Endothelial progenitor cells and left ventricle function in patients with acute myocardial infarction: potential therapeutic considertions.

Endothelial progenitor cells (EPCs) play a key role in angiogenesis and vascular repair, although their exact functions are still disputable. The impact of EPC on left ventricular ejection fraction (LVEF) during acute myocardial infarction (MI) in patients treated with primary percutaneous coronary intervention (PCI) is also under investigation. The aim of this study was to assess the impact of different populations of EPC on LVEF during and 6 months after acute MI treated with primary PCI. The study included 34 patients with documented acute anterior wall MI. The control group consisted of 19 apparently healthy subjects. Blood for EPC assessments was obtained during the first 24 hours after MI and at 7 days and 6 months after PCI. CD34⁺/CD133⁺/CD45⁻, CD34⁺/CD31⁺/CD45⁻, CD34⁺/CD105⁺/CD45⁻, and CD31⁺/CD133⁺/CD45⁻ cell types were studied by flow cytometry. Echocardiography has been performed simultaneously with the EPC measurements. We observed a significant elevation of CD34⁺/CD133⁺/CD45⁻, CD34⁺/CD105⁺/CD45⁻, and CD31⁺/CD133⁺/CD45⁻ EPC at 7 days after PCI in comparison with 24 hours and 6 months after the MI. Patients with preserved LVEF at 7 days after PCI had also higher levels of CD31⁺/CD133⁺/CD45⁻. Acute anterior wall MI treated with primary PCI is followed by enhanced mobilization of EPC among which a high level of CD31⁺/CD133⁺/CD45⁻ subtype was strongly associated with the most preserved LVEF for up to 6 months after the index event. These data may provide some insight for future therapeutic strategies.

Plasma levels of TNF-alpha, IL-6, and IL-10 and their relationship with left ventricular diastolic function in patients with stable angina pectoris and preserved left ventricular systolic performance.

AIMS: The role of inflammation--a key factor underlying coronary artery disease (CAD) and systolic heart failure--in promotion of left ventricular (LV) diastolic dysfunction has not been investigated extensively so far. The aim of this study was: (i) to evaluate plasma levels of TNF-alpha, IL-6, and IL-10 in patients with stable CAD and preserved LV systolic function and (ii) to assess their relationships with LV diastolic function. METHODS: The study population consisted of 126 patients with single vessel and 58 patients with multivessel stable CAD and LV ejection fraction >50%, and 39 healthy controls. Each participant underwent echocardiographic study including estimation of LV diastolic function indices: peak velocities of early (E) and late (A) transmitral flows, deceleration time of E wave, isovolumic relaxation time, E wave (ETT) and A wave (ATT) transit time to the LV outflow tract, and flow propagation velocity of E wave (Ep). Plasma TNF-alpha, IL-6, and IL-10 levels were evaluated by radioimmunometric method. RESULTS: Patients with CAD presented higher TNF-alpha and IL-6 levels and higher values of IL-6/IL-10 and TNF-alpha/IL-10 ratio than the controls. IL-6 levels were higher in patients with multivessel disease than in those with single vessel disease. Significant correlations (all P<0.001) were found for TNF-alpha and Ep (r=-0.41), E/Ep (r=0.45), and ETT (r=0.38). IL-6 correlated with Ep (r=-0.39) and E/A (r=-0.33), whereas IL-10 with ETT (r=0.37), Ep (r=-0.44), and E/Ep (r=0.46). CONCLUSION: In patients with stable CAD and preserved LV systolic performance, plasma levels of TNF-alpha and IL-6 are elevated and there is association between immunoinflammatory activation reflected by plasma levels of cytokines and LV diastolic dysfunction.

Left ventricular function impairment in patients with normal-weight obesity: contribution of abdominal fat deposition, profibrotic state, reduced insulin sensitivity, and proinflammatory activation.

BACKGROUND: Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. METHODS AND RESULTS: One hundred sixty-eight subjects (age, 38±7 years) with BMI <25kg/m(2) and no history of any disease affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (ß=-0.17, P<0.006), C-reactive protein (ß=-0.20, P<0.002) and abdominal fat deposit (ß=-0.20, P<0.003); for tissue S velocity, PICP (ß=-0.21, P<0.002) and abdominal fat deposit (ß=-0.43, P<0.0001); for tissue E velocity, abdominal fat deposit (ß=-0.30, P<0.0001), PICP (ß=-0.31, P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; ß=-0.20, P<0.002); and for E/e'-PICP, IL-18 (both ß=0.18, P<0.01) and HOMA IR (ß=0.16, P<0.04). CONCLUSIONS: In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

Prediction of left ventricular dysfunction progression in patients with a first ST-elevation myocardial infarction--contribution of cystatin C assessment.

OBJECTIVES: Left ventricular (LV) dysfunction is a major cause of poor outcome after myocardial infarction. We sought to investigate the factors that might contribute to the prediction of postinfarct LV dysfunction progression, and whether the addition of cystatin C (CystC) to this assessment might be useful. METHODS: NT-proBNP, CRP, CystC, and troponin I were measured in 150 patients with a first ST-elevation myocardial infarction (STEMI) who were followed up for 6 months. Echocardiography was performed at discharge and follow-up. RESULTS: In multivariable logistic regression, LV ejection fraction decrease at follow-up exceeding 0.2 was independently predicted by CRP [odds ratio (OR): 1.09, 95% confidence interval (CI): 1.05-1.13, P<0.0001], multivessel disease (OR: 8.83, 95% CI: 4.01-19.41, P<0.001), and left anterior descending artery involvement (OR: 5.09, 95% CI: 1.60-16.22, P<0.006); whereas peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity ratio (E/E') exceeding 15 indicating elevated LV filling pressure by CystC (OR: 3.53, 95% CI: 1.11-11.26, P<0.01), diabetes (OR: 4.04, 95% CI: 1.58-10.58, P<0.005), and multivessel disease (OR: 4.09, 95% CI: 1.52-11.05, P<0.006). CRP, NT-proBNP, and CystC were among the independent determinants of clinical outcomes (heart failure hospitalizations, mortality, and recurrent ischemic events). Receiver operator characteristic analyses identified CRP being the most valuable in discriminating LV ejection fraction decrease exceeding 0.2 and CystC in discriminating E/E' exceeding 15. CONCLUSION: Using multiple biomarkers may contribute to the better prediction of LV dysfunction progression and the risk of adverse cardiac events in patients with STEMI. CystC may improve this evaluation, especially with regard to the development of echocardiographic features of elevated LV filling pressure.

Serum levels of interleukin-6, interleukin-10 and C-reactive protein in patients with myocardial infarction treated with primary angioplasty during a 6-month follow-up.

INTRODUCTION: Recent studies indicate that inflammatory and immune factors are involved in the post-infarction cardiac remodeling. OBJECTIVES: We evaluated serum levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and C-reactive protein (CRP) in patients with acute coronary syndrome with ST-segment elevation myocardial infarction (STEMI) in the acute phase of the disease and 6 months later. Moreover we sought to determine the effect of selected clinical parameters on the levels of the inflammatory factors. PATIENTS AND METHODS: The study involved 75 patients with STEMI, aged 36-82 years, treated with primary angioplasty. Blood samples for determination of IL-6, IL-10 and CRP levels were taken on the 3rd and 7th day of hospitalization and after 6 months. RESULTS: In the acute phase of myocardial infarction (MI) the levels of IL-6, IL-10 and CRP, as well as the IL-6/IL-10 and CRP/IL-10 indexes were higher than in the control group. Six months later the CRP level decreased significantly, and the levels of IL-6 and IL-10 and the studied indices normalized. In the acute phase of MI there were positive correlations between the studied factors. The independent predictors of IL-6, IL-10 and CRP levels were body mass index (BMI), troponin I, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and the baseline levels of inflammatory markers. CONCLUSIONS: In the acute phase of MI, inflammatory activation is enhanced with predominant proinflammatory response. In the course of the healing process within 6 months inflammation is suppressed and the balance between pro- and anti-inflammatory activation is restored. The size of MI, BMI, lipid levels and the baseline levels of inflammatory markers influence the levels of inflammatory factors.