The association between C-reactive protein and coronary artery calcification: a systematic review and meta-analysis.

BACKGROUND: While coronary artery calcification (CAC) is recognized as a reliable marker for coronary atherosclerosis, the relationship between the concentration of C-reactive protein (CRP) and the incidence and progression of CAC remains controversial. METHOD: PubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies until October 2023. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was employed to calculate pooled odd ratios (OR) and corresponding 95% confidence intervals, considering heterogeneity among the studies. RESULTS: Out of the 2545 records, 42 cross-sectional and 9 cohort studies were included in the systematic review. The meta-analysis on 12 eligible cross-sectional studies revealed no significant association between CAC and CRP [pooled OR: 1.03 (1.00, 1.06)]. Additionally, an insignificant association was found between CAC and CRP through meta-analysis on three eligible cohort studies [pooled OR: 1.05 (0.95, 1.15)] with no considerable heterogeneity across studies. Sensitivity analyses indicated that the meta-analysis models were robust. There was no evidence of publication bias. CONCLUSION: Based on the meta-analysis findings, elevated levels of CRP did not emerge as a valuable prognostic maker for CAC incidence and progression prediction.

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.

Cardiac troponins and coronary artery calcium score: a systematic review.

An early diagnosis of atherosclerosis, particularly in subclinical status, can play a remarkable role in reducing mortality and morbidity. Because of coronary artery calcification (CAC) nature in radiation exposure, finding biomarkers associated with CAC could be useful in identifying individuals at high risk of CAC score. In this review, we focused on the association of cardiac troponins (hs-cTns) and CAC to achieve insight into the pathophysiology of CAC. In October 2022, we systematically searched Web of Science, Scopus, PubMed, and Embase databases to find human observational studies which have investigated the association of CAC with cardiac troponins. To appraise the included articles, we used the Newcastle Ottawa scale (NOS). Out of 520 records, 10 eligible studies were included. Based on findings from longitudinal studies and cross-sectional analyses, troponin T and I were correlated with occurrence of CAC and its severity. Two of the most important risk factors that affect the correlation between hs-cTns serum levels and CAC were age and gender. The elevation of cardiac troponins may affect the progression of CAC and future cardiovascular diseases. Verifying the association between cardiac troponins and CAC may lead to identify individuals exposed to enhanced risk of cardiovascular disease (CVD) complications and could establish innovative targets for pharmacological therapy.

Non-HDL cholesterol and long-term follow-up outcomes in patients with metabolic syndrome.

BACKGROUND: Non-high-density lipoprotein-cholesterol (non-HDL-C) has been identified as a potential biomarker for metabolic syndrome (MetS). However, its predictive capability for MetS varies among different ethnic groups, necessitating further investigation. This study aimed to assess the role of non-HDL-C in the early diagnosis of MetS in the Iranian population through a longitudinal study with a 10-year follow-up period. METHODS: Our study enrolled 4684 individuals from the MASHAD (Mashhad Stroke and Heart Atherosclerotic Disorder) cohort who were followed for 10 years to examine the association between non-HDL-C and the incidence of MetS. Additionally, the contribution of individual MetS components to the overall burden was evaluated. RESULTS: A total of 1599 subjects developed MetS, while 3085 did not. Non-HDL-C levels ≥ 130 were associated with a 42% higher risk of developing MetS (relative risk (RR), 1.42; 95% confidence interval (CI), 1.25-1.62). Regarding MetS components, elevated waist circumference (WC) showed the strongest association with MetS incidence (RR, 2.32; 95% CI, 1.45-2.9), whereas triglyceride (TG) levels ≥ 150 mg/dL demonstrated the weakest association (RR, 1.23; 95% CI, 1.04-1.46). Additionally, higher HDL-C levels were reported to be 20% protective against the risk of MetS (RR, 0.8; 95% CI, 0.73-0.86). Moreover, fasting blood glucose (FBG) levels ≥ 100 mg/dL were not significantly linked to MetS burden, while systolic blood pressure (BP) levels ≥ 130 mmHg or diastolic BP levels ≥ 85 mmHg increased the risk of MetS incidence (RR, 1.25; 95% CI: 1.11-1.41). CONCLUSIONS: Elevated non-HDL-C and increased WC serve as significant predictors of MetS in Iranians. Strategies targeting non-HDL-C levels and weight loss should be emphasized to mitigate the risk of MetS development.

Predictive value of lipoprotein(a) in coronary artery calcification among asymptomatic cardiovascular disease subjects: A systematic review and meta-analysis.

AIMS: Studies have indicated inconsistent results regarding the association between plasma levels of Lipoprotein(a) [Lp(a)] and coronary artery calcification (CAC). We performed a systematic review and meta-analysis to investigate the association between elevated levels of Lp(a) and risk of CAC in populations free of cardiovascular disease (CVD) symptoms. DATA SYNTHESIS: PubMed, Web of Science, Embase, and Scopus were searched up to July 2022 and the methodological quality was assessed using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratio (OR) and 95% confidence interval. Out of 298 studies, data from 8 cross-sectional (n = 18,668) and 4 cohort (n = 15,355) studies were used in meta-analysis. Cohort studies demonstrated a positive significant association between Lp(a) and CAC, so that individuals with Lp(a)≥30-50 exposed to about 60% risk of CAC incidence compared to those with lower Lp(a) concentrations in asymptomatic CVD subjects (OR, 1.58; 95% CI, 1.38-1.80; l2, 0.0%; P, 0.483); Subgroup analysis showed that a cut-off level for Lp(a) measurement could not statistically affect the association, but race significantly affected the relationship between Lp(a) and CAC (OR,1.60; 95% CI, 1.41-1.81). Analyses also revealed that both men and women with higher Lp(a) concentrations are at the same risk for increased CAC. CONCLUSIONS: Blood Lp(a) level was significantly associated with CAC incidence in asymptomatic populations with CVD, indicating that measuring Lp(a) may be a useful biomarker for diagnosing subclinical atherosclerosis in individuals at higher risk of CAC score. PROSPERO REGISTRATION NUMBER: CRD42022350297.

HDL-cholesterol concentration and its association with coronary artery calcification: a systematic review and meta-analysis.

BACKGROUND: Coronary artery calcification (CAC) is a potential risk marker of coronary atherosclerosis that has high specificity and sensitivity. However, the association between high-density lipoprotein cholesterol (HDL-C) concentration and CAC incidence and progression is controversial. METHODS: PubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies up to March 2023 and assessed the methodological quality using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratios (OR) and 95% confidence interval considering heterogeneity across studies. RESULTS: Of the 2,411 records, 25 cross-sectional (n = 71,190) and 13 cohort (n = 25,442) studies were included in the systematic review. Ten cross-sectional and eight cohort studies were not eligible and were omitted from the meta-analysis. A total of 15 eligible cross-sectional studies (n = 33,913) were included in the meta-analysis and pooled results revealed no significant association between HDL-C and CAC > 0, CAC > 10, or CAC > 100 [pooled OR: 0.99 (0.97, 1.01)]. Meta-analysis of the 5 eligible prospective cohort studies (n = 10,721) revealed no significant protective effect of high HDL-C against CAC > 0 [pooled OR: 1.02 (0.93, 1.13)]. CONCLUSIONS: According to this analysis of observational studies, high HDL-C levels were not found to predict protection against CAC. These results suggest HDL quality rather than HDL quantity is important for certain aspects of atherogenesis and CAC. REGISTRATION NUMBER: CRD42021292077.

Efficacy and Safety of Valproic Acid in Myelodysplastic Syndrome and Acute Myeloid Leukemia; a Narrative Review.

Loads of new therapeutic regimes have been turned up to manage Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), particularly in elderly patients who are unfit for intensive chemotherapy. Despite accumulating research, the best MDS and AML management approach is indeterminate. Myelodysplastic syndrome implies a group of various hematopoietic stem cell disorders that may progress to acute myeloid leukemia. These disorders are more frequent in older adults. To the high rate of morbidity and abundant toxicities related to the therapeutic approaches, also, the treatment would be challenging. The clinical effectiveness of valproic acid, a histone deacetylase inhibitor, in MDS and AML patients is unknown, even though it has demonstrated positive activities to promote differentiation and apoptosis in cancer cells. We investigated the clinical research on the effects of valproic acid in conjunction with various drugs, including low-dose cytarabine, all-trans retinoic acid, DNA-hypomethylating agents, hydrazine, and theophylline. We conclude that VPA is a safe and effective treatment option for MDS and AML patients, particularly when used in conjunction with all-trans retinoic acid, DNA-hypomethylating drugs, and hydralazine. However, more randomized clinical studies are required to identify an ideal regimen.

Prognostic role of osteoprotegerin and risk of coronary artery calcification: a systematic review and meta-analysis.

Aim: Coronary artery calcification (CAC) is a predictor of atherosclerosis. However, the association of osteoprotegerin (OPG) with CAC is still controversial. Methods: Prospective cohort studies that provided odds ratios with 95% CIs were included from PubMed, Embase, Web of Science and Scopus through July 2022. Results: Out of 14 studies included in the systematic review, three studies with 7642 participants were included in the meta-analysis. The pooled odds ratio indicated a significant association between higher OPG levels and accelerated risk of CAC (1.15; 95% CI: 1.03-1.30; p < 0.001) with relatively no heterogeneity between studies (I2 = 0%; p = 0.43). Conclusion: The results indicated that increased concentrations of OPG are positively associated with a 15% elevated odds of CAC after adjustment of major covariates.

This meta-analysis included published data on the relationship between levels of osteoprotegerin, an important molecule in the bone production process, and the risk of accumulation of calcium deposits in the vessels supplying blood to the heart. Since these calcium deposits are an early sign of heart disease and subsequently heart attacks, understanding the mechanisms and finding ways to treat patients earlier can be of great importance. This study found that the higher the osteoprotegerin level a patient has, the higher the patient's chance of having calcium deposits in his or her heart vessels.

Correlation between osteoprotegerin and coronary artery calcification in diabetic subjects: a systematic review of observational studies.

Coronary artery calcification (CAC) is one of the critical cardiovascular complications that lead to elevated morbidity and mortality among patients with type 2 diabetes (T2M). The association between osteoprotegerin (OPG) and CAC could potentially provide a reasonable chance for preventive therapy in type 2 diabetic patients and benefit the rate of mortality. Since measurement of CAC score is relatively expensive and requires radiation exposure, the current systematic review aims to provide clinical evidence for evaluating the prognostic role of OPG in determining CAC risk among subjects with T2M. Web of Science, PubMed, Embase, and Scopus, were investigated until July 2022. We assessed human studies investigating the association of OPG with CAC in type 2 diabetic patients. Quality assessment was performed by Newcastle-Ottawa quality assessment scales (NOS). Out of 459 records, 7 studies remained eligible to be included. Observational studies that provided odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between OPG and the risk of CAC were analyzed by random-effects model. In order to provide a visual summary of our findings, the estimation of pooled OR from cross-sectional studies was reported as 2.86 [95% CI 1.49-5.49], which is consistent with the findings of the cohort study. Results revealed that the association between OPG and CAC was significant among diabetic patients. OPG is hypothesized to be a potential marker in predicting the presence of high coronary calcium score among subjects with T2M that could be recognized as a novel target for further pharmacological investigations.

A pilot study of neuroprotective effect of granulocyte colony-stimulating factor (G-CSF) in patients with carbon monoxide poisoning: a double-blind, randomized, placebo-controlled trial.

Although neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) have been shown in rats exposed to carbon monoxide (CO), this pilot clinical trial was performed to assess the feasibility of treatment with G-CSF in patients with acute CO poisoning. A double-blind, randomized, placebo-controlled pilot clinical trial was conducted on twenty-six patients with acute CO poisoning. G-CSF (90 µg/kg) was administered intravenously for 72 h. Demographic data, routine laboratory tests, differential blood counts, venous blood gas, and adverse reactions were recorded. The primary endpoint was brain ischemia improvement based on CT findings and the secondary endpoints examined improvements in the modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and Barthel Index as well as S-100ß concentrations. Fourteen patients received G-CSF, and 12 received a placebo. Twenty-six were followed for 30 days and no one in both groups died during follow-up. Neurological complications, brain ischemic changes, Barthel, and mRS were compared between the two groups on determined days after the onset of therapeutic intervention, and no significant differences were observed between the two groups. Favorable results were achieved for treated patients by different measures; NIHSS was decreased 72 h after treatment (p = 0.046), and S-100ß levels were significantly higher in the G-CSF group than in the control group, 12 h and 72 h after the treatment. G-CSF appears to have potential effects on several clinical parameters in patients with acute CO poisoning. The trial was registered at the Iranian Registry of Clinical Trials with the ID: (IRCT201607232083N7).

Hepatic Transporters Alternations Associated with Non-alcoholic Fatty Liver Disease (NAFLD): A Systematic Review.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disorder and is usually accompanied by obesity, metabolic syndrome, and diabetes mellitus. NAFLD progression can lead to impaired functions of hepatocytes such as alternations in expression and function of hepatic transporters. The present study aimed to summarize and discuss the results of clinical and preclinical human studies that investigate the effect of NAFLD on hepatic transporters. METHODS: The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to 1 March 2022. The risk of bias was assessed for cross-sectional studies through the Newcastle-Ottawa Scale score. RESULTS: Our review included ten cross-sectional studies consisting of 485 participants. Substantial alternations in hepatic transporters were seen during NAFLD progression to non-alcoholic steatohepatitis (NASH) in comparison with control groups. A significant reduction in expression and function of several hepatic uptake transporters, upregulation of many efflux transporters, downregulation of cholesterol efflux transporters, and mislocalization of canalicular transporter ABCC2 are associated with NAFLD progression. CONCLUSION: Since extensive changes in hepatic transporters could alter the pharmacokinetics of the drugs and potentially affect the safety and efficacy of drugs, close monitoring of drug administration is highly suggested in patients with NASH.

The effect of preconditioning agents on cardiotoxicity and neurotoxicity of carbon monoxide poisoning in animal studies: a systematic review.

BACKGROUND: Carbon monoxide (CO) poisoning is a common intoxication and many people die yearly due to CO poisoning and preconditioning agents attenuate brain and cardiac injury caused by intoxication. It is critical to fully understand the efficacy of new methods to directly target the toxic effect of CO, such as conditioning agents, which are currently under development. This study aims to systematically investigate current evidence from animal experiments and the effects of administration preconditions in acute and late phases after CO poisoning on cardiotoxicity and neurotoxicity. METHODS: Four databases (PubMed, Embase, Scopus, and Web of Science) were systematically searched without language restrictions, and hand searching was conducted until November 2021. We included studies that compare preconditioning agents with the control group after CO poisoning in animals. The SYRCLE RoB tool was used for risk of bias assessments. RESULTS: Thirty-seven studies were included in the study. Erythropoietin, granulocyte colony-stimulating factor (GCSF), hydrogen-rich saline, and N-butylphthalide (NBP) were found to have positive effects on reducing neurotoxicity and cardiotoxicity. As other preconditions have fewer studies, no valuable results can be deduced. Most of the studies were unclear for sources of bias. DISCUSSION: Administration of the examined preconditioning agents including NBP, hydrogen-rich saline, and GCSF in acute and late phases could attenuate neurotoxicity and cardiotoxicity of CO poisoned animals. For a better understanding of mechanisms and activities, and finding new and effective preconditioning agents, further preclinical and clinical studies should be performed to analyze the effects of preconditioning agents.

The visceral adiposity index and lipid accumulation product as predictors of cardiovascular events in normal weight subjects.

INTRODUCTION: Visceral adipose tissue (VAT) has an important role in the incidence of cardiovascular disease (CVD) than obesity by itself. The visceral adiposity index (VAI) and lipid accumulation product (LAP) are surrogate indices for measuring VAT. The aimed of this study was to investigate the association of these markers with cardiovascular events among populations with different BMI category in Mashhad, northeast of Iran. METHOD: The present study comprised a prospective cohort of 9685 men and women (35-65 years) who were recruited from MASHAD study. BMI category was defined as normal weight (BMI <25), over weight (25 ≤ BMI<30) and obese (BMI≥30). Demographic, laboratory evaluations, anthropometric and metabolic parameters were performed. Logistic and Cox regression analyses were used to determine the association and risk of cardiovascular events with VAT and LAP. RESULTS: The mean VAI and LAP in CVD patients were significantly higher than in healthy ones in all 3 groups. In terms of CVD event prediction, VAI and LAP had significant association with the incidence of CVD in the second (RR (95% CI): 2.132 (1.047-4.342) and 2.701 (1.397-5.222), respectively) and third tertiles (RR (95% CI): 2.541 (1.163-5.556) and 2.720 (1.159-6.386), respectively) in the normal group, but this association was only found in the third tertiles (RR (95% CI): 2.448 (1.205-4.971) and 2.376 (1.086-5.199), respectively) in the overweight group. The result couldn't find this association for the obese group. CONCLUSION: In this study, we found that there was a significant association between LAP and VAI and cardiovascular events in normal weight and over-weight groups; however, no significant relationship was found in the obese group.

The Effect of Heparin and Its Preparations on Disseminated Intravascular Coagulation Mortality and Hospitalization: A Systematic Review.

Methods: The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to November 2021. The quality of RCTs was assessed by Cochrane Collaboration's tool and the risk of bias was assessed for cohort studies through NOS score. Results: Out of 3288 articles, eight studies were eligible to be included in this study. Our review retrieved six RCTs and two retrospective cohort studies consisting of 950 participants diagnosed by DIC. A significant effect of heparin on DIC mortality was identified in four studies. Furthermore, heparin was used as a control group in three studies. Conclusions: We concluded that administration of heparin and its preparations in DIC patients could reduce the mortality rate and duration of hospitalization, especially in the earlier stages of DIC.

Evaluation of the efficacy of Thymus kotschyanus extract as an additive treatment in patients with ulcerative colitis: a randomized double-blind placebo-controlled trial.

BACKGROUND: Ulcerative colitis (UC) is one of the chronic diseases which is increasing in prevalence and patients suffer from illness flare-ups. UC standard regimen treatment has various side effects besides the efficacy, so there is an interest in administering complementary medicine to reduce adverse effects and increase the efficacy, as well. The aim of this study was to evaluate the efficacy and anti-inflammatory effect of Thymus kotschyanus as an additive treatment in a randomized double-blind placebo-controlled trial of UC patients. METHODS: Thirty UC out-patients with mesalazine regimen treatment that fulfilled the inclusion criteria were participated in a 12 week trial and were randomly chosen for the treatment and control group. Fifteen patients were administered a placebo as a control and 15 patients were received Thymus kotschyanus extract by a dose of 0.5 g in a day in the treatment group. Laboratory tests were performed at baseline and week 12. The primary outcome was a reduction in fecal calprotectin as the main intestine inflammatory marker. Likewise, reduction in SCCAI, SIDBQ, and SEO indices were considered as secondary aims. RESULTS: Fecal calprotectin was decreased by 54.74% in the treatment group, as compared with the placebo group at week 12 (p = 0.02). A significant reduction in SCCAI was also shown between the two study groups (p = 0.01). Thymus kotschyanus extract was safe and no severe side effects were reported. CONCLUSION: Administration of Thymus kotschyanus revealed improvement in UC symptoms by the intestinal anti-inflammation effect of the plant and could be suggested as a potential additive treatment in UC patients. The study protocol has been registered under the identification code: IRCT20200406046965N2.

Aprepitant, fosaprepitant and risk of ifosfamide-induced neurotoxicity: a systematic review.

Ifosfamide is one of the chemotherapy regimens which potentially causes neurotoxicity in patients up to 30%. Aprepitant is administered as an anti-emetic agent in chemotherapy and regarding the inhibitory effect on CYP3A4, aprepitant can increase the risk of ifosfamide adverse effects. This study aims to systematically investigate the relation of ifosfamide-induced neurotoxicity and aprepitant or fosaprepitant in chemotherapy cancer patients. Four databases including PubMed, Scopus, Web of Science, and Embase were systematically reviewed without language restriction and hand searching was performed until December 2021. Total 1639 publications were retrieved and nine studies fulfilled the eligibility criteria. For quality assessment, we used Newcastle-Ottawa quality assessment scales (NOS) for retrospective cohort studies and Cochrane Collaboration tool to assess the risk of bias for a randomized controlled trial. Overall, the results of our systematic review indicated a positive enhanced trend between neurotoxicity and concomitant use of ifosfamide and aprepitant or fosaprepitant, but the association was not statistically significant. As indicated by our findings, several studies identified low albumin as a risk factor for ifosfamide-induced encephalopathy. However, further clinical studies with a larger population of patients are required to evaluate the clinical significance of ifosfamide-related neurotoxicity and aprepitant or fosaprepitant.

A pilot study of the effects of crocin on high-density lipoprotein cholesterol uptake capacity in patients with metabolic syndrome: A randomized clinical trial.

A randomized clinical trial high-density lipoprotein (HDL) cholesterol uptake capacity (CUC) is reduced in patients with metabolic syndrome (MetS). We have assessed the effect of crocin supplementation on HDL CUC in patients with MetS. Forty-four subjects with MetS were randomly allocated to one of two groups: one group received placebo and the other group received crocin at a dose of 30 mg (two tablets of 15 mg per day) for 8 weeks. Serum biochemical parameters were measured using an AutoAnalyzer BT3000 (BioTechnica). The modified CUC method is a cell free, simple, and high-throughput assay that used to evaluate HDL CUC of serum samples. The decision tree analysis was undertaken using JMP Pro (SAS) version 13. The mean age of the crocin and placebo groups were 38.97 ± 13.33 and 43.46 ± 12.77 years, respectively. There was a significant increase in serum HDL CUC in the crocin group compared to that of the placebo group in patients with MetS (p-value< 0.05). The decision tree analysis showed that serum HDL functionality was more important variable than HDL-C level in predicting patients with hypertension at baseline (p-value < 0.05). Crocin administration (30 mg for a period of 8 weeks) was found to improve serum HDL CUC in patients with MetS. TRIAL REGISTRATION: IRCT2013080514279N1.

Serum HDL cholesterol uptake capacity in subjects from the MASHAD cohort study: Its value in determining the risk of cardiovascular endpoints.

BACKGROUND: The efficiency of high-density lipoprotein (HDL) to efflux cholesterol contributes to the reverse cholesterol transport (RCT) pathway as one of HDL's proposed functions and depends on the ability of HDL to uptake cholesterol. We aimed to investigate cholesterol uptake capacity (CUC) by a newly developed assay in samples from the MASHAD (Mashhad Stroke and Heart Atherosclerotic Disorders) cohort study. METHOD: The study population comprised 153 individuals developed CVD diagnosed by a specialist cardiologist, over 6 years of follow-up, and 350 subjects without CVD. We used a modified CUC method to evaluate the functionality of HDL in serum samples. RESULT: The CUC assay was highly reproducible with values for inter- and intra-assay variation of 13.07 and 6.65, respectively. The mean serum CUC was significantly lower in the CVD group compared to control (p = 0.01). Although, there were no significant differences in serum HDL-C between the groups and there was no significantly association with risk of progressive CVD. Multivariate logistic regression analysis showed that there was a significantly negative association between CUC and risk of CVD after adjustment for confounding parameters (OR = 0.57, 95% CI = 0.38-0.87, p = 0.009). The CUC was also inversely and independently associated with the risk of CVD event using Cox proportional hazards models analysis (HR = 0.62; 95% CI = 0.41-0.94, p = 0.02). We determined the optimum cutoff value of 1.7 a.u for CUC in the population. Furthermore, the CUC value was important in determining the CVD risk stratification derived from data mining analysis. CONCLUSIONS: Reduced HDL functionality, as measured by CUC, appears to predict CVD in population sample from north-eastern Iran.

A cohort study of membranous nephropathy, primary or secondary.

BACKGROUND: Although IgG4 deposit against phospholipase A2 receptor (anti-PLA2R) is predominantly presented in the renal biopsy of patients with primary membranous nephropathy (MN), its diagnostic value of this immune complex has not been fully established. METHODS: In this cohort study, 108 biopsy-proven MN patients with proteinuria were evaluated during two years follow up and were divided into primary and secondary groups. Renal biopsy specimens were pathologically assessed for IgG4 and PLA2R depositions by immunohistochemistry (IHC). Therefore, the relationships between staining severity, MN type and total proteinuria in all patients were determined. RESULTS: Of 108 patients, 73.1% had primary MN and 26.9% were diagnosed as secondary form. IHC staining in patients with primary MN was positive for PLA2R in 76 (96.2%) and IgG4 in 68 (86.1%). Cases with positive PLA2R expression had a significantly higher rate among patients with mild to moderate stages (P = 0.03). No significant relationship was found between intensity of PLA2R and IgG4 deposits with proteinuria and serum creatinine. Based on our data, double positivity/negativity of PLA2R and IgG4 expression adds prominent information to the clinical data and were found to be useful and robust biomarkers for detection of primary MN patients with high sensitivity and specificity (97.1 and 96.3% respectively, PPV = 98.5% and NPV = 92.9%). CONCLUSIONS: Simultaneously expression of PLA2R and IgG4 in renal biopsy specimens of patients with MN could possibly be used as a potential diagnostic method to distinguish primary from secondary MN and also pathological severity of the disease.

Decreased Threshold of Fasting Serum Glucose for Cardiovascular Events: MASHAD Cohort Study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally, and specifically in Iran. Generally, diabetes mellitus is the result of impaired glucose tolerance which together with dyslipidemia are considered as important risk factors of CVD. The aim of this study was to determine the relationship between fasting serum glucose (FSG), lipid profile and CVD endpoints, and to establish an optimal FSG cut-off in the MASHAD cohort study after nearly 6 years of follow-up. METHODS: All the participants of MASHAD study were followed up for 6 years to determine their cardiovascular status. FSG, fasting lipids, and physical examinations were all recorded. To identify the optimal cut- off point of FSG, we carried out receiver operating curve (ROC) analysis. RESULTS: We determined MASHAD cutoff point of blood glucose as 90 mg/dl predicting the CVD outcome. The sensitivity and specificity of the FSG criterion were 54.34% and 71.68%, respectively. The AUC was 0.665 (95% CI 0.656-0.675, P< 0.0001). The adjusted hazard ratio show that FSG is associated with 2.34 increase in CVD risk using MASHAD cutoff point (HR 2.34, 95% 1.73-3.17, P< 0.001). CONCLUSION: These findings suggest that not only FSG and lipid profile are related to CVD outcome in the MASHAD study, but also elevated fasting glucose levels is strongly associated with cardiovascular events in this population. Besides, the fasting glucose at a threshold of 90 mg/dl can be used for screening cardiovascular events among the Iranian population.