Publications by authors named "Farzad Hadaegh"

213 Publications

Sex specific trajectories of central adiposity, lipid indices, and glucose level with incident hypertension: 12 years Follow-up in Tehran lipid and glucose study.

J Transl Med 2021 Feb 23;19(1):84. Epub 2021 Feb 23.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Parvaneh Street, Velenjak, Tehran, Iran.

Aims: To identify sex specific trajectories of waist circumference (WC),triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and fasting plasma glucose (FPG) during adulthood and examine their associations with incident hypertension.

Methods: The cohort consisted of 5030 participants (2051 males) with at least 2 repeated measurement during a median of 12 years follow up. We identified trajectory groups using latent class growth mixture model, their association with hypertension was examined using multivariate Cox-regression analysis.

Results: We found 997 cases of hypertension (483 male). For both exposures, three distinct trajectory groups were identified in both genders. For WC, in women: low-increasing, 82.4%; high-stable, 13.4%; high-increasing, 4.2% and in men: stable, 94.6%; low-increasing, 3.6% and for high- increasing, 1.7%. For TG, in women: stable, 91.3%; decreasing, 5.9%; inverse U-shape, 2.8%; in men: stable, 89.7%; inverse U- shape, 6.2% and for decreasing, 4.1%. Regarding WC, high stable and high-increasing trajectories were associated with hypertension in the multivariate model [(hazard ratio (HR) = 1.66 (95% CI 1.26-2.20) and 2.78(1.79-3.60), respectively]. Among men, this association was shown only for the low-increasing trajectory [2.76: 1.49-5.10]. For TG, among women decreasing and inverse U-shape trajectories were significantly associated with hypertension in the multivariate model [1.32:1.01-1.76] and [2.23:1.58-3.23, respectively]. We did not find any impact of increasing trajectories of FPG and HDL-C on incident hypertension. Considering TC, all individuals followed a stable trajectory.

Conclusion: WC dynamic changes in both gender and TG trajectory among women were significantly associated with incident hypertension.
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http://dx.doi.org/10.1186/s12967-021-02749-xDOI Listing
February 2021

The protective effect of obesity on mortality among those with (or without) CVD cannot be fully explained by collider-stratification bias.

Int J Obes (Lond) 2021 Feb 2. Epub 2021 Feb 2.

Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1038/s41366-021-00756-yDOI Listing
February 2021

Sex-specific incidence rates and risk factors for fracture: A 16-year follow-up from the Tehran lipid and glucose study.

Bone 2021 Jan 30;146:115869. Epub 2021 Jan 30.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objective: To examine the population-based incidence of any-fracture and its potential risk factors in a sex-split cohort of the Iranian population.

Materials And Methods: A total of 3477 men and 4085 women with a mean (SD) age of 47.92(13.1) and 45.88(11.47) years, respectively were entered into the study. The age-standardized incidence rates per 100,000 person-years were reported for the whole population and each sex separately. Cox proportional hazard models were used to estimate hazard ratios (HR) for potential risk factors. Only fractures requiring inpatients' care were considered as the outcome. We also defined major osteoporotic fractures (MOF) as the composite of the fractures that occurred in the vertebral, wrist, hip and pelvic sites among population aged ≥50 years.

Results: During the median (IQR) follow-up of 15.9 years, 4.34%men and 3.75% women experienced at least one incident any-fracture. The annual age-standardized incidence rates (95% CI) among men and women were 330.9 (279.6-388.9) and 319.4(268.1-377.3) per 100,000 person-years, respectively; the corresponding values for incidence of MOF was 202.2(142.3-278.6) in men and 342.1(260.4-441.0) per 100,000 person-years for women. In the multivariable model, among the whole population, age groups ≥50 years, central obesity [HR: 95% CI 1.77(1.32-2.39)], current smoking [1.59(1.15-2.20)] and using steroid medications [2.20(1.04-4.67)] significantly increased the risk of incident fracture (all P < 0.05); however the impact of the first two risk factors were more prominent among women (P for interaction ≤0.01). Moreover, being obese was associated with a lower risk of incident first fracture in the total population [HR: 95% CI: 0.61(0.40-0.92)]. Being men [HR: 95% CI: 0.54(0.30-0.99)] and prediabetes status [HR: 95% CI: 0.53(0.30-0.95)] were also associated with lower risk for MOF.

Conclusion: This is the first report of long-term incidence rate of any-fracture and MOF conducted in the metropolitan city of Tehran. Among modifiable risk factors of fracture, in the whole population smoking habit and using steroid medications and particularly for women central obesity should be considered as main risk factors for preventive strategies. Prediabetes status was associated with lower risk of MOF.
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http://dx.doi.org/10.1016/j.bone.2021.115869DOI Listing
January 2021

The Role of Metabolic Syndrome and its Components in Incident Fracture: A 15-year follow-up among the Iranian Population.

J Clin Endocrinol Metab 2021 Feb 1. Epub 2021 Feb 1.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Context: The relationship between metabolic syndrome (MetS) and the risk of fracture is a matter of debate.

Objectives: To determine the impact of MetS and its components on the risk of hospitalized fractures, during a median follow-up of 15.9 years.

Material & Methods: A total of 7520 participants (4068 women) aged ≥ 30 years were entered into the study. Multivariable Cox proportional hazards regression analyses were applied for data analysis.

Results: The prevalence of Mets was 40.0% and 40.4% in men and women, respectively. During the follow-up, hospitalized fracture was observed in 305 cases (men=152). The multivariable hazard ratio (HR) and 95% confidence interval (CI) of MetS for incident fracture for men and women was 0.72(0.49-1.05, p=0.08) and 1.38(0.96-1.98, p=0.08), respectively. In the fully adjusted model, high fasting plasma glucose (FPG) among men was tended to be associated with a lower risk of fracture [0.67(0.44-1.02, P=0.06)]; among women, high waist circumference (WC) was associated with a greater risk [2.40(1.55-3.73)]. Among the population aged ≥ 50 years in the pooled sample, MetS was not accompanied by the risk of fracture, but high WC was associated with a higher risk [1.58(1.07-2.33)]. For incident hip/pelvic fracture, abdominal obesity -but not MetS per se- was also a strong and independent risk factor.

Conclusions: A significant sex difference in the association between the Mets and its components with incident fracture was observed. Women with central adiposity were at increased risk of hospitalized fracture, whereas, men with high FPG were at decreased risk.
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http://dx.doi.org/10.1210/clinem/dgab023DOI Listing
February 2021

The association of priori and posteriori dietary patterns with the risk of incident hypertension: Tehran Lipid and Glucose Study.

J Transl Med 2021 Jan 25;19(1):44. Epub 2021 Jan 25.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: The aim of this study was to investigate the association of dietary patterns with incident hypertension.

Materials/methods: This prospective study was conducted on 4793 individuals of Tehran lipid and glucose study participants, aged ≥ 18 years who were followed for a median of 6.3 years from 2008-2011 to 2016-2018. A valid and reliable semi-quantitative food frequency questionnaire was used to assess usual dietary intakes. Anthropometrics and blood pressure were assessed at baseline and during follow up examinations. Dietary patterns were derived using principal component analysis (PCA). Healthy eating index (HEI) and dietary approach to stop hypertension (DASH) score were measured based on dietary recommendations. Time-dependent Cox models adjusting for confounders were used to examine the association between dietary patterns and the risk of hypertension.

Results: During follow-up, a total of 727 incident cases of hypertension were identified. The mean ± SD age at baseline was 40.3 ± 13.5 and 37.9 ± 12.1 years in men and women, respectively. Two dietary patterns (the healthy and unhealthy) were extracted by PCA. Compared with participants in the first quartile, a 23% (HR: 1.23; 95%CI 1.00-1.53; P trend: 0.056) increased risk of hypertension was found in the fourth quartile of HEI score. This association was disappeared after further adjustment for confounders. Increasing DASH score, the healthy and unhealthy dietary pattern were not associated with risk of hypertension.

Conclusion: Our findings showed that higher adherences to the posteriori- and priori-dietary patterns were not associated with risk of hypertension in this population.
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http://dx.doi.org/10.1186/s12967-021-02704-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836444PMC
January 2021

National trends in cardiovascular health metrics among Iranian adults using results of three cross-sectional STEPwise approaches to surveillance surveys.

Sci Rep 2021 Jan 8;11(1):58. Epub 2021 Jan 8.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

To examine the trends of 7 cardiovascular health metrics (CVH metrics) incorporate of smoking, physical activity, diet, body mass index (BMI), fasting plasma glucose (FPG), total cholesterol (TC), and blood pressure (BP) level during three cross-sectional STEPwise approaches to surveillance (STEPS), 2007-2016, among Iranian adults. The study population consisted of 19,841 women and 17,243 men, aged 20-65 years. The CVH metrics were categorized as 'ideal', 'intermediate', and 'poor'. The sex-stratified weighted prevalence rate of each CVH metrics was reported. The conditional probability of each poor versus combined intermediate and ideal metric was analyzed using logistic regression. In 2016 compared to 2007, the prevalence of poor BP level (20.4% vs. 23.7%), smoking (13.7% vs. 23.8%), TC ≥ 240 mg/dl (2.4% vs. 11.2%) and FPG < 100 mg/dl (75.6% vs. 82.3%) declined, whereas poor physical activity level (49.7% vs. 30%), poor healthy diet score (38.1% vs. 4.1%), BMI levels ≥ 25 kg/m (62.8% vs. 57.8%) increased. Despite a high prevalence of obesity among women, it remained constant in women but showed an increasing trend in men; moreover, the trends of low physical activity and current smoking were better for women. Despite some improvement in CVH metrics, < 4% of Iranian adults meet ≥ 6 CVH metrics in 2016; this issue needs intervention at the public health level using a multi-component strategy.
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http://dx.doi.org/10.1038/s41598-020-79322-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794314PMC
January 2021

Recurrence of a neuroendocrine tumor of adrenal origin: a case report with more than a decade follow-up.

BMC Endocr Disord 2021 Jan 7;21(1). Epub 2021 Jan 7.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Yamen Street, Velenjak, Tehran, Iran.

Background: Neuroendocrine tumor (NET) with adrenocorticotropic hormone (ACTH) secretion are very rare. To our knowledge, no follow-up study is published for ACTH-secreting NET, regardless of the primary site, to show second occurrence of tumor after a long follow-up, following resection of primary tumor.

Case Presentation: Here, we describe a 49-year-old-man with cushingoid feature, drowsiness and quadriparesis came to emergency department at December 2005. Laboratory tests revealed hyperglycemia, metabolic alkalosis, severe hypokalemia, and chemical evidence of an ACTH-dependent hypercortisolism as morning serum cortisol of 57 μg /dL without suppression after 8 mg dexamethasone suppression test, serum ACTH level of 256 pg/mL, and urine free cortisol of > 1000 μg /24 h. Imaging showed only bilateral adrenal hyperplasia, without evidence of pituitary adenoma or ectopic ACTH producing tumors. Importantly, other diagnostic tests for differentiating Cushing disease (CD) from ectopic ACTH producing tumor, such as inferior petrosal sinus sampling (IPSS), corticotropin releasing hormone (CRH) stimulation test, octreotide scan or fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan were not available in our country at that time. Therefore, bilateral adrenalectomy was performed that led to clinical and biochemical remission of hypercortisolism and decreased ACTH level to < 50 pg/mL, findings suggestive of a primary focus of NET in adrenal glands. After 11 years uncomplicated follow up, the ACTH level elevated up to 341 pg/mL and re-evaluation showed a 2 cm nodule in the middle lobe of the right lung. Surgical excision of the pulmonary nodule yielded a carcinoid tumor with positive immunostaining for ACTH; leading to decrease in serum ACTH level to 98 pg/mL. Subsequently after 7 months, serum ACHT levels rose again. More investigation showed multiple lung nodules with metastatic bone lesions accompanied by high serum chromogranin level (2062 ng/mL), and the patient managed as a metastatic NET, with bisphosphonate and somatostatin receptor analogues.

Conclusion: This case of surgically-treated NET showing a secondary focus of carcinoid tumor after one decade of disease-free follow-up emphasizes on the importance of long-term follow-up of ACTH-secreting adrenal NET.
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http://dx.doi.org/10.1186/s12902-020-00673-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791754PMC
January 2021

Number of parity/live birth(s) and cardiovascular disease among Iranian women and men: results of over 15 years of follow-up.

BMC Pregnancy Childbirth 2021 Jan 7;21(1):28. Epub 2021 Jan 7.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Most previous studies conducted in non-Middle Eastern populations have suggested that an increase in the number of parity/live birth(s) leads to cardiovascular disease (CVD) development, although their findings were inconclusive on this issue for both sexes. Biologic and socioeconomic pathways were suggested to explain this association. We studied this issue among urban Iranian men and women.

Methods: In this population-based cohort study, which included 3929 women and 2571 men aged ≥30 years, data for the number of parity/live birth(s) were obtained by a standard questionnaire. Participants were then annually followed for CVD events. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the number of parity/live birth(s) and other traditional CVD risk factors.

Results: During more than 15 years of follow-up, 456 and 524 CVD events have occurred among women and men, respectively. Among women, a J-shaped association was found between the number of live births and incident CVD with the lowest risk for women with two live births. Among women in multivariable analyses, each unit increase in parity had a HR of 1.05 (CI: 1.01-1.10), and having ≥4 parity was associated with a HR of 1.86 (0.97-3.56, p-value = 0.061). Among men, in comparison with participants who had 1 child, multivariable HRs of having 2, 3, and ≥ 4 children were 1.97 (1.24-3.12), 2.08 (1.31-3.31), and 2.08 (1.30-3.34), respectively.

Conclusion: To the best of our knowledge, the current study is the first report on this issue in the Middle East and North Africa region, a region with a high burden of CVD. It can now be suggested that the number of parity/live birth(s) is linked to CVD among the Iranian population, with this issue being more prominent among men. Further research is needed to support our results and clarify the pathways between the number of parity/live birth(s) and CVD development among Iranian populations by considering potential risk factors, especially psycho-socio-economic risk factors.
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http://dx.doi.org/10.1186/s12884-020-03499-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792076PMC
January 2021

The risk and added values of the atherosclerotic cardiovascular risk enhancers on prediction of cardiovascular events: Tehran lipid and glucose study.

J Transl Med 2021 Jan 6;19(1):25. Epub 2021 Jan 6.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: In 2013 American College of Cardiology and the American Heart Association released a guideline on the management of atherosclerotic cardiovascular disease (ASCVD) including a composite of death from CVD, non-fatal myocardial infarction, or non-fatal stroke (hard CVD). This guideline recommended a risk score that was calculated using pooled cohort equations (ASCVD-PCE). The guideline was updated in 2018/2019 and further risk discussion was suggested for deciding whether to continue or initiate statin therapy among non-diabetic individuals with ASCVD-PCE score ranged 5-20%. They recommended a risk discussion with considering risk enhancing factors (ASCVD-REFs) including family history of premature CVD, chronic kidney disease, triglycerides ≥ 175 mg/dl, low-density lipoprotein cholesterol (LDL-C) ≥ 160 mg/dl, metabolic syndrome (Mets), and for women premature menopause, and hypertensive disorders of pregnancy (HDP). In the current study, we aimed to examine the predictability of recommended ASCVD-REFs on incident hard CVD in non-diabetic individuals with LDL-C 70-189 mg/dl, with ASCVD-PCE risk 5-20% during 10 and 15-year follow-up.

Methods: Among a total of 3546 non-diabetic individuals aged 40-75 years, after excluding those with ASCVD-PCE score < 5% and ≥ 20% (n = 2342), 1204 individuals (women = 332) were included. The univariable and multivariable (further adjusted for ASCVD-PCE) Cox regression analysis were used to evaluate the association of each potential ASCVD-REFs with hard CVD. Additionnaly, the role of different components of Mets and a history of gestational diabetes (GDM)/macrosomia was also examined. The predictive ability of each significant ASCVD-REFs, then was evaluated by the discrimination accuracy and risk reclassification index.

Results: During the 10-year follow-up, 73 hard CVD events occurred. Although in univariable analysis, high blood pressure (BP) component of Mets, GDM/macrosomia, and HDP remained as significant ASCVD-REFs, in the multivariable analysis, only the history of HDP (5.35 (1.22-23.38)) and GDM/macrosomia (3.18 (1.05-9.65)) showed independent risks. During the 15-year follow-up, Mets (1.47 (1.05-2.06)) and its components of high waist circumference (1.40 (1.0-1.95)) and high BP (1.52 (1.07-2.15)) significantly increased the risk. These ASCVD-REFs did not improve discrimination or predictive ability.

Conclusions: In a decade follow-up, only conditions specific for women and in longer follow-up, the presence of Mets perse, and its components of high WC and high BP were shown as significant ASCVD-REFs.
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http://dx.doi.org/10.1186/s12967-020-02686-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789723PMC
January 2021

Adolescent metabolic syndrome and its components associations with incidence of type 2 diabetes in early adulthood: Tehran lipid and glucose study.

Diabetol Metab Syndr 2021 Jan 2;13(1). Epub 2021 Jan 2.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: To investigate the association of youth metabolic syndrome (MetS) and its components, individually and in combination with early adulthood incident type 2 diabetes (T2DM).

Methods: A total of 2798 adolescents aged 11-19 years enrolled in the study. At baseline, MetS, its components including blood pressure (BP), waist circumference (WC), triglycerides (TGs), fasting plasma glucose, and low HDL-C, and different combinations of MetS components were defined. After a mean 11.3 years of follow-up, T2DM was determined. Multivariable Cox proportional hazard regression analysis adjusted for age, sex, family history of T2DM, and adult BMI was used for data analysis. The hazard ratio (HR) and 95% confidence interval (CI) were reported.

Results: During the follow-up, 44 incidents T2DM were developed. Among different individual components, only high WC [HR = 2.63, 95% CI (1.39-4.97)] and high TGs [HR = 1.82, 95% CI (1.00-3.34)] remained as significant predictors only in the age and sex adjusted model. Regarding combinations of MetS components, 'high TGs and high WC' [HR = 2.70, 95% CI (1.27-5.77)], 'high BP and high WC' [HR = 2.52, 95% CI (1.00-6.33)], 'high TGs and high BP' [HR = 2.27, 95% CI (1.02-5.05)] as well as MetS per se [HR = 2.82, 95% CI (1.41-5.64)] had a significant relationship with incident T2DM in the multivariable adjusted model. Among different confounders, being female and having family history of T2DM were consistently associated with higher risk of T2DM, in different combinations of MetS components.

Conclusions: Adolescence MetS and some combinations of MetS components predicted early adulthood T2DM. Thus, adolescents, particularly female ones, with combinations of MetS components as well as those with family history of T2DM could be targeted for lifestyle intervention.
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http://dx.doi.org/10.1186/s13098-020-00608-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778813PMC
January 2021

Trends of low physical activity among Iranian adolescents across urban and rural areas during 2006-2011.

Sci Rep 2020 12 7;10(1):21318. Epub 2020 Dec 7.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-4763, Tehran, Islamic Republic of Iran.

It is well documented that physical inactivity is related to weight gain and a whole host of chronic diseases. This study investigated trends of low physical activity among Iranian adolescents in urban and rural areas between 2006-2011. A total of 12,178 adolescents, aged between 15 and 19 years, participated in National Surveys of Risk Factors for Non-Communicable Diseases. Data on physical activity was obtained using the global physical activity questionnaire. A complex sample survey and multinomial logistic regression were used to model physical activity levels. The percentage of adolescents who had low levels of physical activity increased from 2006 to 2011 in both urban and rural areas. Low and moderate levels of physical activity were lower in rural girls as compared with urban girls, with a prevalence ratio of 0.59 (95% CI 0.47-0.74) and 0.59 (95% CI 0.47-0.74), respectively. The corresponding values for boys residing in rural areas compared with boys in urban areas were 0.56 (95% CI 0.43-0.75) and 0.60 (95% CI 0.48-0.74), respectively. The adolescents' lifestyles showed an increasing trend for physical inactivity in both genders; however, in rural areas, only girls had a rising affinity for a sedentary lifestyle throughout the 2006-2011 years.
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http://dx.doi.org/10.1038/s41598-020-78048-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721745PMC
December 2020

COVID-19 prognosis: what we know of the significance and prognostic value of liver-related laboratory parameters in SARS-CoV-2 infection.

Gastroenterol Hepatol Bed Bench 2020 ;13(4):313-320

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: The present study aims to evaluate the prognostic value of liver-related laboratory parameters in COVID-19.

Background: This is not the first nor will it be the last time that a member of the β-coronaviruses wages a full-scale war against human health. Notwithstanding atypical pneumonia being the primary symptom, the emergence of severe disease mainly resulting from the injury of non-pulmonary organs leaves no alternative, in some cases, other than a dreadful death.

Methods: To provide a well-conceptualized viewpoint representing the prognostic values of liver-related laboratory parameters in COVID-19, a meta-analysis was performed with the calculation of mean difference and 95% confidence intervals of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Bili), and albumin (Alb) in severe and non-severe COVID-19 patients.

Results: While severe COVID-19 cases displayed higher values of ALT, AST, and Bili compared to non-severe patients (mean differences of 7.48, 12.07, and 3.07, respectively), the value of Alb was significantly lower in severe cases (mean differences of -6.15). There was also a correlation between alterations in all of the parameters; however, only correlations between ALT and Bili (R=0.98, p=0.0031), and Bili and Alb (R=-1, p=0.0012) were significant.

Conclusion: Abnormal values of liver-related examinations outwardly contribute to reflect the progression of the disease toward an unfavorable outcome. Therefore, careful scrutiny of these parameters will provide clinicians with invaluable information regarding SARS-CoV-2 infection, at least in terms of liver injury.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682969PMC
January 2020

Incorporating kidney disease measures into cardiovascular risk prediction: Development and validation in 9 million adults from 72 datasets.

EClinicalMedicine 2020 Oct 14;27:100552. Epub 2020 Oct 14.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.

Background: Chronic kidney disease (CKD) measures (estimated glomerular filtration rate [eGFR] and albuminuria) are frequently assessed in clinical practice and improve the prediction of incident cardiovascular disease (CVD), yet most major clinical guidelines do not have a standardized approach for incorporating these measures into CVD risk prediction. "CKD Patch" is a validated method to calibrate and improve the predicted risk from established equations according to CKD measures.

Methods: Utilizing data from 4,143,535 adults from 35 datasets, we developed several "CKD Patches" incorporating eGFR and albuminuria, to enhance prediction of risk of atherosclerotic CVD (ASCVD) by the Pooled Cohort Equation (PCE) and CVD mortality by Systematic COronary Risk Evaluation (SCORE). The risk enhancement by CKD Patch was determined by the deviation between individual CKD measures and the values expected from their traditional CVD risk factors and the hazard ratios for eGFR and albuminuria. We then validated this approach among 4,932,824 adults from 37 independent datasets, comparing the original PCE and SCORE equations (recalibrated in each dataset) to those with addition of CKD Patch.

Findings: We confirmed the prediction improvement with the CKD Patch for CVD mortality beyond SCORE and ASCVD beyond PCE in validation datasets (Δc-statistic 0.027 [95% CI 0.018-0.036] and 0.010 [0.007-0.013] and categorical net reclassification improvement 0.080 [0.032-0.127] and 0.056 [0.044-0.067], respectively). The median (IQI) of the ratio of predicted risk for CVD mortality with CKD Patch vs. the original prediction with SCORE was 2.64 (1.89-3.40) in very high-risk CKD (e.g., eGFR 30-44 ml/min/1.73m with albuminuria ≥30 mg/g), 1.86 (1.48-2.44) in high-risk CKD (e.g., eGFR 45-59 ml/min/1.73m with albuminuria 30-299 mg/g), and 1.37 (1.14-1.69) in moderate risk CKD (e.g., eGFR 60-89 ml/min/1.73m with albuminuria 30-299 mg/g), indicating considerable risk underestimation in CKD with SCORE. The corresponding estimates for ASCVD with PCE were 1.55 (1.37-1.81), 1.24 (1.10-1.54), and 1.21 (0.98-1.46).

Interpretation: The "CKD Patch" can be used to quantitatively enhance ASCVD and CVD mortality risk prediction equations recommended in major US and European guidelines according to CKD measures, when available.

Funding: US National Kidney Foundation and the NIDDK.
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http://dx.doi.org/10.1016/j.eclinm.2020.100552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599294PMC
October 2020

Iranian general populations' and health care providers' preferences for benefits and harms of statin therapy for primary prevention of cardiovascular disease.

BMC Med Inform Decis Mak 2020 11 4;20(1):288. Epub 2020 Nov 4.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: The use of statins for primary prevention of cardiovascular diseases is associated with different benefit and harm outcomes. The aime of this study is how important these outcomes are for people and what people's preferences are.

Methods: We conducted a preference-eliciting survey incorporating a best-worst scaling (BWS) instrument in Iran from June to November 2019. The relative importance of 13 statins-related outcomes was assessed on a sample of 1085 participants, including 913 general population (486 women) and 172 healthcare providers from the population covered by urban and rural primary health care centers. The participants made trade-off decisions and selected the most and least worrisome outcomes concurrently from 13 choice sets; each contains four outcomes generated using the balanced incomplete block design.

Results: According to the mean (SD) BWS scores, which can be (+ 4) in maximum and (- 4) in minimum, in the general population, the most worrisome outcomes were severe stroke (3.37 (0.8)), severe myocardial infarction (2.71(0.7)), and cancer (2.69 (1.33)). While myopathy (- 3. 03 (1.03)), nausea/headache (- 2.69 (0.94)), and treatment discontinuation due to side effects (- 2.24 (1.14)) were the least worrisome outcomes. Preferences were similar between rural and urban areas and among health care providers and the general population with overlapping uncertainty intervals.

Conclusion: The rank of health outcomes may be similar in various socio-cultural contexts. The preferences for benefits and harms of statin therapy are essential to assess benefit-harm balance when recommending statins for primary prevention of cardiovascular diseases.
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http://dx.doi.org/10.1186/s12911-020-01304-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640674PMC
November 2020

Nasopharyngeal B-cell lymphoma with pan-hypopituitarism and oculomotor nerve palsy: a case report and review of the literature.

BMC Endocr Disord 2020 Nov 3;20(1):163. Epub 2020 Nov 3.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Parvaneh Street, P.O. Box: 19395-4763, Tehran, Velenjak, Iran.

Background: Primary nasopharyngeal lymphoma (NPL) is a very rare tumor of Waldeyer ring (WR) lymphoid tissue. It is challenging to differentiate lymphoma infiltration of pituitary from a pituitary adenoma, meningioma infiltration, and other sellar lesions to plan a suitable treatment strategy. We presented for the first time a unique case of NPL with an unusual presentation of oculomotor nerve palsy associated with pan-pituitary involvement in a diabetic patient.

Case Presentation: A 64-year old diabetic woman with no previous history of malignancy presented with intermittent diplopia for about the last nine months. Severe headache, left eye ptosis and hypoglycemic episodes were added to her symptoms after a while. Further complaints include generalized weakness, loss of appetite, generalized musculoskeletal pain, and 6-7 kg weight loss within six months. Her family history was unremarkable. Physical examinations of eyes indicated left eye 3rd, 4th, and 6th nerve palsy. But, she was not anisocoric, and the pupillary reflexes were normal on both eyes. No lymphadenopathy, organomegaly and other abnormalities were found. Magnetic resonance imaging (MRI) showed a heterogeneous enhancement in the seller and suprasellar regions, enlargement of the stalk, parasellar dural enhancement and thickening of the sphenoid sinus without bone erosion. Also, both cavernous sinuses were infiltrated and both internal carotid arteries were encased by the neoplastic lesion. It suggested an infiltrative neoplastic lesion which compressed the cranial nerves. Pituitary hormone levels assessment indicated a pan-hypopituitarism. Following nasopharyngeal mucosal biopsy, the immunohistochemistry (IHC) findings revealed a low-grade non-Hodgkin's B-cell lymphoma. Systemic workup, including cerebrospinal fluid (CSF) studies, bone marrow aspiration, chest and abdominopelvic high-resolution computed tomography (HRCT) indicated no other involvement by the lymphoma. After chemotherapy courses, central adrenal insufficiency, partial central diabetes incipidious (CDI) and central hypothyroidism have been resolved. To our best knowledge, we found 17 cases of NPL with cranial nerve palsy, 1 case of NPL with pan-hypopituitarism and no NPL case with both cranial nerve palsy and pituitary dysfunction.

Conclusions: The incidence of cranial neuropathy in patients with diabetes should not merely be attributed to diabetic neuropathy without further evaluation.
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http://dx.doi.org/10.1186/s12902-020-00644-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607655PMC
November 2020

Sex-specific prevalence of coronary heart disease among Tehranian adult population across different glycemic status: Tehran lipid and glucose study, 2008-2011.

BMC Public Health 2020 Oct 6;20(1):1510. Epub 2020 Oct 6.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-4763, No. 24, Parvaneh Street, Velenjak, Tehran, Iran.

Background: Coronary heart disease (CHD) is one of the leading causes of death. Alarmingly Iranian populations had a high rank of CHD worldwide. The current study aimed to assess the prevalence of CHD across different glycemic categories.

Methods: This study was conducted on 7718 Tehranian participants (Men = 3427) aged ≥30 years from 2008 to 2011. They were categorized based on glycemic status. The prevalence of CHD was calculated in each group separately. CHD was defined as hospital records adjudicated by an outcome committee. The association of different glycemic categories with CHD was calculated using multivariate logistic regression, compared with normal fasting glucose /normal glucose tolerance (NFG/NGT) group as reference.

Results: The age-standardized prevalence of isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), both impaired fasting glucose and impaired glucose tolerance (IFG/IGT), newly diagnosed diabetes mellitus (NDM), and known diabetes mellitus (KDM) were 14.30% [95% confidence interval (CI): 13.50-15.09], 4.81% [4.32-5.29], 5.19% [4.71-5.67], 5.79% [5.29-6.28] and 7.72% [7.17-8.27], respectively. Among a total of 750 individuals diagnosed as cases of CHD (398 in men), 117 (15.6%), 453 (60.4%), and 317 (42.3%) individuals had a history of myocardial infarction (MI), cardiac procedure, and unstable angina, respectively. The age-standardized prevalence of CHD for the Tehranian population was 7.71% [7.18-8.24] in the total population, 8.62 [7.81-9.44] in men and 7.19 [6.46-7.93] in women. Moreover, among diabetic participants, the age-standardized prevalence of CHD was 13.10 [9.83-16.38] in men and 10.67 [8.90-12.44] in women, significantly higher than corresponding values for NFG/NGT and prediabetic groups. Across six levels of glycemic status, CHD was associated with IFG/IGT [odds ratio (OR) and 95% CI: 1.38 (1.01-1.89)], NDM [1.83 (1.40-2.41)], and KDM [2.83 (2.26-3.55)] groups, in the age- and sex-adjusted model. Furthermore, in the full-adjusted model, only NDM and KDM status remained to be associated with the presence of CHD by ORs of 1.40 (1.06-1.86) for NDM and 1.91 (1.51-2.43) for KDM.

Conclusion: The high prevalence of CHD, especially among diabetic populations, necessitates the urgent implementation of behavioral interventions in the Tehranian population, according to evidence-based guidelines for the clinical management of diabetic patients.
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http://dx.doi.org/10.1186/s12889-020-09595-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539419PMC
October 2020

Sex Differences in Rates of Change and Burden of Metabolic Risk Factors Among Adults Who Did and Did Not Go On to Develop Diabetes: Two Decades of Follow-up From the Tehran Lipid and Glucose Study.

Diabetes Care 2020 Dec 5;43(12):3061-3069. Epub 2020 Oct 5.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Objective: We investigated the cumulative burden and linear rates of change of major metabolic risk factors (MRFs) among Iranian adults in whom type 2 diabetes did and did not develop.

Research Design And Methods: We included 7,163 participants (3,069 men) aged 20-70 years at baseline with at least three examinations during 1999-2018. Individual growth curve modeling was used for data analysis. Statistical interactions for sex by diabetes status were adjusted for age, family history of diabetes, smoking status, and physical activity level.

Results: Study sample included 743 (316 men) new case subjects with diabetes. In both men and women, compared with individuals in whom diabetes did not develop, individuals in whom diabetes developed had a higher burden of all MRFs and a greater rate of change in BMI, fasting plasma glucose (FPG), systolic blood pressure (SBP), and diastolic blood pressure; however, the differences in burden and rate of change between those who did and did not develop diabetes were greater in women than in men. During the transition to diabetes, women experienced more adverse change in BMI, FPG, triglyceride, and HDL cholesterol (HDL-C) (diabetes-sex interaction values <0.05) and faster rates of change in BMI, FPG, HDL-C, and total cholesterol (interaction values <0.01) and SBP (interaction = 0.055) than men.

Conclusions: The greater exposure of women to and burden of MRFs before onset of diabetes may have implications for implementing sex-specific strategies in order to prevent or delay diabetes complications.
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http://dx.doi.org/10.2337/dc20-1112DOI Listing
December 2020

The impact of triglyceride-glucose index on incident cardiovascular events during 16 years of follow-up: Tehran Lipid and Glucose Study.

Cardiovasc Diabetol 2020 09 29;19(1):155. Epub 2020 Sep 29.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24 Aarabi St. Velenjak, P.O. Box: 19395-4763, Tehran, Iran.

Background: To investigate whether the Triglyceride-Glucose index (TyG-index) is associated with increased risk of cardiovascular diseases (CVD)/coronary heart disease (CHD).

Methods: A total of 7521 Iranians aged ≥ 30 years (male = 3367) were included in the study. Multivariate Cox regression analyses (adjusted for age, gender, waist circumference, body mass index, educational level, smoking status, physical activity, family history of CVD, type 2 diabetes, hypertension, low and high density lipoprotein cholesterol, and lipid lowering drugs) were used to assess the risk of incident CVD/CHD across quintiles and for 1-standard deviation (SD) increase in the TyG-index. The cut off point for TyG-index was assessed by the minimum value of [Formula: see text]. We also examined the added value of the TyG-index in addition to the Framingham risk score when predicting CVD.

Results: During follow-up, 1084 cases of CVD (male = 634) were recorded. We found a significant trend of TyG-index for incident CVD/CHD in multivariate analysis (both Ps for tend ≤ 0.002). Moreover, a 1-SD increase in TyG-index was associated with significant risk of CVD/CHD in multivariate analysis [1.16 (1.07-1.25) and 1.19 (1.10-1.29), respectively]. The cut-off value of TyG-index for incident CVD was 9.03 (59.2% sensitivity and 63.2% specificity); the corresponding value of TyG-index for incident CHD was 9.03 (60.0% sensitivity and 62.8% specificity), respectively. Although no interaction was found between gender and TyG-index for CVD/CHD in multivariate analysis (both Ps for interaction > 0.085), the significant trend of TyG-index was observed only among females for incident CVD (P = 0.035). A significant interaction was found between age groups (i.e. ≥ 60 vs < 60 years) and TyG-index for CVD outcomes in the multivariate model (P-value for interaction = 0.046). Accordingly, a significant association between the TyG-index and outcomes was found only among the younger age group. Among the population aged < 60 the addition of TyG-index to the Framingham risk score (FRS) did not show improvement in the predictive ability of the FRS, using integrated discrimination improvement.

Conclusion: The TyG-index is significantly associated with increased risk of CVD/CHD incidence; this issue was more prominent among the younger population. However, adding TyG-index to FRS does not provide better risk prediction for CVD.
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http://dx.doi.org/10.1186/s12933-020-01121-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526412PMC
September 2020

Correction To: Sex-Specific Incidence Rates and Risk Factors for Hypertension During 13 Years of Follow-up: The Tehran Lipid and Glucose Study.

Glob Heart 2020 Jul 29;15(1):49. Epub 2020 Jul 29.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR.

[This corrects the article DOI: 10.5334/gh.780.].
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http://dx.doi.org/10.5334/gh.847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413166PMC
July 2020

Diabetes Management during the COVID-19 Pandemic: An Iranian Expert Opinion Statement.

Arch Iran Med 2020 08 1;23(8):564-567. Epub 2020 Aug 1.

Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran.

The coronavirus infection is an evolving pandemic with high morbidity and mortality, especially in people with comorbidities. The case fatality rate (CFR) is 9.2% in the presence of diabetes, while it is 1.4% in those without any comorbidity. Diabetes is a prevalent disease globally; hence, healthcare professionals are highly concerned about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic progression. Current evidence does not support higher incidence of coronavirus disease 2019 (COVID-19) in people with diabetes (PWD). However, people with diabetes are considered high risk for developing complications. Optimal metabolic control is a challenging concept, especially in the presence of an acute and severe respiratory viral infection. In this consensus, we considered the challenging issues in management of patients with diabetes during the COVID-19 pandemic. The consensus covers various aspects of outpatient as well as inpatient care based on the current evidence.
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http://dx.doi.org/10.34172/aim.2020.61DOI Listing
August 2020

Long-term effectiveness of a lifestyle intervention on the prevention of type 2 diabetes in a middle-income country.

Sci Rep 2020 08 25;10(1):14173. Epub 2020 Aug 25.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P O Box: 19395-4763, Tehran, Iran.

This study aims to assess the effects of a community-based lifestyle intervention program on the incidence of type 2 diabetes (T2D). For this purpose, three communities in Tehran were chosen; one community received a face-to-face educational session embedded in a long-term community-wide lifestyle intervention aimed at supporting lifestyle changes. We followed up 9,204 participants (control: 5,739, intervention: 3,465) triennially from 1999 to 2015 (Waves 1-5). After a median follow-up of 3.5 years (wave 2), the risk of T2D was 30% lower in the intervention community as compared with two control communities by (Hazard-ratio: 0.70 [95% CI 0.53; 0.91]); however, the difference was not statistically significant in the following waves. After a median follow-up of 11.9 years (wave 5), there was a non-significant 6% reduction in the incidence of T2D in the intervention group as compared to the control group (Hazard-ratio: 0.94 [0.81, 1.08]). Moreover, after 11.9 years of follow-up, the intervention significantly improved the diet quality measured by the Dietary Approaches to Stop Hypertension concordance (DASH) score. Mean difference in DASH score in the intervention group versus control group was 0.2 [95% CI 0.1; 0.3]. In conclusion, the intervention prevented T2D by 30% in the short-term (3.5 years) but not long-term; however, effects on improvement of the diet maintained in the long-term.Registration: This study is registered at IRCT, a WHO primary registry ( https://irct.ir ). The registration date 39 is 2008-10-29 and the IRCT registration number is IRCT138705301058N1.
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http://dx.doi.org/10.1038/s41598-020-71119-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447773PMC
August 2020

Effect of Bedtime Melatonin Administration in Patients with Type 2 Diabetes: A Triple-Blind, Placebo-Controlled, Randomized Trial.

Iran J Pharm Res 2019 ;18(Suppl1):258-268

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran .

Melatonin is widely available as over the counter product. Despite promising effects of melatonin supplementation on glycemic control, there is a significant heterogeneity between studies. The current study aimed at determining the effect of melatonin on fasting blood glucose (FBG), insulin resistance/sensitivity indices, glycosylated hemoglobin A1c (HbA1c), and high sensitivity C-reactive protein (hs-CRP) among type 2 diabetes mellitus (T2D) population during 8 weeks in a randomized, triple-blind, placebo-controlled trial. Thirty four subjects with the mean age ± standard deviation of 57.74 ± 8.57 years and 36 subjects with the mean age of 57.61 ± 9.11 years were allocated to 6 mg nightly melatonin and placebo groups, respectively. Melatonin and placebo groups were matched by age, gender, body mass index, and duration of diabetes. Also, there was no significant difference in laboratory findings except for HbA1c, which was lower in the placebo group (7.00 ± 0.89% vs 7.60 ± 1.47%, =0.042). After trial completion, the increase of serum levels of melatonin was greater in the intervention than the placebo group (3.38 ± 1.33 vs 0.94 ± 1.28 ng/L, =0.192). Moreover, compared to placebo group, among melatonin users, homeostasis model assessment of insulin resistance (HOMA1-IR) tended to be unfavorable at the end of follow-up [-0.51 (-1.76-0.81) vs. 0.28 (-1.24-1.74), =0.20]; the similar trend was also shown for insulin sensitivity index (HOMA1-S) [2.33 (-3.59-12.46) vs. -2.33 (-10.61-9.16), =0.148]. No differences were observed in FBG, HbA1C, and hs-CRP changes between the trial groups. The current study did not support the improving effect of melatonin on glucose homeostasis.
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http://dx.doi.org/10.22037/ijpr.2019.112011.13485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393042PMC
January 2019

Trends in cardiovascular risk factors in diabetic patients in comparison to general population in Iran: findings from National Surveys 2007-2016.

Sci Rep 2020 07 16;10(1):11724. Epub 2020 Jul 16.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 23, Parvaneh Street, Velenjak, Tehran, Iran.

To determine levels of change in risk factors for cardiovascular disease among people with and without a previous diagnosis of diabetes from 2007 to 2016 in Iran. Data were obtained from five rounds of the World Health Organization STEPwise approach to Surveillance (STEPS) cross-sectional surveys. Participants were 7665 and 93,733 adults with and without known diabetes, respectively, aged 25-65 years. We used logistic and linear regressions to assess the trends of risk factors. Individuals with known diabetes compared to those without the condition, experienced greater reductions in mean levels of systolic blood pressure (3.0 vs. 0.5 mmHg among women and 3.9 vs. 1.6 mmHg among men), diastolic blood pressure (6.4 vs. 5.11 mmHg in women and 3.3 vs. 1.8 mmHg in men), and non-HDL cholesterol (42.4 vs. 27.2 mg/dL among women and 30.3 vs. 21.0 mg/dL among men) throughout these years. Men with diabetes also showed a greater reduction in the prevalence of daily cigarette smoking compared to their non-diabetic counterparts (7.3% vs. 2.3%). Fasting plasma glucose decreased among subjects with diabetes but increased among those without diabetes. Significant increases were observed in proportions who met goals for blood pressure, triglycerides, non-HDL cholesterol and LDL cholesterol in both groups; however, almost half of diabetic subjects did not achieve risk factor goals in 2016. Secondary prevention in diabetic patients was more effective than primary prevention in the general population; however, the rate of diabetic patients who met the designated goals for each risk factor was still suboptimal.
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http://dx.doi.org/10.1038/s41598-020-68640-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366682PMC
July 2020

Prediction of Cardiovascular Disease Mortality in a Middle Eastern Country: Performance of the Globorisk and Score Functions in Four Population-Based Cohort Studies of Iran.

Int J Health Policy Manag 2020 Jul 15. Epub 2020 Jul 15.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.34172/ijhpm.2020.103DOI Listing
July 2020

Multi-state analysis of hypertension and mortality: application of semi-Markov model in a longitudinal cohort study.

BMC Cardiovasc Disord 2020 07 6;20(1):321. Epub 2020 Jul 6.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Most previous research has studied the association of hypertension with cardiovascular disease (CVD) and all-cause mortality by focusing on the transition from the initial state to a single outcome. We investigated the impact of hypertension, defined according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) (new) and the Seventh Report of the Joint National Committee (JNC7) (old), on CVD death and all-cause mortality considering non-fatal CVD as an intermediate event between two CVD-free and mortality states.

Methods: A total of 3002 Iranian population (47.4% men), aged ≥50 years were followed from 1999 to 2014. Two multi-state semi-Markov models with three transitions were defined for CVD death and all-cause mortality as two outcomes. The multivariable Cox model was used to estimate the effect of hypertension on transition hazards. The mean of 15-year life expectancy of participants in each transition was estimated using the restricted mean survival time.

Results: The ACC/AHA guideline increased the prevalence of hypertension from 43.3 to 68.6%. Among CVD-free individuals, hypertension was significantly associated with increased risk of non-fatal CVD [Hazard Ratio, 1.52 (1.28-1.81) and 1.48 (1.21-1.80)], CVD death [2.96 (2.06-4.25) and 1.98 (1.30-3.04)] and all-cause mortality [1.64 (1.32-2.05) and 1.31 (1.01-1.69)] according the old and new guidelines, respectively. However, after incident non-fatal CVD, the association between hypertension and mortality events was not significant according to both definitions. Hypertensive participants experienced a first non-fatal CVD about 0.9 and 0.6 years earlier than normotensive population according to JNC7 and the 2017 ACC/AHA guidelines, respectively.

Conclusion: Hypertension, according to JNC7 and the ACC/AHA guidelines, significantly increased the risk of mortality events among CVD-free population although the risk was attenuated using ACC/AHA guideline. Hypertension also decreased the number of years lived without CVD and early onset of CVD, and consequently, an increase in the time spent with these diseases. After non-fatal CVD, hypertension had no significant impact on mortality risk according to both guidelines.
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http://dx.doi.org/10.1186/s12872-020-01599-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336626PMC
July 2020

External validation of the European risk assessment tool for chronic cardio-metabolic disorders in a Middle Eastern population.

J Transl Med 2020 07 2;18(1):267. Epub 2020 Jul 2.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: High burden of chronic cardio-metabolic disorders including type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease (CVD) have been reported in the Middle East and North Africa region. We aimed to externally validate a non-laboratory risk assessment tool for the prediction of the chronic cardio-metabolic disorders in the Iranian population.

Methods: The predictors included age, body mass index, waist circumference, use of antihypertensive medications, current smoking, and family history of cardiovascular disease and/or diabetes. For external validation of the model in the Tehran lipids and glucose study (TLGS), the Area under the curve (AUC) and the Hosmer-Lemeshow (HL) goodness of fit test were performed for discrimination and calibration, respectively.

Results: Among 1310 men and 1960 women aged 28-85 years, 29.5% and 47.4% experienced chronic cardio-metabolic disorders during the 6 and 9-year follow-up, respectively. The model showed acceptable discrimination, with an AUC of 0.72 (95% CI 0.69-0.75) for men and 0.73 (95% CI 0.71-0.76) for women. The calibration of the model was good for both genders (min HL P = 0.5). Considering separate outcomes, AUC was highest for CKD (0.76 (95% CI 0.72-0.79)) and lowest for T2DM (0.65 (95% CI 0.61-0.69)), in men. As for women, AUC was highest for CVD (0.82 (95% CI 0.78-0.86)) and lowest for T2DM (0.69 (95% CI 0.66-0.73)). The 9-year follow-up demonstrated almost similar performances compared to the 6-year follow-up. Using Cox regression in place of logistic multivariable analysis, model's discrimination and calibration were reduced for prediction of chronic cardio-metabolic disorders; the issue which had more effect on the prediction of incident CKD among women. Moreover, adding data of educational levels and marital status did not improve, the discrimination and calibration in the enhanced model.

Conclusion: This model showed acceptable discrimination and good calibration for risk prediction of chronic cardio-metabolic disorders in short and long-term follow-up in the Iranian population.
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http://dx.doi.org/10.1186/s12967-020-02434-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331242PMC
July 2020

Serum Thyroid Peroxidase Antibody Level and Incident Hypertension in Iranian Men: A Suggestion for the Role of Thyroid Autoimmunity.

Endocr Metab Immune Disord Drug Targets 2020 ;20(10):1711-1718

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Dysfunction of the thyroid gland has profound effects on the cardiovascular system.

Objective: We aimed to explore the relation of serum thyroid peroxidase antibody (TPO-Ab), as a marker of thyroid autoimmunity with incident hypertension among a euthyroid population.

Methods: A total of 3681 participants (1647 men) entered the study. Multivariate Cox proportional hazard models were conducted to estimate the association between TPO-Ab and incident hypertension.

Results: The mean age (standard deviation) of the participants was 37.5 (12.8) years. During a median follow-up of 12.2 years, 511 men and 519 women developed hypertension. The multivariable hazard ratios (HRs) and related 95% confidence intervals (CIs) of 1-unit increase in natural logarithm (ln) of TPO-Ab for incident hypertension were 1.09 (1.00-1.19), 1.03 (0.97-1.10), and 1.05 (1.00-1.11) for men, women, and total population, respectively. Moreover, considering the TPO-Ab status as a categorical variable (i.e. TPO-Ab positive or TPO-Ab negative), the multivariate-adjusted HRs (95% CIs) of TPO-Ab positivity for incident hypertension, were 1.33 (0.95-1.85), 1.12 (0.86-1.45) and 1.19 (0.97- 1.46) for men, women, and total population, respectively.

Conclusion: Elevated serum TPO-Ab level can contribute to the development of hypertension among euthyroid men during a long follow-up; suggesting a role for thyroid autoimmunity.
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http://dx.doi.org/10.2174/1871530320666200624163035DOI Listing
January 2020

The external validity and performance of the no-laboratory American Diabetes Association screening tool for identifying undiagnosed type 2 diabetes among the Iranian population.

Prim Care Diabetes 2020 12 7;14(6):672-677. Epub 2020 Jun 7.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biostatistics and Epidemiology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Aims: The aim of this study is to assess the American Diabetes Association (ADA) risk score as a self-assessment screening tool for undiagnosed type 2 diabetes (T2DM) in Iran.

Methods: In a national survey of risk factors for non-communicable diseases, we included 3458 Iranian adults. The discrimination and validity were assessed using the area under the curve (AUC), sensitivity, specificity, Youden's index, positive and negative predictive values (PPV and NPV). The frequency of high-risk Iranian population who need a glucose test and those who need intervention were also estimated.

Results: The AUC was 73.7% and the suggested ADA score of ≥5 yielded a sensitivity of 51.6%, specificity 82.4%, NPV 98.3%, and PPV 7.9%. This threshold results in classifying 18.6% of the Iranians, equals to 8.5 million, as high-risk and 1.5% of the population, about 700,000, would need intervention. However, our study suggested score ≥4 that identified 34% of the population as high-risk and 2% of the population would need intervention.

Conclusion: Our findings support the ADA suggested threshold for identifying high-risk individuals for undiagnosed T2DM; however, a lower threshold is also recommended for higher sensitivity. The ADA screening tool could help the public health system for low-cost screening.
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http://dx.doi.org/10.1016/j.pcd.2020.04.001DOI Listing
December 2020

Sex-Specific Incidence Rates and Risk Factors for Hypertension During 13 Years of Follow-up: The Tehran Lipid and Glucose Study.

Glob Heart 2020 04 8;15(1):29. Epub 2020 Apr 8.

Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR.

Background: Hypertension, with a prevalence of 25.6% is a serious public health concern in Iran.

Objective: To investigate the population-based incidence of hypertension and its potential risk factors in Tehranian adults during a median follow-up of 13.1 years.

Methods: A total of 6,533 non-hypertensive participants (women = 3,639), aged ≥20 years participated in the study. Crude and age-standardized incidence rates per 1000 person-years were calculated for each sex, separately. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all potential risk factors.

Results: The crude and age-standardized incidence rates (95% CI) of hypertension per 1000 person-years were 29.7 (27.8-31.6) and 34.9 (32.5-37.4) among men and 25.8 (24.3-27.3) and 38.7 (35.5-42.0) among women, respectively. The incidence rate of hypertension in younger age groups was higher among men. However, after the 4 decade, the incidence rate was higher among women. Significant interactions of sex with age groups, body mass index categories, marital status, hypertriglyceridemia and glycemic categories were found in multivariable analyses (all p-values < 0.05). In the multivariable model, the risk in both sexes was found to be significantly associated with older age, obesity, and normal or high normal blood pressure (BP). Moreover, factors such as being overweight [HR: 1.20 (1.00-1.44)], former smoking [2.15 (1.52-3.04)], hypertriglyceridemia [1.23 (1.06-1.43)] and pre-diabetes status [1.19 (1.02-1.39)] were significant predictors of incident hypertension among women. Central obesity was found to be a significant predictor among men [1.26 (1.03-1.54)]. The optimism-corrected Harrell's C index (95% CI) in the categorical adjusted model was 0.75 (0.74-0.79) among men and 0.75 (0.74-0.76) among women.

Conclusion: In the Tehranian population, nearly 2.7% of total participants (3% of men and 2.6% of women) develop hypertension each year. Obesity and high BP levels are the main modifiable risk factors in both sexes. Hypertriglyceridemia, prediabetes and former smoking are risk factors for hypertension among women.
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http://dx.doi.org/10.5334/gh.780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218790PMC
April 2020

Sex-specific clustering of metabolic risk factors and cancer risk: a longitudinal study in Iran.

Biol Sex Differ 2020 04 25;11(1):21. Epub 2020 Apr 25.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Yemen Street, Shahid Chamran Highway, P.O. Box: 19395-4763, Tehran, Iran.

Background: Cancer is a major cause of death in low- and middle-income countries. A large number of studies have shown that some of the metabolic risk factors (MRFs) tend to cluster in individuals. We examined the synergistic effects of multiple MRFs and cancer risk among Iranian adults.

Methods: Among 8593 (3929 men) participants aged ≥ 30 years, the self-organizing map (SOM) was applied to clustering of four MRFs including high fasting plasma glucose (HFPG), high total cholesterol (HTC), high systolic blood pressure (HSBP), and high body mass index (HBMI). The Cox proportional hazards model was used to investigate the association between clusters with cancer incidence during a median of 14.0 years of follow-up.

Results: During the study period, 265 new cases of cancer were identified among participants at risk. The incidence density rate was 2.5 per 1000 person years in total population. About 32 and 40% of men and women, respectively, had three or four MRFs. We identified seven clusters of MRFs in both men and women. In both genders, MRFs were clustered in those with older age. Further, inverse associations were found between current smoking in men, and education level and passive smoking in women and clustering of MRFs. In men, a cluster with 100% HSBP and HBMI had the highest risk for overall cancer. While, among women, a cluster with 100% HFPG and 93% HBMI yielded the highest risk for cancer. The risk was decreased when HBMI accompanied by HTC.

Conclusions: Clustering patterns may reflect underlying link between MRFs and cancer and could potentially facilitate tailored health promotion interventions.
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http://dx.doi.org/10.1186/s13293-020-00296-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183600PMC
April 2020