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1.  Role of phytoestrogens in prevention and management of type 2 diabetes 
World Journal of Diabetes  2015;6(2):271-283.
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.
PMCID: PMC4360420  PMID: 25789108
Type 2 diabetes; Phytoestrogen; Isoflavone; Lignan; Epidemiological study; Clinical trial
2.  The cumulative incidence of conventional risk factors of cardiovascular disease and their population attributable risk in an Iranian population: The Isfahan Cohort Study 
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.
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.
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.
PMCID: PMC4260292  PMID: 25538928
Cardiovascular disease; cumulative incidence; Iran; risk factor
3.  Efficacy of omeprazole on cough, pulmonary function and quality of life of patients with sulfur mustard lung injury: A placebo-control, cross-over clinical trial study 
Gastro-esophageal reflux disease (GERD) is prevalent and related to more severe disease in patients with respiratory problems. We evaluated the effects of antireflux therapy in warfare victims of exposure to Mustard gas with chronic cough.
Materials and Methods:
This randomized, double-blind, placebo-controlled, cross-over study was conducted on 45 cases of sulfur mustard injury with chronic cough (≥8 weeks) and GERD. Patients were randomized into two groups, receiving either 20 mg twice daily omeprazole-placebo (OP) or matching placebo (placebo-omeprazole [PO]) for 4 months, followed by a 1-month washout period and the alternative treatment for 4 months. Assessments included GERD and cough, quality of life, and pulmonary function using spirometry. Leicester Cough Questionnaire and SF-36 were used for measuring quality of life.
Patients in the OP group experienced a more decrease than those in the PO group in severity of Leicester cough scores during the first 4-month of trial. After crossing the groups, the OP group experienced an increase (P = 0.036) and the PO group experienced a nonsignificant decrease (P = 0.104) in the severity of scores. The OP group also experienced improvement in GERD symptoms and quality of life at the end of the trial, but changes in the PO group was not significant. There was no significant change in respiratory function indices in any groups.
Long-term treatment with high-dose omeprazole improved GERD as well as cough, and quality of life, but not changed respiratory function indices in sulfur mustard injured cases with respiratory symptoms.
PMCID: PMC4310073  PMID: 25657745
Chronic cough; gastro-esophageal reflux disease; mustard gas
4.  Comparison of competing risks models based on cumulative incidence function in analyzing time to cardiovascular diseases 
ARYA Atherosclerosis  2014;10(1):6-12.
Competing risks arise when the subject is exposed to more than one cause of failure. Data consists of the time that the subject failed and an indicator of which risk caused the subject to fail.
With three approaches consisting of Fine and Gray, binomial, and pseudo-value, all of which are directly based on cumulative incidence function, cardiovascular disease data of the Isfahan Cohort Study were analyzed. Validity of proportionality assumption for these approaches is the basis for selecting appropriate models. Such as for the Fine and Gray model, establishing proportionality assumption is necessary. In the binomial approach, a parametric, non-parametric, or semi-parametric model was offered according to validity of assumption. However, pseudo-value approaches do not need to establish proportionality.
Following fitting the models to data, slight differences in parameters and variances estimates were seen among models. This showed that semi-parametric multiplicative model and the two models based on pseudo-value approach could be used for fitting this kind of data.
We would recommend considering the use of competing risk models instead of normal survival methods when subjects are exposed to more than one cause of failure.
PMCID: PMC4063516  PMID: 24963307
Competing Risks; Cumulative Incidence Function; Fine and Gray Model; Binomial Approach; Pseudo-value Approach; Cardiovascular Diseases
5.  Healthy Bread Initiative: Methods, Findings, and Theories—Isfahan Healthy Heart Program 
The scientific evidences show that the content, baking methods, and types of bread can make health impacts. Bread, as a major part of Iranian diet, demonstrates a significant potential to be targeted as health promotion subject. Healthy Food for Healthy Communities (HFHC) was a project of Isfahan Healthy Heart Program (IHHP), consisting of a wide variety of strategies, like Healthy Bread (HB) Initiative. The HB Initiative was designed to improve the behaviour of both producers and consumers, mainly aiming at making high-fibre, low-salt bread, eliminating the use of baking soda, providing enough rest time for dough before baking (at least one hour), and enough baking time (at least one minute in oven). A workshop was held for volunteer bakers, and a baker-to-baker training protocol under direct supervision was designed for future volunteers. Cereal Organization was persuaded to provide less refined flour that contained more bran. Health messages in support of new breads were disseminated by media and at bakeries by health professionals. Evaluation of the HB Initiative was done using before-after assessments and population surveys. While HB was baked in 1 (0.01%) bakery at baseline, 402 (41%) bakeries in the intervention area joined the HB Initiative in 2009. Soda was completely eliminated and fibre significantly increased from 4±0.4 g% before study to 12±0.6 g% after the intervention (p<0.001). The preparation and baking times remarkably increased. Wastage of bread decreased from 13±1.8 g% to 2±0.5 g% and was expressed as the most important advantage of this initiative by consumers. People who lived in Isfahan city consumed whole bread 6 times more than those who lived in reference area Arak (p<0.001). The HB Initiative managed to add new breads as a healthy choice that were compatible with local dishes and made a model to solve the long-standing problems of bread. It used various health promotion approaches but was best consistent with Beattie's model.
PMCID: PMC3702358  PMID: 23617204
Bread; Community trial; Health promotion; Nutrition; Iran
6.  Physical activity, sex, and socioeconomic status: A population based study 
ARYA Atherosclerosis  2013;9(1):51-60.
The purpose of the present study was to investigate physical activity by socioeconomic status (SES) and sex in an Iranian adult population.
In a cross-sectional study, 6622 adults, who participated in the Isfahan Healthy Heart program (IHHP) surveys in 2004 and 2005 and were living in urban areas, were studied. Daily leisure time, household, occupational, and transportation physical activity, and total physical activity were calculated and compared in 3 socioeconomic status groups classified by the two-step cluster analysis procedure.
Statistically significant variations were found in all physical activity levels, except transportation, by sex. Men were more active than women in all fields, except household physical activity. Leisure time physical activity of men and women were significantly higher in higher SES levels. There was an opposite correlation between SES and total physical activity in men.
Considering the importance of physical activity as a component of a healthy lifestyle, differences among varying socioeconomic status and sex must be considered while planning for healthy lifestyle programs. Women with low SES, in particular, may need more attention.
PMCID: PMC3653259  PMID: 23696760
Physical Activity; Socioeconomic Status; Leisure Time; Gender; Cluster Analysis
7.  The effectiveness of stress management intervention in a community-based program: Isfahan Healthy Heart Program 
ARYA Atherosclerosis  2012;7(4):176-183.
This study was designed to assess the effectiveness of stress management training in improving the ability of coping with stress in a large population.
Five cross-sectional studies using multistage cluster random sampling were performed on adults aged ≥ 19 years between 2000 to 2005 in Isfahan and Najafabad (Iran) as intervention cities and Arak, Iran as the control city within the context of Isfahan Healthy Heart Program. Stress management training was adapted according to age and education levels of the target groups. In a 45-minute home interview, demographic data, General Health Questionnaire (GHQ) and stress management questionnaires were collected. Data was analyzed by t-test, linear regression and general linear model.
Trends of both adaptive and maladaptive coping skills and GHQ scores from baseline to the last survey were statistically significant in both intervention and reference areas (P < 0.001). While adaptive coping skills increased significantly, maladaptive coping skills decreased significantly in the intervention areas. Furthermore, stress levels decreased significantly in the intervention compared to the reference area.
Stress management programs could improve coping strategies at the community level and can be considered in designing behavioral interventions
PMCID: PMC3413087  PMID: 23205052
Stress Management; Community; Intervention; Coping Strategies
8.  Is prehypertension a risk factors for cardiovascular diseases among Iranian women? 
Numerous studies have reported prehypertension (pre-HTN) as a risk factor for the cardiovascular diseases as hypertension (HTN).
The present study aimed to evaluate the effects of pre-HTN on cardiovascular incidences among the females of Isfahan cohort study (ICS).
Materials and Methods:
Healthy female at baseline were followed for a median of 6.7 years. They were divided into 3 groups of normal blood pressure, pre-HTN (120/80 < BP < 139/89 mmHg) and HTN (BP > 140/90 mmHg) based on their baseline measurements. The endpoints were ischemic heart disease (IHD), stroke, CVD (combination of IHD and stroke) and mortality.
Normal BP, pre-HTN and HTN were observed in 1073 (33%), 1185 (36%), and 994 (31%) participants, respectively. One hundred and ninety-eight subjects developed CVDs and 110 died. In the HTN group, the hazard ratio [HRs (95% confidence interval)] adjusted for age and other risk factors were 3.44 (1.95–6.09) for IHD (P value < 0.001), 1.28 (0.59–2.77) for stroke (P value = 0.536) 4.89 (1.37–17.45) for CVD mortality (P value < 0.001) and 1.70 (0.98–2.96) for all cause mortality (P value = 0.060). Although, pre-HTN significantly increased the risk of IHD incidence in the crude model (HR 2.21, 95% CI 1.23–3.97) and after adjustments for age (HR 1.85, 95% CI 1.02–3.33), (P value < 0.001) the association did not remain statistically significant after including other risk factors in the model.
Hypertension (HTN) to be a strong risk factor for CVD and IHD. However, in contrast to previous researches, pre-HTN was not found to be a risk factor for CVD, IHD or death independent to other risk factors in women.
PMCID: PMC3698654  PMID: 23825995
Cardiovascular disease; cohort study; coronary artery disease; hypertension; mortality; prehypertension
9.  Psychological Status and Quality of Life in relation to the Metabolic Syndrome: Isfahan Cohort Study 
Objective. Current study was designed to investigate the association of metabolic syndrome (MetS) with depression, anxiety, psychological distress, and quality of life (QoL). Design. Two hundred and fifteen contributors with MetS and 253 participants without MetS were randomly selected from 2151 participants of Isfahan Cohort Study who were residents of Isfahan city. Measurements consisted of fasting blood samples, anthropometrics, and self-reported data of 12-item General Health Questionnaire, Hospital Anxiety and Depression Scale, and European Quality of Life-5 Dimension. Binary logistic regression analysis was used to find the association between MetS and four psychological factors. Results. Participants mean age was 56.3 ± 9.8 years. Male/female ratio was 0.86 (217/251). Mean score of depression (P = 0.003), anxiety (P = 0.018), distress (P = 0.047), and QoL (P ≤ 0.001) was significantly higher in MetS group. There were significant increasing relationships between depression (OR 1.10, 95% CI 1.03–1.22), anxiety (OR 1.03, 95% CI 1.05–1.11), and QoL (OR 1.13, 95% CI 1.05–1.23) and MetS when associations were adjusted for other risk factors, but it was not the case for distress (OR 1.03, 95% CI 0.99–1.08). Conclusion. It might be better to consider MetS as a combination of biological and psychological risk factors. Thus, a person with metabolic disease should be recognized as a patient with these factors and be screened for all of them.
PMCID: PMC3363984  PMID: 22675350
10.  The correlation between blood pressure and hot flashes in menopausal women 
ARYA Atherosclerosis  2012;8(1):32-35.
As blood pressure is higher in menopausal women than their peers with similar Body mass index (BMI), and considering hot flashes as one of the most common symptoms of menopause, this study was conducted to examine the 24-hour changes of blood pressure in menopausal women experiencing hot flashes.
This cross-sectional study was performed on 26 menopausal 47-53 year-old women divided into 2 groups of 13. None of them had a history of internal diseases, hypertension, and hormone medications. Their blood pressure and heartbeat were recorded by a blood pressure Holter for 24 hours. The data was analyzed through student t-test and analysis of variance (ANOVA) using SPSS11.5.
Systolic blood pressure of the symptomatic group was significantly higher than the asymptomatic group during waking hours (P < 0.05). However, the heartbeats and systolic blood pressure of the symptomatic group were higher than those in the other group in 24 hours. This difference was not statistically significant (P > 0.05).
Similar to hot flashes, the increase in systolic blood pressure may arise from central sympathetic activity. Peripheral vasoconstriction and increased cardiac output, both caused by baroreflex dysfunction, might also have been responsible for increments in systolic blood pressure. Therefore, prospective studies are required to determine how the growing increase in blood pressure and the prevalence of hypertension differ in both groups.
PMCID: PMC3448399  PMID: 23056098
Women; Menopause; Blood Pressure; Hot Flashes
11.  Metabolic syndrome in menopausal transition: Isfahan Healthy Heart Program, a population based study 
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.
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.
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.
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.
PMCID: PMC2958965  PMID: 20923542
12.  Relationship Between Carotid Intima-Media Thickness with some Inflammatory Biomarkers, Ghrelin and Adiponectin in Iranians with and without Metabolic Syndrome in Isfahan Cohort Study 
ARYA Atherosclerosis  2010;6(2):56-61.
Recent studies have confirmed inflammatory factors and metabolic syndrome (MetS) as important cardiovascular disease (CVD) risk factors. Recently measurement of carotid intima-media thickness (IMT) has been used for evaluation of early atherosclerosis. This study was designed to assess the correlation between IMT with some inflammatory biomarkers, ghrelin and adiponectin in people with and without MetS in a cohort sample in Isfahan province.
Among participants of Isfahan Cohort Study (ICS) by random sampling, 88 participants were selected and divided into case (with MetS) and control (without MetS) groups. A questionnaire including demographic data and CVD risk factors was completed for all of the participants. Physical examination and blood pressure, height, weight and waist circumference measurements were done for all subjects. Vascular echocardiography was done for evaluation of IMT of each carotid artery of both sides. Interlukin-6 (IL-6), interlukin-10 (IL-10), highly sensitive C-reactive protein (hs-CRP), ghrelin and adiponectin levels were measured using ELIZA method. Data were entered in SPSS15 software and analyzed by t-test, chi square, Pearson correlation and linear regression analyze.
The mean waist circumference, BMI, systolic blood pressure, diastolic blood pressure, hs-CRP and IMT of left carotid artery were significantly higher in participants with Mets. There was significant correlation between left carotid IMT and IL-6 level in all patients (P = 0.03). After adjustment for age and sex, significant relationship in groups with MetS was only reported between the left IMT and IL-6 (P = 0.02). There was no relation between IMT and other inflammatory markers in subjects with and without MetS.
Significant correlation between IL-6 and IMT was reported in patients with MetS. While no significant correlation between IL-10, adiponectin and ghrelin with IMT was observed in metabolic syndrome group.
PMCID: PMC3347812  PMID: 22577415
Intima-media thickness (IMT); Carotid artery; hs-CRP; Ghrelin; Adiponectin IL-6; IL-10

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