Determinants of Antibody Responses to SARS-CoV-2 Vaccines: Population-Based Longitudinal Study (COVIDENCE UK).

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.

Egg consumption and risk of cardiovascular events among Iranians: results from Isfahan Cohort Study (ICS).

PURPOSE: The association between egg consumption and cardiovascular events remains controversial. This study aims to evaluate this association in cardiovascular events including myocardial infarction (MI), ischemic coronary heart disease (ICHD), stroke, cardiovascular disease (CVD), and CVD mortality in an Iranian population. METHODS: This prospective cohort study included 6504 adults (age ≥ 35 years) with no history of CVD event at baseline. The frequency of egg consumption was assessed using a validated food frequency questionnaire. Participants were followed for 12 years and incidence of new CVD cases were determined through active examinations and linkages to multiple registries. Cox frailty models were conducted to calculate adjusted hazard ratios (HR)s for cardiovascular events associated with egg consumption. RESULTS: Over a median follow-up of 12 years, fully adjusted model [adjusted for age, sex, education, residency, smoking, daily physical activity, family history of CVD, metabolic syndrome, aspirin, body mass index and Global Dietary Index] revealed a null association between egg and cardiovascular events. Compared with non-consumers (&lt;1 time/week), higher egg consumption (≥3 time/week) was not associated with incident MI (HR = 1.44, 95% CI: 0.86, 2.41; P = 0.48), ICHD (HR = 1.26, 95% CI: 0.80, 1.99; P = 0.41), stroke (HR = 0.79, 95% CI: 0.46, 1.38; P = 0.71) and CVD (HR = 1.05, 95% CI: 0.79, 1.40; P = 0.93). CONCLUSION: These findings suggest that higher egg consumption is not associated with increased risk of MI, ICHD, stroke, and CVD among Iranians. Larger studies with longer duration of follow-up are warranted to explore these associations in populations with higher egg consumption.

High Sensitivity C-Reactive Protein Predictive Value for Cardiovascular Disease: A Nested Case Control from Isfahan Cohort Study (ICS).

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.

A 10-year Isfahan cohort on cardiovascular disease as a master plan for a multi-generation non-communicable disease longitudinal study: methodology and challenges.

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.

Cardiovascular disease events and its predictors in women: Isfahan Cohort Study (ICS).

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.

Meat, Dietary Heme Iron, and Risk of Type 2 Diabetes Mellitus: The Singapore Chinese Health Study.

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.

Dairy Food Intake Is Inversely Associated with Risk of Hypertension: The Singapore Chinese Health Study.

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.

Association between the ratio of triglyceride to high-density lipoprotein cholesterol and incident type 2 diabetes in Singapore Chinese men and women.

BACKGROUND: Increased triglycerides (TG) and decreased high-density lipoprotein cholesterol (HDL-C) are risk factors for type 2 diabetes (T2D). The relationship between TG:HDL-C ratio and T2D risk is not clear, and it is not known whether the association is modified by gender, body mass index, or fasting status. This study examined the relationship between TG:HDL-C ratio and risk of incident T2D, and the predictive ability of the ratio on top of other diabetes risk factors. METHODS: Blood biomarkers were determined in 571 T2D cases and 571 controls nested within a prospective, population-based cohort study, the Singapore Chinese Health Study. Participants were free of diagnosed diabetes, cardiovascular disease, and cancer at the time of blood collection (1999-2004). Incident self-reported T2D cases were identified at follow-up interview (2006-10). Controls were matched 1: 1 for age, sex, dialect group, and date of blood collection. Multivariable logistic regression was used to compute the odds ratio (OR) and 95 % confidence interval (CI). RESULTS: The ORs (95 % CI) of T2D per 1-SD increment in TG and TG: HDL-C ratio were 1.70 (1.39-2.09) and 1.72 (1.37-2.17), respectively. The relationships were stronger among females than males (Pinteraction = 0.028 and 0.017, respectively), and stronger among lean (<23 kg/m2 ) than overweight/obese participants (Pinteraction = 0.051 and 0.046, respectively). Both TG and TG: HDL-C improved T2D prediction to a similar degree. CONCLUSIONS: Both TG and TG:HDL-C ratio are independent risk factors for incident T2D, and confer greater risk in women and lean participants. The TG: HDL-C ratio is not a better predictor of diabetes than TG alone.

Formaldehyde removal from wastewater and air by using UV, ferrate(VI) and UV/ferrate(VI).

Formaldehyde removal from an air stream absorbed into a water stream in a packed bed continuously and then removed by employing a combination of UV and ferrate(VI) as a highly-powerful oxidant in a continuous stirred tank. In addition, the removal of formaldehyde from water was investigated in both batch and continuous modes. The results of the study performed on formaldehyde-contaminated water treatment can be used for both air and water treatment process design. The primary objective of this study is to compare the performance of using UV and ferrate(VI) individually with that of using UV/ferrate(VI) simultaneously to remove formaldehyde from both air and water. Moreover, the effects of several factors such as pH, ferrate(VI) concentration and temperature on formaldehyde removal from water using ferrate(VI) method were evaluated. The results of the current study in batch condition showed that the best initial pH and ferrate(VI) concentration to obtain the highest formaldehyde removal are 2 and 1 mg/l, respectively. The results of this part of research also reveal that temperatures rise from 25 °C to 50 °C increases formaldehyde removal from 69% to 97%; however, further increase in temperature has an adverse effect on removal efficiency. The combination of UV and ferrate(VI) enhances formaldehyde removal efficiency to very close to 100% within 35 min. In continuous air stream treatment, maximum formaldehyde removal of 94% was obtained by using a packed bed scrubber with gas over liquid flow rates ratio of 1.28 m3/m3. Although the results of this study shows that ferrate(VI) method for removal of formaldehyde can be considered as a promising alternative for both water and air treatment, further economic studies are required for this process to be commercialized.

The impact of health-related quality of life on the incidence of ischaemic heart disease and stroke; a cohort study in an Iranian population.

OBJECTIVE: The aim of study was to evaluate the impact of health-related quality of life (QoL) on the occurrence of ischaemic heart disease (IHD) and stroke using a validated questionnaire. METHODS: We followed the 3,283 subjects, aged ≥ 35 years and without history of cardiovascular events (CVE) over four years from 2007 to 2011 from the Isfahan cohort study. The World Health Organization QoL questionnaire (WHOQOL-BREF), which contains four separate domains, was used to assess QoL. Incidence rates of IHD and stroke were recorded during follow-up. Socioeconomic demographic data including marital state, educational level, occupation, income and place of living and metabolic risk factors such as diabetes mellitus (DM), hypertension (HTN), dyslipidaemia, body mass index and smoking were also recorded. RESULTS: More IHD (42%) and stroke (57%) patients were illiterate; while the educational status was significantly different only in the IHD group (P = 0.000). Differences in income and occupation were notable in patients with stroke and IHD, respectively, compared to subjects without them (P < 0.050). DM and HTN were significantly higher in IHD and stroke patients in comparison with subjects without CVE (P = 0.000). Two-way multivariate analyses of covariance test after age, educational status and metabolic risk factors adjustment showed that subjects with stroke had a significantly higher score in all QoL domains in comparison with individuals without stroke (P < 0.050). There was no significant association between QoL domains and IHD incidence (P > 0.050). CONCLUSION: This study indicates that there is no association between QoL and IHD incidence although there was a significant relationship between higher QoL and incidence of stroke.

Urine phyto-oestrogen metabolites are not significantly associated with risk of type 2 diabetes: the Singapore Chinese health study.

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.

Do Cardiometabolic Risk Factors Relative Risks Differ for the Occurrence of Ischemic Heart Disease and Stroke?

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.

Does the impact of metabolic syndrome on cardiovascular events vary by using different definitions?

BACKGROUND: Metabolic Syndrome (MetS) is a complex disorder which increases the risk of chronic diseases, including cardiovascular diseases and diabetes mellitus. As a result of modern lifestyles, the prevalence of MetS has been rising globally. This study aims to investigate whether overall prevalence of MetS varies when using different definitions of MetS and to identify the best and most predictive definition of the MetS for cardiovascular disease (CVD) events over 10 years in a cohort of an Iranian population. METHOD: Adults aged ≥ 35 years from urban and rural regions in central Iran were selected at baseline and followed up for more than 10 years. Data on socio-demographic characteristics, anthropometry, blood pressure and smoking status were collected at baseline. In addition, various biochemical indices were assessed. MetS was defined based on five available definitions, and cardiovascular events during 10 years follow up were confirmed by an expert group. The hazard ratios were calculated by the Cox proportional hazards model. RESULTS: The highest prevalence of MetS was observed by using AHA-NHBI definition (36.9%), followed by JIS definition (31.2%). On the other hand, EGIR (8.8%) provided the lowest prevalence. The risk of developing CVD, irrespective of definitions, was approximately two fold higher in the presence of MetS. After controlling for possible confounders, AHA-NHBI definition was found to be the best predictor of CVD. CONCLUSION: This study demonstrated a great variability in the prevalence of MetS among Iranian adults when using different definitions of MetS. CVD risk was significantly higher in MetS participants, as well as in participants with any risk factors of MetS; however, the AHA-NHBI definition was found to be the best predictor of CVD. Thus protective measures, including lifestyle modifications, plus control of individual risk factors is necessary to prevent cardiovascular events.

Relation of active, passive, and quitting smoking with incident type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Cigarette smoking remains the leading avoidable cause of disease burden worldwide, and observational studies have linked various smoking behaviours (active smoking, passive smoking, and smoking cessation) with risk of type 2 diabetes. We did a meta-analysis of prospective studies to investigate the associations between various smoking behaviours and diabetes risk. METHODS: We systematically searched MEDLINE (up to May 3, 2015) and Embase (up to April 16, 2014) for reports of prospective studies, using search terms related to smoking, diabetes mellitus, and studies with a prospective design. We supplemented this strategy with manual searches of the reference lists of retrieved publications and relevant reviews. We included prospective studies that reported risk of type 2 diabetes by baseline smoking status. We calculated pooled relative risks (RRs) with 95% CIs using random-effects models, and did subgroup analyses by participant and study characteristics. FINDINGS: We identified 88 eligible prospective studies with 5 898 795 participants and 295 446 incident cases of type 2 diabetes. The pooled RR of type 2 diabetes was 1·37 (95% CI 1·33-1·42) for comparing current smoking with non-smoking (84 studies with 5 853 952 participants), 1·14 (1·10-1·18) for comparing former smoking with never smoking (47 studies with 2 930 391 participants), and 1·22 (1·10-1·35) for comparing never smokers with and without exposure to passive smoke (seven studies with 156 439 participants). The associations persisted in all subgroups, and we identified a dose-response relation for current smoking and diabetes risk: compared with never smokers, the RRs were 1·21 (1·10-1·33) for light smokers, 1·34 (1·27-1·41) for moderate smokers, and 1·57 (1·47-1·66) for heavy smokers. Based on the assumption that the association between smoking and diabetes risk is causal, we estimated that 11·7% of cases of type 2 diabetes in men and 2·4% in women (ie, about 27·8 million cases in total worldwide) were attributable to active smoking. Compared with never smokers, the pooled RR from ten studies with 1 086 608 participants was 1·54 (95% CI 1·36-1·74) for new quitters (<5 years), 1·18 (1·07-1·29) for middle-term quitters (5-9 years), and 1·11 (1·02-1·20) for long-term quitters (≥10 years). INTERPRETATION: Active and passive smoking are associated with significantly increased risks of type 2 diabetes. The risk of diabetes is increased in new quitters, but decreases substantially as the time since quitting increases. If the association between smoking and risk of type 2 diabetes is causal, public health efforts to reduce smoking could have a substantial effect on the worldwide burden of type 2 diabetes. FUNDING: Chinese National Thousand Talents Program for Distinguished Young Scholars, US National Institutes of Health, the Chinese National 111 Project, and the Program for Changjiang Scholars and Innovative Research Team in University from the Chinese Ministry of Education.

Relation of Smoking With Total Mortality and Cardiovascular Events Among Patients With Diabetes Mellitus: A Meta-Analysis and Systematic Review.

BACKGROUND: The prevalence of smoking in diabetic patients remains high, and reliable quantification of the excess mortality and morbidity risks associated with smoking is important for diabetes management. We performed a systematic review and meta-analysis of prospective cohort studies to evaluate the relation of active smoking with risk of total mortality and cardiovascular events among diabetic patients. METHODS AND RESULTS: We searched Medline and Embase databases through May 2015, and multivariate-adjusted relative risks were pooled by using random-effects models. A total of 89 cohort studies were included. The pooled adjusted relative risk (95% confidence interval) associated with smoking was 1.55 (1.46-1.64) for total mortality (48 studies with 1,132,700 participants and 109,966 deaths), and 1.49 (1.29-1.71) for cardiovascular mortality (13 studies with 37,550 participants and 3163 deaths). The pooled relative risk (95% confidence interval) was 1.44 (1.34-1.54) for total cardiovascular disease (16 studies), 1.51 (1.41-1.62) for coronary heart disease (21 studies), 1.54 (1.41-1.69) for stroke (15 studies), 2.15 (1.62-2.85) for peripheral arterial disease (3 studies), and 1.43 (1.19-1.72) for heart failure (4 studies). In comparison with never smokers, former smokers were at a moderately elevated risk of total mortality (1.19; 1.11-1.28), cardiovascular mortality (1.15; 1.00-1.32), cardiovascular disease (1.09; 1.05-1.13), and coronary heart disease (1.14; 1.00-1.30), but not for stroke (1.04; 0.87-1.23). CONCLUSIONS: Active smoking is associated with significantly increased risks of total mortality and cardiovascular events among diabetic patients, whereas smoking cessation is associated with reduced risks in comparison with current smoking. The findings provide strong evidence for the recommendation of quitting smoking among diabetic patients.

Role of phytoestrogens in prevention and management of type 2 diabetes.

Type 2 diabetes (T2D) has become a major public health threat across the globe. It has been widely acknowledged that diet plays an important role in the development and management of T2D. Phytoestrogens are polyphenols that are structurally similar to endogenous estrogen and have weak estrogenic properties. Emerging evidence from pre-clinical models has suggested that phytoestrogens may have anti-diabetic function via both estrogen-dependent and estrogen-independent pathways. In the current review, we have summarized the evidence linking two major types of phytoestrogens, isoflavones and lignans, and T2D from epidemiological studies and clinical trials. The cross-sectional and prospective cohort studies have reported inconsistent results, which may due to the large variations in different populations and measurement errors in dietary intakes. Long-term intervention studies using isoflavone supplements have reported potential beneficial effects on glycemic parameters in postmenopausal women, while results from short-term small-size clinical trials are conflicting. Taken together, the current evidence from different study designs is complex and inconsistent. Although the widespread use of phytoestrogens could not be recommended yet, habitual consumption of phytoestrogens, particularly their intact food sources like soy and whole flaxseed, could be considered as a component of overall healthy dietary pattern for prevention and management of T2D.

Determinants of incident prediabetes and type 2 diabetes in a 7-year cohort in a developing country: The Isfahan Cohort Study.

BACKGROUND: This study aimed to identify determinants of new onset type-2 diabetes (T2D) and prediabetes in a region with high rate of T2D but scarcity of evidence. METHODS: Participants free of T2D were identified in a population-based study of adults older than 35 years living in the rural and urban areas of three districts in Iran in 2001 and were re-examined after 7 years. Biochemical measurements, anthropometric data, blood pressure, smoking status and dietary intake were determined at both measurement points through identical protocols and procedures. Data analysis was done using multivariate ordered logistic regressions. RESULTS: Incidence rate of prediabetes and T2D was 32.3 (95%CI, 29.7-35.1) and 18.9 (17.1-20.9) per 1000 person-year, respectively. Odds of progression to prediabetes and T2D were increased with ageing, living in rural area (OR = 1.28), unhealthy diet (OR = 1.32), overweight (OR = 1.45), obesity (OR = 1.97), waist gain (OR = 1.37), high waist-to-hip ratio (OR = 1.35), hypertension (OR = 1.35), and hypertriglyceridemia (OR = 1.50); but reduced with higher education (OR = 0.76) and weight loss (OR = 0.67) in the adjusted models. In those with prediabetes at baseline, parental history of T2D (OR = 2.26), obesity (OR = 2.59), high waist circumference (OR = 2.03), and hypertriglyceridemia (OR = 1.94) were associated with developing T2D. No factor was found to be associated with regression from prediabetes to normoglycemia in adjusted models. CONCLUSIONS: Current data endorses proposed statistical projections for the future trend of diabetes, and highlights the potential role of obesity specifically visceral type.

The cumulative incidence of conventional risk factors of cardiovascular disease and their population attributable risk in an Iranian population: The Isfahan Cohort Study.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death in Iran. The present study evaluated the 7-year incidence of CVD risk factors among the participants of Isfahan cohort study (ICS). MATERIALS AND METHODS: ICS was a longitudinal study on adults over 35 years of age from the urban and rural areas in three counties in central Iran. Data on clinical examination and blood measurements were collected in 2001. Subjects were followed and similar data were collected in 2007. Cumulative incidence was calculated through dividing new cases of each risk factor by the population free of that risk factor at baseline. Incidence proportion was determined for major CVD risk factors including hypertension (HTN), hypercholesterolemia (HC), hypertriglyceridemia (HTg), obesity, diabetes mellitus (DM), metabolic syndrome (MetS), and smoking. RESULTS: A total number of 6323 adults free of CVDs were recruited. After 7 years of follow-up, 3283 individuals were re-evaluated in 2007. The participants' age was 49.2 ± 10.3 years in 2001 (mean ± SD). The 7-year cumulative incidence of HTN, HC, HTg, overweight, obesity, DM, MetS, and smoking was 22.8%, 37.4%, 28.0%, 26.3%, 7.4%, 9.5%, 23.9%, and 5.9% in men and 22.2%, 55.4%, 33.5%, 35.0%, 18.8%, 11.3%, 36.1%, and 0.7% in women, respectively. Among those with overweight or obesity, 14.7% of men and 7.9% of women decreased their weight up to the normal level. CONCLUSIONS: The present study revealed a high incidence of CVD risk factors especially dyslipidemia, obesity, MetS and HTN. Therefore, the application of life-style modification interventions seems necessary.

Determinants of weight change in a longitudinal study of Iranian adults: Isfahan Cohort Study.

BACKGROUND: The extensive rise in the prevalence of obesity is a matter of great concern and poses a global threat to people's health. Obesity and overweight are considered to be the consequence of a collection of conditions including genetic, social, environmental, behavioral, and physical factors. The aim of this study was to investigate the determinants of weight change over seven years in a prospective study in an Iranian population. METHODS: The Isfahan Cohort Study (ICS) is an ongoing longitudinal study started in 2001. A total of 6504 adults aged ≥ 35 years participated in this study. Subjects were followed every 2 years by phone calls. The interview and measurements were repeated in 2007 for 3284 subjects with the same protocol as the baseline study. Obesity indices, including body mass index (BMI) and waist circumference (WC) were measured at both time points. For the purpose of data analysis, multiple multinomial logistic regression, Chi-square, and ANOVA tests were used. RESULTS: In males, weight gain was more frequent from normal to overweight (11.7%), while in females, weight gain was observed more from overweight to obesity (11.4%). Younger individuals gained weight more than older individuals (P < 0.001); it was the same for lower education level (P = 0.007).  Weight gain was negatively (OR: 0.98, 95% CI: 0.97-0.99 in male and OR: 0.96, 95% CI: 0.95-0.98 in female) and weight loss was positively (OR: 1.03, 95% CI: 1.01-1.05 in male and OR: 1.02, 95% CI: 1.01-1.04 in female) associated with age in both sexes. Education more than 12 years in women and between 6-12 years in men was negatively associated with weight gain while smoking was positively related to weight loss in females and weight gain in males. CONCLUSION: Our data showed that multiple factors affect weight change, among which age, smoking, and education are important determinants in Iranian adults.

Opium decreases the age at myocardial infarction and sudden cardiac death: a long- and short-term outcome evaluation.

UNLABELLED:   BACKGROUND: Opium dependence is a recognized individual and public health threat, but little is known about its association with acute myocardial infarction (AMI) or sudden cardiac death (SCD). METHODS: In a cross-sectional study followed by a one-year matched longitudinal cohort, all 569 men hospitalized with AMI in all Cardiac Care Units (CCU) of Isfahan, Iran, were recruited in a six-month period. In addition, 123 out-of-hospital deaths were included that were diagnosed as SCD at the same duration. Among those discharged alive, 126 opium dependents were matched with 126 nondependents (mostly nonusers) according to age and smoking status, and were followed for one year. Opium dependence was measured using the ICD10 criteria and Severity of Dependence Scale (SDS) questionnaire. The method was validated by morphine blood levels. Biochemical measurements, blood pressure, blood cell counts, anthropometrics, and ejection fraction were measured at baseline and repeated at the end of follow-up.  RESULTS: There were 118 (17.1%) patients with an average of 17.4 ± 10.4 years of abuse who met the criteria for opium dependency. Opium dependence decreased the age at event by 3.6 (95% CI: 1.2 - 6.0) years and was independent of smoking (P = 0.003). In terms of cardiovascular risk factors such as ejection fraction, in addition to post-AMI mortality and morbidity, no significant associations were noted at baseline or after one year of follow-up. The odds ratio of sustained smoking after AMI was 1.92 (95% CI: 1.04 - 3.52) in opium dependents (P = 0.033). CONCLUSION: Despite public opinion, opium did not improve cardiovascular risk factors, or post-AMI mortality and morbidity. Conversely, there were irrefutable findings regarding the detrimental effects of opium dependence.