Circulatory resistin levels in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic relapsing-remitting systemic disease of the gastrointestinal tract with rising incidence. Studies have shown that adipocytes play a crucial role in patients with IBD by actively participating in systemic immune responses. The present study was designed to investigate the correlation between the circulatory levels of resistin, as an adipokine, and active and remission phases of IBD in comparison with healthy controls. METHODS: Relevant articles were retrieved from PubMed, Embase, the Web of Science, and Scopus from inception until June 2023. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of plasma/serum resistin levels between IBD patients, patients in remission, and healthy controls were conducted through random-effect meta-analysis. RESULTS: A total of 19 studies were included, assessing 1836 cases. Meta-analysis indicated that generally, serum/plasma resistin levels were higher in IBD patients in comparison with healthy controls (SMD 1.33, 95% CI 0.58 to 2.08, p-value < 0.01). This was true for each of the UC and CD separate analyses, as well. Moreover, it was shown that higher serum/plasma resistin levels were detected in the active phase of IBD than in the remission phase (SMD 1.04, 95% CI 0.65 to 1.42, p-value = 0.01). Finally, higher serum/plasma resistin levels were found in the remission phase compared to healthy controls (SMD 0.60, 95% CI 0.15 to 1.06, p-value < 0.01). CONCLUSION: The results of this systematic review and meta-analysis support the conclusion that circulating resistin levels are increased in IBD (both UC and CD). Also, higher resistin levels were recorded in the remission phase of IBD in comparison with healthy controls. This indicates that further studies may provide valuable insights into the role of resistin in the pathogenesis of IBD.

Study rationale and design of a study of EMPAgliflozin's effects in patients with type 2 diabetes mellitus and Coronary ARtery disease: the EMPA-CARD randomized controlled trial.

BACKGROUND: Recent trials have revealed that sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are effective against hyperglycemia and also reduce micro- and macro-vascular complications in patients with type 2 diabetes mellitus (T2DM). Most of the beneficial cardiovascular effects have been investigated in patients with heart failure and coronary artery disease (CAD). Yet, few human studies have been conducted to investigate the molecular mechanisms underlying these clinically beneficial effects in patients with CAD. Accordingly, the EMPA-CARD trial was designed to focus on the molecular effects of empagliflozin in patients with T2DM and CAD. METHODS: In this multicenter, triple-blind randomized controlled trial, patients with documented known T2DM and CAD will be recruited. They will be randomized on a 1:1 ratio and assigned into two groups of empagliflozin 10 mg/daily and placebo. The primary endpoint is the effect of empagliflozin on changes of plasma interleukin 6 (IL-6) after 26 weeks of treatment. The secondary endpoints will consist of changes in other inflammatory biomarkers (Interleukin 1-beta and high-sensitive C-reactive protein), markers of oxidative stress, platelet function, and glycemic status. DISCUSSION: The EMPA-CARD trial mainly tests the hypothesis that SGLT2 inhibition by empagliflozin may improve inflammatory status measured as reduction in inflammatory biomarkers in patients with T2DM and CAD. The results will provide information about the underlying mechanisms of SGLT2 inhibition that mediate the beneficial effects of this medication on clinical outcomes. TRIAL REGISTRATION: Iranian Registry of Clinical Trials. www.IRCT.ir , Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

Circulating Levels of Calprotectin as a Biomarker in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Calprotectin, also known as MRP8/14, is generated by immune cells and is altered in several inflammatory diseases. Studies have assessed their levels in patients with coronary artery disease (CAD) and its subtypes (stable CAD and acute coronary syndrome [ACS]). Herein, we aimed to systematically investigate these associations through a systematic review and meta-analysis. METHODS: A systematic search was conducted in four online databases, including PubMed, Scopus, Embase, and the Web of Science. Relevant studies were retrieved, screened, and extracted. Random-effect meta-analysis was performed for the calculation of standardized mean difference (SMD) and 95% confidence interval (CI). Blood calprotectin levels were compared between CAD patients and controls, as well as CAD subtypes. RESULTS: A total of 20 studies were included in the systematic review and meta-analysis, comprising 3300 CAD patients and 1230 controls. Patients with CAD had significantly higher calprotectin levels (SMD 0.81, 95% CI 0.32-1.30, p < 0.01). Similarly, patients with ACS were reported to have higher levels compared to those with stable CAD. However, there was no significant difference in terms of blood calprotectin levels between stable CAD cases and healthy controls. Finally, studies have shown that calprotectin could be used as a diagnostic biomarker of CAD while also predicting major adverse events and mortality in these patients. CONCLUSION: Based on our findings, calprotectin, as an inflammatory marker, could be used as a possible biomarker for patients with CAD and ACS. These suggest the possibility of pathophysiological pathways for this involvement and warrant further research on these associations as well as their clinical utility.

Empagliflozin improves left ventricular ejection fraction and end systolic volume in patients with type 2 diabetes mellitus and coronary artery disease: a post-hoc analysis of EMPA-CARD trial.

Background: Sodium glucose co-transporter2 (SGLT2) inhibitors have exhibited cardioprotective properties in diabetes patients. The aim of this study was to investigate the effect of Empagliflozin on changes in echocardiographic parameters. Methods: This was a post hoc analysis of the EMPA-CARD trial which was a multicenter, triple-blind randomized controlled trial. Type 2 diabetes mellitus patients with concomitant history of coronary artery disease were randomized on a 1:1 ratio into two groups receiving either 10 mg/day Empagliflozin or placebo. Patients with a history of heart failure (NYHA class 3-4) and ejection fraction (EF) < 40% were excluded. Trans-thoracic echocardiography was performed at baseline and at 26 weeks of intervention. Results: A total of 69 (Empagliflozin = 39 and placebo = 30) patients underwent echocardiography. Significant changes were observed for left ventricular ejection fraction [standard error (SE) = 0.76; beta (95% correlation interval (CrI)] = -5.558 (-7.25; -4.18) and left ventricular end-systolic volume (SE = 1.38; beta (95% CrI) = 3.915 (1.2; 0.66). Other echocardiographic parameters relating to right ventricular or atrial function did not change significantly. Conclusion: Empagliflozin can have cardioprotective benefits in subjects without HF. Further studies are required to determine the effect of Empagliflozin in non-HF patients. Trial registration: The original EMPA-CARD study has been registered in Iranian Registry of Clinical Trials. www.IRCT.ir, Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

Empagliflozin improves high-sensitive cardiac troponin-I and high-density lipoprotein cholesterol in patients with type 2 diabetes mellitus and coronary artery disease: a post-hoc analysis of EMPA-CARD Trial.

Background: Empagliflozin is a sodium glucose cotransporter-2 (SGLT2) inhibitor that has been suggested to improve cardiac function and vascular recovery. The risk of coronary artery diseases is much higher in diabetic patients and is associated with greater morbidity and mortality. High-sensitivity cardiac troponin-I (hs-cTnI) is an important prognostic biomarker in cardiac diseases. Therefore, this study aimed to investigate the effect of empagliflozin compared to placebo on changes in hs-cTnI and lipid profile after 26 weeks of treatment. Methods: This was an ancillary study in a randomized trial of patients with concomitant type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) (The EMPA-CARD study). Patients who were already on standard anti-diabetic/anti-ischemic medications were randomized to receive either placebo or empagliflozin 10 mg/daily. Serum hs-cTnI and lipid profile were measured at baseline and after 26 weeks. Results: Of the 95 randomized patients, hs-cTnI and lipid profile were measured for a total of 77 patients. No significant difference was observed regarding the baseline characteristics between the two arms. Compared to placebo, empagliflozin significantly reduced hs-cTnI after 26 weeks (mean difference (MD) of -13.242, 95%CI: -14.151 to -12.333, p < 0.001). In the empagliflozin group, non-significant reductions in total cholesterol, LDL-C, and triglyceride have resulted; however, there was an increase in HDL-C level (MD = 2.40,95%CI:0.16-4.60, p < 0.04). Conclusion: Empagliflozin compared to placebo was superior in reducing circulating hs-cTnI that may indicate improvements in cardiomyocytes function in patients with T2DM and CAD. Moreover, empagliflozin had a modest impact on the serum lipid profile biomarkers. Trial registration: The original EMPA-CARD study has been registered in Iranian Registry of Clinical Trials. www.IRCT.ir, Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

The effect of EMPAgliflozin on markers of inflammation in patients with concomitant type 2 diabetes mellitus and Coronary ARtery Disease: the EMPA-CARD randomized controlled trial.

Systemic inflammation and oxidative burden in patients with type 2 diabetes mellitus (T2DM) causes deleterious cardiovascular outcomes. We sought to investigate the clinical antioxidative and anti-inflammatory effects of empagliflozin. Platelet function, oxidant and antioxidant biomarkers and pro-inflammatory agents at baseline and at 26 weeks were measured. A total of 95 patients (41.05% male, mean age 62.85 ± 7.91 years, mean HbA1c 7.89 ± 0.96%) with concomitant T2DM and coronary artery disease (CAD) were randomized (1:1) to receive empagliflozin (10 mg/daily) or placebo. Patients treated with empagliflozin had lower levels of interleukin 6 (IL-6) (adjusted difference (adiff): - 1.06 pg/mL, 95% CI - 1.80; - 0.32, P = 0.006), interleukin 1ß (IL-1ß) and high-sensitive C-reactive protein (Hs-CRP) (adiff: - 4.58 pg/mL and - 2.86 mg/L; P = 0.32 and 0.003, respectively) compared to placebo. There were elevations in super oxidase dismutase (SOD) activity, glutathione (GSHr), and total antioxidant capacity (TAC) with empagliflozin (adiff: 3.7 U/mL, 0.57 muM, and 124.08 mmol/L, 95% CI 1.36; 6.05, 0.19; 0.95, and 47.98; 200.18, P = 0.002, 0.004, and 0.002, respectively). While reactive oxygen species (ROS) improved significantly (adiff: - 342.51, 95% CI - 474.23; - 210.79, P < 0.001), the changes in catalase activity (CAT), malondialdehyde (MDA), or protein carbonyl groups (PCG) were not significant. Moreover, the P-selectin antigen expression on platelet surface was significantly reduced (adiff: - 8.81, 95% CI - 14.87; - 2.75, P = 0.005). Markers of glycemic status (fasting blood glucose, HbA1c, and HOMA-IR (homeostatic model assessment for insulin resistance) significantly improved (P < 0.001). Among patients with T2DM and CAD, 6-month treatment with empagliflozin can mitigate inflammation, platelet activity and oxidative stress and is associated with clinical cardiovascular benefits.Trial Registration Iranian Registry of Clinical Trials. www.IRCT.ir , Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

Association between ST-segment resolution after primary angioplasty and short-term outcomes in patients with acute myocardial infarction.

BACKGROUND: The aim of this study was to evaluate the relationship between the early/late complete ST-resolution and short-term cardiovascular outcomes in patients undergoing primary angioplasty. METHODS: This was a prospective cross-sectional study of patients with acute myocardial infarction who candidate for primary percutaneous coronary intervention (PCI) during 1 year. An ECG obtained at the time of admission, 90 minutes and 24 hour after PCI. Patients were followed up for in hospital and 1-year outcomes and then data assessed according to the ST segment resolution (STR) (complete ≥70% and incomplete <70% STR). RESULTS: Overall, 124 patients included in the study. The rates of complete STR were 44.4% after 90 minutes and 82.3% after 24 hours. Patients with early complete STR had significant lower rates of heart failure after 1-year follow-up (32% versus 46%, OR: 1.88, 95% CI: 1.42-2.50, P=0.005) but not like patients with late STR. No significant relationship was observed between early/late complete STR and re-infarction, stroke, re-hospitalization and death during 1-year follow-up (P>0.05). Moderate correlations were found between percentage of ST resolution after 90 minutes and EF before discharge and final EF (correlation coefficient: 0.395 and 0.488, respectively, P<0.001). CONCLUSIONS: Early complete STR can be an indicator for development of heart failure after 1-year follow-up.

Risk Factors Associated with Heart Valve Thrombosis in Patients with Prosthetic Heart Valve Dysfunction.

BACKGROUND: Thrombotic and thromboembolic events are important causes of mortality and morbidity in patients with prosthetic heart valve. The aim of this study is to evaluate the factors that may contribute to prosthetic heart valve thrombosis. METHODS: This was a cross-sectional study in Rajaie Heart Center on patients with prosthetic heart valve malfunction, within a year. According to the echocardiographic and fluoroscopic findings, the patients were divided into two groups (thrombosis and non-thrombosis groups). The patients' demographic, clinical and laboratory data were recorded and analyzed with SPSS software. RESULTS: A total of 142 patients participated in this study. Ninety-four patients (66.2%) were diagnosed with thrombosis. There was a significant relationship between thrombosis and inadequate anti-coagulation (international normalized rati [INR] <2.5) (odds ratio [OR]: 4.15, 95% CI: 1.98-9.87, P = 0.003), history of infection (OR: 12.81, 95% CI: 3.52-19.02, P<0.001), prothrombin time (PT) check interval (OR: 2.38, 95% CI: 1.63-8.47, P = 0.019), atrial fibrillation (AF) rhythm (OR: 3.96, 95% CI: 1.75-8.09, P = 0.019), and plasma fibrinogen level (OR: 6.90, 95% CI: 2.58-14.69). CONCLUSION: Based on this study, inadequate anti-coagulation, AF rhythm, recent infection and plasma fibrinogen level were the factors most contributing to prosthetic valve thrombosis. As there were many cases of thrombosis in patients with history of infection, this factor can be considered for risk assessment in prosthetic valve.