Association of high-sensitivity C-reactive protein and hematologic-inflammatory indices with risk of cardiovascular diseases: a population-based study with partial least squares structural equation modeling approach.

Partial least squares structural equation modeling is a simple approach that may be used to determine the factors associated with diseases. In the current study, we aimed to explore the most associated high-sensitivity C-reactive protein (hs-CRP) as well as hematologic-inflammatory indices for the risk of cardiovascular disease (CVD). A total of 7362 healthy (non-CVD) participants aged 35-65 years old from baseline investigation were evaluated in the Phase 2 follow-up. Of these, 1022 individuals were found to have CVDs in the second phase (10-year follow-up) of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. We used partial least squares structural equation modeling to develop a prediction model for association of CVD risk factors and hs-CRP as well as hematologic-inflammatory indices in the study population. According to the study, age had the most significant impact on the presence of CVD. Increasing in age by one unit raises the risk of CVD by 0.166. Also, serum hs-CRP was found to have the second-highest impact on CVD; increasing in age by one unit raises the risk of CVD by 0.042. The study also discovered a strong and significant correlation between red cell distribution width (RDW) and CVD. Moreover, the study found that several factors such as hemoglobin (HGB), neutrophil (NEUT), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and platelet-to-lymphocyte ratio (PLR) have indirect effects on CVD that are mediated by hs-CRP while controlling for age, sex and social-economic factors. Generally, the results showed that age, hs-CRP, and RDW were the most important risk factors on CVD.

Evaluating the Association of Anthropometric Indices With Total Cholesterol in a Large Population Using Data Mining Algorithms.

BACKGROUND: Unbalanced levels of serum total cholesterol (TC) and its subgroups are called dyslipidemia. Several anthropometric indices have been developed to provide a more accurate assessment of body shape and the health risks associated with obesity. In this study, we used the random forest model (RF), decision tree (DT), and logistic regression (LR) to predict total cholesterol based on new anthropometric indices in a sex-stratified analysis. METHOD: Our sample size was 9639 people in which anthropometric parameters were measured for the participants and data regarding the demographic and laboratory data were obtained. Aiding the machine learning, DT, LR, and RF were drawn to build a measurement prediction model. RESULTS: Anthropometric and other related variables were compared between both TC <200 and TC ≥200 groups. In both males and females, Lipid Accumulation Product (LAP) had the greatest effect on the risk of TC increase. According to results of the RF model, LAP and Visceral Adiposity Index (VAI) were significant variables for men. VAI also had a stronger correlation with HDL-C and triglyceride. We identified specific anthropometric thresholds based on DT analysis that could be used to classify individuals at high or low risk of elevated TC levels. The RF model determined that the most important variables for both genders were VAI and LAP. CONCLUSION: We tend to present a picture of the Persian population's anthropometric factors and their association with TC level and possible risk factors. Various anthropometric indices indicated different predictive power for TC levels in the Persian population.

Oxidative balance and mental health: Exploring the link between prooxidant-antioxidant balance and depression in hypertensive and normotensive individuals, accounting for sex differences.

BACKGROUND: Existing studies have suggested a link between oxidative stress levels and depression. Additionally, factors such as gender and conditions like hypertension have been shown to influence oxidative stress. This ten-year follow-up cohort study aims to examine the association between prooxidant-antioxidant balance (PAB) and the onset of depression and its symptoms in both hypertensive and normotensive individuals, while considering gender differences. METHODS: The data for this study was obtained from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study, a cohort study conducted in eastern Iran. Serum PAB levels were measured in 1702 hypertensive and 4096 normotensive individuals aged 35 to 65 years. After ten years, the participants' depression status was evaluated using the Beck questionnaire, and depression symptoms were investigated using the BDI-II structural model, which includes somatic, affective, and cognitive symptoms. RESULT: The analysis indicates that in hypertensive male participants, the highest tertile of PAB is associated with an increased risk of depression (ß: 1.22, 95 % CI: -0.046, 2.485; P = 0.059) and symptoms of depression, including cognitive (ß: 2.937, 95 % CI: 0.511, 5.362; P = 0.018) and somatic (ß: 2.654, 95 % CI: 0.37, 4.939; P = 0.023) symptoms. However, there was no significant association between affective symptoms and PAB tertiles. Additionally, there was no significant link between depression and depressive symptoms in female hypertensive and normotensive individuals. CONCLUSION: In male hypertensive patients, but not in normotensive individuals of both genders and hypertensive women, depression and its associated symptoms, including somatic and cognitive symptoms, are associated with elevated levels of oxidative stress, as evidenced by higher serum PAB values. PAB is not associated with affective symptoms. Future studies should focus on the gender-specific nature of this relationship and work to clarify its underlying mechanisms.

Uric acid is associated with type 2 diabetes: data mining approaches.

Background: Several blood biomarkers have been related to the risk of type 2 diabetes mellitus (T2D); however, their predictive value has seldom been assessed using data mining algorithms. Methods: This cohort study was conducted on 9704 participants recruited from the Mashhad Stroke and Heart Atherosclerotic disorders (MASHAD) study from 2010 to 2020. Individuals who were not between the ages of 35 and 65 were excluded. Serum levels of biochemical factors such as creatinine (Cr), high-sensitivity C reactive protein (hs-CRP), Uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct and total bilirubin (BIL.D, BIL.T), lipid profile, besides body mass index (BMI), waist circumference (WC), blood pressure, and age were evaluated through Logistic Regression (LR) and Decision Tree (DT) methods to develop a predicting model for T2D. Results: The comparison between diabetic and non-diabetic participants represented higher levels of triglyceride (TG), LDL, cholesterol, ALT, BIL.D, and Uric acid in diabetic cases (p-value < 0.05). The LR model indicated a significant association between TG, Uric acid, and hs-CRP, besides age, sex, WC, and blood pressure, hypertension and dyslipidemia history with T2D development. DT algorithm demonstrated dyslipidemia history as the most determining factor in T2D prediction, followed by age, hypertension history, Uric acid, and TG. Conclusion: There was a significant association between hypertension and dyslipidemia history, TG, Uric acid, and hs-CRP with T2D development, along with age, WC, and blood pressure through the LR and DT methods.

Investigation of the relationship between atherogenic index, anthropometric characteristics, and 10-year risk of metabolic syndrome: a population-based study.

BACKGROUND: People with metabolic syndrome (MetS) are at a higher risk of coronary artery disease, diabetes mellitus, stroke, osteoarthritis, and some types of cancers. Finding markers which are available and inexpensive are most useful for the prediction of MetS. The present study aimed to determine the relationship between atherogenic index and anthropometric indicators and the 10-year risk of MetS. METHODS: During the 10-year follow-up on Mashhad stroke and heart atherosclerotic disorder (MASHAD study), 4684 subjects who did not MetS at baseline were recruited in this study. The anthropometric indices and atherogenic index including atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI-I, CRI-I), and atherogenic coefficient (AC) were measured. SPSS-23 was used for all statistical analyses. RESULT: Among subjects who did not have MetS at baseline 1599 cases (34.1%) developed MetS. The anthropometric and lipid indices were significantly elevated in patients with MetS compared to the healthy ones (p < 0.001). It was revealed that an increase of one unit in AIP and AC can raise the risk of MetS 22.7% (OR: 1.227 (95% CI, 1.166-1.291)) and 37.7% (OR: 1.377 (95% CI, 1.291-1.468)), respectively. Moreover, increasing one unit of WHtR decreases the risk of MetS by 8.5% (OR: 0.915 (95% CI, 0.886-0.946)). CONCLUSION: The results of this longitudinal study showed that increasing AC and AIP could enhance the risk of MetS. The present study also indicated that AC and AIP are useful predictors in the clinical setting for identifying individuals with MetS in the Iranian adult population.

Association Between Serum Levels of Anti-heat Shock Protein 27 Antibody and Liver Cell Injury in Chronic Hepatitis B.

Heat Shock Protein 27 (HSP27), an anti-HBV factor, exists in the intracellular and extracellular spaces. As an inflammatory modulator, serum HSP27 (sHSP27) is associated with elevated pro-inflammatory cytokines and a higher likelihood of hepatocellular carcinoma in chronic hepatitis. SHSP27 results in natural antibody production (anti-HSP27-Ab) that is more stable and easily detectable compared to sHSP27. We aimed to investigate any potential association between anti-HSP27-Ab level and chronic hepatitis B (CHB) progression and inflammation indicated by liver cell injury and HBV replication. This cross-sectional study was conducted on 91 patients with CHB and 92 individuals without CHB. Following demographic data collection, anti-HSP27-Ab, serum lipids including total cholesterol, triglyceride, LDL-C, HDL-C, and aminotransferase levels were measured using enzymatic assays in participants' serum samples. HBV DNA was also measured by quantitative PCR in CHB patients. Bivariate and multivariate analyses showed a significantly higher mean level of anti-HSP27-Ab in CHB than in healthy individuals (0.304 vs. 0.256AU/ml, P value = 0.015). These levels held significant differences in the CHB subgroups of male patients, at the age of 50 years and above, with non-smoking status, elevated aminotransferase levels, and hypotriglyceridemia (P value < 0.05). However, no difference was found between the antibody levels and HBV DNA copies (P value > 0.05). This study provides evidence that anti-HSP27 antibody levels can reflect the degree of liver necrosis indicated by aminotransferase levels. Regarding the higher incidence rate of HBV-associated complications in 50 to 60-year-old men, monitoring the antibody can be beneficial in managing this group of CHB patients, which deserves further investigation.

The association of dietary indices for hyperinsulinemia and insulin resistance with the risk of metabolic syndrome: a population-based cross-sectional study.

We aimed to investigate the association between an empirical dietary index for hyperinsulinemia (EDIH), empirical dietary index for insulin resistance (EDIR), and MetS and its components in an adult Iranian population. In this cross-sectional study, a total of 6482 participants aged 35-65 years were recruited as part of the MASHAD cohort study. Dietary intakes were assessed using a validated food frequency questionnaire (FFQ). The International Diabetes Federation (IDF) criteria were used to define MetS. Multivariable logistic regression models were applied to determine the association between EDIH, EDIR, and MetS and its components. The mean age and BMI of participants were 48.44±8.20 years, and 27.98±4.73 kg/m2, respectively. Around 59% of the population was female. Of the total population, 35.4% had MetS. According to the full-adjusted model, there was no significant association between higher quartiles of EDIH and EDIR and odds of MetS (Q4 EDIH; OR (95%CI):0.93 (0.74-1.18), Q4 EDIR; OR (95%CI):1.14 (0.92-1.40). Regarding MetS components, EDIR was associated with increased odds of hypertension and diabetes (Q4 EDIR; OR (95%CI):1.22 (1.04-1.44) and 1.22 (1.01-1.47), respectively). EDIH was also associated with decreased odds of hypertriglyceridemia (Q4 EDIH; OR (95%CI): 0.72 (0.60-0.87)). This study showed no significant association between hyperinsulinemia and insulin resistance potential of diet and odds of MetS among Iranian adults. However, EDIR was significantly associated with increased odds of hypertension and diabetes as MetS components.

Serum Zinc and Copper Concentrations and Dyslipidemia as Risk Factors of Cardiovascular Disease in Adults: Data Mining Techniques.

This study aimed to examine the relationship between serum cholesterol levels and the ratio of zinc (Zn) and copper (Cu) in the blood serum and the incidence of cardiovascular disease (CVD). In Phase I of the study, 9704 individuals between the age of 35 and 65 years were recruited. Phase II of the cohort study comprised 7561 participants who completed the 10-year follow-up. The variables which were measured at the baseline of the study included gender, age, systolic blood pressure (SBP), diastolic blood pressure (DBP); biochemical parameters including serum Cu, Zn, copper-zinc ratio (Cu/Zn), zinc-copper ratio (Zn/Cu); fasted lipid profile consisting of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) as well as fasting serum glucose, and triglycerides-glucose (TyG) index. Decision tree (DT) and logical regression (LR) models were applied to examine the relationship between the aforementioned factors and CVD. CVD was diagnosed in 837 individuals (378 males and 459 females) out of 7561 participants. According to the LR models, SBP, TC, HDL, age, Zn/Cu, and TyG index for males and SBP, age, TyG index, HDL, TC, Cu/Zn, and Cu for females had the highest correlation with CVD (p-value ≤ 0.033). Based on the DT algorithm, 88% of males with SPB < 129.66 mmHg, younger age (age < 53 years), TyG index < 9.53, 173 ≤ TC < 187 mg/dL, and HDL ≥ 32 mg/dL had the lowest risk of CVD. Also, 98% of females with SBP < 128 mmHg, TyG index < 9.68, age < 44, TC < 222 mg/dL, and HDL ≥ 63.7 mg/dL had the lowest risk of CVD. It can be concluded that the Zn/Cu for men and Cu/Zn for women, along with dyslipidemia and SBP, could significantly predict the risk of CVD in this cohort from northeastern Iran.

Health Risk Assessment of Exposure to Heavy Metals in Wheat Flour from Iran Markets: Application of Monte Carlo Simulation Approach.

The significance of flour in the Iranian diet underscores the need to ensure its safety from chemical pollutants. This study aimed to evaluate the potential health risks posed by certain heavy metals, such as Fe, Zn, Cu, Al, Co, Hg, Cr, Ni, Pb, and Cd, in wheat flour available in the Iranian market. A total of 248 flour samples were collected from 11 provinces in Iran during the winter of 2021. The health risks associated with heavy metals in children and adults were evaluated using USEPA health risk assessment guidance for superfund part A and Monte Carlo Simulation. The average concentration of Fe, Zn, Cu, Al, Co, Hg, Cr, Ni, Pb, and Cd, was equal to 30.62 ± 59.24, 4.94 ± 13.64, 1.24 ± 3.08, 2.85 ± 4.98, 0.03 ± 0.01, 0.12 ± 0.03, 1.42 ± 1, 0.23 ± 0.05, 1.71 ± 0.65, and 0.02 ± 0.004 mg/kg dry weight, respectively. Analysis of Fe, Cr, Al, Hg and Cr in all flour samples showed that the average concentration of these metals were greater than the standards levels set by the WHO/FAO. The results of the non-carcinogenic risks (HI) showed that the hazard index values (children: 0.969 ± 1.04, adult: 0.837 ± 0.905) of heavy metals through the consumption of flour to both study population were acceptable. The results of the carcinogenic risks (CR) based on Cd, and Pb concentration showed that the CR values from ingestion of flour to the children and adults population were 1.45 × 10-5 ± 5.08 × 10-5 and 1.26 × 10-5 ± 4.40 × 10-5, respectively. The results of Monte Carlo simulation showed that conventional deterministic health risk evaluation could overestimate risk outcomes. Likewise, Cr has 68.8% and 69.1% probability of non-carcinogenic risk to children and adult, respectively, and 80% and 79.8% probability of CR for adults and children respectively for Pb, suggesting that Cr and Pb is a priority control heavy metals. Therefore, it is recommended to continuously monitor the levels of heavy metals in wheat and its derived food products to ensure food safety.

Effect of dairy products fortified with vitamin d3 on restless legs syndrome in women with premenstrual syndrome, abdominal obesity and vitamin d deficiency: a pilot study.

BACKGROUNDS: Restless legs syndrome (RLS) is an unpleasant condition that affects the quality of life of patients. Its prevalence in increased in women with premenstrual syndrome (PMS). Vitamin D plays a key role in female reproduction through its impact on calcium homeostasis and neurotransmitters. We aimed to evaluate the effect of dairy products fortified with Vitamin D3 on RLS in women with PMS. MATERIALS AND METHODS: We conducted a 2.5-month, randomized, total-blinded clinical trial to evaluate the effectiveness of low-fat milk and yogurt fortified with vitamin D on RLS in women with PMS. Among 141 middle-aged women with abdominal obesity, 71 and 70 cases received fortified and non-fortified low-fat dairy products, respectively. All subjects completed a Symptoms Screening Tool (PSST) and RLS questionnaires. RESULTS: The results showed that in the women with severe PMS (PSST > 28), serum levels of vitamin D increased significantly following vitamin D fortification. The mean restless legs score in the severe PMS subgroup (PSST > 28) was significantly lower after the intervention (p < 0.05. Serum Vitamin D levels significantly differed between intervention and control groups in all individuals (PSST < 19, PSST 19-28, and PSST > 28) (p < 0.05), but no significant differences were found between RLS scores of the intervention and control groups in the three PMS subgroups (p > 0.05). CONCLUSION: Fortifying dairy products with vitamin D3 can increase the serum levels of vitamin D and reduce the RLS severity in women with severe PMS, but not in other groups.

Prediction of the 10-year incidence of type 2 diabetes mellitus based on advanced anthropometric indices using machine learning methods in the Iranian population.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a growing chronic disease that can lead to disability and early death. This study aimed to establish a predictive model for the 10-year incidence of T2DM based on novel anthropometric indices. METHODS: This was a prospective cohort study comparing people with (n = 1256) and without (n = 5193) diabetes mellitus in phase II of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. The association of several anthropometric indices in phase I, including Body Mass Index (BMI), Body Adiposity Index (BAI), Abdominal Volume Index (AVI), Visceral Adiposity Index (VAI), Weight-Adjusted-Waist Index (WWI), Body Roundness Index (BRI), Body Surface Area (BSA), Conicity Index (C-Index) and Lipid Accumulation Product (LAP) with T2DM incidence (in phase II) were examined; using Logistic Regression (LR) and Decision Tree (DT) analysis. RESULTS: BMI followed by VAI and LAP were the best predictors of T2DM incidence. Participants with BMI < 21.25 kg/m2 and VAI ≤ 5.9 had a lower chance of diabetes than those with higher BMI and VAI levels (0.033 vs. 0.967 incident rate). For BMI > 25 kg/m2, the chance of diabetes rapidly increased (OR = 2.27). CONCLUSIONS: BMI, VAI, and LAP were the best predictors of T2DM incidence.

Hematological Indices and Genetic Variants of Premature Ovarian Insufficiency: Machine Learning Approaches.

BACKGROUND: Premature Ovarian Insufficiency (POI) is associated with infertility. Little is known about the potential circulating biomarkers that could be used to predict POI. We have investigated the possible association between white and red blood cells, platelet indices, and eight established single nucleotide polymorphisms (SNPs) associated with POI risk. METHOD: 117 women with premature menopause (PM) and 183 healthy women without a history of menopause before age 40 were recruited for this study. The tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra ARMS PCR) and allele-specific oligonucleotides-polymerase chain reaction (ASO-PCR) were carried out for genotyping for eight SNPs reported to be associated with POI. Decision tree analysis was applied to test the diagnostic value of hematological parameters to identify the risk of POI. RESULTS: Women with POI had lower neutrophil (NEUT) and white blood cell (WBC), whereas red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and mean cell hemoglobin (MCH) were higher. Platelet (PLT) count was also lower in affected women. Our data also indicated that HGB and HCT count were significantly associated with rs16991615 and rs244715. Mean Platelet volume (MPV) and platelet distribution width (PDW) were associated with rs244715, rs1046089, rs4806660, and rs2303369. The rs16991615 was also associated with RBC count, and rs451417 was associated with NEUTs. The decision tree (DT) model reveals that women with the NEUT count at a cut-off value of less than 2.8 and HCT equal to or more than 38.7% could be identified as high-risk cases for POI. Overall, we found the DT approach had a sensitivity = 85%, specificity = 72%, and accuracy = 74%. CONCLUSION: The genetic variants involved in POI are associated with changes in reproductive hormone levels and with changes in hematological indices.

Anxiety, a significant risk factor for coronary artery disease: what is the best index.

BACKGROUND: Coronary artery disease (CAD) is known as the leading cause of disability and death globally. Anxiety disorders are also recognized as common types of mental disorders that substantially impact global health. Iran ranks among the countries with a high incidence of CAD and anxiety disorders. Therefore, the present study aims to determine the potential association and epidemiological aspects of anxiety and CAD within the population of Mashhad, the second most popoulos city in Iran. METHODS: The present study is based on extracted data from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study which is a 10-year prospective cohort study intended to assess the effects of various CAD risk factors among Mashhad city residents. Anxiety scores were assessed at the baseline using Beck Anxiety Inventory and individuals were classified based on the BAI 4-factor structure model which included autonomic, cognitive, panic, and neuromotor components. Accordingly, the association between baseline anxiety scores and the BAI four-factor model with the risk of CAD events was analyzed using SPSS software version 21. RESULTS: Based on the results, 60.4% of the sample were female, and 5.6% were classified as having severe forms of anxiety. Moreover, severe anxiety was more prevalent in females. Results showed a 1.7% risk of CAD (p-value < 0.001) over 10 years with one unit increase in anxiety score. Based on the 4-factor model structure, we found that only panic disorder could significantly increase the risk of CAD by 1.1% over the 10-year follow-up (p-value < 0.001). CONCLUSION: Anxiety symptoms, particularly panic disorder, are independently and significantly associated with an increased overall risk of developing CAD over a 10-year period. Therefore, further studies are warranted to investigate the mechanisms through which anxiety may cause CAD, as well as possible interventions to mitigate these processes.

The associations between plant-based dietary indices with depression and quality of life and insomnia among Iranian adolescent girls in 2015.

Although previous research has explored the link between plant-based diets and mental health outcomes, there has been limited study on the quality levels of plant foods in this context. This study was conducted on 733 adolescent girls from cities in northeastern Iran. The validated Iranian version of the Insomnia Severity Index, SF-12v2 questionnaire and Persian version of the Beck Depression Inventory used to assess insomnia and poor quality of life (QoL) and depression, respectively. Dietary intakes assessed using a valid and reliable food frequency questionnaire. The association of scores of plant based dietary index (PDI) and poor QoL, depression and insomnia explored by binary logistic regression. The unadjusted model showed subjects in the highest quartile of healthy PDI had lower chances of insomnia than those in the lowest quartile (OR: 0.50; 95% CI 0.27-0.91, P = 0.024). The association persisted across various adjusted models. Subjects in the highest quartile of unhealthy PDI (uPDI) had higher chances of depression than those in the lowest quartile (OR: 1.83; 95% CI 1.09-3.08, P = 0.022). The significance of the association was maintained after adjusting for other confounders. A healthy plant-based dietary index is associated with a lower odds of insomnia. An unhealthy plant-based dietary index was associated to an increased chance of depression. Findings need to be confirmed by future studies.

Association of major and minor ECG abnormalities with traditional cardiovascular risk factors in the general population: a large scale study.

Cardiovascular disease (CVD) can be determined and quantified using the electrocardiogram (ECG) analysis. Identification of the risk factors associated with ECG abnormalities may advise prevention approaches to decrease CVD burden. In this study we aimed to investigate the association between CVD risk factors and minor and major ECG abnormalities in a general Iranian adult population. This study was conducted in 2010 and covered a population of 9035 males and females aged 35 to 65 years recruiting from the phase I of Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. The participants were drawn by a stratified cluster random sampling technique. The Bivariate and multinomial logistic regression analysis were conducted considering gender stratification to explore the association of ECG abnormalities with traditional cardiovascular risk factors. There was a significant association between minor and major ECG abnormalities and hypertension (HTN), type 2 diabetes (T2DM), smoking, and physical activity (p < 0.005). There was a significant trend, in both genders, for increasing major abnormalities as the number of CVD risk factors increased. But, only in women, the minor abnormalities increase in frequency as the number of CVD risk factors increased. The results of multinomial logistic regression showed that men with HTN [ARRR = 1.25, 95% CI 0.99, 1.57] and T2DM [ARRR = 1.31, 95% CI 0.99, 1.74] had the highest likelihood to have major abnormalities, although these are not statistically significant. For women, those with HTN had the highest likelihood to have major [ARRR = 1.36, 95% CI 1.13, 1.63] and minor [ARRR = 1.35, 95% CI 1.15, 1.58] abnormalities. Also, women aged > 60 years were more likely to have major [ARRR = 2.01, 95% CI 1.49, 2.74] and minor [ARRR = 1.59, 95% CI 1.20, 2.10] abnormalities compared to women aged < 45 years. Age and HTN were significantly associated with major and minor ECG abnormalities in women, and, on the other hand, HTN and T2DM were associated with major abnormalities in men. Taken together, these findings suggest that healthcare providers should advise preventive approaches to the asymptomatic adults with both major and minor electrocardiographic abnormalities that may predict cardiovascular risk.

Syndecans and diabetic complications: A narrative review.

Syndecan (SDC) is a member of the heparan sulfate proteoglycan (HSPG) family. It appears to play a role in the aetiology of diabetic complications, with decreased levels of SDCs being reported in the kidney, retina, and cardiac muscle in models of diabetes mellitus (DM). The reduced levels of SDCs may play an important role in the development of albuminuria in DM. Some studies have provided the evidence supporting the mechanisms underlying the role of SDCs in DM. However, SDCs and the molecular mechanisms involved are complex and need to be further elucidated. This review focuses on the underlying molecular mechanisms of SDCs that are involved in the development and progression of the complications of DM, which may help in developing new strategies to prevent and treat these complications.

Association of atherosclerosis indices, serum uric acid to high-density lipoprotein cholesterol ratio and triglycerides-glucose index with hypertension: A gender-disaggregated analysis.

This study assessed the association between atherosclerosis indices, serum uric acid to high-density lipoprotein cholesterol ratio (UHR) and triglyceride-glucose (TyG) index and the prevalence of hypertension among MASHAD cohort participants. In this cross-sectional study, the participants were divided into hypertensive and non-hypertensive subjects. The atherosclerosis indices, UHR and TyG index of the two groups were compared. Logistic regression analyses were used to determine the associations of these indices with hypertension in both sex. Receiver operating characteristic (ROC) curve analysis was used to establish the cut-off values for differentiating hypertensive from non-hypertensive subjects. p-values < .05 were considered statistically significant. Data related to 9675 subjects (3035 hypertensive and 6640 non-hypertensive) were analyzed. The mean values of atherosclerosis indices, UHR and TyG index were significantly higher (p < .001) in the hypertensives compared to non-hypertensives. After adjustment for potential confounders, among men, the TyG index (OR = 1.360; 95% CI: 1.210-1.530; p < .001) remained an independent factor for hypertension. Among women, atherogenic index of plasma (OR = 1.005; 95% CI: 1.002-1.007; p < .001), UHR (OR = 1.043; 95% CI: 1.026-1.060; p < .001) and TyG index (OR = 1.519; 95% CI: 1.376-1.677; p < .001) remained independent factors for hypertension. ROC curve analysis revealed that compare to the other indices, TyG index had a better predictive value for hypertension in both sex, especially in women.

The therapeutic impact of programmed death - 1 in the treatment of colorectal cancer.

Colorectal cancer (CRC) is the most common type of newly diagnosed cancer. Metastatic spread and multifactorial chemoresistance have limited the benefits of current therapies. Hence, it is imperative to identify new therapeutic agents to increase treatment efficacy. One of CRC's most promising immunotherapeutic targets is programmed death-1 (PD-1), a cell surface receptor that regulates immune responses. In this paper, we provide an overview of the therapeutic impact of PD-1 in the treatment of CRC. Cancer cells can exploit the PD-1 pathway by upregulating its programmed death-ligand 1 (PD-L1) ligand to evade immune surveillance. The binding of PD-L1 to PD-1 inhibits T cell function, leading to tumor immune escape. PD-1 inhibitors, such as pembrolizumab and nivolumab, block the PD-1/PD-L1 interaction. Clinical trials evaluating PD-1 inhibitors in advanced CRC have shown promising results. In patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors characterized by high mutation rates and increased immunogenicity, PD-1 blockade has demonstrated remarkable efficacy. As a result, pembrolizumab and nivolumab have received accelerated approval by regulatory authorities for the treatment of MSI-H/dMMR metastatic CRC. Additionally, combination approaches, such as combining PD-1 inhibitors with other immunotherapies or targeted agents, are being explored. Despite the success of PD-1 inhibitors in CRC, challenges still exist. Immune-related adverse events can occur and require close monitoring. In conclusion, PD-1 inhibitors have demonstrated significant therapeutic impact, particularly in patients with MSI-H/dMMR tumors.

Association of Three Novel Inflammatory Markers: Lymphocyte to HDL-C Ratio, High-Sensitivity C-Reactive Protein to HDL-C Ratio and High-Sensitivity C-Reactive Protein to Lymphocyte Ratio With Metabolic Syndrome.

OBJECTIVE: We aimed to compare the association of three novel inflammatory indicators with metabolic syndrome (MetS) among Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort participants. METHODS: According to the International Diabetes Federation (IDF) criteria, the cohort participants were divided into the MetS(+) and MetS(-) groups. The lymphocyte to high-density lipoprotein cholesterol (HDL-C) ratio (LHR), high-sensitivity C-reactive protein (hs-CRP) to HDL-C ratio (HCHR) and hs-CRP to lymphocyte ratio (HCLR) were calculated and were compared between the groups. Binary logistic regression (LR) analysis was performed to find the association of the indices with the presence of MetS among men and women. Receiver-operating characteristic (ROC) curve analysis was used to establish cut-off values in predicting MetS for men and women. p-Values <0.05 were considered as statistically significant. RESULTS: Among a total of 8890 participants (5500 MetS(-) and 3390 MetS(+)), LHR, HCHR and HCLR were significantly higher in the MetS(+) group than in MetS(-) group (p < 0.001). In LR analysis, after adjusting for multiple cofounders, LHR remained an independent factor for the presence of MetS among men (OR: 1.254; 95% CI: 1.202-1.308; p < 0.001) and women (OR: 1.393; 95% CI: 1.340-1.448; p < 0.001). HCHR also remained an independent factor for the presence of MetS only in women (OR: 1.058; 95% CI: 1.043-1.073; p < 0.001). ROC curve analysis showed that LHR had the higher AUC for predicting MetS in both men (AUC: 0.627; 95% CI: 0.611-0.643; p < 0.001) and women (AUC: 0.683; 95% CI: 0.670, 0.696; p < 0.001). CONCLUSION: This suggests that among both genders, the LHR as an inexpensive and easy-to-access marker has a better diagnostic performance and could be a promising alternative to the traditional expensive inflammatory markers such as hs-CRP for the evaluation of inflammation in patients with MetS.

Association of a genetic variant in angiopoietin-like 3 with serum HDL-C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years.

BACKGROUND: Loss-of-function (LOF) variants of the angiopoietin-like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations and thereby affect the risk of cardiovascular disease (CVD). OBJECTIVE: In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. METHODS: One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow-up. After a 12-h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra-ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. RESULTS: Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01-2.02, p = 0.041). There was a 1.3-fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non-carriers (OR = 1.32, 95%CI = 1.06-1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL-C. CONCLUSION: We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.