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.

Digoxin and Outcomes in Patients with Heart Failure and Preserved Ejection Fraction (HFpEF) Patients: A Systematic Review and Meta- Analysis.

BACKGROUND: One of the major indications for digoxin use is the treatment of heart failure (HF). Although the clinical application of digoxin in long-term outcomes in patients with HF and reduced ejection fraction (HFrEF) patients is well explained, the association between digoxin therapy and outcomes in patients with HF and preserved ejection fraction (HFpEF) is not very clear. OBJECTIVES: The aim of this study was to show the clinical efficacy of digoxin on long-term outcomes in subjects with HFpEF. METHODS: PubMed, Embase, Scopus and Web of Science (ISI) electronic databases were searched until May 2021 to obtain relevant studies. The primary outcome was all-cause mortality attributed to treatment with digoxin. The secondary outcomes were "all-cause hospitalization", "hospitalization because of HF" and "all-cause mortality or hospitalization of HF". RESULTS: Seven studies with more than 23000 patients with HFpEF, of which more than 4900 were treated with digoxin, fulfilled the eligibility criteria and were included in this meta-analysis. Treatment with digoxin was associated with a neutral effect on all-cause mortality (HR 1.04, 95 % CI 0.91-1.20, I2 = 57.9 %), all-cause hospitalization (HR 0.97, 95 % CI 0.88-1.07, I2 = 0.0 %), HFhospitalization (HR 0.96, 95 % CI 0.90-1.02, I2 = 41.4 %), and all-cause mortality or HFhospitalization (HR 1.07, 95 % CI 0.91-1.26, I2 = 81.2 %). In subgroup meta-analyses based on ejection fraction (EF), treatment with digoxin did not significantly alter these outcomes in each subset of patients. CONCLUSION: The results of this meta-analysis suggest that digoxin does not have any significant effect on long-term outcomes of HFpEF patients, including "all-cause mortality", "all-cause hospitalization", "hospitalization because of HF" and "all-cause mortality or hospitalization of HF".

Assessment of the Efficacy of Withania somnifera Root Extract in Patients with Generalized Anxiety Disorder: A Randomized Double-blind Placebo- Controlled Trial.

BACKGROUND: Anxiety disorders are the most universal psychiatric problems in the general population. Due to their chronic nature, these diseases are managed with a multi-drug regimen lasting for a long period of time. Medication discontinuation leads to 25% and 80% recurrence in the first month and the first year, respectively. Despite several treatment approaches, there is no specific and optimal method for patient management. Therefore, it is necessary to find some new therapeutic approaches with fewer side effects. Withania somnifera is a plant with GABAergic property responsible for its anxiolytic effect. The aim of this study was to investigate the effect of W. somnifera root extract as an alternative therapy to reduce standard Generalized Anxiety Disorder (GAD) symptoms. METHODS: Forty patients who met the inclusion criteria (with a confirmed diagnosis of GAD as stated in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) took part in this randomized double-blind placebo-controlled trial and were randomly selected for participation in the treatment group (W. somnifera extract, 1g/day; n = 22) or the placebo group (n = 18). All patients were under treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) and were prescribed one capsule of the extract or placebo per day for six weeks. The Hamilton anxiety rating scale (HAM-A) was used to assess the severity of GAD symptoms at baseline as well as the second and sixth weeks of the trial. RESULTS: Comparison of the HAM-A scores during the course of the trial revealed a significant amelioration ofHAM-A score in the treatment group versus placebo (14 and 8 units reduction, respectively (P < 0.05)). Moreover, there was a significant difference in the reduction of GAD score between the second (P =0.04) and sixth week (P =0.02) in the treatment group. The extract was safe and no adverse effect was observed during the trial. CONCLUSION: W. somnifera extract offers some potential advantages as a safe and effective adjunctive therapy to SSRIs in GAD. The clinical trial protocol has been registered under the Iranian Registry of Clinical Trials (IRCT20180615040105N1).

Aldosterone and Mineralocorticoid Receptor Antagonists on Pulmonary Hypertension and Right Ventricular Failure: A Review.

There is an increasing number of therapeutic agents being developed for the treatment of pulmonary artery hypertension (PAH) which is a condition characterized by raised pulmonary artery pressure and right heart failure. Despite our better understanding of the pathophysiology of PAH, the treatment outcomes are still suboptimal. There is growing evidence suggesting the role of increases in the levels of aldosterone, which is a mineralocorticoid hormone, in the pathophysiology of PAH; however, the extent to which hyperaldosteronism is associated with PAH in patients is unclear. There are also a few studies assessing the effects of mineralocorticoid receptor antagonists (MRA) in PAH. MRAs are a recognized treatment for heart failure and hypertension. In this review, we focus on the relationship between aldosterone level in patients with PAH and right ventricular failure and the effect of MRAs on the PAH severity.

Antipsychotic Drugs and Risk of Developing Venous Thromboembolism and Pulmonary Embolism: A Systematic Review and Meta-Analysis.

BACKGROUND: Antipsychotic (AP) medications are the cornerstone treatment for schizophrenia and some other psychiatric diseases. However, some observational studies suggest that these medications might increase the risk of venous thromboembolism (VTE) and pulmonary embolism (PE). OBJECTIVES: The aim of this study was to assess whether AP medications are associated with the development of VTE or PE, and to assess the risk based on any type of AP drugs, quality of studies and after adjustment of risk factors. DATA SOURCES: To identify relevant studies, we searched PubMed and EMBASE databases up to February 2019. We also searched the reference lists of relevant articles for related studies. STUDY SELECTION: Twenty studies fulfilled the eligibility criteria and were included in our meta-analysis after screening relevant observational cohort and case-control studies. PRIMARY OUTCOME: The primary outcome of our meta-analysis was the occurrence of all VTE or PE only attributed to exposure to AP medications compared with non-exposure to AP medications. RESULTS: Exposure to AP drugs was associated with a significant increase in the risk of VTE (RR 1.53, 95% CI 1.30-1.80, I2 = 85%) and PE (RR 3.69, 95% CI 1.23-11.07, I2 = 90%). In the subgroup metaanalysis, the use of low-potency AP drugs was associated with a higher risk of VTE, (RR 1.90, 95% CI 1.04-3.47, I2 = 78%). CONCLUSION: AP exposure was associated with a 1.5-fold increase in the risk of VTE and a 3.7-fold increase in the risk of PE. Low-potency AP drugs were associated with a higher risk of VTE. However, high heterogeneity among studies limits the generalizability of the results.

50 bp deletion in promoter superoxide dismutase 1 gene and increasing risk of cardiovascular disease in Mashhad stroke and heart atherosclerotic disorder cohort study.

Cardiovascular disease (CVD), one of the main mortality causes worldwide is considered to be affected by general oxidative stress and inadequacy antioxidant system. Superoxide dismutase 1 (SOD1), a cytosolic antioxidant enzyme has a key role in neutralizing the excessive prooxidant by scavenging the super oxide anions. SOD1 polymorphic variants exhibit the altered activity properties. In the current study, we are aimed to investigate the association between the SOD1 polymorphism and CVD prevalence. A 6-years case control follow up study was designed to genotype the 526 participants (311 controls and 215 cases) for studying the 50 bp INS/DEL polymorphism at SOD1 promoter gene and analyze their blood lipid profile and anthropometric characteristics. Among the two possible alleles of the SOD1 gene (Wild [W] and Mutant [M]) the meaningful association was detected between the Mutants' frequency and the prevalence of CVD patients (p-value <.001). The W and M allele refer to inserted and deleted 50 bp in the polymorphic site of the SOD1 promoter, respectively. The WM and MM genotypes' frequency which indicate the wild heterozygotes and Mutant homozygotes, respectively, were significantly correlated with the prevalence of cardiovascular disease (p-value <.001). The present study has the potential to introduce the 50 bp INS/DEL polymorphism of SOD1 genotyping as a novel unique diagnostic approach for screening the high risk CVD.

Oxidative stress and inflammation, two features associated with a high percentage body fat, and that may lead to diabetes mellitus and metabolic syndrome.

Obesity is an important feature of the metabolic syndrome and is associated with an increased risk of type 2 diabetes mellitus, cardiovascular disease, and some cancers. The aim of this study was to determine the relationship between body fat percentage and an imbalance of the prooxidant/antioxidant balance (PAB), serum superoxide dismutase (SOD1) and inflammation (serum hs-CRP) and increase risk of metabolic syndrome and diabetes mellitus. In this study, 9154 individuals were recruited as part of the Mashhad Stroke and Heart Association Disorder (MASHAD) study. Subjects were categorized into two groups according to body fat percentage as defined >25% in male and > 30% in female, according to gender. Biochemical factors, including serum PAB, SOD1, and hs-CRP were measured in all subjects. SPSS version 18 was used for statistical analyses for all. GraphPad Prism 6 for figures was used. Of total number of subjects (9154), 6748 (73.7%) were found to have a high body fat (BF) percentage. Serum hs-CRP and PAB were significantly higher in individuals with a high BF percentage (P < 0.05) but SOD1 was not significantly different between the two groups (P > 0.05). BF percentage, serum PAB and serum hs-CRP were significantly higher in individuals with metabolic syndrome and diabetes versus those without metabolic syndrome and diabetes mellitus (P < 0.05), however serum SOD1 was significantly lower in individuals with metabolic syndrome (P < 0.005). Oxidative stress and inflammation are two factors that may link the presence of high BF percentage with the development of metabolic syndrome, diabetes, and cardiovascular disease. © 2018 BioFactors, 45(1):35-42, 2019.

Erythropoietin Reduces Post-PCI Arrhythmias in Patients With ST-elevation Myocardial Infarction.

BACKGROUND: Arrhythmia is the foremost cause of sudden death after myocardial infarction (MI). Animal models have recently shown that erythropoietin (EPO) can reduce the incidence of arrhythmia after MI. METHODS: We investigated the effects of administrating 33,000 IU EPO on the occurrence of post-MI arrhythmia in 40 patients with ST-elevation MI who were randomly assigned in either EPO or placebo groups. Arrhythmias were blindly documented using full 12-lead configuration during 24 hours after percutaneous coronary intervention (PCI) by a cardiologist. Afterward, CK-MB, hematologic, and hemodynamic data were examined within 2 weeks after MI. RESULTS: A comparison made between the 2 groups showed significant differences in the incidence of arrhythmias (20% in EPO group and 35% in placebo group, P = 0.043). However, no significant differences in type of arrhythmias were observed between the groups. There was no significant difference between levels of CK-MB in the 2 groups during 24 hours (P = 0.186). Hematologic and hemodynamic data showed no significant changes 2 weeks after PCI. CONCLUSION: High-dose administration of EPO in patients with ST-elevation MI who have been treated by primary PCI and standard antiplatelet therapy reduces the occurrence of arrhythmias. For clinical interpretation of the results, further well-designed trials are required.