Diagnostic and predictive abilities of myokines in patients with heart failure.

Myokines are defined as a heterogenic group of numerous cytokines, peptides and metabolic derivates, which are expressed, synthesized, produced, and released by skeletal myocytes and myocardial cells and exert either auto- and paracrine, or endocrine effects. Previous studies revealed that myokines play a pivotal role in mutual communications between skeletal muscles, myocardium and remote organs, such as brain, vasculature, bone, liver, pancreas, white adipose tissue, gut, and skin. Despite several myokines exert complete divorced biological effects mainly in regulation of skeletal muscle hypertrophy, residential cells differentiation, neovascularization/angiogenesis, vascular integrity, endothelial function, inflammation and apoptosis/necrosis, attenuating ischemia/hypoxia and tissue protection, tumor growth and malignance, for other occasions, their predominant effects affect energy homeostasis, glucose and lipid metabolism, adiposity, muscle training adaptation and food behavior. Last decade had been identified 250 more myokines, which have been investigating for many years further as either biomarkers or targets for heart failure management. However, only few myokines have been allocated to a promising tool for monitoring adverse cardiac remodeling, ischemia/hypoxia-related target-organ dysfunction, microvascular inflammation, sarcopenia/myopathy and prediction for poor clinical outcomes among patients with HF. This we concentrate on some most plausible myokines, such as myostatin, myonectin, brain-derived neurotrophic factor, muslin, fibroblast growth factor 21, irisin, leukemia inhibitory factor, developmental endothelial locus-1, interleukin-6, nerve growth factor and insulin-like growth factor-1, which are suggested to be useful biomarkers for HF development and progression.

An overview of circulating and urinary biomarkers capable of predicting the transition of acute kidney injury to chronic kidney disease.

INTRODUCTION: Acute kidney injury (AKI) defined by a substantial decrease in kidney function within hours to days and is often irreversible with higher risk to chronic kidney disease (CKD) transition. AREAS COVERED: The authors discuss the diagnostic and predictive utilities of serum and urinary biomarkers on AKI and on the risk of AKI-to-CKD progression. The authors focus on the relevant literature covering evidence of circulating and urinary biomarkers' capability to predict the transition of AKI to CKD. EXPERT OPINION: Based on the different modalities of serum and urinary biomarkers, multiple biomarker panel seems to be potentially useful to distinguish between various types of AKI, to detect the severity and the risk of AKI progression, to predict the clinical outcome and evaluate response to the therapy. Serum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary uromodulin, serum extracellular high mobility group box-1 (HMGB-1), serum cystatin C and urinary liver-type fatty acid-binding protein (L-FABP) were the most effective in the prediction of AKI-to-CKD transition regardless of etiology and the presence of critical state in patients. The current clinical evidence on the risk assessments of AKI progression is mainly based on the utility of combination of functional, injury and stress biomarkers, mainly NGAL, L-FABP, HMGB-1 and cystatin C.

Predictors of Kidney Function Outcomes and Their Relation to SGLT2 Inhibitor Dapagliflozin in Patients with Type 2 Diabetes Mellitus Who Had Chronic Heart Failure.

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have a favorable impact on the kidney function in patients with heart failure (HF), while there is no clear evidence of what factors predict this effect. The aim of the study was to identify plausible predictors for kidney function outcome among patients with HF and investigate their association with SGLT2i. METHODS: We prospectively enrolled 480 patients with type 2 diabetes mellitus (T2DM) treated with diet and metformin and concomitant chronic HF and followed them for 52 weeks. In the study, we determined kidney outcome as a composite of ≥ 40% reduced estimated glomerular filtration rate from baseline, newly diagnosed end-stage kidney disease or kidney replacement therapy. The relevant medical information and measurement of the biomarkers (N-terminal natriuretic pro-peptide, irisin, apelin, adropin, C-reactive protein, tumor necrosis factor-alpha) were collected at baseline and at the end of the study. RESULTS: The composite kidney outcome was detected in 88 (18.3%) patients of the entire population. All patients received guideline-recommended optimal therapy, which was adjusted to phenotype/severity of HF, cardiovascular risk and comorbidity profiles, and fasting glycemia. Levels of irisin, adropin and apelin significantly increased in patients without clinical endpoint, whereas in those with composite endpoint the biomarker levels exhibited a decrease with borderline statistical significance (p = 0.05). We noticed that irisin ≤ 4.50 ng/ml at baseline and a ≤ 15% increase in irisin serum levels added more valuable predictive information than the reference variable. However, the combination of irisin ≤ 4.50 ng/ml at baseline and ≤ 15% increase in irisin serum levels (area under curve = 0.91; 95% confidence interval = 0.87-0.95) improved the discriminative value of each biomarker alone. CONCLUSION: We suggest that low levels of irisin and its inadequate increase during administration of SGLT2i are promising predictors for unfavorable kidney outcome among patients with T2DM and concomitant HF.

Biomarkers of Atrial Fibrillation Recurrence in Patients with Paroxysmal or Persistent Atrial Fibrillation Following External Direct Current Electrical Cardioversion.

Atrial fibrillation (AF) is associated with atrial remodeling, cardiac dysfunction, and poor clinical outcomes. External direct current electrical cardioversion is a well-developed urgent treatment strategy for patients presenting with recent-onset AF. However, there is a lack of accurate predictive serum biomarkers to identify the risks of AF relapse after electrical cardioversion. We reviewed the currently available data and interpreted the findings of several studies revealing biomarkers for crucial elements in the pathogenesis of AF and affecting cardiac remodeling, fibrosis, inflammation, endothelial dysfunction, oxidative stress, adipose tissue dysfunction, myopathy, and mitochondrial dysfunction. Although there is ample strong evidence that elevated levels of numerous biomarkers (such as natriuretic peptides, C-reactive protein, galectin-3, soluble suppressor tumorigenicity-2, fibroblast growth factor-23, turn-over collagen biomarkers, growth differential factor-15) are associated with AF occurrence, the data obtained in clinical studies seem to be controversial in terms of their predictive ability for post-cardioversion outcomes. Novel circulating biomarkers are needed to elucidate the modality of this approach compared with conventional predictive tools. Conclusions: Biomarker-based strategies for predicting events after AF treatment require extensive investigation in the future, especially in the presence of different gender and variable comorbidity profiles. Perhaps, a multiple biomarker approach exerts more utilization for patients with different forms of AF than single biomarker use.

Cardiac Hepatopathy: New Perspectives on Old Problems through a Prism of Endogenous Metabolic Regulations by Hepatokines.

Cardiac hepatopathy refers to acute or chronic liver damage caused by cardiac dysfunction in the absence of any other possible causative reasons of liver injury. There is a large number of evidence of the fact that cardiac hepatopathy is associated with poor clinical outcomes in patients with acute or actually decompensated heart failure (HF). However, the currently dominated pathophysiological background does not explain a role of metabolic regulative proteins secreted by hepatocytes in progression of HF, including adverse cardiac remodeling, kidney injury, skeletal muscle dysfunction, osteopenia, sarcopenia and cardiac cachexia. The aim of this narrative review was to accumulate knowledge of hepatokines (adropin; fetuin-A, selenoprotein P, fibroblast growth factor-21, and alpha-1-microglobulin) as adaptive regulators of metabolic homeostasis in patients with HF. It is suggested that hepatokines play a crucial, causative role in inter-organ interactions and mediate tissue protective effects counteracting oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and necrosis. The discriminative potencies of hepatokines for HF and damage of target organs in patients with known HF is under on-going scientific discussion and requires more investigations in the future.

Predictive value of serum irisin for chronic heart failure in patients with type 2 diabetes mellitus.

We hypothesize that serum irisin can have additional discriminative potency for heart failure (HF) in individuals with type 2 diabetes mellitus (T2DM). The study group comprised 226 consecutive T2DM patients (153 patients with any HF phenotypes and 30 patients without HF) aged 41 to 65 years. The plasma levels N-terminal brain natriuretic pro-peptide (NT-proBNP) and irisin were detected by ELISA at the baseline of the study. We found that the most appropriate cut-off value of irisin (HF versus non-HF) were 10.4 ng/mL (area under curve [AUC] = 0.96, sensitivity = 81.0%, specificity = 88.0%; P = 0.0001). Cutoff point of NT-proBNP that distinguished patients with HF and without it was 750 pmol/L (AUC = 0.78; sensitivity = 72.7%, specificity 76.5%, p = 0.0001). Using multivariate comparative analysis we established that concentrations of irisin < 10.4 ng/mL (odds ration [OR] = 1.30; P = 0.001) and NT-proBNP > 750 pmol/mL (OR = 1.17; P = 0.042), left atrial volume index (LAVI) > 34 mL/m2 (OR = 1.06; P = 0.042) independently predicted HF. Irisin being added to NT-proBNP improved predictive modality for HF, whereas combination of NT-proBNP and LAVI > 34 mL/m2 did not. In conclusion, we established that irisin had independent predicted potency for HF in patients with established T2DM.

Serum Levels of Irisin Predict Cumulative Clinical Outcomes in Heart Failure Patients With Type 2 Diabetes Mellitus.

Background: The aim of this study was to investigate the role of serum irisin level in predicting clinical outcome in heart failure (HF) patients with type 2 diabetes mellitus (T2DM). Methods: 153 T2DM patients with HF aged 41-62 years were prospectively recruited for the study. Serum levels of irisin and NT-proBNP were measured by ELISA. Laboratory tests including HbA1c, fasting glucose, blood creatinine, insulin, lipids and creatinine with estimation of GFR were performed along with echocardiography at baseline. The observation period was 56 weeks. Results: We identified 76 composite cardiovascular (CV) outcomes, which included CV death and death from all causes, resuscitated cardiac death, non-fatal/fatal acute myocardial infarction or stroke, and HF hospitalization. Therefore, the entire patient cohort was divided into 2 groups with (n = 76) and without (n = 77) composite CV outcomes. We found that the concentrations of NT-proBNP were higher in HF patients with T2DM who had a CV composite outcome than in patients without CV composite outcome (p = 0.001). In contrast, the relationship was exactly reversed for irisin, as HF and T2DM patients with CV composite outcome had significantly lower irisin levels (p = 0.001). Unadjusted multivariate Cox regression analyses showed that LVEF < 40%, LAVI > 39 ml/m2, NT-proBNP > 2,250 pmol/ml, and irisin < 6.50 ng/ml were the strongest predictors of CV outcomes in HF patients with T2DM. After adjustment for LVEF, serum levels of NT-proBNP and irisin remained independent predictors of end points. Furthermore, divergence of Kaplan-Meier curves pointed out that patients with NT-proBNP > 2,250 pmol/ml and irisin < 6.50 ng/ml had worse prognosis than those with any other compartment of the bomarkers' levels. Conclusion: Adding irisin to NT-proBNP significantly improved discriminative value of the whole model. HF patients with T2DM had significantly worse clinical outcomes when showing the constellation NT-proBNP > 2,250 pmol/ml and irisin < 6.50 ng/ml, respectively, in comparison to patients with opposite trends for both biomarkers.

Shift of conventional paradigm of heart failure treatment: from angiotensin receptor neprilysin inhibitor to sodium-glucose co-transporter 2 inhibitors?

Current clinical guidelines for heart failure (HF) contain a brand new therapeutic strategy for HF with reduced ejection fraction (HFrEF), which is based on neurohumoral modulation through the use of angiotensin receptor neprilysin inhibitors. There is a large body of evidence for the fact that sodium-glucose co-transporter 2 inhibitors may significantly improve all-cause mortality, cardiovascular mortality and hospitalization for HF in patients with HFrEF who received renin-angiotensin system blockers including angiotensin receptor neprilysin inhibitors, ß-blockers and mineralocorticoid receptor antagonists. The review discusses that sodium-glucose co-transporter 2 inhibitors have a wide spectrum of favorable molecular effects and contribute to tissue protection, improving survival in HFrEF patients.

Myokines and Heart Failure: Challenging Role in Adverse Cardiac Remodeling, Myopathy, and Clinical Outcomes.

Heart failure (HF) is a global medical problem that characterizes poor prognosis and high economic burden for the health system and family of the HF patients. Although modern treatment approaches have significantly decreased a risk of the occurrence of HF among patients having predominant coronary artery disease, hypertension, and myocarditis, the mortality of known HF continues to be unacceptably high. One of the most important symptoms of HF that negatively influences tolerance to physical exercise, well-being, social adaptation, and quality of life is deep fatigue due to HF-related myopathy. Myopathy in HF is associated with weakness of the skeletal muscles, loss of myofibers, and the development of fibrosis due to microvascular inflammation, metabolic disorders, and mitochondrial dysfunction. The pivotal role in the regulation of myocardial and skeletal muscle rejuvenation, attenuation of muscle metabolic homeostasis, and protection against ischemia injury and apoptosis belongs to myokines. Myokines are defined as a wide spectrum of active molecules that are directly synthesized and released by both cardiac and skeletal muscle myocytes and regulate energy homeostasis in autocrine/paracrine manner. In addition, myokines have a large spectrum of pleiotropic capabilities that are involved in the pathogenesis of HF including cardiac remodeling, muscle atrophy, and cardiac cachexia. The aim of the narrative review is to summarize the knowledge with respect to the role of myokines in adverse cardiac remodeling, myopathy, and clinical outcomes among HF patients. Some myokines, such as myostatin, irisin, brain-derived neurotrophic factor, interleukin-15, fibroblast growth factor-21, and growth differential factor-11, being engaged in the regulation of the pathogenesis of HF-related myopathy, can be detected in peripheral blood, and the evaluation of their circulating levels can provide new insights to the course of HF and stratify patients at higher risk of poor outcomes prior to sarcopenic stage.

Adverse Cardiac Remodelling after Acute Myocardial Infarction: Old and New Biomarkers.

The prevalence of heart failure (HF) due to cardiac remodelling after acute myocardial infarction (AMI) does not decrease regardless of implementation of new technologies supporting opening culprit coronary artery and solving of ischemia-relating stenosis with primary percutaneous coronary intervention (PCI). Numerous studies have examined the diagnostic and prognostic potencies of circulating cardiac biomarkers in acute coronary syndrome/AMI and heart failure after AMI, and even fewer have depicted the utility of biomarkers in AMI patients undergoing primary PCI. Although complete revascularization at early period of acute coronary syndrome/AMI is an established factor for improved short-term and long-term prognosis and lowered risk of cardiovascular (CV) complications, late adverse cardiac remodelling may be a major risk factor for one-year mortality and postponded heart failure manifestation after PCI with subsequent blood flow resolving in culprit coronary artery. The aim of the review was to focus an attention on circulating biomarker as a promising tool to stratify AMI patients at high risk of poor cardiac recovery and developing HF after successful PCI. The main consideration affects biomarkers of inflammation, biomechanical myocardial stress, cardiac injury and necrosis, fibrosis, endothelial dysfunction, and vascular reparation. Clinical utilities and predictive modalities of natriuretic peptides, cardiac troponins, galectin 3, soluble suppressor tumorogenicity-2, high-sensitive C-reactive protein, growth differential factor-15, midregional proadrenomedullin, noncoding RNAs, and other biomarkers for adverse cardiac remodelling are discussed in the review.

Circulating Cardiac Biomarkers in Diabetes Mellitus: A New Dawn for Risk Stratification-A Narrative Review.

The aim of this narrative review is to update the current knowledge on the differential choice of circulating cardiac biomarkers in patients with prediabetes and established type 2 diabetes mellitus (T2DM). There are numerous circulating biomarkers with unconfirmed abilities to predict clinical outcomes in pre-DM and DM individuals; the prognostication ability of the cardiac biomarkers reported here has been established, and they are still being studied. The conventional cardiac biomarkers, such as natriuretic peptides (NPs), soluble suppressor tumorigenisity-2, high-sensitivity circulating cardiac troponins and galectin-3, were useful to ascertain cardiovascular (CV) risk. Each cardiac biomarker has its strengths and weaknesses that affect the price of usage, specificity, sensitivity, predictive value and superiority in face-to-face comparisons. Additionally, there have been confusing reports regarding their abilities to be predictably relevant among patients without known CV disease. The large spectrum of promising cardiac biomarkers (growth/differential factor-15, heart-type fatty acid-binding protein, cardiotrophin-1, carboxy-terminal telopeptide of collagen type 1, apelin and non-coding RNAs) is discussed in the context of predicting CV diseases and events in patients with known prediabetes and T2DM. Various reasons have been critically discussed related to the variable findings regarding biomarker-based prediction of CV risk among patients with metabolic disease. It was found that NPs and hs-cTnT are still the most important tools that have an affordable price as well as high sensitivity and specificity to predict clinical outcomes among patients with pre-DM and DM in routine clinical practice, but other circulating biomarkers need to be carefully investigated in large trials in the future.

Altered signature of apoptotic endothelial cell-derived microvesicles predicts chronic heart failure phenotypes.

Aim: to evaluate the associations between signatures of apoptotic endothelial cell-derived microvesicles (MVs) with phenotypes of chronic heart failure (HF). Methods: The study cohort consisted of 388 prospectively involved subjects with HF patients with predominantly reduced left ventricular ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF) and HF with mid-range ejection fraction (HFmrEF). All biomarkers were measured at baseline. Results: The number of circulating CD31+/annexin V+ MVs in HFrEF and HFmrEF patients was similar. The number of circulating CD144+/annexin V+ MVs in HFrEF patients was significantly higher than HFmrEF and HFpEF. We determined that a combination of number of circulating CD31+/annexin V+ MVs and Gal-3 was the best predictor of HFpEF and that number of circulating CD144+/annexin V+ MVs is able to increase predictive capabilities of soluble ST2 (sST2) and Gal-3 for HFrEF. Conclusion: We found that the number of circulating CD31+/annexin V+ MVs may improve a predictive capacity for conventional HF biomarkers.

Circulating endothelial-derived apoptotic microparticles and insulin resistance in non-diabetic patients with chronic heart failure.

BACKGROUND: The objective of this study was to assess the relationship between insulin resistance and apoptotic endothelial-derived microparticles (EMPs) in patients with chronic heart failure (CHF). METHODS: The study involved 300 CHF patients (186 males) aged 48-62 years with angiographically proven coronary artery disease and/or previously defined myocardial infarction. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). EMPs phenotype was determined by flow cytofluorometry. RESULTS: Depending on HOMA-IR cut-off point (over and <2.77 mmol/L×µU/mL) all patients were divided into two cohorts with (n=171) or without (n=129) IR, respectively. Circulating EMPs were higher in CHF patients with IR than in patients without IR. Interestingly, EMPs were directly related to NYHA functional class of CHF, HOMA-IR, NT-pro-BNP, hs-CRP and BMI. There was a significant association between the level of EMPs and HbA1c, gender (r=0.318, p<0.001 for male), age and smoking. On univariate and multivariate regression analysis we found that the NYHA class of CHF,NT-pro-BNP, hs-CRP, and left ventricular ejection fraction (LVEF) appeared to be independent predictors of increased circulatory apoptotic EMPs. The addition of HOMA-IR to the standard model (NYHA class CHF) improved the relative IDI by 19.9% for increased EMPs. For category-free NRI, 10% of events and 24% of non-events were correctly reclassified by the addition of HOMA-IR to the standard model for increased circulating EMPs. CONCLUSIONS: IR may be a contributing factor increasing circulating levels of apoptotic EMPs in non-diabetic CHF patients.

Diabetes mellitus related biomarker: The predictive role of growth-differentiation factor-15.

Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine, which belongs to super family of the transforming growth factor beta. GDF-15 is widely presented in the various cells (macrophages, vascular smooth muscle cells, adipocytes, cardiomyocytes, endothelial cells, fibroblasts), tissues (adipose tissue, vessels, tissues of central and peripheral nervous system) and organs (heart, brain, liver, placenta) and it plays an important role in the regulation of the inflammatory response, growth and cell differentiation. Elevated GDF-15 was found in patients with established CV diseases including hypertension, stable coronary artery disease, acute coronary syndrome, myocardial infarction, ischemic and none ischemic-induced cardiomyopathies, heart failure, atrial fibrillation, as well as stroke, type two diabetes mellitus (T2DM), chronic kidney disease, infection, liver cirrhosis, malignancy. Therefore, aging, smoking, and various environmental factors, i.e. chemical pollutants are other risk factors that might increase serum GDF-15 level. Although GDF-15 has been reported to be involved in energy homoeostasis and weight loss, to have anti-inflammatory properties, and to predict CV diseases and CV events in general or established CV disease population, there is no large of body of evidence regarding predictive role of elevated GDF-15 in T2DM subjects. The mini review is clarified the role of GDF-15 in T2DM subjects.

Predictive value of circulating osteonectin in patients with ischemic symptomatic chronic heart failure.

BACKGROUND: Osteonectin (OSN) plays a pivotal role in cardiac remodeling, but predictive value for OSN in ischemic chronic heart failure (CHF) has not been defined. The aim of the study was to evaluate the prognostic value of OSN for cumulative survival and hospitalization among patients with ischemic-induced CHF. METHODS: A total of 154 patients with ischemic symptomatic moderate-to-severe CHF were enrolled in the study at discharge from the hospital. Observation period was up to 3 years (156 weeks). Blood samples for biomarkers measurements were collected at baseline prior to study entry. ELISA methods for measurements of circulating level of OSN were used. RESULTS: During a median follow-up of 2.18 years, 21 participants died and 106 subjects were re-admitted. Medians of circulating levels of OSN in survival and died patient cohorts were 670.96 ng/mL (95% confidence interval [CI] = 636.53-705.35 ng/mL) and 907.84 ng/mL (95% CI = 878.02-937.60 ng/mL). Receiver operation characteristic curve analysis has shown that cut off point of OSN concentration for cumulative survival function was 845.15 ng/mL. It has been found a significant divergence of Kaplan-Meier survival curves in patients with high (>845.15 ng/mL) and low (<845.15 ng/mL) concentrations of OSN. Circulating OSN independently predicted all-cause mortality (odds ratio [OR] = 1.23; 95% CI = 1.10-1.36; p < 0.001), CHF-related death (OR = 1.46; 95% CI = 1.22-1.80; p < 0.001), and also CHF-related re-admission (OR = 1.92; 95% CI = 1.77-2.45; p < 0.001) within 3 years of observation period. CONCLUSION: Increased circulating secreted protein acidic and rich in cysteine family member OSN associates with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization due to CHF.

Diabetes mellitus and cellular replacement therapy: Expected clinical potential and perspectives.

Diabetes mellitus (DM) is the most prevailing disease with progressive incidence worldwide. Despite contemporary treatment type one DM and type two DM are frequently associated with long-term major microvascular and macrovascular complications. Currently restoration of failing ß-cell function, regulation of metabolic processes with stem cell transplantation is discussed as complements to contemporary DM therapy regimens. The present review is considered paradigm of the regenerative care and the possibly effects of cell therapy in DM. Reprogramming stem cells, bone marrow-derived mononuclear cells; lineage-specified progenitor cells are considered for regenerative strategy in DM. Finally, perspective component of stem cell replacement in DM is discussed.

Circulating endothelial progenitor cells as markers for severity of ischemic chronic heart failure.

INTRODUCTION: Despite a high potential of endothelial progenitor cells (EPCs) for diagnostic purposes, the EPC role in developing ischemic chronic heart failure (CHF) has not been determined obviously. The objective of this study was to assess the counts of CD45(+)CD34(+), CD45(-)CD34(+), CD14(+)CD309(+), and CD14(+)CD309(+)Tie2(+) phenotyped circulating EPCs of various subpopulations in patients with ischemic CHF. METHODS AND RESULTS: The study involved 153 patients (86 male), aged 48-62 years, with angiographically proven coronary artery disease (CAD) and 25 healthy volunteers. CHF was diagnosed in 109 patients (71.2%). Mononuclear cell populations were phenotyped by flow cytofluorimetry. Cardiovascular risk factors, such as type 2 diabetes mellitus, hyperlipidemia, arterial hypertension, and adherence to smoking, may have a negative effect on circulating EPC counts in CAD patients regardless of the presence of CHF. The depletion of the CD14(+)CD309(+)- and CD14(+)CD309(+)Tie2(+)-phenotyped circulating EPC counts is associated with the severity of left ventricular dysfunction, whereas the CD45(+)CD34(+)- and CD45(-)CD34(+)-mononuclear cell counts are more representative of the severity of atherosclerotic coronary artery lesions. CONCLUSION: The authors found that New York Heart Association functional class of CHF, left ventricular ejection fraction <42%, the N-terminal pro-B-type natriuretic peptide level >554 pg/mL, and Е/Еm ratio >15 U had the highest predictive value for the depletion of the EPC count in CAD patients.