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Background/Objectives: Evidence about the relation between dietary patterns and cardiovascular disease (CVD) is scarce in Middle Eastern countries. This study was performed to examine the association between major dietary patterns and CVD mortality in Iranian adults. Subjects/Methods: This population-based prospective cohort study was conducted among 4834 randomly selected participants aged [greater-than or slanted equal to]35 years from urban and rural areas of central Iran (2001-2009) (the Isfahan Cohort Study). Dietary intakes were assessed using a food frequency questionnaire, and major dietary patterns were identified by means of exploratory factor analysis. Subjects or their next of kin were interviewed biannually looking for possible occurrence of events. Cardiovascular mortality was defined as fatal myocardial infarction, fatal stroke and sudden cardiac death. Results: During the median follow-up of 9.0 years and 50 282 person-years, we found a total of 118 CVD mortalities. Four major dietary patterns were identified: 'Western', 'Mediterranean', 'Animal fat' and 'Fast food'. Adherence to the Mediterranean dietary pattern was protectively associated with CVD mortality, such that those in the highest quartile were 46% (hazard ratio (HR): 0.54; 95% confidence interval (CI): 0.32-0.91; P-value for trend=0.03) less likely to have incident CVD mortality than those in the lowest quartile. Further adjustment for potential confounders strengthened this association (HR: 0.42; 95% CI: 0.19-0.96; P-value for trend=0.02). We found no significant association between adherence to the Western, animal fat and fast food dietary patterns and CVD mortality. Conclusions: Adherence to a Mediterranean dietary pattern was associated with reduced risk for cardiovascular mortality even in a developing country setting., Author(s): N Mohammadifard [sup.1] , M Talaei [sup.1] [sup.2] , M Sadeghi [sup.3] , S Oveisegharan [sup.4] , J Golshahi [sup.5] , A Esmaillzadeh [sup.6] [sup.7] , N Sarrafzadegan [sup.1] [...]

OBJECTIVES: To determine the prevalence of permanent and transient congenital hypothyroidism (CH) in Isfahan, Iran. METHODS: In 256 primarily diagnosed CH patients identified through the neonatal screening programme from May 2002 to February 2005, treatment was discontinued for 4 weeks and T4 and thyroid stimulating hormone (TSH) were measured. Permanent or transient CH was determined from the results of the thyroid function tests and the radiologic findings. Patients with TSH levels >6 (mIU/l) were diagnosed with permanent CH. RESULTS: Results were available from 204 patients, of whom 122 patients were diagnosed with permanent CH (59.8%) (prevalence 1:748 births), and 82 with transient hypothyroidism (prevalence 1:1114). Permanent CH was associated with higher initial TSH levels than transient hypothyroidism (P < 0.05). The most common aetiology of CH was dyshormonogenesis. CONCLUSION: The rates of both permanent and transient CH in our study were higher than the comparable worldwide rates. The transient group had low T4 levels, suggesting that iodine contamination should be investigated. The aetiology of CH was also different from that recorded in many other studies. [ABSTRACT FROM AUTHOR]

Abstract Introduction There is a remarkable increase in cardiovascular disease after menopause. On the other hand, metabolic syndrome as a collection of risk factors has a known effect on cardiovascular diseases. Hormone changes are considered as one of the main relevant factor regarding cardiovascular disease as well as some recognized relationship with metabolic syndrome's components. This study was carried out in order to search for prevalence of metabolic syndrome during menopausal transition. Method In a cross sectional study in urban and rural areas of Isfahan, Najafabad and Arak cities, 1596 women aged more than 45 years were investigated using Isfahan Healthy Heart Program's (IHHP) samples. Participants were categorized into three groups of pre-menopause, menopause and post-menopause. Leisure time physical activity and global dietary index were included as life style factors. The association of metabolic syndrome and its components with menopausal transition considering other factors such as age and life style was analyzed. Results there were 303, 233 and 987 women in premenopausal, early menopausal and postmenopausal groups respectively. Metabolic syndrome was found in 136(44.9%) premenopausal participants and significantly increased to 135(57.9%) and 634(64.3%) in early menopausal and postmenopausal participants respectively, when age was considered (P = 0.010). Except for hypertension and hypertriglyceridemia, there was no significant difference between three groups of menopausal transition when metabolic syndrome's components were considered. Conclusion In contrary to the claims regarding the role of waist circumference and blood glucose in increasing of metabolic syndrome during the menopausal transition, this study showed this phenomenon could be independence of them.

Lower lung function is associated with lower cognitive function and an increased risk of dementia. This has not been adequately explained and may partly reflect shared developmental pathways. In UK Biobank participants of European ancestry, we tested the association between lung function measures (forced vital capacity and forced expiratory volume in 1 s to forced vital capacity ratio; n = 306 476) and cognitive traits including nine cognitive function test scores ( n = 32 321-428 609), all-cause dementia, Alzheimer's disease and vascular dementia (6805, 2859 and 1544 cases, respectively, and ∼421 241 controls). In the same population, we derived summary statistics for associations between common genetic variants in 55 lung development genes and lung function measures and cognitive traits using adjusted linear/logistic regression models. Using a hypothesis-driven Bayesian co-localization analysis, we finally investigated the presence of shared genetic signals between lung function measures and cognitive traits at each of these 55 genes. Higher lung function measures were generally associated with higher scores of cognitive function tests as well as lower risk of dementia. The strongest association was between forced vital capacity and vascular dementia (adjusted hazard ratio 0.74 per standard deviation increase, 95% confidence interval 0.67-0.83). Of the 55 genes of interest, we found shared variants in four genes, namely: CSNK2B rs9267531 (forced vital capacity and forced expiratory volume in 1 s to forced vital capacity ratio with fluid intelligence and pairs matching), NFATC3 rs548092276 & rs11275011 (forced expiratory volume in 1 s to forced vital capacity ratio with fluid intelligence), PTCH1 rs2297086 & rs539078574 (forced expiratory volume in 1 s to forced vital capacity ratio with reaction time) and KAT8 rs138259061 (forced vital capacity with pairs matching). However, the direction of effects was not in keeping with our hypothesis, i.e. variants associated with lower lung function were associated with better cognitive function or vice versa. We also found distinct variants associated with lung function and cognitive function in KAT8 (forced vital capacity and Alzheimer's disease) and PTCH1 (forced vital capacity and forced expiratory volume in 1 s to forced vital capacity ratio with fluid intelligence and reaction time). The links between CSNK2B and NFATC3 and cognitive traits have not been previously reported by genome-wide association studies. Despite shared genes and variants, our findings do not support the hypothesis that shared developmental signalling pathways explain the association of lower adult lung function with poorer cognitive function., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Epidemiological evidence suggests that a higher intake of sugar during pregnancy is associated with a higher risk of childhood asthma and atopy. However, randomised trial evidence supporting such a link is lacking. This study aimed to examine whether a low glycaemic index (GI) dietary intervention during pregnancy decreases the risk of childhood asthma and eczema. This is a secondary analysis of 514 children from the ROLO trial. Healthy women were randomised to receive an intervention of low GI dietary advice or routine care from early pregnancy. Mothers reported current doctor-diagnosed eczema in their children at 2 years ( n 271) and current doctor-diagnosed asthma and eczema in their children at 5 ( n 357) and 9-11 years ( n 391) of age. Multivariable logistic regression models were used test the effect of the intervention on child outcomes overall and stratified by maternal education. There was a suggestion of a reduction in asthma at 5 years of age in children whose mothers received the low GI dietary intervention during pregnancy compared with usual care (adjusted OR 0·46 (95 % CI 0·19, 1·09); P = 0·08). In stratified adjusted analyses, the intervention was associated with a reduced risk of asthma at 5 years of age in children born to mothers with incomplete tertiary level education but not in those with complete tertiary level education (OR 0·14 (95 % CI 0·02, 0·69); P = 0·010 and OR 1·03 (95 % CI 0·34, 3·13); P = 0·94, respectively). A low GI diet in pregnancy may reduce the risk of developing asthma in childhood, particularly amongst children born to mothers with lower educational attainment.

Background: Although red meat consumption has been associated with risk of atherosclerotic coronary artery disease and stroke, no prospective study has examined this with the risk of chronic limb-threatening ischemia (CLTI)., Methods: In a prospective study of 63,257 Chinese in Singapore, who were aged 45-74 years old at recruitment, diet was assessed via a validated semi-quantitative food frequency questionnaire. Incident CLTI cases were ascertained via linkage with nationwide hospital records for lower extremity amputation or angioplasty for peripheral arterial disease. Multivariable Cox models were used to examine associations between quartiles of meat intake and CLTI risk., Results: After a mean follow-up of 18.8 years, there were 1069 cases of CLTI. Higher intake of red meat intake was associated with increased risk of CLTI in a stepwise manner. Comparing extreme quartiles of red meat intake, the hazard ratio (HR) for the association with CLTI risk was 1.24 [95% confidence interval (CI) = 1.03-1.49; P-trend = 0.02]. In stratified analysis, red meat intake had a stronger association with CLTI risk among those without diabetes [HR (95% CI) comparing extreme quartiles = 1.41 (1.10-1.80); P-trend = 0.03] than among those with diabetes at baseline [HR (95% CI) comparing extreme quartiles = 1.04 (0.79-1.38); P-trend = 0.05] (P-interaction = 0.03). Otherwise, the associations were not different by sex, BMI, smoking status, hypertension, alcohol consumption, or history of cardiovascular diseases. Using a theoretical model in substitution analysis that substituted three servings per week of red meat with poultry or fish/shellfish, the relative risk of CLTI was reduced by 13-14%., Conclusions: Consumption of red meat was associated with higher CLTI risk in this Asian cohort. Substituting red meat with poultry or fish/shellfish may reduce this risk., (© 2024. The Author(s).)

Background: Many mothers in high-income countries (HIC) do not breastfeed to the World Health Organisation's recommendation of two years. This is particularly true for low-income women (LIW). They often face additional socio-structural barriers that encourage early discontinuation and are inadequately supported by current healthcare interventions. Teleinterventions are flexible and widely used following the global pandemic and increase maternal autonomy over intervention delivery. They show promise in improving other maternal conditions in LIW, including postpartum depression. Teleinterventions can increase breastfeeding rates in the wider maternal population, however their efficacy for this underserved population has not yet been systematically assessed. This meta-analysis aimed to identify if teleinterventions increase 'exclusive' or 'any' breastfeeding by LIW in HIC at 1-, 3-4, and 6-months postpartum., Methods: We searched five online databases for randomised controlled trials assessing breastfeeding teleinterventions for LIW in HIC. Risk ratios (RR) were used to calculate the average effect of teleinterventions on 'any' and 'exclusive' breastfeeding at at 1-, 3-4, and 6-months postpartum using random effects meta-analysis. Study bias was assessed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB2), and outcome quality was evaluated against GRADE criteria., Results: Nine studies met inclusion criteria: six providing telephone calls, two text messages and one an online support group. All the studies were conducted in the United States, with small sample sizes and a high risk of bias. Pooled results indicate teleinterventions modestly increase 'any' and 'exclusive' breastfeeding at all time points, with a statistically significant increase in 'exclusive' breastfeeding after 3-4 months (RR 1.12, 95% CI [1.00,1.25]). At 3-4 months teleinterventions providing peer support were more effective than educational teleinterventions at promoting any and exclusive breastfeeding. Evidence for all outcomes were rated 'low' or 'very low' quality using the GRADE tool, mainly due to high attrition and low power., Conclusions: Despite insufficient high-quality research into breastfeeding teleinterventions for LIW, our results suggest teleinterventions may improve exclusive and any breastfeeding. Given breastfeeding is particularly low in LIW population from HIC, our findings are promising and require further exploration by larger, methodologically sound trials in other HIC., (© 2024. The Author(s).)

Objective: Obesity is a known risk factor for diabetes, but the effect of weight changes on the incidence of diabetes is not yet determined. This study aims to evaluate the long-term effects of weight change [based on body mass index (BMI)] on the incidence of diabetes mellitus (DM) in a middle eastern population., Method: In the Isfahan Cohort Study (ICS) 6504 adults equal or greater than 35 years of age were recruited at 2001 and were followed until 2013. Absolute BMI changes (ΔBMI) were calculated by subtracting the baseline BMI from the BMI measured at follow-ups. To compare participants with different baseline BMI easier, relative changes in BMI were quantified as the percentage of changes from baseline. DM was assessed based on standard definitions. Multivariable Cox regression was used to determine the association between ΔBMI and the incidence of diabetes., Results: During follow-ups, 261 new cases of diabetes were recorded, with an IR of 3401.29 per 100,000 P-Y. The highest number of new cases of type 2 DM belongs to participants with overweight and obesity who had minimal BMI changes (less than 5% of their baseline BMI limits; 42 and 38 new cases, respectively). Participants who were obese at baseline and had lost more than 10% or gained 5-10% of baseline BMI were in the groups with the highest IR [360.05-95% CI (239.3-541.8) and 322.39-95% CI (178.5-582.1) respectively]. There was no significant association between BMI changes and the incidence of DM in the participants with normal BMI, overweight, and obesity at baseline in cure and adjusted models., Conclusions: This study showed there was no significant association between diabetes mellitus incidence and BMI changes., Competing Interests: None., (©2023 Pacini Editore SRL, Pisa, Italy.)

Background: Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms., Methods: COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data for 16 potential long COVID symptoms and health-related quality of life (HRQoL), reported between January 21 and February 15, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (≥4 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). This study is registered with ClinicalTrials.gov, NCT04330599., Findings: We included 10,171 participants (1311 [12.9%] with SARS-CoV-2 infection, 472 [4.6%] with non-COVID-19 ARI). Both types of infection were associated with increased prevalence/severity of most symptoms and decreased HRQoL compared with no infection. Participants with SARS-CoV-2 infection had increased odds of problems with taste/smell (odds ratio 19.74, 95% CI 10.53-37.00) and lightheadedness or dizziness (1.74, 1.18-2.56) compared with participants with non-COVID-19 ARIs. Separate LCA models identified three symptom severity groups for each infection type. In the most severe groups (representing 22% of participants for both SARS-CoV-2 and non-COVID-19 ARI), SARS-CoV-2 infection presented with a higher probability of problems with taste/smell (probability 0.41 vs 0.04), hair loss (0.25 vs 0.16), unusual sweating (0.38 vs 0.25), unusual racing of the heart (0.43 vs 0.33), and memory problems (0.70 vs 0.55) than non-COVID-19 ARI., Interpretation: Both SARS-CoV-2 and non-COVID-19 ARIs are associated with a wide range of symptoms more than 4 weeks after the acute infection. Research on post-acute sequelae of ARIs should extend from SARS-CoV-2 to include other pathogens., Funding: Barts Charity., Competing Interests: PEP declares grants paid to their institution from the National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI). The remaining authors declare no competing interests., (© 2023 The Author(s).)

Purpose: The link between metabolic syndrome (MetS) and various stressors has not been thoroughly investigated. We aimed to examine the relationship between MetS and different perceived stressors., Methods: In this study, we included participants of the Isfahan Cohort study from three counties in central Iran, with data in the 2007 ( n  = 3178) and 2013 ( n  = 1693) follow-up stages. We examined the association between distress and perceived stress domains (including job security, job conflicts, personal conflicts, loss and separation, social relations, and health concerns) and MetS., Results: MetS was identified in 35.8% of participants in the 2007 cohort and 46.2% in the 2013 cohort. In the fully adjusted analysis, the odds ratio (OR) (95%CI) for MetS according to psychological status was 1.65 (1.64-1.65) for psychological distress level, 1.09 (1.01-1.20) for psychological distress score, and 1.21 (1.09-1.42) for total perceived stress score. There was also evidence of association for social relations, personal conflicts, job conflicts, job security, health concern, loss and separation, educational concerns, and sexual life subscales., Conclusion: Perceived stressors and some of their subscales were associated with MetS., Competing Interests: Conflicts of interestAll authors declare that there is no conflict of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Cardiovascular diseases (CVD) are the predominant cause of early death worldwide. Identification of people with a high risk of being affected by CVD is consequential in CVD prevention. This study adopts Machine Learning (ML) and statistical techniques to develop classification models for predicting the future occurrence of CVD events in a large sample of Iranians., Methods: We used multiple prediction models and ML techniques with different abilities to analyze the large dataset of 5432 healthy people at the beginning of entrance into the Isfahan Cohort Study (ICS) (1990-2017). Bayesian additive regression trees enhanced with "missingness incorporated in attributes" (BARTm) was run on the dataset with 515 variables (336 variables without and the remaining with up to 90% missing values). In the other used classification algorithms, variables with more than 10% missing values were excluded, and MissForest imputes the missing values of the remaining 49 variables. We used Recursive Feature Elimination (RFE) to select the most contributing variables. Random oversampling technique, recommended cut-point by precision-recall curve, and relevant evaluation metrics were used for handling unbalancing in the binary response variable., Results: This study revealed that age, systolic blood pressure, fasting blood sugar, two-hour postprandial glucose, diabetes mellitus, history of heart disease, history of high blood pressure, and history of diabetes are the most contributing factors for predicting CVD incidence in the future. The main differences between the results of classification algorithms are due to the trade-off between sensitivity and specificity. Quadratic Discriminant Analysis (QDA) algorithm presents the highest accuracy (75.50 ± 0.08) but the minimum sensitivity (49.84 ± 0.25); In contrast, decision trees provide the lowest accuracy (51.95 ± 0.69) but the top sensitivity (82.52 ± 1.22). BARTm.90% resulted in 69.48 ± 0.28 accuracy and 54.00 ± 1.66 sensitivity without any preprocessing step., Conclusions: This study confirmed that building a prediction model for CVD in each region is valuable for screening and primary prevention strategies in that specific region. Also, results showed that using conventional statistical models alongside ML algorithms makes it possible to take advantage of both techniques. Generally, QDA can accurately predict the future occurrence of CVD events with a fast (inference speed) and stable (confidence values) procedure. The combined ML and statistical algorithm of BARTm provide a flexible approach without any need for technical knowledge about assumptions and preprocessing steps of the prediction procedure., (© 2023. The Author(s).)

Background: Longitudinal epidemiological data are scarce examining the relationship between dietary patterns and respiratory outcomes in childhood. We investigated whether three distinct dietary patterns in mid-childhood were associated with lung function and incident asthma in adolescence., Methods: In the Avon Longitudinal Study of Parents and Children, 'processed', 'traditional', and 'health-conscious' dietary patterns were identified using principal components analysis from food frequency questionnaires at 7 years of age. Post-bronchodilator forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), and forced expiratory flow at 25-75% of FVC (FEF 25-75 ) were measured at 15.5 years and were transformed to z-scores based on the Global Lung Function Initiative curves. Incident asthma was defined by new cases of doctor-diagnosed asthma at age 11 or 14 years., Results: In multivariable-adjusted models, the 'health-conscious' pattern was positively associated with FEV 1 (regression coefficient comparing top versus bottom quartile of pattern score 0.16, 95% CI 0.01 to 0.31, P for trend 0.04) and FVC (0.18, 95% CI 0.04 to 0.33, P for trend 0.02), while the 'processed' pattern was negatively associated with FVC (- 0.17, 95% CI - 0.33 to - 0.01, P for trend 0.03). Associations between the 'health-conscious' and 'processed' patterns and lung function were modified by SCGB1A1 and GPX4 gene polymorphisms. We found no evidence of an association between the 'traditional' pattern and lung function, nor between any pattern and FEF 25-75 or incident asthma., Conclusions: A 'health-conscious' diet in mid-childhood was associated with higher subsequent lung function, while a diet high in processed food was associated with lower lung function., (© 2023. The Author(s).)

Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake., (© 2023. The Author(s).)

Background: Little is known about how demographic, behavioural, and vaccine-related factors affect risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations., Methods: This prospective, population-based, UK study in adults (≥16 years) vaccinated against SARS-CoV-2 assessed risk of breakthrough SARS-CoV-2 infection up to February, 2022, for participants who completed a primary vaccination course (ChAdOx1 nCoV-19 or BNT162b2) and those who received a booster dose (BNT162b2 or mRNA-1273). Cox regression models explored associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and test-positive breakthrough infection, adjusted for local weekly SARS-CoV-2 incidence., Findings: 1051 (7·1%) of 14 713 post-primary participants and 1009 (9·5%) of 10 665 post-booster participants reported breakthrough infection, over a median follow-up of 203 days (IQR 195-216) and 85 days (66-103), respectively. Primary vaccination with ChAdOx1 ( vs BNT162b2) was associated with higher risk of infection in both post-primary analysis (adjusted hazard ratio 1·63, 95% CI 1·41-1·88) and after an mRNA-1273 booster (1·26 [1·00-1·57] vs BNT162b2 primary and booster). Lower risk of infection was associated with older age (post-primary: 0·97 [0·96-0·97] per year; post-booster: 0·97 [0·97-0·98]), whereas higher risk of infection was associated with lower educational attainment (post-primary: 1·78 [1·44-2·20] for primary/secondary vs postgraduate; post-booster: 1·46 [1·16-1·83]) and at least three weekly visits to indoor public places (post-primary: 1·36 [1·13-1·63] vs none; post-booster: 1·29 [1·07-1·56])., Interpretation: Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough infection after primary and booster vaccinations., Funding: Barts Charity, UK Research and Innovation Industrial Strategy Challenge Fund., Competing Interests: R.A.L. has received grants from UKRI Medical Research Council, UKRI Economic and Social Research Council, Health Data Research UK, and Health and Care Research Wales. R.A.L. is a member of the Welsh Government COVID-19 Technical Advisory group, in an unremunerated role. A.S. is a member of the Scottish Government's Standing Committee on Pandemics, the Scottish Science Advisory Council, the UK Government's New and Emerging Respiratory Virus Threats Risk Stratification Subgroup and the Department of Health and Social Care's COVID-19 Therapeutics Modelling Group. He was a member of the Scottish Government Chief Medical Officer's COVID-19 Advisory Group and AstraZeneca's Thrombotic Thrombocytopenic Taskforce. All of A.S.’ roles are unremunerated. A.R.M. declares receipt of funding to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord DSM Nutritional Products, Thornton & Ross, and Hyphens Pharma. A.R.M. also declares support for attending meetings from the following companies who manufacture or sell vitamin D supplements: Pharma Nord and Abiogen Pharma. A.R.M. also declares participation on the Data and Safety Monitoring Board for the Chair, DSMB, VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology). A.R.M. also declares unpaid work as a Programme Committee member for the Vitamin D Workshop. A.R.M. also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord, Synergy Biologics, and Cytoplan. All other authors declare no competing interests., (© 2022 The Authors.)

Antibody responses to SARS-CoV-2 vaccines vary for reasons that remain poorly understood. A range of sociodemographic, behavioural, clinical, pharmacologic and nutritional factors could explain these differences. To investigate this hypothesis, we tested for presence of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies before and after 2 doses of ChAdOx1 nCoV-19 (ChAdOx1, AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine between December 2020 and July 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacologic and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Additionally, percentage differences in antibody titres between groups were estimated in the sub-set of participants who were seropositive post-vaccination using linear regression. Anti-spike antibodies were undetectable in 378/9101 (4.2%) participants at a median of 8.6 weeks post second vaccine dose. Increased risk of post-vaccination seronegativity associated with administration of ChAdOx1 vs. BNT162b2 (adjusted odds ratio (aOR) 6.6, 95% CI 4.2−10.4), shorter interval between vaccine doses (aOR 1.6, 1.2−2.1, 6−10 vs. >10 weeks), poor vs. excellent general health (aOR 3.1, 1.4−7.0), immunodeficiency (aOR 6.5, 2.5−16.6) and immunosuppressant use (aOR 3.7, 2.4−5.7). Odds of seronegativity were lower for participants who were SARS-CoV-2 seropositive pre-vaccination (aOR 0.2, 0.0−0.6) and for those taking vitamin D supplements (aOR 0.7, 0.5−0.9). Serologic responses to vaccination did not associate with time of day of vaccine administration, lifestyle factors including tobacco smoking, alcohol intake and sleep, or use of anti-pyretics for management of reactive symptoms after vaccination. In a sub-set of 8727 individuals who were seropositive post-vaccination, lower antibody titres associated with administration of ChAdOx1 vs. BNT162b2 (43.4% lower, 41.8−44.8), longer duration between second vaccine dose and sampling (12.7% lower, 8.2−16.9, for 9−16 weeks vs. 2−4 weeks), shorter interval between vaccine doses (10.4% lower, 3.7−16.7, for <6 weeks vs. >10 weeks), receiving a second vaccine dose in October−December vs. April−June (47.7% lower, 11.4−69.1), older age (3.3% lower per 10-year increase in age, 2.1−4.6), and hypertension (4.1% lower, 1.1−6.9). Higher antibody titres associated with South Asian ethnicity (16.2% higher, 3.0−31.1, vs. White ethnicity) or Mixed/Multiple/Other ethnicity (11.8% higher, 2.9−21.6, vs. White ethnicity), higher body mass index (BMI; 2.9% higher, 0.2−5.7, for BMI 25−30 vs. <25 kg/m2) and pre-vaccination seropositivity for SARS-CoV-2 (105.1% higher, 94.1−116.6, for those seropositive and experienced COVID-19 symptoms vs. those who were seronegative pre-vaccination). In conclusion, we identify multiple determinants of antibody responses to SARS-CoV-2 vaccines, many of which are modifiable.

Background: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking., Methods: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020, and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively., Results: Of 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with  higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48-2.33), international travel (1.20, 1.07-1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06-1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m 2 (1.24, 1.11-1.39), South Asian vs. White ethnicity (1.65, 1.10-2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04-1.46). Light physical exercise associated with  lower risk (0.80, 0.70-0.93, for ≥ 10 vs. 0-4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m 2 (aGMR 1.10, 1.02-1.19), South Asian vs. White ethnicity (1.22, 1.04-1.44), frontline health/care occupation (1.24, 95% CI 1.11-1.39), international travel (1.11, 1.05-1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02-1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity., Conclusions: Higher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups., (© 2022. The Author(s).)

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

Background: Longitudinal epidemiological data are scarce on the relationship between dietary intake of vitamin A and respiratory outcomes in childhood. We investigated whether a higher intake of preformed vitamin A or pro-vitamin β-carotene in mid-childhood is associated with higher lung function and with asthma risk in adolescence., Methods: In the Avon Longitudinal Study of Parents and Children, dietary intakes of preformed vitamin A and β-carotene equivalents were estimated by food frequency questionnaire at 7 years of age. Post-bronchodilator forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (FEF 25-75% ) were measured at 15.5 years and transformed to z-scores. Incident asthma was defined by new cases of doctor-diagnosed asthma at age 11 or 14 years., Results: In multivariable adjusted models, a higher intake of preformed vitamin A was associated with higher lung function and a lower risk of incident asthma: comparing top versus bottom quartiles of intake, regression coefficients for FEV 1 and FEF 25-75% were 0.21 (95% CI 0.05-0.38; p trend =0.008) and 0.18 (95% CI 0.03-0.32; p trend =0.02), respectively; odds ratios for FEV 1 /FVC below the lower limit of normal and incident asthma were 0.49 (95% CI 0.27-0.90; p trend =0.04) and 0.68 (95% CI 0.47-0.99; p trend =0.07), respectively. In contrast, there was no evidence for association with β-carotene. We also found some evidence for modification of the associations between preformed vitamin A intake and lung function by BCMO1 , NCOR2 and SCGB1A1 gene polymorphisms., Conclusion: A higher intake of preformed vitamin A, but not β-carotene, in mid-childhood is associated with higher subsequent lung function and lower risk of fixed airflow limitation and incident asthma., Competing Interests: Conflict of interest: M. Talaei has nothing to disclose. Conflict of interest: D.A. Hughes has nothing to disclose. Conflict of interest: O. Mahmoud has nothing to disclose. Conflict of interest: P.M. Emmett reports grants from Nestle Nutrition, personal fees for consultancy from the European Food Safety Authority, outside the submitted work. Conflict of interest: R. Granell has nothing to disclose. Conflict of interest: S. Guerra has nothing to disclose. Conflict of interest: S.O. Shaheen has nothing to disclose., (Copyright ©The authors 2021.)

Longitudinal evidence on the relation between dietary intake of n -3 (ω-3) very-long-chain polyunsaturated fatty acids, i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mid-childhood and asthma risk is scarce. We aimed to investigate whether a higher intake of EPA and DHA from fish in childhood is associated with a lower risk of incident asthma.In the Avon Longitudinal Study of Parents and Children, dietary intakes of EPA and DHA from fish were estimated by food frequency questionnaire at 7 years of age. We used logistic regression, controlling for confounders, to analyse associations between intake of EPA and DHA (quartiles) and incidence of doctor-diagnosed asthma at age 11 or 14 years, and explored potential effect modification by a fatty acid desaturase ( FADS ) polymorphism (rs1535). Replication was sought in the Swedish BAMSE birth cohort.There was no evidence of association between intake of EPA plus DHA from fish and incident asthma overall (n=4543). However, when stratified by FADS genotype, the odds ratio comparing the top versus bottom quartile among the 2025 minor G allele carriers was 0.49 (95% CI 0.31-0.79; p trend =0.006), but no inverse association was observed in the homozygous major A allele group (OR 1.43, 95% CI 0.83-2.46; p trend =0.19) (p interaction =0.006). This gene-nutrient interaction on incident asthma was replicated in BAMSE.In children with a common FADS variant, higher intake of EPA and DHA from fish in childhood was strongly associated with a lower risk of incident asthma up to mid-adolescence., Competing Interests: Conflict of interest: M. Talaei has nothing to disclose. Conflict of interest: E. Sdona has nothing to disclose. Conflict of interest: P.C. Calder has nothing to disclose. Conflict of interest: L.R. Jones reports grants from Nestle Nutrition, outside the submitted work. Conflict of interest: P.M. Emmett reports grants from Nestle Nutrition, outside the submitted work. Conflict of interest: R. Granell has nothing to disclose. Conflict of interest: A. Bergström has nothing to disclose. Conflict of interest: E. Melén has nothing to disclose. Conflict of interest: S.O. Shaheen has nothing to disclose., (Copyright ©The authors 2021.)

Background: Besides the traditional cardiovascular risk factor, some novel risk factors like occupation and career can play an important role in cardiovascular disease (CVDs) incidence., Objective: To assess the association between occupational categories and their positions with cardiovascular events (CVEs) in an Iranian male population., Methods: We followed 2134 men aged 35-65 years for 14 years during the Isfahan Cohort Study (2001-2015) for CVEs including ischemic heart disease and stroke. Firstly, Occupations were classified into 10 categories of International Standard Classification of Occupation (ISCO). Each category was then classified into one of the 4 pre-specified categories, namely high/low skilled white collars and high/low skilled blue collars. White-collar workers referred to managerial and professional workers in contrast with blue collar workers, whose job requires manual labor., Results: The mean age of studied participants was 46.9 (SD 8.3) years. 286 CVE incidents were recorded; unstable angina had the highest rate (46%); fatal stroke, the lowest (3%). There were no significant difference was observed between white and blue collars in terms of CVE incidence, as well as their high and low skilled subgroups. Hazard ratio analysis indicated a significantly higher risk of CVEs only for low-skilled white-collar workers (crude HR 1.47, 95% CI 1.01 to 2.13); this was not significant after adjustment for confounding variables., Conclusion: There is no association between occupational categories and incidence of cardiovascular events among Iranian male population.

Introduction: In spite of traditional cardiovascular risk factor, the different occupations can play an important role in cardiovascular disease (CVDs) incidence. We aimed to assess the correlation between the occupational classes, based on the International Standard Classification of Occupation (ISCO), and CVDs in Iran as a developing country., Methods: We followed the 2440 men, aged 35-65 years and without history of CVDs over fourteen years; 2001 to 2015 during the Isfahan Cohort Study. ISCO was used to classify occupations into 10 categories. Incidence rates of ischemic heart diseases and stroke were recorded. Socioeconomic demographic data including marital state, income and place of living and metabolic risk factors were also recorded., Results: The mean age was 46.97 ± 8.31 years old. 272 cardiovascular events (CVEs) were recorded that unstable angina was the highest recorded with 49% prevalence and the fatal stroke had the lowest outbreak (1%). The unemployed/jobless group and elementary occupations (9th ISCO category) had higher and lower relative frequency in CVEs respectively. There was non-significant decrease in CVEs in all of categories except of 4 th (clerical support workers) and 10th (armed forces) groups in comparison to unemployed/jobless subjects (P > 0.05). After considering of the group 7 as a reference group (most absolute CVEs frequency), in fully adjustment analysis group 4 had significant risk for CVEs (P = 0.04)., Conclusions: This study indicates that working as clerical support workers (4 th ISCO category) is associated with higher significant risk for IHD and stroke incidence in comparison to craft and related trades workers (7 th group of ISCO)., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (©2020 Pacini Editore srl, Pisa, Italy.)

Background: High sensitivity C-reactive protein (hs-CRP) was proven to be an independent risk factor for cardiovascular diseases (CVDs). The aim of this study was to investigate the benefits of assessing hs-CRP among individuals with different cardiovascular risk factors., Methods: This nested case-control study was obtained from the Isfahan Cohort Study (ICS). Anyone who has been suffering from any CVDs, including myocardial infarction, unstable angina, sudden cardiac death and stroke was put in the case group. Density sampling method was utilized to choose the control group who had no aforementioned CVDs during follow-up. Four quartiles of hs-CRP (Q1: 0.1-2.3, Q2: 2.4-3, Q3: 3.1-4 and Q4: 4.1-14 mg/l) were assessed defining odds ratios (OR) of CVDs prediction in different CVDs risk factor categories. Confidence intervals of 95% are put in brackets., Results: A total of 502 cases and 538 controls were recruited. All hs-CRP quartiles showed increased CVDs likelihood compared to normal subjects in terms of diabetes mellitus (DM) and hypertension (HTN). Second quartile showed a 1.93 [1.33-2.81] and 3.34 [1.36-8.17] increased risks in patients with hypertriglyceridemia or dyslipidemia, respectively. Smokers in the third quartile group revealed increased CVDs risk. The fourth quartile showed significant increased risks in patients suffering from hypercholesterolemia (OR = 1.91 [1.33-2.74]), high LDL-C (OR = 1.88 [1.33-2.66]), and hypertriglyceridemia (OR = 2.31 [1.57-3.41])., Conclusions: Our findings suggested that assessing hs-CRP is beneficial for predicting CVDs in patients with HTN and DM. Furthermore, specific patients with lipid abnormalities or history of smoking benefits from checking hs-CRP., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Background: The current diagnostic cornerstone for septic arthritis contains gram stains, bacterial culture, and cell count with a differential of aspirated synovial fluid. Recently, a synovial leukocyte esterase (LE) test has been used for diagnosing septic arthritis. Since this test measures the esterase activity of leukocytes, there is always a dilemma for using this test in patients with inflammatory arthritis., Methods: We collected the synovial fluid specimens as part of the general diagnostic protocol for patients suspected of Juvenile Idiopathic Arthritis (JIA) or Septic Arthritis (SA). Each group included 34 patients. We compared the result of the synovial LE test with the result of the culture of each patient., Results: The mean ages of patients were 64.14 ± 31.27 and 50.88 ± 23.19 months in the JIA group and septic arthritis group, respectively. The LE test results were positive in 30 specimens, trace in 3 and negative in one in the first-time test and were positive in 31 specimens and trace in 3 in the second-time test, while it was negative in all patients with JIA. Hence, the sensitivity of the synovial LE test was 80.8%, the specificity, PPV, and NPV were 78.6, 70.0, 86.8% respectively based on a positive culture., Conclusion: The leukocyte esterase strip test can be used as a rapid, bedside method for diagnosing or excluding bacterial infections in different body fluids. The synovial LE test can be used as an accurate test to rapidly rule in or out an acute articular bacterial infection, even in patients with concurrent inflammatory arthritis.

Background Although hypertension is an established risk factor for chronic kidney disease, less is known about the relationship of pulse pressure (PP), a measure of arterial stiffness, with chronic kidney disease. We investigated the association of systolic blood pressure (BP), diastolic BP, PP, and mean arterial pressure with the risk of end-stage renal disease (ESRD) in the prospective population-based Singapore Chinese Health Study. Methods and Results We used data from 30 636 participants who had BP measured at ages 46 to 85 years during follow-up I interviews between 1999 and 2004. Information on lifestyle factors was collected at recruitment from 1993 to 1998, and selected factors were updated at follow-up I. We identified 463 ESRD cases over an average 11.3 years of follow-up I by linkage with the nationwide Singapore Renal Registry. Cox proportional hazards regression models were used to assess the relations between different BP indexes and ESRD risk. Each BP index was positively associated with ESRD when studied individually. However, when PP was included as a covariate, systolic and diastolic BP and mean arterial pressure were no longer associated with ESRD. Conversely, PP remained significantly associated with ESRD risk in a dose-dependent manner ( P trend <0.001) after adjusting for systolic or diastolic BP. Compared with the lowest group (<45 mm Hg) of PP, the hazard ratio was 5.25 (95% CI, 3.52-7.84) for the highest group (≥85 mm Hg). The association between hypertension and ESRD risk was attenuated and no longer significant after adjusting for PP. Conclusions Our findings provide a basis for targeting reduction of arterial stiffness to decrease ESRD risk.

A 10-year longitudinal population-based study entitled Isfahan Cohort Study (ICS) was conducted in 2001-2011 with cardiovascular disease (CVD) as the primary outcome. We considered ICS as a master plan for a multi-level non-communicable disease (NCD) study named Isfahan Cohort Study 2 (ICS2). ICS2 is a multi-generation 10-year cohort study with new goals and outcomes that have been started in 2013, recruiting a sub-sample of ICS (n = 1487) and a new recruited sample (n = 1355) aged 35 years and over, all living in urban and rural areas of two counties in central Iran. In addition, 2500 of participant's adult children were selected randomly, as well as 1000 of their grandchildren. The aim of ICS2 is to detect the incidence of some NCDs including CVD, cancers, and diabetes and to identify the impact of their behavioral, metabolic, environmental, and genetic risk factors. In addition, studying lifestyle behaviors in three generations in a hierarchical manner of parents, their children and grandchildren in ICS2 will improve our knowledge on other determinants such as epigenetics of NCDs.

Objective: The aim of the present study was to assess different obesity indices, as well as their best cut-off point, to predict the occurrence of hypertension (HTN) in an Iranian population., Methods: In a population-based study, subjects aged 35 years and older were followed for 7 years. Blood pressure was measured at baseline and after the follow-up. Anthropometry indices included body mass index (BMI), body adiposity index (BAI), the waist-to-height ratio (WHtR), the waist-to-hip ratio (WHpR), and waist and hip circumferences (WC and HC). Logistic regression was employed to calculate the odds ratio (OR) and 95% confidence intervals (CI) per standard deviation (SD) increment. The operating characteristic analysis was used to derive the best cut-off value for each index., Results: Among original 6504 participants, 2450 subjects who had no cardiovascular diseases (CVD) and HTN at baseline were revisited, and 542 (22.1%) new cases of HTN were detected. There were minimal differences between most indices in the adjusted models; however, the best HTN predictors were BMI (OR per SD 1.32; 95% CI 1.12-1.56) and almost equally WC (1.35; 1.13-1.60) in men and WC (1.20; 1.04-1.39) in women. As a binary predictor, BMI with a cut-off point of 24.9 kg/m2 in men (1.91; 1.40-2.62) and WC with a cut-off point of 98 cm in women (1.57; 1.17-2.10) were the best in adjusted models. WC, WHpR, and WHtR were significantly associated with an increased risk of HTN only in participants whose weight was normal (BMI, 18.5-24.9 kg/m2)., Conclusion: Therefore, BMI in men and WC in women were the best predictors of HTN, both as continuous and binary factors at their appropriate cut-off points.

Background The association of the Dietary Approaches to Stop Hypertension ( DASH ) dietary pattern with stroke and coronary artery disease ( CAD ) mortality has not been evaluated in Asian populations, and the role of mineral intakes as potential mediators is not clear. Methods and Results We used data from 57 078 participants of the Singapore Chinese Health Study aged 45 to 74 years at baseline (1993-1998). Information on usual diet was collected by a validated 165-item food frequency questionnaire at recruitment, and mortality information was obtained via registry linkage up to December 31, 2014. We constructed DASH scores based on quintiles of intake of 7 predefined food items and sodium. Cox proportional hazard models were used to calculate hazard ratios and corresponding 95% CIs. Greater adherence to the DASH dietary pattern was significantly associated with a lower risk of CAD (hazard ratio between extreme quintiles, 0.76; 95% CI , 0.65-0.90; P trend<0.001) and stroke (hazard ratio, 0.62; 95% CI , 0.50-0.78; P trend<0.001) mortality. We found an inverse association between potassium intake and CAD mortality and a direct association between sodium intake and stroke mortality. No other significant associations were observed for potassium, sodium, magnesium, and calcium intakes in relation to CAD or stroke mortality. Adjustment for mineral intakes did not materially change the association of the DASH score with CAD or stroke mortality. Conclusions Adherence to the DASH dietary pattern was associated with substantially lower risk of CAD and stroke mortality in an Asian population, and this inverse association did not appear to be substantially mediated by intakes of sodium, potassium, magnesium, and calcium.

Background: Previous studies revealed that the level of 25-hydroxyvitamin D [25(OH)D] could be consider as one the risk factors for the occurrence of cardiovascular diseases (CVDs). This study aimed to evaluate the relationship between serum 25(OH)D level and CVD events in individuals with and without metabolic syndrome (MetS) in an Iranian population., Methods: In this nested case-control study conducted as a part of the Isfahan Cohort Study (ISC), 55 patients with CVD events were selected as case group, and 55 sex- and age-matched individuals without CVD events as control group. These participants were divided into the two main groups based on the presence of MetS at baseline., Results: The level of 25(OH)D in individuals with and without MetS was significantly lower among patients with CVD compared to those without CVD events at the baseline of study and after the follow-up (P = 0.036 and P = 0.039, respectively). The level of 25(OH)D significantly decreased risk of incidence of CVD events in individuals without MetS after adjusting for age, sex, nutrition, and exposure to sunlight [0.19 (0.05-0.73); P = 0.016]. There was not any significant relationship between the amount of 25(OH)D at the baseline and CVD events in individuals with MetS., Conclusion: In individuals with MetS, the level of 25(OH)D is not related to CVD events; as MetS directly influence the pathophysiology of mechanisms which are responsible for CVD events, and maybe this effect obscure the effect of 25(OH)D.

[This corrects the article DOI: 10.1371/journal.pone.0202554.].

Objectives: While the effect of physical activity on knee osteoarthritis (KOA) remains controversial, how sitting and sleep durations affect KOA is unknown. We evaluated the association between durations of physical activity, sitting and sleep, and incidence of total knee replacement (TKR) due to severe KOA., Methods: We used data from the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese, aged 45-74 years at recruitment from 1993-1998. Height, weight, lifestyle factors, hours of sitting and sleep per day, and hours of moderate activity, strenuous sports or vigorous work per week were assessed through in-person interviews using structured questionnaires. Incident cases of TKR were identified via record linkage with nationwide hospital discharge database., Results: Compared to those with <0.5 hour/week of moderate physical activity, participants with ≥5 hour/week had increased risk of TKR risk [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.00-1.35]. Conversely, duration of sitting activities, especially sitting at work, was associated with reduced risk in a stepwise manner. Compared to <4 hour/day of sitting, those with ≥12 hour/day had the lowest risk (HR 0.76, 95% CI 0.60-0.96, p for trend = 0.02). Sleep duration was inversely associated with reduced risk of TKR in a dose-dependent manner; compared to those with sleep ≤ 5 hour/day, participants with ≥ 9 hour/day had the lowest risk (HR 0.55, 95% CI) 0.43-0.70, p for trend <0.001)., Conclusion: While prolonged sitting or sleeping duration could be associated with reduced risk of severe KOA, extended duration of physical activity could be associated with increased risk., Competing Interests: The authors have declared that no competing interests exist.

Background: The new American College of Cardiology/American Heart Association high blood pressure (BP) guidelines in the United States have lowered definition of hypertension by defining normal as systolic/diastolic BP <120/80 mm Hg; elevated BP as systolic between 120 and 129 mm Hg and diastolic <80 mm Hg; and stage 1 hypertension as systolic between 130 and 139 mm Hg or diastolic between 80 and 89 mm Hg., Methods and Results: We investigated the association between the new hypertension definition and cardiovascular disease mortality among Chinese in Singapore. We used data from 30 636 participants of a population-based cohort, the SCHS (Singapore Chinese Health Study), who had BPs measured using a standard protocol at ages 46 to 85 years between 1994 and 2005. Information on lifestyle factors was collected at recruitment (1993-1998) and follow-up 1 interviews (1999 and 2004). Mortality was identified via nationwide registry linkage up to December 31, 2016. Neither elevated BP (hazard ratio, 0.89; 95% confidence interval, 0.74-1.07) nor stage 1 hypertension (hazard ratio, 0.94; 95% confidence interval, 0.81-1.11) was associated with increased risk of cardiovascular mortality compared with normal BP in the whole cohort. Stage 1 hypertension was associated with increased cardiovascular risk only in those <65 years of age and without a history of cardiovascular disease (hazard ratio, 1.40; 95% confidence interval, 1.01-1.94), but not in those ≥65 years of age or with a history of cardiovascular disease., Conclusions: Our data suggest that the newly defined stage 1 hypertension may not be associated with increased cardiovascular mortality across all ages among Chinese in Singapore, but that the at-risk subpopulation is limited to those <65 years of age and without a prior cardiovascular disease., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

We evaluated the relationships of red meat, poultry, fish, and shellfish intakes, as well as heme iron intake, with the risk of type 2 diabetes mellitus (T2D).The Singapore Chinese Health Study is a population-based cohort study that recruited 63,257 Chinese adults aged 45-74 years from 1993 to 1998. Usual diet was evaluated using a validated 165-item semiquantitative food frequency questionnaire at recruitment. Physician-diagnosed T2D was self-reported during 2 follow-up interviews in 1999-2004 and 2006-2010. During a mean follow-up of 10.9 years, 5,207 incident cases of T2D were reported. When comparing persons in the highest intake quartiles with those in the lowest, the multivariate-adjusted hazard ratio for T2D was 1.23 (95% confidence interval (CI): 1.14, 1.33) for red meat intake (P for trend < 0.001), 1.15 (95% CI: 1.06, 1.24) for poultry intake (P for trend = 0.004), and 1.07 (95% CI: 0.99, 1.16) for fish/shellfish intake (P for trend = 0.12). After additional adjustment for heme iron, only red meat intake remained significantly associated with T2D risk (multivariate-adjusted hazard ratio = 1.13, 95% CI: 1.01, 1.25; P for trend = 0.02). Heme iron was associated with a higher risk of T2D even after additional adjustment for red meat intake (multivariate-adjusted hazard ratio = 1.14, 95% CI: 1.02, 1.28; P for trend = 0.03). In conclusion, red meat and poultry intakes were associated with a higher risk of T2D. These associations were mediated completely for poultry and partially for red meat by heme iron intake., (© The Author(s) 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.)

The relationship between body mass index (BMI) and end-stage renal disease (ESRD) is confounded by co-morbidities associated with both conditions. Furthermore, the association at low range BMI is controversial. We studied this association in the Singapore Chinese Health Study, a population-based prospective cohort that recruited Singaporean Chinese men and women 45-74 years of age from 1993 to 1998. Self-reported weight, height, lifestyle factors, usual diet, and medical history were collected via an interviewer-administered questionnaire. Incident ESRD cases were identified via record linkage with the nationwide ESRD registry. The computed Cox proportional hazard regression was adjusted for potential risk factors. After an average follow-up of 15.5 years, 827 incident ESRD cases were identified. Compared with a normal BMI of 18.5 to under 23 kg/m 2 , the hazard ratios and (95% confidence intervals) of ESRD risk for BMIs under 18.5, 23 to under 27.5, and 27.5 kg/m 2 or more were 0.54 (0.37-0.79), 1.40 (1.20-1.64) and 2.13 (1.74-2.59), respectively. This significantly trended, linear, dose-dependent association was only present among those with no history of diabetes, hypertension, coronary heart disease, and stroke at baseline, but not significantly among those with any of these co-morbidities. Thus, BMI itself is a risk factor for ESRD in the general population and this association is present in those without pre-existing diabetes, hypertension, coronary heart disease, and stroke., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological evidence from Western populations suggests that dairy food intake may reduce the risk of hypertension, probably through its calcium content. However, there are no epidemiological studies among Asian populations with generally lower dairy and calcium consumption., Objective: The relation between dairy or calcium intake and risk of hypertension was evaluated in a Chinese population in Singapore., Methods: The analysis included 37,124 Chinese men and women aged 45-74 y who participated in the Singapore Chinese Health Study in 1993-1998. The subjects included in the present study had no history of cancer, hypertension, or cardiovascular disease at baseline and completed ≥1 follow-up interview. Diet at baseline was assessed by using a validated 165-item semiquantitative food-frequency questionnaire. The occurrence of new, physician-diagnosed hypertension was ascertained through follow-up interviews during 1999-2004 and 2006-2010. The Cox proportional hazard regression method was used to compute HRs and 95% CIs with adjustment for potential confounders., Results: Dairy food intake was inversely associated with the risk of hypertension in a dose-dependent manner: HRs across quartiles were 1.00 (lowest quartile, reference), 0.97 (95% CI: 0.92, 1.02), 0.98 (95% CI: 0.92, 1.03), and 0.93 (95% CI: 0.88, 0.98) (P-trend = 0.01). Milk accounted for ∼80% of all dairy products consumed in this population. Daily milk drinkers had a lower risk of hypertension (HR: 0.94; 95% CI: 0.89, 0.99) than did nondrinkers. Nondairy calcium intake contributed 80% of total calcium intake. Although dairy calcium intake was associated with a lower risk of hypertension (HR comparing extreme quartiles: 0.88; 95% CI: 0.83, 0.94; P-trend < 0.001), there was no association for nondairy calcium intake (HR: 1.02; 95% CI: 0.94, 1.10; P-trend = 0.58)., Conclusions: Baseline dairy food intake, and specifically that of milk, may reduce the risk of developing hypertension in Chinese adults, and this may not be associated with the calcium component., Competing Interests: 2 Author disclosures: M Talaei, A Pan, J-M Yuan, and W-P Koh, no conflicts of interest., (© 2017 American Society for Nutrition.)

Introduction: As a lack of validated data about cardiovascular (CV) events and its risk factors (RFs) in women of Eastern Mediterranean region, we aimed to evaluate common predictors of CV events among Iranian women. Methods: Isfahan cohort study (ICS) is a prospective cohort that followed 6323 residents (51.3% women, aged 35-75 years) from three counties and their rural districts in central Iran. Common cardiovascular disease (CVD) RFs namely hypertension (HTN), diabetes mellitus, dyslipidemia, abdominal obesity, smoking, low apolipoproteins A ( apo-A) and high apolipoprotein B (apo-B) were evaluated. End points (CV events) were defined as fatal and nonfatal myocardial infarction, sudden cardiac death (SCD), unstable angina and stroke. Results: After 9 years of follow-up, 265 CV events were detected. The mean age of women with CV event was 57.6±10.9; about 8 years older than those without event. All CV RFs were significantly more prevalent in women with CV event except for low HDL cholesterol, overweight and low apo-A. HTN, diabetes, high triglyceride (TG), high LDL-C and obesity were significantly associated with CV events after adjustment for age, smoking and menopausal status (hazard ratios [95% CI]: 2.56 [1.93, 3.95], 2.43 [1.76, 3.35], 2.02 [1.49, 2.74], 1.59 [1.20, 2.11] and 1.49 [1.16-1.92], respectively), while low HDL cholesterol and abdominal obesity were not predictors for CV events (hazard ratios [95% CI]: 1.26 [0.96, 1.65], 1.71 [0.99, 2.96], respectively). Conclusion: In ICS, HTN, diabetes mellitus and high triglyceride are strong predictors for CV events in Iranian women. As almost all strong risk markers of CVD events are preventable, health policy makers have to give urgent consideration to make preventive public health strategies.

We evaluated the relationship between urine concentrations of phyto-oestrogens (isoflavones and lignans) and risk of incident type 2 diabetes in middle-aged and elderly Chinese residing in Singapore. Urine metabolites of isoflavones and lignans were assayed by HPLC among 564 diabetes cases and 564 matched controls in a case-control study nested within the Singapore Chinese Health Study cohort. Participants were free of diagnosed diabetes, CVD and cancer at morning urine collections during 1999-2004. Cases were participants who reported to have physician-diagnosed diabetes at follow-up visits during 2006-2010, whereas controls were randomly selected among those who remained free of diabetes and were matched to the index cases by age, sex, dialect group and date of urine collection. Conditional logistic regression models were used to calculate OR and 95 % CI with adjustment for potential confounders. The mean age of the participants at the time of urine collection was 59·8 years, and the average interval between urine collection and diabetes diagnosis was 4·0 years. The multivariate-adjusted OR for diabetes were 1·00 (reference), 0·76 (95 % CI 0·52, 1·11), 0·78 (95 % CI 0·53, 1·14) and 0·79 (95 % CI 0·54, 1·15) across quartiles of urine isoflavones (P for trend=0·54), and were 1·00 (reference), 0·87 (95 % CI 0·60, 1·27), 1·10 (95 % CI 0·77, 1·56) and 0·93 (95 % CI 0·63, 1·37) for lignans (P for trend=0·93). The results were similar in men and women, as well as for individual metabolites of isoflavones (genistein, daidzein, glycitin and equol) or lignans (enterodiol and enterolactone). The present study did not find a significant association between urine phyto-oestrogen metabolites and risk of type 2 diabetes in Chinese adults.

Background: The effects of the risk factors of ischemic heart disease (IHD) and stroke on the occurrence of these diseases differ between different populations., Objectives: To study the difference in the effects of different cardiovascular (CVD) risk factors on the incidence of IHD and stroke in an Iranian adult population., Patients and Methods: The Isfahan Cohort Study (ICS) is a longitudinal study that followed up 6323 subjects older than 35 years with no history of CVD since 2001. Of the original sample, only 5431 participants were contacted and followed up until 2011. The end points were the occurrence of IHD (defined as fatal and non-fatal myocardial infarction, unstable angina, and sudden cardiac death) and stroke. After 10 years of follow-up, 564 new cases of IHD and 141 new cases of stroke were detected. The relative risks (RRs) of cardiometabolic risk factors such as hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, high low-density lipoprotein cholesterol (LDL-C) level, low high-density lipoprotein cholesterol (HDL-C) level, current smoking, obesity, high waist-to-hip ratio, family history of CVD, and metabolic syndrome were compared between IHD and stroke patients. The ratio of relative risks (RRR) was calculated for comparing two RRs and estimated adjusted RRR was calculated by using generalized linear regression with a log link and binomial distribution., Results: The RRs of the occurrence of IHD and stroke in diabetic patients were 1.94 and 3.26, respectively, and the difference was statistically different (P = 0.016). The RR of high LDL-C was significantly higher for IHD than for stroke (P = 0.045), while all the other risk factors showed similar RRs for IHD and stroke, with no significant difference in their RRR, including hypertension. Diabetes and hypertension had the highest RRs for IHD, followed by diabetes, metabolic syndrome, and hypertension for stroke., Conclusions: The effect of diabetes mellitus on stroke was more significant than on IHD, and the effect of high LDL-C level was more significant on IHD than on stroke, other risk factors, including hypertension, have similar RRs for IHD and stroke. Health care professionals need more training regarding the RRs of these risk factors in the Iranian society, and health decision makers should consider it in their future policies.