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Abstract Background Glycemic variability (GV) is developing as a marker of glycemic control, which can be utilized as a promising predictor of complications. To determine whether long-term GV is associated with incident eGFR decline in two cohorts of Tehran Lipid and Glucose Study (TLGS) and Multi-Ethnic Study of Atherosclerosis (MESA) during a median follow-up of 12.2 years. Methods Study participants included 4422 Iranian adults (including 528 patients with T2D) aged ≥ 20 years from TLGS and 4290 American adults (including 521 patients with T2D) aged ≥ 45 years from MESA. The Multivariate Cox proportional hazard models were used to assess the risk of incident eGFR decline for each of the fasting plasma glucose (FPG) variability measures including standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) both as continuous and categorical variables. The time of start for eGFR decline and FPG variability assessment was the same, but the event cases were excluded during the exposure period. Results In TLGS participants without T2D, for each unit change in FPG variability measures, the hazards (HRs) and 95% confidence intervals (CI) for eGFR decline ≥ 40% of SD, CV, and VIM were 1.07(1.01–1.13), 1.06(1.01–1.11), and 1.07(1.01–1.13), respectively. Moreover, the third tertile of FPG-SD and FPG-VIM parameters was significantly associated with a 60 and 69% higher risk for eGFR decline ≥ 40%, respectively. In MESA participants with T2D, each unit change in FPG variability measures was significantly associated with a higher risk for eGFR decline ≥ 40%.Regarding eGFR decline ≥ 30% as the outcome, in the TLGS, regardless of diabetes status, no association was shown between FPG variability measures and risk of eGFR decline in any of the models; however, in the MESA the results were in line with those of GFR decline ≥ 40%.Using pooled data from the two cohorts we found that generally FPG variability were associated with higher risk of eGFR decline ≥ 40% only among non-T2D individuals. Conclusions Higher FPG variability was associated with an increased risk of eGFR decline in the diabetic American population; however, this unfavorable impact was found only among the non-diabetic Iranian population.

Abstract Background Identifying patterns of variation in obesity indices and other cardiometabolic risk factors before the diagnosis of type 2 diabetes could provide insight into the critical period when drastic changes occurred and facilitate targeted interventions for the prevention of diabetes. Therefore, this study sought to explore patterns of change in obesity indices and other cardiometabolic risk factors before diabetes diagnosis. Methods We investigated 6305 participants (43.7% men) aged 20–65 from the Tehran Lipid and Glucose Study (TLGS) who were free of diabetes at baseline. First, we jointly estimated developmental multi-trajectories of obesity indices using multivariate latent class growth mixed model, and then patterns of cardiometabolic risk factors within the identified multi-trajectories were assessed using mixed-effects models. Results Three patterns of change in obesity indices were identified. Most participants belonged to the “progressing” group (83.4%; n = 742), with a slight but steadily rising in obesity indices until diagnosis in both men and women. All multi-trajectory groups showed similar exponential increases in fasting and 2-h plasma glucose concentrations 6 years before diagnosis and linear increases in blood pressure and total and LDL cholesterol throughout follow-up. Patterns of triglyceride and HDL cholesterol accompanied each group’s patterns of change in obesity indices. Conclusion Three patterns of the joint progression of obesity indices before diabetes diagnosis were accompanied by similar blood glucose patterns and other cardiometabolic risk factors. These findings suggest the impact of the increasing trend of obesity indices and other metabolic factors on the incidence of diabetes and emphasize the importance of assessing the metabolic risk factors at each visit.

Background White matter hyperintensities (WMHs) are a major risk factor for stroke and dementia, but their pathogenesis is incompletely understood. It has been debated how much risk is accounted for by conventional cardiovascular risk factors (CVRFs), and this has major implications as to how effective a preventative strategy targeting these risk factors will be. Methods and Results We included 41 626 UK Biobank participants (47.2% men), with a mean age of 55 years (SD, 7.5 years), who underwent brain magnetic resonance imaging at the first imaging assessment beginning in 2014. The relationships among CVRFs, cardiovascular conditions, and WMH volume as a percentage of total brain volume were examined using correlations and structural equation models. Only 32% of the variance in WMH volume was explained by measures of CVRFs, sex, and age, of which age accounted for 16%. CVRFs combined accounted for ≈15% of the variance. However, a large portion of the variance (well over 60%) remains unexplained. Of the individual CVRFs, blood pressure parameters together accounted for ≈10.5% of the total variance (diagnosis of hypertension, 4.4%; systolic blood pressure, 4.4%; and diastolic blood pressure, 1.7%). The variance explained by most individual CVRFs declined with age. Conclusions Our findings suggest the presence of other vascular and nonvascular factors underlying the development of WMHs. Although they emphasize the importance of modification of conventional CVRFs, particularly hypertension, they highlight the need to better understand risk factors underlying the considerable unexplained variance in WMHs if we are to develop better preventative approaches.

Abstract Background Assessing the risk of cardiovascular disease (CVD) is crucial in preventive cardiology. We aimed to determine the trend of CVD risk among individuals with and without diabetes during two decades of follow-up in a Middle Eastern cohort. Methods We studied 8,450 individuals (55.5% women) aged 40–75 years who participated in the Tehran Lipid and Glucose Study (TLGS). Diabetes status and CVD risk factors were evaluated in six examinations from 1999 to 2018. The individual 10-year CVD risk score was calculated using the ACC/AHA recommended risk equation. We used generalized estimating equation models (GEE) to assess the time trends of CVD risk factors and CVD risk scores in diabetic and non-diabetic groups separately. Results The age-adjusted ACC/AHA risk score significantly decreased in non-diabetic women and men (from 3.2% to 1.6% in women and 6.8% to 5.0% in men; p for trend

Background: This study assesses the effect of blood lipid indices and lipid ratios on cardiovascular diseases (CVDs) using inverse probability-of-exposure weighted estimation of marginal structural models (MSMs). Methods: A pooled dataset of two US representative cohort studies, including 16736 participants aged 42–84 years with complete information at baseline, was used. The effect of each lipid index, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), ratios of TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C on coronary heart disease (CHD) and stroke were estimated using weighted Cox regression. Results: There were 1638 cases of CHD and 1017 cases of stroke during a median follow-up of 17.1 years (interquartile range: 8.5 to 25.7). Compared to optimal levels, the risk of CVD outcomes increased substantially in high levels of TC, LDL-C, TC/HDL-C, and LDL-C/HDL-C. If everyone had always had high levels of TC (≥240 mg/dL), risk of CHD would have been 2.15 times higher, and risk of stroke 1.35 times higher than if they had always had optimal levels (

Abstract Background Studies on knowledge, attitude, and practice (KAP) can be valuable for public health to help to develop targeted educational programs and assess the effectiveness of intervention programs. The purpose of this study was to develop and examine the validity and reliability of a questionnaire on knowledge, attitude, and practice (KAP) regarding cardiovascular diseases (CVDs), their risk factors, and symptoms among an Iranian general population. Methods This cross-sectional study was conducted on an Iranian population older than 20 years referred to some of Tehran’s healthcare centers. An initial 62-item questionnaire was developed, and the face, content, and construct validities were assessed. Results In all, 300 adults with a mean age (SD) of 39.79 (12.1) years participated in this study. Based on the results of the content validity, a questionnaire with 30 essential items was designed. Exploratory factor analysis suggested a four-factor subscale with 29 finalized items (CVD-KAP29), and acceptable goodness of fit indices was demonstrated by confirmatory factor analysis. The Cronbach’s alpha and McDonald’s ω coefficients were higher than 0.60 for all domains except the nutrition and smoking subscales. Conclusions Results provided evidence of the validity of the CVD-KAP29 for KAP studies for cardiovascular diseases in the general population.

Abstract Background Understanding the distinct patterns (trajectories) of variation in blood lipid levels before diagnosing cardiovascular disease (CVD) might carry important implications for improving disease prevention or treatment. Methods We investigated 14,373 participants (45.5% men) aged 45–84 from two large US prospective cohort studies with a median of 23 years follow-up. First, we jointly estimated developmental trajectories of lipid indices, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations using group-based multi-trajectory modeling. Then, the association of identified multi-trajectories with incident CVD, heart failure, and all-cause mortality were examined using Cox proportional hazard model. Results Seven distinct multi-trajectories were identified. The majority of participants (approximately 80%) exhibited decreasing LDL-C but rising TG levels and relatively stable HDL-C levels. Compared to the individuals with healthy and stable LDL-C, HDL-C, and TG levels, those in other groups were at significant risk of incident CVD after adjusting for other conventional risk factors. Individuals with the highest but decreasing LDL-C and borderline high and rising TG levels over time were at the highest risk than those in other groups with a 2.22-fold risk of CVD. Also, those with the highest and increased triglyceride levels over time, over optimal and decreasing LDL-C levels, and the lowest HDL-C profile had a nearly 1.84 times CVD risk. Even individuals in the multi-trajectory group with the highest HDL-C, optimal LDL-C, and optimal TG levels had a significant risk (HR, 1.45; 95% CI 1.02–2.08). Furthermore, only those with the highest HDL-C profile increased the risk of heart failure by 1.5-fold (95% CI 1.07–2.06). Conclusions The trajectories and risk of CVD identified in this study demonstrated that despite a decline in LDL-C over time, a significant amount of residual risk for CVD remains. These findings suggest the impact of the increasing trend of TG on CVD risk and emphasize the importance of assessing the lipid levels at each visit and undertaking potential interventions that lower triglyceride concentrations to reduce the residual risk of CVD, even among those with the optimal LDL-C level.

Abstract Background Understanding long-term patterns (trajectories) of cardiovascular diseases (CVD) risk and identifying different sub-groups with the same underlying risk patterns could help facilitate targeted cardiovascular prevention programs. Methods A total of 3699 participants of the Tehran Lipid and Glucose Study (TLGS) (43% men, mean age = 53.2 years), free of CVD at baseline in 1999–2001 and attending at least one re-examination cycle between the second (2002–2005) and fourth cycles (2009–2011) were included. We examined trajectories of CVD risk, based on the ACC/AHA pooled cohort equation, over ten years and subsequent risks of incident CVD during eight years later. We estimated trajectories of CVD risk using group-based trajectory modeling. The prospective association of identified trajectories with CVD was examined using Cox proportional hazard model. Results Three distinct trajectories were identified (low-low, medium-medium, and high-high risk). The high-high and medium-medium CVD risk trajectories had an increasing trend of risk during the time; still, this rising trend was disappeared after removing the effect of increasing age. Upon a median 8.4 years follow-up, 146 CVD events occurred. After adjusting for age, the medium-medium and high-high trajectories had a 2.4-fold (95% CI 1.46–3.97) and 3.46-fold (95% CI 1.56–7.70) risk of CVD compared with the low-low group, respectively. In all trajectory groups, unfavorable increasing in fasting glucose, but favorable raising in HDL and decreasing smoking and total cholesterol happened over time. Conclusions Although the risk trajectories were stable during the time, different risk factors varied differently in each trajectory. These findings emphasize the importance of attention to each risk factor separately and implementing preventive strategies that optimize CVD risk factors besides the CVD risk.

Abstract Background The Framingham hypertension risk score is a well-known and simple model for predicting hypertension in adults. In the current study, we aimed to assess the predictive ability of this model in a Middle Eastern population. Methods We studied 5423 participants, aged 20–69 years, without hypertension, who participated in two consecutive examination cycles of the Tehran Lipid and Glucose Study (TLGS). We assessed discrimination based on Harrell’s concordance statistic (c-index) and calibration (graphical comparison of predicted vs. observed). We evaluated the original, recalibrated (for intercept and slope), and revised (for beta coefficients) models. Results Over the 3-year follow-up period, 319 participants developed hypertension. The Framingham hypertension risk score performed well in discriminating between individuals who developed hypertension and those who did not (c-index = 0.81, 95% CI: 0.79–0.83). Initially, there was a systematic underestimation of the original risk score (events predicted), which was readily corrected by a simple model revision. Conclusions The revised Framingham hypertension risk score can be used as a screening tool in public health and clinical practice to facilitate the targeting of preventive interventions in high-risk Middle Eastern people.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40–100 nm). They are a transporter of lipids, proteins, and genetic material involved in mammalian cell–cell signaling, biological processes, and cell signaling. Exosomes have been identified as playing a role in rheumatoid arthritis-related joint inflammation (RA). Uniquely functioning extracellular vesicles (EVs) are responsible for the transport of autoantigens and mediators between distant cells. In addition, paracrine factors, such as exosomes, modulate the immunomodulatory function of mesenchymal stem cells (MSCs). In addition to transporting genetic information, exosomes convey miRNAs between cells and have been studied as drug delivery vehicles. In animal models, it has been observed that MSCs secrete EVs with immunomodulatory properties, and promising results have been observed in this area. By understanding the diversity of exosomal contents and their corresponding targets, it may be possible to diagnose autoimmune diseases. Exosomes can be employed as diagnostic biomarkers for immunological disorders. We here discuss the most recent findings regarding the diagnostic, prognostic, and therapeutic potential of these nanoparticles in rheumatoid arthritis and provide an overview of the evidence pertaining to the biology of exosomes in RA.

Introduction: Several controversial evidences have been recently reported on the use of prostate-specific antigens in the diagnosis of polycystic ovary syndrome (PCOS). This systematic review and meta-analysis study was performed with aim to determine the levels of prostate-specific antigens (PSA) in patients with PCOS. Methods: In this systematic and meta-analytical review, an electronic search was conducted in the databases of PubMed, Web of Science, Scopus, and Cochran Library. EndNote X6, Stata 14, and Review Manager 5.3 were used to manage the searched articles, data analysis, and quality evaluation. Begg's test and Egger's test were used to evaluate the publication bias. Results: In this study, 17 studies with 1,467 participants were included. Meta-analysis results showed that the amount of Prostate specific antigen in PCOS patients was significantly higher than the control group (Standardized mean difference: 1.83, 95% CI: 1.26-2.39; P

Background: Some studies have investigated the effects of iron on breast carcinogenesis and reported different findings about the association between Fe and breast cancer risk. This study was conducted to estimate this effect using meta-analysis method. Methods: A total of 20 articles published between 1984 and 2017 worldwide were selected through searching PubMed, Scopus, Embase, Web of Science, and Cochrane Library. Keywords such Breast Cancer, Neoplasm, Trace elements, Iron, Breast tissue concentration, Plasma concentration, Scalp hair concentration, toenail concentration and their combination were used in the search. Results: The total number of participants was 4,110 individuals comprising 1,624 patients with breast cancer and 2,486 healthy subjects. Fe concentration was measured in the various subgroups in both case and control groups. There were significant correlations between Fe concentration and breast cancer in breast tissue subgroup (SMD: 0.67 [95% CI: 0.17 to 1.17; P=0.009]). Whereas, there was no meaningful difference in Fe status between women with and without breast cancer related to scalp hair and plasma subgroups; (SMD: -3.74 [95% CI: -7.58 to 0.10; P=0.056] and (SMD:-1.14[95% CI: -2.30 to 0.03; P=0.055], respectively. Conclusion: The present meta-analysis indicated a positive and straight association between iron concentrations and risk of breast cancer but because of high heterogeneity we recommend more accurate future studies

Abstract Background The neurofibromatoses (NF) are a group of genetic disorders that interfere negatively with the quality of life (QoL) and influence physical, emotional and social statuses. Studying the effects of neurofibromatoses on various aspects of QoL seems important to implement beneficial strategies in increasing the QoL of NF patients. The aim of this study was to review the literature on quality of life in patients with NF and quantitatively evaluate the effects of Neurofibromatosis on various aspects of quality of life by synthesizing available studies. Methods This article is written according to the PRISMA checklist. Different databases including PubMed, Scopus, Google scholar and Web of Science were searched to identify studies that examined QoL of patients with neurofibromatosis. The relevant data obtained from these papers were analyzed by a random-effects model. The heterogeneity of studies was calculated using the I2 index and Egger test was used to determine publication bias. The information was analyzed by R and STATA Ver 14. Results Twelve studies were selected as eligible for this research and were included in the final analysis. The number of participants in the study was 7314 individuals containing 910 NF patients (642 NF1 and 268 NF2) and 6404 healthy subjects. The mean scores of sub-scales of QoL were significantly lower in NF patients compared with control except for the scale of cohesion. Family and NF patients had lower quality of life in all aspects of QoL than controls. Also, this meta-analysis shows that NF negatively effects on physical function, bodily pain, mental health, social function and general health. Subgroup analysis showed that NF had negative effects on all sub-scales of QoL if the study was conducted in adults and used a SF-36 questionnaire. Conclusion This meta-analysis suggests that NF is a broad spectrum disease, affecting physical function, bodily pain, mental health, social function and general health.

Background and purpose: This review study and meta-analysis aimed at providing evidence on helmet use and its efficacy on death and various types of head injuries caused by motorcycle crashes in different countries. Methods & Materials: Relevant databanks such as PubMed, Scopus, Web of Science, Science Direct, Embase and some relevant websites were searched for suitable studies. Two authors independently performed article selection, quality assessment and data extraction. Data analysis was done in Stata Software V14 applying random effects model. Results: Overall, 107 studies -with different qualities- were entered into the current systematic review and 100 studies were entered into our meta-analysis. Total rate of helmet use in motorcycle riders and occupants were 63% (95%CI: 56-69%) and 41% (95%CI: 33-48), respectively. The studies that examined the effectiveness of helmet use in reducing head, face and neck injuries, (while controlling the confounders) showed that wearing helmet could reduce the risk of death by 45% (OR= 0.55, 95%CI: 0.41-0.68) and the risk of head and face injuries by 57% (OR=0.43, 95% CI: 0.36-0.50). But it was found that helmet may not considerably reduce the risk of neck injury. Conclusion: In spite of the efficacy of helmet use on reducing the rate of deaths and head injuries among motorcyclists after a traffic collision, its use is still low and varies in different countries. But, the findings suggest that more use of helmets can facilitate global efforts to reduce road traffic injuries.

Background: Leukemia makes up about 8% of all cancers. Understanding the epidemiology of leukemia is very effective in planning for this cancer. According to lack of information in the field, the present study aimed to investigate the epidemiology and trend of incidence of leukemia in Iran during 2003 to 2010. Methods: This cross-sectional study was conducted using the analysis data from the Iranian National Cancer Registration System and Disease Management Center, Ministry of Health and Medical Education during the years 2003 to 2010. The incidence rates were calculated by age and gender and the trend of incidence of the disease by sex during this period was achieved. Findings: Evaluation of cancer registration data in the years 2003 to 2010 showed the ascending trend of leukemia in Iran. 21814 cases of leukemia were recorded in the whole country that increased from 1734 cases in 2003 to 3461 cases in 2010. The highest and the lowest incidence in women and men were reported in years 2009 and 2003, respectively. In the provinces of country, the highest reported incidence in women was in Yazd and the lowest incidence was in Semnan, Kermanshah, Qom and Kohgiluyeh and Boyer Ahmad; and for men, the highest incidence was in Yazd and the lowest incidence was in Zanjan, North and South Khorasan, Semnan, Ardebil and Kohgiluyeh and Boyer Ahmad. The sex ratio of male to female was 1.64. Conclusion: Based on the results, the incidence of leukemia in Iran is rising. Although a proportion of this increase may be due to improvements in cancer registration system but the probability of increase of incidence of leukemia exists because of the associated risk factors. Thus, the identification of the risk factors in different regions of Iran to prevent and to detect the disease at an early stage in recommended for disease control.

Abstract Background: Cancer in the elderly is rising increasingly. According to the population structure in Iran, it is necessary to conduct a study to examine the and trends in cancer incidence in the elderly in Iran. So, the aim of this study was to investigate the epidemiology and epidemiology trends in cancer incidence in Iranian elderly from 2003 to 2009. Materials and Methods: This cross-sectional study was conducted by analyzing existing data obtained from the National Cancer Registry System in Iran. In this stucly, all records of elderly cancer cases in Iran during 2003 to 2009 were investigated. The age- specific incidence rates of reported cases were estimated by using direct standardization method and the world standard population. We used Cochrane Armitage Test for linear trend by Winpepi software to study the trends in cancer incidence. Results: stuolying statistics of Cancer Registry center shows that the incidence of cancer increases with age and most cases of cancer occur commonly in elderly people (aged over 60), so that, the highest number of cancer cases diagnosed in people aged 80-84, but it decreases after the age of 85. The most common cancer among the elders, in this period (2003-2009), was the skin cancer. Also, according to the statistics, cancers are more prevalent among older men than older women. Conclusion: with due attention to the results, the trend of incidence of cancer and its various types in the elders is increasing with age. The implementation of screening programs and necessary trainings in the field of early detection and the avoidance of exposure to risk factors to reduce the risk of cancer in Iranian elderly can be useful.

Background: The current study was conducted to estimate the integrated mean of Quality Of Life (QOL) of the general population of different countries around the world and to compare them on the grounds of the Human Development Index (HDI). Methods: Well-known international databases such as Medline, Scopus, Science Direct, Google Scholar & Google, and domestic databases including SID, IranMedex, Irandoc & Magiran were searched in 2015. The data were analyzed with the Random Effect Model, using Stata 11 software. Results: Ninety-seven studies were selected for the final analysis. The overall QOL mean in the very high HDI subgroup was 74.26 (CI=72.40-76.12), which was the highest value. The lowest mean score was observed in the psychological domain (M=67.37; CI=66.23-68.52). In the high HDI subgroup, the highest mean was observed in the social relationships domain (M=64.16; CI=61.99-66.34), and the lowest mean was observed in the environment domain (M=58.76; CI=56.50-61.03). In the medium HDI subgroup, the highest mean was calculated for the overall QOL score (M=62.62; CI=56.35-68.92), and the lowest mean was estimated for the environment domain (M=56.98; CI=53.54-60.43). The highest mean in the low HDI subgroup was observed in the physical health domain (M=68.17; CI=67.43-70.52), and the lowest mean was calculated for the environment domain (M=53.14; CI=51.57-54.72). There was considerable heterogeneity in all the subgroups and domains; the values reported here are the weighted means of QOL for different countries. Conclusion: Overall, the highest means of various QOL domains were observed in the very high HDI subgroup.