9%) were the most frequently used drugs. Agents acting on the renin-angiotensin system were the mostly used cardiovascular system drugs among men and those above 60 years old, while beta-blocking agents were mostly prevalent among cardiovascular system drugs in women with CVDs. CONCLUSION: Given the high prevalence of polypharmacy among CVDs patients, and subsequent complications, programs to educate both physicians and patients to prevent this issue is crucial.