Circular RNAs: a small piece in the heart failure puzzle.

Cardiovascular disease, specifically heart failure (HF), remains a significant concern in the realm of healthcare, necessitating the development of new treatments and biomarkers. The RNA family consists of various subgroups, including microRNAs, PIWI-interacting RNAs (piRAN) and long non-coding RNAs, which have shown potential in advancing personalized healthcare for HF patients. Recent research suggests that circular RNAs, a lesser-known subgroup of RNAs, may offer a novel set of targets and biomarkers for HF. This review will discuss the biogenesis of circular RNAs, their unique characteristics relevant to HF, their role in heart function, and their potential use as biomarkers in the bloodstream. Furthermore, future research directions in this field will be outlined. The stability of exosomal circRNAs makes them suitable as biomarkers, pathogenic regulators, and potential treatments for cardiovascular diseases such as atherosclerosis, acute coronary syndrome, ischemia/reperfusion injury, HF, and peripheral artery disease. Herein, we summarized the role of circular RNAs and their exosomal forms in HF diseases.

Kinin-kallikrein system: New perspectives in heart failure.

Heart failure (HF) is a pervasive clinical challenge characterized by compromised cardiac function and reduced quality of life. The kinin-kallikrein system (KSS), a multifaceted peptide cascade, has garnered substantial attention due to its potential role in HF. Through activation of B1 and/or B2 receptors and downstream signaling, kinins modulate various physiological processes, including inflammation, coagulation, pain, blood pressure control, and vascular permeability. Notably, aberrations in KKS components have been linked to HF risk. The elevation of vasodilatory bradykinin (BK) due to kallikrein activity reduces preload and afterload, while concurrently fostering sodium reabsorption inhibition. However, kallikrein's conversion of prorenin to renin leads to angiotensinsII upregulation, resulting in vasoconstriction and fluid retention, alongside increased immune cell activity that fuels inflammation and cardiac remodeling. Importantly, prolonged KKS activation resulting from volume overload and tissue stretch contributes to cardiac collagen loss. The conventional renin-angiotensin-aldosterone system (RAAS) inhibitors used in HF management may inadvertently intensify KKS activity, exacerbating collagen depletion and cardiac remodeling. It is crucial to balance the KKS's role in acute cardiac damage, which may temporarily enhance function and metabolic parameters against its detrimental long-term effects. Thus, KKS blockade emerges as a promising strategy to impede HF progression. By attenuating the link between immune system function and tissue damage, KKS inhibition can potentially reduce cardiac remodeling and alleviate HF symptoms. However, the nuanced roles of BK in various acute conditions necessitate further investigation into the sustained benefits of kallikrein inhibitors in patients with chronic HF.

First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults.

This guideline is the first Iranian guideline developed for the diagnosis, management, and treatment of hyperlipidemia in adults. The members of the guideline developing group (GDG) selected 9 relevant clinical questions and provided recommendations or suggestions to answer them based on the latest scientific evidence. Recommendations include the low-density lipoprotein cholesterol (LDL-C) threshold for starting drug treatment in adults lacking comorbidities was determined to be over 190 mg/dL and the triglyceride (TG) threshold had to be >500 mg/dl. In addition to perform fasting lipid profile tests at the beginning and continuation of treatment, while it was suggested to perform cardiovascular diseases (CVDs) risk assessment using valid Iranian models. Some recommendations were also provided on lifestyle modification as the first therapeutic intervention. Statins were recommended as the first line of drug treatment to reduce LDL-C, and if its level was high despite the maximum allowed or maximum tolerated drug treatment, combined treatment with ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, or bile acid sequestrants was suggested. In adults with hypertriglyceridemia, pharmacotherapy with statin or fibrate was recommended. The target of drug therapy in adults with increased LDL-C without comorbidities and risk factors was considered an LDL-C level of <130 mg/dl, and in adults with increased TG without comorbidities and risk factors, TG levels of <200 mg/dl. In this guideline, specific recommendations and suggestions were provided for the subgroups of the general population, such as those with CVD, stroke, diabetes, chronic kidney disease, elderly, and women.

Prevalence of, association with, severity of, and prognostic role of serum hemoglobin level in acutely decompensated heart failure patients.

BACKGROUND: The role of hemoglobin (Hb) level in the short-term prognosis of patients with acute decompensated heart failure (ADHF) remains a matter of debate. We aimed to declare the prevalence of, association with, severity of, and prognostic role of SHL with ADHF. METHODS: Using the data from the Persian Registry Of Cardiovascular Disease/ Heart Failure (PROVE-HF) study, we assessed the association between anemia and polycythemia (Hb < 13 g/dLit, > 16.5 g/dLit in males and < 12 g/dLit, and > 16 g/dLit in females, respectively) and short-term mortality using Cox proportional hazard modeling, with adjustment of clinically relevant variables. RESULTS: Of 3652 ADHF patients, anemia was seen in 1673 patients (48.40%). The prevalence of mild, moderate, and severe anemia was 42.33% (n = 1546), 3.23% (n = 118), and 0.24% (n = 9), respectively. Also, 422 patients (11.55%) had polycythemia. Compared to non-anemic patients, anemic patients were mainly male, older, and were more likely to have diabetes mellitus (DM), renal dysfunction, hypertension (HTN), and thyroid disease. Significant predictors of short-term mortality were lower systolic and diastolic blood pressure, lower Hb level, and higher blood urea nitrogen (BUN). Anemic patients had higher all-cause mortality [adjusted hazard ratio (aHR) 1.213, 95% confidence interval [CI] 1.054-1.396]. Moderate anemia increased mortality by approximately 80% in males (aHR 1.793, 95% CI 1.308-2.458) and females (aHR 1.790, 95% CI 1.312-2.442), respectively. Polycythemia had no association with short-term mortality in both genders (P-value > 0.05). CONCLUSIONS: This study revealed that anemia is an adverse prognostic factor for short-term mortality in ADHF patients, with higher mortality in moderately anemic patients.

Neutrophil to lymphocyte ratio (NLR) prognostic effects on heart failure; a systematic review and meta-analysis.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR), as a recent inflammatory index, has been reported to be a prognostic tool in different diseases. However, implication of this ratio in heart failure (HF) is less investigated. In this systematic review and meta-analysis, we aimed to assess the potential impact of NLR on HF clinical outcomes. METHODS: Relevant English published records in PubMed, Scopus, Embase, and Web of Science were screened up to July 2023. Articles reporting clinical outcomes (follow-up or in-hospital mortality, readmission, HF prediction, extended hospital stay length, pulmonary vascular resistance, atrial fibrillation, renal disease and functional capacity) in HF sufferers were collected for further analysis with addition of NLR difference stratified by death/survived and HF status. RESULTS: Thirty-six articles (n = 18231) were finally selected which reported NLR in HF sufferers (mean: 4.38, 95% confidence interval (CI): 4.02-4.73). We found 25 articles reported NLR and total mortality (either follow-up death (N = 19): 4.52 (95% CI: 4.03-5.01) or in-hospital death (N = 10): 5.33 (95% CI: 4.08-6.57)) with mean NLR of 4.74 (95% CI: 4.28-5.20). NLR was higher among deceased patients compared to survived ones (standard mean difference: 0.67 (95% CI: 0.48-0.87), P < 0.001)). NLR was found to be related with higher mortality risk (continuous variable: hazard ratio (HR): 1.12, 95% CI: 1.02-1.23, P = 0.013), categorical variable: HR: 1.77, 95% CI: 1.27-2.46, P = 0.001, T2 vs. T1: HR:1.56, 95%CI: 1.21-2.00, P = 0.001, T3 vs. T1: HR:2.49, 95%CI: 1.85-3.35, P < 0.001). Other aforementioned variables were not feasible to analyze due to presence of few studies. CONCLUSIONS: NLR is a simple and acceptable prognostic tool for risk stratification and prioritizing high risk patients in clinical settings, especially in resource limited nations.

Quality of Palliative Care Guidelines in Patients with Heart Failure: A Systematic Review of Quality Appraisal using AGREE II Instrument.

Objectives: While the principles for developing clinical practice guidelines (CPGs) are well established, the quality of published guidelines is very diverse. The present study was conducted to evaluate the quality of existing CPGs in palliative care for heart failure patients. Material and Methods: The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses. A systematic search was conducted in the Excerpta Medica Database, MEDLINE/PubMed, CINAHL databases and Guideline internet sites: National Institute for Clinical Excellence, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, Guidelines International Network and National Health and Medical Research Council for CPGs published through April 2021. Criteria for including CPGs were: Containing palliative measures for patients with heart failure over 18 years old and preferably interprofessional guidelines that focus on only one dimension of palliative care or focus on diagnosis, definition and treatment were excluded from the study. After initial screening, five appraisers rated the quality of the final selection of CPGs using the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II). Results: From 1501 records, seven guidelines were selected for analysis. The 'scope and purpose' and 'clarity of presentation' domains obtained the highest mean and 'rigor of development' and 'applicability' domains obtained the lowest mean scores. Three categories of recommendations were: (1) Strongly recommended (guidelines 1, 3, 6 and 7); (2) recommended with modifications (guideline 2) and (3) not recommended (guidelines 4 and 5). Conclusion: Clinical guidelines for palliative care in patients with heart failure were of moderate-to-high quality, with the main deficiencies occurring in the rigor of development and applicability domains. The results inform clinicians and guideline developers of the strengths and weaknesses of each CPG. To improve the quality of palliative care CPGs in the future, it is recommended that developers pay detailed attention to all domains of the AGREE II criteria. Funding agent: Isfahan University of Medical Sciences. (IR.MUI.NUREMA.REC.1400.123).

Priority setting in cardiovascular research in Iran using standard indigenous methods.

Background: Determining cardiovascular disease (CVD) research priorities is essential given the high burden of these diseases, limited financial resources, and competing priorities. This study aimed to determine the research priorities in CVD field in Iran using standard indigenous methods. Materials and Methods: An extensive search was done in relevant international and national studies. Then, an indigenous standard multistage approach based on multicriteria decision analysis steps was adapted to local situation and implemented. This process included forming a working group of experts in priority setting methodology, identifying the context and prioritization framework, discussing the methodology with the National Network of CVD Research (NCVDR) members who ultimately determined the priority research topics, weighted topics criteria, ranked topics, and reviewed all determined research priorities for final report. Results: Thirteen cardiovascular research priorities were determined by the NCVDR members. The first five priorities based on their scores include studies in hypertension, prevention and control of ischemic heart disease (IHD) and its risk factors, burden of IHD, Registration of CVDs, and COVID-19 and CVDs. Conclusion: Cardiovascular research priorities were determined using a standard indigenous approach by national experts who are the NCVDR members. These priorities can be used by researchers and health decision makers.

A meta-analysis of microRNA expression profiling studies in heart failure.

Heart failure (HF) is a major consequence of many cardiovascular diseases with high rate of morbidity and mortality. Early diagnosis and prevention are hampered by the lack of informative biomarkers. The aim of this study was to perform a meta-analysis of the miRNA expression profiling studies in HF to identify novel candidate biomarkers or/and therapeutic targets. A comprehensive literature search of the PubMed for miRNA expression studies related to HF was carried out. The vote counting and robust rank aggregation meta-analysis methods were used to identify significant meta-signatures of HF-miRs. The targets of HF-miRs were identified, and network construction and gene set enrichment analysis (GSEA) were performed to identify the genes and cognitive pathways most affected by the dysregulation of the miRNAs. The literature search identified forty-five miRNA expression studies related to CHF. Shared meta-signature was identified for 3 up-regulated (miR-21, miR-214, and miR-27b) and 13 down-regulated (miR-133a, miR-29a, miR-29b, miR-451, miR-185, miR-133b, miR-30e, miR-30b, miR-1, miR-150, miR-486, miR-149, and miR-16-5p) miRNAs. Network properties showed miR-29a, miR-21, miR-29b, miR-1, miR-16, miR-133a, and miR-133b have the most degree centrality. GESA identified functionally related sets of genes in signaling and community pathways in HF that are the targets of HF-miRs. The miRNA expression meta-analysis identified sixteen highly significant HF-miRs that are differentially expressed in HF. Further validation in large patient cohorts is required to confirm the significance of these miRs as HF biomarkers and therapeutic targets.

The association between platelet-to-lymphocyte ratio with mortality among patients suffering from acute decompensated heart failure.

BACKGROUND: Platelet-to-lymphocyte ratio (PLR) is an inflammation index suggested to have the prognostic capability in heart failure (HF). We sought to investigate the association of PLR with cardiovascular disease (CVD) mortality and creatinine (Cr) rise among Iranian individuals suffering from acute decompensated HF (ADHF). METHODS: This retrospective cohort study was in the context of the Persian Registry Of cardioVascular diseasE/Heart Failure (PROVE/HF) study. 405 individuals with ADHF admitted to the emergency department were recruited from April 2019 to March 2020. PLR was calculated by division of platelet to absolute lymphocyte counts and categorized based on quartiles. We utilized the Kaplan-Meier curve to show the difference in mortality based on PLR quartiles. Cr rise was defined as the increment of at least 0.3 mg/dl from baseline. Cox proportional hazard ratio (HR) was used to investigate the association of PLR with CVDs mortality. RESULTS: Mean age of participants was 65.9 ± 13.49 years (males: 67.7%). The mean follow-up duration was 4.26 ± 2.2 months. CVDs mortality or re-hospitalization was not significantly associated with PLR status. Multivariate analysis of PLR quartiles showed a minimally reduced likelihood of CVDs death in 2nd quartile versus the first one (HR 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.054). Cr rise had no remarkable relation with PLR status in neither model. CONCLUSION: PLR could not be used as an independent prognostic factor among ADHF patients. Several studies are required clarifying the exact utility of this index.

Comparison of multiple blood pressure frequency methods with optimum blood pressure measurement among Iranian individuals.

BACKGROUND: Proper blood pressure (BP) measurement frequency method is less evaluated to optimize hypertension (HTN) status among different nations due to cultural patience variations. The aim of this study was to compare the first (BP1), second (BP2), and the mean of first and second (BP1,2) and all the three (BP1,2,3) with the second and third BP measurements in Iranian individuals. MATERIALS AND METHODS: This cross-sectional study was done on 2264 individuals aged 18 years or more living in Isfahan city, Iran. Their BPs were assessed from right arms by the standard tools and methods after 5 min of rest in a quiet room by a trained staff. The mean second and third readings were considered as reference, and the other aforementioned variables were compared with it. RESULTS: The mean age of total population was 40.9 ± 16.1 years (males: 52%). Men had significant higher means of systolic BP (SBP) and diastolic BP (DBP) with any measurement frequency methods than women (P < 0.001 and P = 0.009). Considerable clinical significant (≥5 mmHg) ranges were mostly observed in BP1 compared with BP2,3. SBP2 and DBP2 indices showed insignificant differences compared with reference mean. Moreover, abnormal BP levels (≥140/90 mmHg) were mostly observed in terms of BP1 measurement with no remarkable variability in BP2 reading in comparison to the reference. CONCLUSION: Our considerable data suggested that BP2 could appropriately categorize BP status similar to BP2,3 and it may be rational for physicians considering this mean and excluding the first BP measurement as a sole criterion for HTN assessment in Iranian adults. Multiple researches are necessary quantifying appropriate frequencies of BP reading.

Effects of somatostatin analog treatment on cardiovascular parameters in patients with acromegaly: A systematic review.

BACKGROUND: There is a belief that in patients with acromegaly, first-generation somatostatin analogs (SSAs) might improve cardiovascular (CV) structure and function. However, most published clinical trials involved only a few patients and their results are rather variable. We aimed to conduct a systematic review on available studies on the impact of these drugs on CV parameters. MATERIALS AND METHODS: A literature search was conducted in MEDLINE (OVID), EMBase, Cochrane, and ISI Web of Science for citations published until April 30 2018 to identify studies on our objective that considered changes in CV parameters. For this search, we established a Boolean search strategy using keywords related to "acromegaly," "Somatostatin analog," and "cardiovascular diseases and parameters." All study types except for case reports or conference abstracts were included. Twenty-four studies (n = 558) fulfilled the inclusion criteria and were selected for final analysis. RESULTS: In 12 studies (n = 350), decrease in heart rate (HR) and in 4 studies (n = 128), decrease in blood pressure (BP) was significant. In 15 studies (n = 320), left ventricular mass index (LVMi) changes were significant. In 9 studies (n = 202), the early diastole to peak velocity flow in late diastole (E/A ratio) was evaluated, and in 5 of them (n = 141), the improvement was significant. Eighteen studies (n = 366) examined changes in left ventricular ejection fraction (LVEF), 5 of which (n = 171) reported that these changes were significant. Decrease of left ventricular end-diastolic diameter was reported in only 2 studies (n = 27). CONCLUSION: We found that first-generation SSAs have a beneficial effect on cardiac parameters such as HR and LVMi. For other parameters such as LVEF, BP, LV diameter, and E/A ratio, we were not able to draw a firm conclusion.

Survival rate and predictors of mortality in patients hospitalised with heart failure: a cohort study on the data of Persian registry of cardiovascular disease (PROVE).

OBJECTIVES: Heart failure (HF) has a high rate of hospitalisation and mortality. We examined its risk factors, survival rate and the predictors. METHODS: In this prospective cohort study, demographic, clinical and treatment data of 1223 patients hospitalised with HF were extracted from the Persian Registry Of cardio Vascular diseasE (PROVE)/HF registry. Survival rate and HR and their association with other variables were assessed. RESULTS: 835 (68.3%) were censored, while 388 (31.7%) patients were deceased. Mean age and frequency of hypotension during hospitalisation, tachycardia, pulmonary hypertension and anaemia, hyponatremia, heart valve disease and renal disease of the deceased patients was significantly higher than censored patients (15.2vs6.1%, 51.1vs40.1%, 24.4vs16.7%, 39.0vs31.8%, respectively, p<0.05). ACE inhibitor (ACEI)/angiotensin receptor blocker (ARB) (89.8%vs82.1%, respectively) and beta blocker (BB) (81.1%vs75.5%, respectively) were higher in follow-up in the censored group (p<0.001 and 0.02, respectively). Crude Cox regression analysis identified age, tachycardia, hypotension, anaemia, pulmonary hypertension and heart valve disease as predictors of mortality (HR >1) and using ACEI/ARB and BB as predictors of life (HR <1, p<0.05). After adjustment, all variables lost their significance, except BB (HR 0.63, p=0.03) and tachycardia (HR 1.74, p=0.01) and New York Heart Association (NYHA) class IV (HR 1.90, p=0.04) became significant predictors. CONCLUSIONS: We found a high mortality rate (31.7%). As NYHA class IV and tachycardia were significant predictors of mortality after adjustment, an effective measure can be treatment of underlying diseases, which deteriorate patients' conditions. Monitoring of medications for at-risk group, especially BB that predicts life, is important.

A Comparison of the Clinical Outcomes of Minimum and Maximum Hematocrit Levels During Cardiopulmonary Bypass (CPB) in Low-risk Patients Undergoing Coronary Artery Bypass Graft Surgery (CABG): A Cross-sectional Study.

Background: This study investigated the clinical outcomes at the minimum and maximum levels of hematocrit (HCT) during cardiopulmonary bypass (CPB) in low-risk patients undergoing coronary artery bypass graft (CABG) surgery. Materials and Methods: In this cross-sectional study, 85 patients who underwent CABG with an ejection fraction of greater than 35% were selected. Based on the HCT range during CPB, patients were divided into two groups: minimum HCT: HCT = 16-18% and maximum HCT: HCT = 25-27%. Then the operation outcomes, amount of drainage, and transfusion were recorded and compared between these groups. Results: In the middle tube 8 h after surgery and left tube 24 h after surgery, the amount of drainage in the minimum HCT group with mean of 71.00 ± 130.9 and 60.65 ± 71.23, respectively, was significantly lower than the maximum HCT group with mean of 101.5 ± 246.50 and 123.76 ± 93.17, respectively (P value < 0.05). The incidence of cognitive disorders in the maximum HCT group was significantly higher than in the minimum HCT group (11.1% vs. 0%, P value = 0.041). Also, the mean transfusion of packed red blood cell (PRBC) and fresh frozen plasm (FFP) during CPB in the maximum HCT group, with mean of 346.7 ± 86.22 and 396.1 ± 21.05, respectively, were significantly higher than the minimum HCT group with mean of 178.8 ± 80.91 and 136.8 ± 46.77, respectively (P value < 0.05). After CPB, there was no significant difference in transfusion products (P value > 0.05). Conclusion: According to the results of this study, patients undergoing CABG surgery with maximum HCT level versus minimum HCT level during CPB, need more packed cells and fresh frozen plasma products transfusion, which will be associated with the complication of cognitive impairment.

Systematic review and meta-analysis of levothyroxine effect on blood pressure in patients with subclinical hypothyroidism.

This study aims to evaluate the effect of levothyroxine therapy on blood pressure (BP) in patients with subclinical hypothyroidism (SCH). Were searched Six databases, and randomized controlled trials (RCT) and prospective cohort studies evaluating the effect of levothyroxine therapy on BP in patients with SCH were included. 37 articles (9 RCTs and 28 prospective cohorts) were included in this meta-analysis. Pooled analysis of RCT studies was insignificant; however, pooled analysis of 28 prospective cohort studies showed a significant difference before and after the therapy, reducing both systolic blood pressure (SBP) and diastolic blood pressure (DBP) (MD=-4.02 [-6.45, -4.58] and MD=-2.13 [-3.69, -0.56], both P-values<0.05). Levothyroxine therapy can play a role in lowering BP in patients with SCH. However, this effect is more observed in Caucasians, SCH patients with higher initial TSH followed by more remarkable TSH change to normal levels, and SCH patients with hypertension.

Acute Heart Failure as a First Manifestation of Primary Adrenal Insufficiency: Highly Lethal If Not Diagnosed!

Background: Primary adrenal insufficiency is an uncommon condition that manifests as nonspecific symptoms such as fatigue, weight loss, salt craving, and hyperpigmentation. Common cardiovascular presentations of AI are hypotension, arrhythmias, and syncope. However, acute heart failure is an uncommon presentation. Case Presentation. Here, a 26-year-old man was hospitalized with vasopressor-resistant cardiogenic shock, which was finally attributed to an adrenal crisis. His past medical history was notable for Hashimoto's disease, controlled with oral levothyroxine. Conclusion: AI should be considered among patients with cardiogenic shock who are unresponsive to conventional inotropes. Additionally, a history of autoimmune diseases may increase the suspicion of AI. Although the presentation of cardiogenic shock in a patient with undiagnosed AI is considered a rarity, delay in prompt treatment can lead to life-threatening conditions.

MicroRNA-155 and exosomal microRNA-155: Small pieces in the cardiovascular diseases puzzle.

MicroRNAs (miRs, miRNAs) are known to have a part in various human illnesses, such as those related to the heart. One particular miRNA, miR-155, has been extensively studied and has been found to be involved in hematopoietic lineage differentiation, immunity, viral infections, inflammation, as well as vascular remodeling. These processes have all been connected to cardiovascular diseases, including heart failure, diabetic heart disease, coronary artery disease, and abdominal aortic aneurysm. The impacts of miR-155 depend on the type of cell it is acting on and the specific target genes involved, resulting in different mechanisms of disease. Although, the exact part of miR-155 in cardiovascular illnesses is yet not fully comprehended, as some studies have shown it to promote the development of atherosclerosis while others have shown it to prevent it. As a result, to comprehend the underlying processes of miR-155 in cardiovascular disorders, further thorough study is required. It has been discovered that exosomes that could be absorbed by adjacent or distant cells, control post-transcriptional regulation of gene expression by focusing on mRNA. Exosomal miRNAs have been found to have a range of functions, including participating in inflammatory reactions, cell movement, growth, death, autophagy, as well as epithelial-mesenchymal transition. An increasing amount of research indicates that exosomal miRNAs are important for cardiovascular health and have a major role in the development of a number of cardiovascular disorders, including pulmonary hypertension, atherosclerosis, acute coronary syndrome, heart failure, and myocardial ischemia-reperfusion injury. Herein the role of miR-155 and its exosomal form in heart diseases are summarized.

Comparative Effectiveness of Antidiabetic Drugs as an Additional Therapy to Metformin in Women with Polycystic Ovary Syndrome: A Systematic Review of Metabolic Approaches.

Background: Metformin is commonly prescribed to treat polycystic ovary syndrome (PCOS) patients, but in some cases, it may not be effective even at high doses or may cause intolerable side effects. Therefore, recent studies have examined the impact of combining metformin with other antidiabetic medications. Methods: A systematic search was performed in Scopus, PubMed, Web of Science, and Embase up to 30 June 2023. All interventional studies that assessed the efficacy of different antidiabetic agents were included. Results: Among the 3488 records found in the primary search, 16 papers were included. Our study showed that dipeptidyl peptidase-4 inhibitors (DPP4i) had the most significant impact on glycemic profile, while thiazolidinediones (TZDs) had the most influence on lipid levels. However, it was observed that patients taking only metformin experienced a greater increase in high-density lipoprotein cholesterol (HDL-C) levels. Glucagon-like peptide-1 receptor agonists (GLP1RAs) effectively modified various anthropometric measurements, such as weight, body mass index, waist circumference, and waist-to-hip ratio. The effects of different antidiabetic drugs on hormone levels were inconclusive, although testosterone levels were more affected by GLP1RA, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and TZDs. None of the combined therapies showed a significant change in blood pressure. Conclusion: Since PCOS is a metabolic disorder, choosing the best combination of antidiabetic drugs in the clinical course of PCOS patients will be very important. Today, it seems that we need a new metabolic approach for better treatment of the metabolic aspects of these patients.

The impact of platelet-to-lymphocyte ratio on clinical outcomes in heart failure: a systematic review and meta-analysis.

BACKGROUND: Inflammation has been suggested to play a role in heart failure (HF) pathogenesis. However, the role of platelet-to-lymphocyte ratio (PLR), as a novel biomarker, to assess HF prognosis needs to be investigated. We sought to evaluate the impact of PLR on HF clinical outcomes. METHODS: English-published records in PubMed/Medline, Scopus, and Web-of-science databases were screened until December 2023. Relevant articles evaluated PLR with clinical outcomes (including mortality, rehospitalization, HF worsening, and HF detection) were recruited, with PLR difference analysis based on death/survival status in total and HF with reduced ejection fraction (HFrEF) patients. RESULTS: In total, 21 articles (n = 13,924) were selected. The total mean age was 70.36 ± 12.88 years (males: 61.72%). Mean PLR was 165.54 [95% confidence interval (CI): 154.69-176.38]. In total, 18 articles (n = 10,084) reported mortality [either follow-up (PLR: 162.55, 95% CI: 149.35-175.75) or in-hospital (PLR: 192.83, 95% CI: 150.06-235.61) death rate] and the mean PLR was 166.68 (95% CI: 154.87-178.50). Further analysis revealed PLR was significantly lower in survived HF patients rather than deceased group (152.34, 95% CI: 134.01-170.68 versus 194.73, 95% CI: 175.60-213.85, standard mean difference: -0.592, 95% CI: -0.857 to -0.326, p < 0.001). A similar trend was observed for HFrEF patients. PLR failed to show any association with mortality risk (hazard ratio: 1.02, 95% CI: 0.99-1.05, p = 0.289). Analysis of other aforementioned outcomes was not possible due to the presence of few studies of interest. CONCLUSION: PLR should be used with caution for prognosis assessment in HF sufferers and other studies are necessary to explore the exact association.

Platelet to lymphocyte ratio and heart failureInflammation plays a role in heart failure (HF), and a blood test called the platelet-to-lymphocyte ratio (PLR) might be helpful in predicting patients' outcomes. We found that deceased HF patients had higher PLR values in comparison to those who survived, irrespective of cardiac pump function, with similar pattern for patients with decreased cardiac function (HF with reduced ejection fraction). However, this biomarker failed to show any significant association with death risk. In conclusion, PLR may have some potential to help predict HF prognosis, but it needs more research and physicians should probably be cautious about using PLR alone in clinical settings.

Prognostic Implication of Preprocedural Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-analysis.

Pulmonary hypertension (PH) is a common comorbidity in patients with aortic stenosis (AS) who are candidates for transcatheter aortic valve implantation (TAVI). Herein, we sought to elucidate the prognostic value of preprocedural PH on the early and late mortality after TAVI. The Cochrane Library, Scopus, PubMed, Web of Science, Embase, and ProQuest were screened using a predefined search query. We considered odds ratios (ORs) as the measure of effect. Meta-regression analysis was applied to investigate the potential impact of baseline characteristics on the outcomes. Egger's and Begg's tests were used to assess the publication bias. Thirty-three studies comprising 34 datasets representing 68,435 patients were included in the analysis. Regardless of the definition and severity of PH, pooled data analysis indicated that preprocedural PH was associated with higher cardiac and overall 30-day [OR, 1.45 (1.15-1.82) and OR, 1.75 (1.42-2.17), respectively], and 1-year mortality [OR, 1.63 (1.35-1.96) and OR, 1.59 (1.38-1.82), respectively]. Meta-regression analysis demonstrated that older age, higher New York Heart Association function class, history of hypertension, diabetes, and lower left ventricular ejection fraction were predictors of higher mortality rate following TAVI. Moreover, we found that preprocedural PH is significantly associated with higher in-hospital mortality and 30-day acute kidney injury. Our results demonstrated that preprocedural PH is associated with higher early and late cardiac and overall mortality following TAVI; however, this finding is limited regarding the considerable inconsistency in the definition of PH and PH severity among studies.

Lipid accumulation product and visceral adiposity index for incidence of cardiovascular diseases and mortality; results from 13 years follow-up in Isfahan cohort study.

Background: /Aims: Visceral adiposity index (VAI) and lipid accumulation product (LAP) are novel anthropometric indices that have shown an association with metabolic syndrome; however, limited data are available regarding the predictive performance of these indices for the incidence of cardiovascular diseases (CVD) and mortality. Methods: This study was performed on the data retrieved from Isfahan Cohort Study (ICS). ICS is an ongoing population-based cohort study conducted in 3 counties in central Iran. Pearson correlation analysis was performed between LAP, VAI, and metabolic parameters. Cox regression analysis and receiver operative characteristics (ROC) curve analysis were performed in order to evaluate the ability of VAI and LAP for the incidence of CVD, CVD-associated mortality, and all-cause mortality. We further compared the predictive performance of VAI and LAP with body mass index (BMI). Results: LAP and VAI were significantly correlated with all metabolic variables, including blood pressure, fasting blood glucose, and lipid profile components. Univariate regression analysis indicated a significant association between LAP and VAI and CVD incidence. In multivariate analysis, only VAI was significantly associated with CVD incidence. Regarding CVD mortality, only VAI in the multivariate analysis revealed a significant association. Interestingly, Both VAI and LAP were negatively associated with all-cause mortality. ROC curve analysis indicated the superior performance of LAP and VAI for predicting CVD incidence compared to BMI; however, BMI was better in predicting all-cause mortality. Conclusion: Compared to BMI, LAP and VAI have better predictive performance for the incidence of CVD. In contrast, BMI was superior to VAI and LAP in the prediction of all-cause mortality.