Factors associated with prolonged QTc interval in Iranian population: MASHAD cohort study.

AIM: QTc interval prolongation is a growing global issue which can cause torsades de pointes, a potentially fatal arrhythmia. We aimed to identify risk factors for prolonged QT interval in men and women. METHODS: The Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study collected electrocardiogram interval data. QT was corrected for heart rate using the Bazett's formula. Ordinal logistic regression with crude (univariable) and adjusted (multivariate) association analyses in the form of odds ratio and corresponding 95% confidence interval (CI) were used to identify the factors associated with QTc prolongation. RESULTS: A total of 8878 individuals including 5318 females and 3560 males, aged 35 to 65 years, were included in this cross-sectional study. Participants with QTc prolongation were more likely to be older and have hypercholesterolemia, hypertension (HTN), and Type 2 diabetes mellitus (T2DM), but to have lower levels of physical activity (P < 0.05). Age (OR = 1.68, 95%CI = 1.18-2.39), hypercholesterolemia (OR = 1.77, 95%CI = 1.24-2.51), HTN (OR = 1.36, 95%CI = 1.06-1.73), T2DM (OR = 1.59, 95%CI = 1.19-2.13), severe anxiety (OR = 1.80, 95%CI = 1.05-3.11) and mild depression (OR = 1.38, 95%CI = 1.01-1.88) were independent risk factors for prolonged QTc interval in men. For women, only HTN (OR = 1.29, 95%CI = 1.02-1.63) and T2DM (OR = 1.50, 95%CI = 1.14-1.97) were independent risk factors. CONCLUSIONS: Older age, Hypercholesterolemia, HTN, T2DM, severe anxiety and mild depression in men, and HTN and T2DM in women were associated with high risk of prolonged QTc interval. Healthcare practitioners should be aware of the risk factors of QTc interval prolongation and should exercise caution in the management of certain patients.

The associations of oxidative stress and inflammatory markers with obesity in Iranian population: MASHAD cohort study.

BACKGROUND: Low-grade inflammation and stress oxidative condition play a role in the pathogenesis of obesity, and the serum levels of these markers, such as pro-oxidant-antioxidant balance (PAB), high-sensitivity C-reactive protein (hs-CRP), and uric acid may indicate obesity progression. In this study, we aimed to investigate the relationship between obesity with PAB, hs-CRP, and uric acid in the Iranian population. METHODS: This study was derived from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. A total of 7985 subjects aged 35 to 65 years were divided into three groups according to body mass index (BMI) as: normal, overweight and obese groups. Anthropometric indices and biochemical parameters such as PAB, superoxide dismutase type 1 (SOD1), hs-CRP, and uric acid were measured in all the participants. We evaluated the association of obesity with inflammatory factors by using multivariate regression analysis. Also, those participants with hypertension, an endocrine disorder, history of cardiovascular diseases and diabetes mellitus were excluded from the study. RESULTS: There was a positive significant correlation between BMI and serum PAB, hs-CRP and uric acid (p < 0.001). While no statistically significant relation was observed between BMI and SOD1 (p = 0.85). Multivariate regression analysis showed that the risk of overweight and obesity increased 1.02 and 1.03-fold according to increase 10 units of PAB raise in comparison to reference group (normal weight) [(odds ratio (OR): 1.02, 95% CI (1.01-1.03)] and [OR: 1.03, 95% CI (1.01-1.04)], respectively). In addition, hs-CRP serum concentration was significantly associated with a high risk of obesity [(OR: 1.02; 95% CI (1.01-1.03)]. While the high levels of serum uric acid were associated with increased odds of overweight and obesity risk [OR: 1.4; CI (1.39-1.58) and OR: 1.76; CI (1.63-1.89), respectively]. CONCLUSIONS: Generally, we showed a significant association between BMI and serum PAB, hs-CRP values and uric acid levels, suggesting the role of these factors as risk stratification factors for obesity.

Prediction of cardiovascular disease risk by serum zinc and copper concentrations and anthropometric measurements.

INTRODUCTION: We aimed to investigate the association between cardiovascular disease (CVD) and various anthropometric indices, as well as the serum levels of copper (Cu) and zinc (Zn), copper-zinc ratio (Cu/Zn ratio) and zinc-copper ratio (Zn/Cu ratio), in a large population sample from northeastern Iranian. METHOD: 9704 individuals aged 35 to 65 were enrolled in the first phase of the study. After a 10-year follow-up, 7560 participants were enrolled into the second phase. The variables used in this study included demographic characteristics, such as gender and age; biochemical parameters including: serum Zn, Cu, Cu/Zn ratio, and Zn/Cu ratio; anthropometric parameters including: waist circumference (WC), body mass index (BMI), and waist-to-hip ratio (WHR). The relationship between the aforementioned indices and CVD was examined using decision tree (DT) and logistic regression (LR) models. RESULTS: A total of 837 individuals were diagnosed with CVD among the 7560 participants. LR analysis showed that BMI, age, WH zinc-copper ratio (Zn/Cu ratio), and serum Zn/Cu ratio were significantly associated the development of CVD in men, and WHR, age, BMI, serum Cu, and Cu/Zn ratio in women. DT analysis showed that, age was the most important predictor of CVD in both genders. 71% of women, older than 49 years, with a WHR≥ 0.89, serum Cu< 75 (µg/dl), BMI≥ 22.93 (kg/m2), and serum Cu≥ 14 (µg/dl), had the highest risk of CVD. In men, among those who were ≥ 53 years, with a WHR≥ 0.98, serum Zn/Cu ratio< 1.69, and BMI≥ 22.30, had the highest risk of CVD. CONCLUSION: Among Iranian adult population, BMI, age, and WHR were one of the predictors of CVD for both genders. The Zn/Cu ratio was CVD predictor for men while Cu/Zn ratio was CVD predictor for women.

Association of T-wave electrocardiogram changes and type 2 diabetes: a cross-sectional sub-analysis of the MASHAD cohort population using the Minnesota coding system.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) has become a major health concern with an increasing prevalence and is now one of the leading attributable causes of death globally. T2DM and cardiovascular disease are strongly associated and T2DM is an important independent risk factor for ischemic heart disease. T-wave abnormalities (TWA) on electrocardiogram (ECG) can indicate several pathologies including ischemia. In this study, we aimed to investigate the association between T2DM and T-wave changes using the Minnesota coding system. METHODS: A cross-sectional study was conducted on the MASHAD cohort study population. All participants of the cohort population were enrolled in the study. 12-lead ECG and Minnesota coding system (codes 5-1 to 5-4) were utilized for T-wave observation and interpretation. Regression models were used for the final evaluation with a level of significance being considered at p < 0.05. RESULTS: A total of 9035 participants aged 35-65 years old were included in the study, of whom 1273 were diabetic. The prevalence of code 5-2, 5-3, major and minor TWA were significantly higher in diabetics (p < 0.05). However, following adjustment for age, gender, and hypertension, the presence of TWAs was not significantly associated with T2DM (p > 0.05). Hypertension, age, and body mass index were significantly associated with T2DM (p < 0.05). CONCLUSIONS: Although some T-wave abnormalities were more frequent in diabetics, they were not statistically associated with the presence of T2DM in our study.

Association between biochemical and hematologic factors with COVID-19 using data mining methods.

BACKGROUND AND AIM: Coronavirus disease (COVID-19) is an infectious disease that can spread very rapidly with important public health impacts. The prediction of the important factors related to the patient's infectious diseases is helpful to health care workers. The aim of this research was to select the critical feature of the relationship between demographic, biochemical, and hematological characteristics, in patients with and without COVID-19 infection. METHOD: A total of 13,170 participants in the age range of 35-65 years were recruited. Decision Tree (DT), Logistic Regression (LR), and Bootstrap Forest (BF) techniques were fitted into data. Three models were considered in this study, in model I, the biochemical features, in model II, the hematological features, and in model II, both biochemical and homological features were studied. RESULTS: In Model I, the BF, DT, and LR algorithms identified creatine phosphokinase (CPK), blood urea nitrogen (BUN), fasting blood glucose (FBG), total bilirubin, body mass index (BMI), sex, and age, as important predictors for COVID-19. In Model II, our BF, DT, and LR algorithms identified BMI, sex, mean platelet volume (MPV), and age as important predictors. In Model III, our BF, DT, and LR algorithms identified CPK, BMI, MPV, BUN, FBG, sex, creatinine (Cr), age, and total bilirubin as important predictors. CONCLUSION: The proposed BF, DT, and LR models appear to be able to predict and classify infected and non-infected people based on CPK, BUN, BMI, MPV, FBG, Sex, Cr, and Age which had a high association with COVID-19.

The potential therapeutic applications of CRISPR/Cas9 in colorectal cancer.

The application of the CRISPR-associated nuclease 9 (Cas9) system in tumor studies has led to the discovery of several new treatment strategies for colorectal cancer (CRC), including the recognition of novel target genes, the construction of animal mass models, and the identification of genes related to chemotherapy resistance. CRISPR/Cas9 can be applied to genome therapy for CRC, particularly regarding molecular-targeted medicines and suppressors. This review summarizes some aspects of using CRISPR/Cas9 in treating CRC. Further in-depth and systematic research is required to fully realize the potential of CRISPR/Cas9 in CRC treatment and integrate it into clinical practice.

Serum uric acid to high-density lipoprotein ratio as a novel indicator of inflammation is correlated with the presence and severity of metabolic syndrome: A large-scale study.

INTRODUCTION: We investigated the association of serum uric acid to high-density lipoprotein ratio (UHR) with the presence and severity of metabolic syndrome (MetS) among MASHAD cohort participants. METHODS: In this cross-sectional study, according to International Diabetes Federation criteria, the cohort participants were divided into MetS (+) and MetS (-) groups. MetS (+) were classified into Group 1 (those with 3 MetS criteria), Group 2 (those with 4 MetS criteria) and Group 3 (those with 5 MetS criteria). UHR was compared among the groups. RESULTS: Data related to 9637 subjects including 3824 MetS (+) and 5813 MetS (-) were analysed. The mean UHR was significantly higher (p < .001) in the MetS (+) group compared with the MetS (-) group. UHR increased as the MetS severity increased (p < .001). ROC analysis revealed that UHR greater than 9.5% has 89.07% sensitivity and 77.03% specificity in differentiating MetS (-) from MetS (+) subjects. CONCLUSION: Among MASHAD cohort study participants, a significant association between UHR and MetS was found. Furthermore, there is an increase in UHR as the severity of MetS increases. Registration number of MASHAD cohort study: 85134.

Prediction of type 2 diabetes mellitus using hematological factors based on machine learning approaches: a cohort study analysis.

Type 2 Diabetes Mellitus (T2DM) is a significant public health problem globally. The diagnosis and management of diabetes are critical to reduce the diabetes complications including cardiovascular disease and cancer. This study was designed to assess the potential association between T2DM and routinely measured hematological parameters. This study was a subsample of 9000 adults aged 35-65 years recruited as part of Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study. Machine learning techniques including logistic regression (LR), decision tree (DT) and bootstrap forest (BF) algorithms were applied to analyze data. All data analyses were performed using SPSS version 22 and SAS JMP Pro version 13 at a significant level of 0.05. Based on the performance indices, the BF model gave high accuracy, precision, specificity, and AUC. Previous studies suggested the positive relationship of triglyceride-glucose (TyG) index with T2DM, so we considered the association of TyG index with hematological factors. We found this association was aligned with their results regarding T2DM, except MCHC. The most effective factors in the BF model were age and WBC (white blood cell). The BF model represented a better performance to predict T2DM. Our model provides valuable information to predict T2DM like age and WBC.

Effect of statins on abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a prevalent condition which causes progressive growth and rupture of aortic wall with a high death rate. Several studies have found that treatment with statins may decrease the progress of AAA and the risk of rupture by suppressing the inflammatory mediators, decreasing oxidative stress, and inhibiting mechanisms involved in extracellular matrix (ECM) degradation. Moreover, some studies have reported that prehospital therapy with statins can decrease mortality after surgery. The novelty of this paper is that different studies including those performed in humans and animals were reviewed and the potential mechanisms by which statins can have an effect on AAA were summarized. Overall, the evidence suggested an association between treatment with statins and improvement of AAA.

Application of the Truncated Zero-Inflated Double Poisson for Determining of the Effecting Factors on the Number of Coronary Artery Stenosis.

BACKGROUND: Risk factors of coronary heart disease have been discussed in the literature; however, conventional statistical models are not appropriate when the outcome of interest is number of vessels with obstructive coronary artery disease. In this paper, a novel statistical model is discussed to investigate the risk factors of number of vessels with obstructive coronary artery disease. METHODS: This cross-sectional study was conducted on 633 elderly cardiovascular patients at Ghaem Hospital, Mashhad, Iran from September 2011 to May 2013. Clinical outcome is number of vessels with obstructive coronary artery disease (=0, 1, 2, 3), and predictor variables are baseline demographics and clinical features. A right-truncated zero-inflated double Poisson regression model is performed which can accommodate both underdispersion and excess zeros in the outcome. The goodness-of-fit of the proposed model is compared with conventional regression models. RESULTS: Out of 633 cardiovascular patients, 327 were male (51.7%). Mean age was ~65 ± 7 years (for individuals with zero, one ,and two coronary artery stenosis) and ~66 ± 7 years (for individuals with three coronary artery stenosis). BMI (0.04 ± 0.01, p = 0.011) and female gender (0.19 ± 0.09, p = 0.032) were significant associated with the count part of the model, and only BMI (-0.47 ± 0.2, p = 0.011) was significantly predictive of logit part of the model. The goodness-of-fit measurements indicate that the proposed model outperforms the conventional regression models. CONCLUSION: The proposal regression model shows a better fit compared to the standard regression analysis in modeling number of vessels with obstructive coronary artery disease. Hence, using truncated zero-inflated double Poisson regression model-as an alternative model-is advised to study the risk factors of number of involved vessels of coronary artery stenosis.

Relationship Between Clinical, Demographic and Socioeconomic Factors with Suicide Ideation; A Cross-sectional Study.

BACKGROUND: Suicide has grown in global prevalence as a public health problem. We aimed to evaluate the association of socioeconomic factors, biochemical and hematologic tests, and suicide ideation. METHODS: In this cross-sectional study, 8267 Iranian adults aged 35 - 65 years old were enrolled. The assessment of suicide ideation was made by the completion of Beck's depression inventory (BDI) questionnaire; according to one specific item on the questionnaire: "have you ever decided to suicide in the past week?" RESULTS: According to our results, 6.9 % of subjects had ideation of suicide. The results showed high levels of FBG, RBC, MCHC, and hs-CRP were associated with suicide ideation. Obese, single subjects, and current-smokers had a higher risk of suicide ideation. CONCLUSION: Increased physical activity, obesity, and smoking are associated with a high risk of suicide ideation; whilst, a high MCHC is related to a low risk of suicide ideation in Iranian adults.

Dietary protein is the strong predictor of coronary artery disease; a data mining approach.

BACKGROUNDS: Coronary artery disease (CAD) is the major cause of mortality and morbidity globally. Diet is known to contribute to CAD risk, and the dietary intake of specific macro- or micro-nutrients might be potential predictors of CAD risk. Machine learning methods may be helpful in the analysis of the contribution of several parameters in dietary including macro- and micro-nutrients to CAD risk. Here we aimed to determine the most important dietary factors for predicting CAD. METHODS: A total of 273 cases with more than 50% obstruction in at least one coronary artery and 443 healthy controls who completed a food frequency questionnaire (FFQ) were entered into the study. All dietary intakes were adjusted for energy intake. The QUEST method was applied to determine the diagnosis pattern of CAD. RESULTS: A total of 34 dietary variables obtained from the FFQ were entered into the initial study analysis, of these variables 23 were significantly associated with CAD according to t-tests. Of these 23 dietary input variables, adjusted protein, manganese, biotin, zinc and cholesterol remained in the model. According to our tree, only protein intake could identify the patients with coronary artery stenosis according to angiography from healthy participant up to 80%. The dietary intake of manganese was the second most important variable. The accuracy of the tree was 84.36% for the training dataset and 82.94% for the testing dataset. CONCLUSION: Among several dietary macro- and micro-nutrients, a combination of protein, manganese, biotin, zinc and cholesterol could predict the presence of CAD in individuals undergoing angiography.

The role of potassium in atherosclerosis.

BACKGROUND: Atherosclerosis (AS) is a chronic progressive inflammatory condition with a leading prevalence worldwide. Endothelial dysfunction leads to low-density lipoprotein trafficking into subendothelial space and the subsequent form of oxidized LDL (ox-LDL) within intimal layer, perpetuating the vicious cycle of endothelial dysfunction. K+ exerts beneficial effects in vascular wall by reducing LDL oxidization, vascular smooth muscle cells (VSMCs) proliferation, and free radical generation. K+ also modulates vascular tone through a regulatory effect on cell membrane potential. MATERIALS AND METHODS: The most relevant papers on the association between 'potassium channels' and 'atherosclerosis' were selected among those deposited on PubMed from 1990 to 2020. RESULTS: Here, we provide a short narrative review that elaborates on the role of K+ in atherosclerosis. This review also update the current knowledge about potential pharmacological agents targeting K+ channels with a special focus on pleiotropic activities of agents such as statins, sulfonylureas and dihydropyridines. CONCLUSION: In this review, the mechanism of different K+ channels on vascular endothelium will be summarized, mainly focusing on their pathophysiological role in atherosclerosis and potential therapeutic application.

Reference intervals for routine biochemical markers and body mass index: A study based on healthcare center database in northeastern Iran.

Age- and sex-specific reference intervals (RIs) for some biochemical tests may be useful for their interpretation, due to the variations in lifestyle and genetic, or ethnic factors. The aim of this study was to obtain RIs for some routine biochemical markers including a serum lipid profile, fasting blood glucose (FBG), aspartate and alanine aminotransferase (AST and ALT), uric acid, and body mass index (BMI) in subjects who attended primary healthcare centers. The large database of primary healthcare centers uses RIs to report results for children, adolescents, and young and old adults. RIs were obtained by using the indirect method, recommended by the CLSI Ep28-A3 guidelines. RIs for FBG, BMI, and serum lipid profile, including triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in people aged 18 to 120 years, were obtained without age/sex segmentation. RIs for serum AST, ALT, and uric acid were obtained without age segmentation, though these RIs were higher in males than females. The RIs for AST, ALT, and uric acid were higher in men, while the RIs for the other variables were similar in both sexes. This is the first study reporting the use of indirect RIs for BMI.

Comprehensive hematological reference intervals in a healthy adult male population.

Reference intervals (RIs) are important tools for improving medical decision-making. Hematology reference values can be influenced by important covariates such as genetic and environmental factors, rendering it essential to define RIs for specific populations. Therefore, we aimed to establish accurate and robust RIs for hematological markers in a healthy adult male Iranian population. This cross-sectional study was conducted in a population of 723 males aged 20-60 years old. Hematological parameters were routinely measured using a Sysmex auto analyser system (KX-21 N). The quality of assays was monitored using commercial quality control samples. The nonparametric rank method, as recommended by the Clinical and Laboratory Standards Institute (CLSI) guidelines, was used to calculate the 2.5th and 97.5th percentiles as the lower and upper reference limits, respectively. Of the 12 hematological parameters assessed, only mean platelet volume (MPV) demonstrated significant age-specific differences, requiring two partitions from 20 to 35 years (8.7-12.2 fL) and 35 to 65 years (8.5-11.5 fL). The remaining hematological parameters (e.g. leukocyte, erythrocyte, and platelet parameters) could be defined by one age range. This study established RIs for 12 routinely used hematological parameters in a healthy male population living in the northeastern region of Iran. Established RIs differed from those previously reported by other cohorts, highlighting the importance of population-specific RIs.

Dobutamine stress-induced ischemic right ventricular dysfunction in patients with three-vessel coronary artery disease.

BACKGROUND: Dobutamine stress echocardiography (DSE) is a non-invasive technique to detect coronary artery diseases (CAD). There are limited studies on evaluation of the right ventricular function by stress echocardiography. The appropriate evaluation of RV function and early diagnosis of its failure can help to improve outcomes for the patients undergoing cardiac surgery. OBJECTIVE: To determine right ventricular dysfunction in patients with three-vessel CAD by using DSE. METHODS: This cross-sectional study was among 13 patients who were candidates for coronary artery bypass grafting (CABG) referred to Ghaem Hospital, Mashhad, Iran; from September 2015 to May 2016. After a physical examination and initial measures, DSE was performed and echocardiographic parameters were recorded by a cardiologist. Paired-samples t-test was performed using SPSS Software v.16.0 for data analysis. RESULTS: The study included 13 patients (9 males) with a mean age of 65.4±7.6 years. The mean of TAPS was 16.9±4.5 mm and 15.7±2.9 mm before and after stress echocardiography, respectively (p=0.69). Systolic right ventricular (SRV) peak increased from before DSE compared with after DSE (8.0±2.2 vs. 13.7±4.2 mm/s, p<0.001). In addition, after dobutamine injection, right ventricular (RV) cardiac output decreased in 7 patients and one patient was affected by post-ejection shortening. CONCLUSION: It seems that TAPS and RV cardiac output after injection of dobutamine, can be used as markers for the recognition of ischemic RV dysfunction.