Biomarkers of endothelial dysfunction are associated with poor outcome in COVID-19 patients: A systematic review and meta-analysis.

Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We conducted a systematic review and meta-analysis of the published evidence in this respect. A systematic literature search of PubMed and Scopus databases was performed to find studies investigating biomarkers of endothelial dysfunction in COVID-19 patients. Pooled standardized mean differences and their 95% confidence intervals were calculated for each biomarker using random effect model. 74 studies with 7668 patients were included. In comparison to patients with good outcome, those with poor outcome had higher levels of von Willebrand factor (vWF) (SMD: 0.83, 95% CI: 0.59-1.07, p < 0.00001), vWF:ADAMTS13 (1.23, (0.77-1.7), p < 0.00001), angiopoietin-2 (Ang-2) (1.06 (0.6-1.51), p < 0.0001), E-selectin (1.09 (0.55-1.63), p < 0.0001), P-selectin (0.59 (0.24-0.94), p = 0.001), syndecan-1 (0.99 (0.6-1.37), p < 0.00001), mid-regional pro-adrenomedullin (MR-proADM) (1.52 (1.35-1.68), p < 0.00001), vascular endothelial growth factor (0.27 (0.02-0.53), p = 0.03), soluble fms-like tyrosine kinase-1 (sFLT-1) (1.93 (0.65-3.21), p = 0.03) and lower levels of ADAMTS13 antigen (-0.69 (-0.9 to -0.47) p < 0.00001) and activity (-0.84 (-1.06 to -0.61) p < 0.0000). Plasminogen activator inhibitor-1 and tissue plasminogen activator levels were not different between the two groups (p < 0.05). There were elevated levels of endothelial dysfunction biomarkers in COVID-19 patients with poor outcome, indicating their possible role in disease severity and prognosis. In particular, MR-proADM, vWF, syndecan-1 and sFLT-1 showed a significant association with poor outcome in these patients.

Cytokines and their role in cardiovascular diseases.

The evaluation of diagnostic and prognostic biomarkers has always been a hot topic in various diseases. Considering that cardiovascular diseases (CVDs) have the highest mortality and morbidity rates in the world, various studies have been conducted so far to find CVD associated biomarkers, including cardiac troponin (cTn) and NT-proBNP. Cytokines are components of the immune system that are involved in the pathogenesis of CVD due to their contribution to the inflammation process. The level of cytokines varies in many cardiovascular diseases. For instance, the plasma level of IL-1α, IL-18, IL-33, IL-6 and IL-8 is positively correlated with atherosclerosis and that of some other interleukins such as IL-35 is negatively correlated with acute myocardial infarction or cardiac angina. Due to its pivotal role in the inflammation process, IL-1 super family is involved in many CVDs, including atherosclerosis. IL-20 among the interleukins of IL-10 family has a pro-atherogenic role, while others, such as IL-10 and IL-19, play an anti-atherogenic role. In the present review, we have collected the latest published evidence in this respect to discuss valuable cytokines from the diagnostic and prognostic stand point in CVDs.

Ethnic differences in the lifestyle behaviors and premature coronary artery disease: a multi-center study.

BACKGROUND: Diverse ethnic groups that exist in Iran may differ regarding the risk factors such as hypertension, hyperlipidemia, dyslipidemia, diabetes mellitus, and family history of non-communicable disease. Premature Coronary Artery Disease (PCAD) is more endemic in Iran than before. This study sought to assess the association between ethnicity and lifestyle behaviors in eight major Iranian ethnic groups with PCAD. METHODS: In this study, 2863 patients aged ≤ 70 for women and ≤ 60 for men who underwent coronary angiography were recruited in a multi-center framework. All the patients' demographic, laboratory, clinical, and risk factor data were retrieved. Eight large ethnicities in Iran, including the Farses, the Kurds, the Turks, the Gilaks, the Arabs, the Lors, the Qashqai, and the Bakhtiari were evaluated for PCAD. Different lifestyle components and having PCAD were compared among the ethnical groups using multivariable modeling. RESULTS: The mean age of the 2863 patients participated was 55.66 ± 7.70 years. The Fars ethnicity with 1654 people, was the most subject in this study. Family history of more than three chronic diseases (1279 (44.7%) was the most common risk factor. The Turk ethnic group had the highest prevalence of ≥ 3 simultaneous lifestyle-related risk factors (24.3%), and the Bakhtiari ethnic group had the highest prevalence of no lifestyle-related risk factors (20.9%). Adjusted models showed that having all three abnormal lifestyle components increased the risk of PCAD (OR = 2.28, 95% CI: 1.04-1.06). The Arabs had the most chance of getting PCAD among other ethnicities (OR = 2.26, 95%CI: 1.40-3.65). While, the Kurds with a healthy lifestyle showed the lowest chance of getting PCAD (OR = 1.96, 95%CI: 1.05-3.67)). CONCLUSIONS: This study found there was heterogeneity in having PACD and a diverse distribution in its well-known traditional lifestyle-related risk factors among major Iranian ethnic groups.

The relationship between nut consumption and premature coronary artery disease in a representative sample of Iranians: Iran-premature coronary artery disease (IPAD) study.

OBJECTIVE: The cardioprotective effects of nuts are well established. However, the positive impacts of nuts in preventing CVD at a younger age, a condition known as premature coronary artery disease (PCAD), is still debated. Therefore, we aim to determine the association between nuts and PCAD occurrence and its severity in different Iranian ethnicities. DESIGN: This case-control study was conducted within the framework of the Iran-premature coronary artery disease (I-PAD) study, an ongoing multi-centric study on Iranian patients of different ethnicities. SETTING: This multi-centric case-control study was conducted in among 3253 persons under the age of 70 years in women and 60 years in men from different ethnicities in Iran. PARTICIPANTS: Information on nut consumption was collected using a validated FFQ. Subjects were selected from among the candidates for angiography. Cases were those whose coronary angiography showed stenosis of more than 75 % in at least one vessel or more than 50 % of the left main artery, while the control group participants had normal angiography results. RESULTS: In the crude model, compared to the first quartile, the highest quartile of nut consumption was significantly associated with a lower risk of PCAD (OR = 0·26, 95 % CI (0·21, 0·32); Pfor trend = 0·001). In the top quartile of nut intake, a substantial decrease in PCAD was observed after controlling for putative confounders (OR = 0·32; 95 % CI (0·24, 0·43); Pfor trend = 0·001). Additionally, a 75 % decrease in the risk of severe PCAD was observed in the participants in the highest quartile of nut intake. CONCLUSION: A significant inverse association was observed between nut intake and the risk and severity of PCAD in the Iranian population. Large-scale clinical trials are required to confirm these findings.

COVID-19: imbalance of multiple systems during infection and importance of therapeutic choice and dosing of cardiac and anti-coagulant therapies.

The renin-angiotensin-aldosterone system and its metabolites play an important role in homeostasis of body, especially the cardiovascular system. In this study, we discuss the imbalance of multiple systems during the infection and the importance of therapeutic choice, dosing, and laboratory monitoring of cardiac and anti-coagulant therapies in COVID-19 patients. The crosstalk between angiotensin, kinin-kallikrein system, as well as inflammatory and coagulation systems plays an essential role in COVID-19. Cardiac complications and coagulopathies imply the crosstalks between the mentioned systems. We believe that the blockage of bradykinin can be a good option in the management of COVID-19 and CVD in patients and that supportive treatment of respiratory and cardiologic complications is needed in COVID-19 patients. Ninety-one percent of COVID-19 patients who were admitted to hospital with a prolonged aPTT were positive for lupus anticoagulant, which increases the risk of thrombosis and prolonged aPTT. Therefore, the question that is posed at this juncture is whether it is safe to use the prophylactic dose of heparin particularly in those with elevated D-dimer levels. It should be noted that timing is of high importance in anti-coagulant therapy; therefore, we should consider the level of D-dimer, fibrinogen, drug-drug interactions, and risk factors during thromboprophylaxis administration. Fibrinogen is an independent predictor of resistance to heparin and should be considered before thromboprophylaxis. Alteplase and Futhan might be a good choice to assess the condition of heparin resistance. Finally, the treatment option, dosing, and laboratory monitoring of anticoagulant therapy are critical decisions in COVID-19 patients.

Involvement of circulating inflammatory factors in prognosis and risk of cardiovascular disease.

Cardiovascular disease (CVD) is an inflammatory disease that different factors play a crucial role in the development of clinical outcome of this disease. Inflammation could have effects on initiation, progression, and clinical complications of CVD. Previous studies have indicated that delineating the underlying mechanisms of inflammatory factors involved in this disease should be considerably beneficial both as predictive markers and targets for advancement of appropriate therapeutic approaches in offsetting development and progression of cardiovascular complications. Mechanisms of inflammatory factors involved in CVD combined with the development of atherosclerosis, reperfusion injury, and myocardial infarction caused by changes in processes such as endothelial cells function and hemostasis can contribute to the development of clinical outcome in CVD. Therefore, it can be stated that recognition of inflammatory mechanisms involved in this disease can be a promising tool for evaluation of prognosis in CVD patients. In this article, our goal is to evaluate the possible role of changes in the expressions of inflammatory factors in CVD as well as their relationship with prognosis of this disease.

Protective role of heat shock transcription factor 1 in heart failure: A diagnostic approach.

OBJECTIVE: Nonexpression or expression inhibition of protective factors has been determined in the occurrence of heart failure (HF). Heat shock transcription factor 1 (HSF1) is among such factors, which reduces the incidence of HF by controlling cardiac hypertrophy and fibrosis. In this study, molecular mechanisms for nonexpression of HSF1 in HF patients have been investigated. MATERIALS AND METHODS: This review paper is based on the material obtained via PubMed search of 1996-2018. The key search terms were "heart failure," "heat shock transcription factor 1," "hypertrophy", "fibrosis," and "apoptosis." RESULTS: Although factors such as janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and heat shock proteins (HSPs) may respectively increase and decrease susceptibility to HF, in some circumstances, these factors may unexpectedly prevent HF progression. CONCLUSION: Finally, identification of molecular pathways expressed by various factors could be used to design appropriate treatments or to employ strategies inducing the expression of HSF1 to prevent HF.

Clonal hematopoiesis: Genes and underlying mechanisms in cardiovascular disease development.

The clonal hematopoiesis when occurring without hematologic abnormalities is defined as clonal hematopoiesis of indeterminate potential (CHIP). Aging causes accumulation of somatic mutations, and hematopoietic stem cells (HSCs) can develop clonal expansion of different lineages by these mutations. CHIP has a correlation with cancer and cardiovascular disease (CVD) through acquired mutations in genes. DNMT3A, TET2, ASXL1, and JAK2 genes as well as other genes are the most common somatic mutations causing CHIP and CVD in an older age. Other factors such as cholesterol level, laboratory tests and indexes also affect CVD. In addition, mutations in adenosine triphosphate-binding cassette transporters and also chronic stress in nervous system can result in HSCs proliferation and CVD. However, laboratory tests and indexes are not sensitive for CVD diagnosis. But the therapeutic interventions can be helpful to prevent CVD cases by targeting somatic mutations, chemokine receptors, and growth factors in HSCs. Also, new drugs can control CVD by targeting of cells and their signaling pathways in HSCs. Therefore, more investigations are needed and more questions should be answered for the relationship between CHIP and CVD as a challenging issue in future.

Strategies to inhibit arsenic trioxide-induced cardiotoxicity in acute promyelocytic leukemia.

OBJECTIVE: Arsenic trioxide (ATO) is a drug commonly used for the treatment of acute promyelocytic leukemia (APL). Although ATO has been shown to cause significant improvement in patients, it is associated with serious side effects, which sometimes lead to the patient's death. In this review paper, we examine the reports of ATO-induced cardiotoxicity in APL patients and evaluate the strategies to reduce the incidence of such toxicity. METHODS: The key search terms were "arsenic trioxide," "acute promyelocytic leukemia," "cardiotoxicity," "molecular pathway," and "biomarker." RESULTS: Studies have indicated the involvement of several molecular pathways in ATO-induced cardiotoxicity. These pathways increase the production of reactive oxygen species by interfering with intracellular calcium homeostasis as well as impairing the transfer of calcium into endoplasmic reticulum and mitochondria. On the other hand, increasing or decreasing expressions of some microRNAs (miRs) have been shown to play a role in cardiotoxicity. CONCLUSION: Finally, it can be stated that given the essential role of molecular pathways in cardiotoxicity and considering the fact these pathways impair the regulation of miRs expression, identification of molecular pathways involved in ATO-induced cardiotoxicity aimed at targeting miRs could be a new therapeutic strategy to prevent cardiotoxicity.

T-bet transcription factor in cardiovascular disease: Attenuation or inflammation factor?

T-bet is a major transcription factor increasing inflammatory responses in the immune system. Recently, it has been shown that this factor leads to inflammation in cardiovascular disease (CVD). In this study, we examine the dual role of T-bet in inducing and suppressing inflammatory reactions as well as angiogenesis induction due to inflammatory cytokines in CVD. Relevant literature was identified by a Pubmed search (1992-2018) of English-language papers using the terms "T-bet," "Cardiovascular disease," "Immune response," and "Angiogenesis." Although T-bet causes differentiation of Th1 cells and activation of immune cells such as NK and DC, it suppresses inflammatory responses and replaces damaged vessels with new ones by activating regulatory T-cells and stimulating angiogenesis. It can be stated that T-bet acts as double-edged sword. Therefore, the identification of pathways that can increase the function of T-bet in activating Tregs and inducing angiogenesis might be used as a new therapeutic option in future investigations.

Wnt/ß-catenin in ischemic myocardium: interactions and signaling pathways as a therapeutic target.

Cardiovascular disease (CVD) is still a factor of mortality in the whole world. Through canonical and noncanonical pathways and with different receptors, the Wnt/ß-catenin signaling pathway plays an essential role in response to heart injuries. Wnt regulates the mobilization and proliferation of cells in endothelium and epicardium in an infarcted heart. Therefore, with its profibrotic effects as well as its antagonism with other proteins, Wnt/ß-catenin signaling pathway leads to beneficial effects on fibrosis and cardiac remodeling in myocardium. In addition, Wnt increases the proliferation and differentiation of cardiac progenitors in an ischemic heart. Complex interactions and dual activity of Wnt, the changes in its expression, and mutations that can change its activity during heart development have an adverse effect on cardiac myocardium after injury. However, targeting the Wnt in myocardium with cellular and molecular pathways can be suggested to improve and repair ischemic heart. Given these challenges, in this review article, we deal with the role of Wnt/ß-catenin signaling pathway as well as its interactions with other cells and molecules in an ischemic myocardium.

Evaluation of complete blood count parameters in cardiovascular diseases: An early indicator of prognosis?

BACKGROUND: Studies have been conducted to evaluate the correlation between complete blood count (CBC) indices and cardiovascular diseases (CVDs). Considering the dispersion of these studies as well as reports on prognostic value of CBC parameters in CVDs, we have summarized these findings as a review article for the first time. METHODS: Relevant English language literature was searched and retrieved from Google Scholar search engine and PubMed database (1996-2018). We used "Complete blood count", "Cardiovascular disease", "Red cell distribution width", and "Mean platelet volume" as keywords. RESULTS: Numerous studies indicated that red cell distribution width (RDW) is an independent prognostic biomarker in relation to CVD diseases. MPV is another considerable prognostic biomarker for CVDs. Elevations of inflammatory markers such as neutrophil to lymphocyte ratio (NLR) in CVD patients (especially in myocardial infarction and heart failure) can be considered as a factor of poor prognosis. CONCLUSIONS: RDW can be used as a valuable independent biomarker to investigate the prognosis of patients with heart failure (HF), atherosclerosis, myocardial infarction (MI), and other CVDs. Rapid and stable increase in MPV makes it a reliable prognostic/diagnostic parameter in CVDs such as MI and unstable angina. Among different inflammatory markers the evaluation of total white blood cell count, NLR, monocyte to high-density lipoprotein ratio (MHR) and platelet to lymphocyte ratio (PLR) may have a high value in predicting the prognosis of different CVDs including MI, HF and atherosclerosis in patients.

Cardiac Complications and COVID-19: A Review of Life-threatening Co-morbidities.

The novel 2019 coronavirus disease (COVID-19) was first reported in the last days of December 2019 in Wuhan, China. The presence of certain co-morbidities, including cardiovascular diseases (CVDs), are the basis for worse outcomes in patients with COVID-19. Relevant English-language literature was searched and retrieved from the Google Scholar search engine and PubMed database up to 2023 using COVID-19, SARS-CoV-2, Heart failure, Myocardial infarction, and Arrhythmia and Cardiac complication as keywords. Increased hemodynamic load, ischemia-related dysfunction, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, and excessive or insufficient extracellular matrix proliferation are associated with heart failure (HF) in COVID-19 patients. Inflammatory reaction due to the excessive release of inflammatory cytokines, leads to myocardial infarction (MI) in these patients. The virus can induce heart arrhythmia through cardiac complications, hypoxia, decreased heart hemodynamics, and remarkable inflammatory markers. Moreover, studies have linked cardiac complications in COVID-19 with poor outcomes, extended hospitalization time, and increased mortality rate. Patients with COVID-19 and CVDs are at higher mortality risk and they should be given high priority when receiving the treatment and intensive care during hospitalization.

The prognostic potential of long noncoding RNA XIST in cardiovascular diseases: a review.

There is a significant mortality rate associated with cardiovascular disease despite advances in treatment. long Non-coding RNAs (lncRNAs) play a critical role in many biological processes and their dysregulation is associated with a wide range of diseases in which their downstream pathways are disrupted. A lncRNA X-inactive specific transcript (XIST) is well known as a factor that regulates the physiological process of chromosome dosage compensation for females. According to recent studies, lncRNA XIST is involved in a variety of cellular processes, including apoptosis, proliferation, invasion, metastasis, oxidative stress and inflammation, through molecular networks with microRNAs and their downstream targets in neoplastic and non-neoplastic diseases. Because these cellular processes play a role in the pathogenesis of cardiovascular diseases, we aim to investigate the role that lncRNA XIST plays in this process. Additionally, we wish to determine whether it is a prognostic factor or a potential therapeutic target in these diseases.

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Emerging roles of HOTAIR lncRNA in the pathogenesis and prognosis of cardiovascular diseases.

Highlights HOTAIR, a long noncoding RNA, plays a role in the regulation of proteins involved in the pathogenesis of cardiovascular disease. Furthermore, it has been identified as a biomarker of this type of disease. Several factors and cells contribute to atherosclerosis, a progressive disease. However, the prognosis of HOTAIR in this disease varies depending on the path in which it plays a role. For this condition, there is no single prognosis to consider.

King's Theory of Goal Attainment: Quality of Life for People With Myocardial Infarction.

The aim of this study was to evaluate the effects of a theory of goal attainment-based care plan on quality of life among patients with myocardial infarction. One hundred two patients were randomly assigned to two groups. The intervention group received a theory of goal attainment-based care plan during their hospital stay and a two-month follow-up assessment after hospital discharge. Quality of life was assessed using the Persian version of the MacNew Heart Disease Health-Related Quality of Life questionnaire. Despite no significant difference between the groups with respect to the pretest mean scores of quality of life and its dimensions (p > .05), the posttest mean scores of quality of life and its dimensions in the intervention group were significantly greater than those of the control group (p < .001). Moreover, while the mean scores of quality of life and its dimensions significantly increased in the intervention group (p < .001), they did not significantly change in the control group (p > .05), except for the mean score of physical functioning (p = .032).

lncRNA TUG1 as potential novel biomarker for prognosis of cardiovascular diseases.

Globally, cardiovascular diseases (CVDs) are among the leading causes of death. In light of the high prevalence and mortality of CVDs, it is imperative to understand the molecules involved in CVD pathogenesis and the signaling pathways that they initiate. This may facilitate the development of more precise and expedient diagnostic techniques, the identification of more effective prognostic molecules and the identification of potential therapeutic targets. Numerous studies have examined the role of lncRNAs, such as TUG1, in CVD pathogenesis in recent years. According to this review article, TUG1 can be considered a biomarker for predicting the prognosis of CVD.

Considering that cardiovascular diseases (CVDs) are very common and can be fatal, we must have a method for assessing heart health and its probability of worsening in order to prevent and treat these diseases. In order to accomplish this, it is possible to look for biomarkers in bodily fluids that are indicative of CVD. The purpose of this article is to examine a molecule called TUG1, which is found in varying levels in patients suffering from CVD. There is an impact of TUG1 on the growth, death and inflammation response of heart cells. The potential application of TUG1 as a biomarker to predict the severity and progression of heart disease is therefore not surprising.

Glycemic index, glycemic load, dietary insulin index, and dietary insulin load in relation to cardiometabolic risk factors among participants with atherosclerosis: a cross-sectional study.

BACKGROUND: We examined the cross-sectional associations of dietary Glycemic Index (GI), Glycemic Load (GL), Dietary Insulin Index (DII), and Dietary Insulin Load (DIL) with cardiovascular disease (CVD) factors in subjects with atherosclerosis. METHODS: The present cross-sectional study was conducted on subjects with atherosclerosis. Regular dietary intake was assessed using a 168-item semi-quantitative food frequency questionnaire (FFQ) and GI, GL, DIL, and DII were also calculated. Odds Ratio (OR) and 95% Confidence Intervals (CIs) were estimated for general and central obesity according to the GI, GL, DII, and DIL. RESULTS: According to the continuous score of GL, there was a significant positive association between GL and central obesity for women in all models. Regarding the association between DIL score and biochemical variables, there was a significant positive association between Na and Aspartate transaminase (AST) with DII. Moreover, there was a significant positive association between LDL-c(p = 0.03) and AST (p = 0.04)with DIL score in all 3 models. CONCLUSION: In this study, GL was associated with greater odds of central obesity in women, but not in men. Neither dietary DII nor DIL was associated with BMI and central obesity. GI, GL, DII, and DIL were significantly associated with some CVD risk biomarkers in subjects with atherosclerosis.

Circular RNAs-mediated angiogenesis in human cancers.

Circular RNAs (circRNAs) as small non-coding RNAs with cell, tissue, or organ-specific expression accomplish a broad array of functions in physiological and pathological processes such as cancer development. Angiogenesis, a complicated multistep process driving a formation of new blood vessels, speeds up tumor progression by supplying nutrients as well as energy. Abnormal expression of circRNAs reported to affect tumor development through impressing angiogenesis. Such impacts are introduced as constant with different tumorigenic features known as "hallmarks of cancer". In addition, deregulated circRNAs show possibilities to prognosis and diagnosis both in the prophecy of prognosis in malignancies and also their prejudice from healthy individuals. In the present review article, we have evaluated the angiogenic impacts and anti-angiogenic managements of circRNAs in human cancers.