Association of Soluble Suppression of Tumorigenesis-2 (ST2) with Endothelial Function in Patients with Ischemic Heart Failure.

Soluble suppression of tumorigenesis-2 (sST2) has been introduced as a marker associated with heart failure (HF) pathophysiology and status. Endothelial dysfunction is a component underlying HF pathophysiology. Therefore, we examined the association of arterial wall properties with sST2 levels in patients with HF of ischemic etiology. We enrolled 143 patients with stable HF of ischemic etiology and reduced left ventricular ejection fraction (LVEF) and 77 control subjects. Flow-mediated dilation (FMD) was used to evaluate endothelial function and pulse wave velocity (PWV) to assess arterial stiffness. Although there was no significant difference in baseline demographic characteristics, levels of sST2 were increased in HF compared to the control (15.8 (11.0, 21.8) ng/mL vs. 12.5 (10.4, 16.3) ng/mL; p < 0.001). In the HF group, there was a positive correlation of sST2 levels with age (rho = 0.22; p = 0.007) while there was no association of LVEF with sST2 (rho = -0.119; p = 0.17) nor with PWV (rho = 0.1; p = 0.23). Interestingly, sST2 was increased in NYHA III [20.0 (12.3, 25.7) ng/mL] compared to patients with NYHA II (15.0 (10.4, 18.2) ng/mL; p = 0.003) and inversely associated with FMD (rho = -0.44; p < 0.001) even after adjustment for possible confounders. In patients with chronic HF of ischemic etiology, sST2 levels are increased and are associated with functional capacity. There is an inverse association between FMD and sST2 levels, highlighting the interplay between the dysfunctional endothelium and HF pathophysiologic mechanisms.

The Acute Impact of Different Types of Aerobic Exercise on Arterial Wave Reflections and Inflammation.

OBJECTIVES: Whilst physical activity is linked to cardiovascular health, it has lately been recognized that different types of exercise exert diverse effects on the cardiovascular system. Therefore, we investigated the acute effects of continuous moderate-intensity aerobic exercise (CAE) and high-intensity interval aerobic exercise (hIAE) on arterial function and inflammation. METHODS: Twenty healthy men (mean age 22.6 ± 3.3 years) were recruited in this crossover study. Each of the 20 volunteers participated in two separate sessions (hIAE and CAE). The augmentation index (AIx) of aortic pressure waveforms and serum levels of interleukin-17 (IL-17) were measured before and after each exercise session. RESULTS: There were no significant differences in baseline hemodynamic and inflammatory measurements before CAE and hIAE. Compared to baseline, AIx was significantly improved after CAE (p = 0.04), while there was no significant change after hIAE (p = 0.65). Serum levels of IL-17 were significantly elevated after CAE (p = 0.042), while hIAE had no significant effect on IL-17 levels (p = 0.47). Interestingly, there was an inverse association between the elevation of IL-17 levels and the AIx improvement after CAE (p = 0.05). CONCLUSION: These findings provide additional evidence concerning the cardiovascular effects of different types of exercise training through modification of peripheral hemodynamics and the inflammatory process.

The prognostic role of galectin-3 and endothelial function in patients with heart failure.

BACKGROUND: Heart failure (HF) is nowadays classified as HF with reduced ejection fraction (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF). Endothelial dysfunction (assessed by flow-mediated dilatation [FMD]), increased arterial stiffness (assessed by carotid-femoral pulse-wave velocity [PWV]), and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF. METHODS: In this study we prospectively enrolled 340 patients with stable ischemic HF. We assessed the brachial artery FMD, carotid-femoral PWV, and galectin-3 levels, and patients were followed up for MACE according to HF group. RESULTS: Interestingly, the FMD values exhibited a stepwise improvement according to left ventricular ejection fraction (LVEF) (HFrEF: 4.74 ± 2.35% vs. HFmrEF: 4.97 ± 2.81% vs. HFpEF: 5.94 ± ± 3.46%, p = 0.01), which remained significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors, and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% confidence interval: 0.166-1.814, p = 0.019). Single-vessel coronary artery disease was more frequent in the group of HFpEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p = 0.049). PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51 ± 2.35% vs. 5.32 ± 2.67%, p = 0.02), and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p = 0.01). CONCLUSIONS: Flow-mediated dilatation displayed a linear improvement with LVEF in patients with ischemic HF. Deteriorated values are associated with MACE. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF.

Differential Expression of microRNAs in Acute and Chronic Heart Failure.

BACKGROUND: MicroRNAs modify protein expression at the post-transcriptional level, and their circulating levels may help identify the underlying molecular pathways. OBJECTIVE: The purpose of this study was to assess the differential expression of microRNAs related to myocardial cell energy substrate, autophagy, and ischaemia in chronic and acute heart failure (HF). METHODS: In this case-control study, we studied 19 patients with acute HF (AHF) and 19 patients with chronic HF (CHF). Basic demographic and clinical characteristics were collected from the patients upon arrival, at 48 hours, and at 120 hours. Blood samples for microRNAs measurements (miR-22, -92a, and -499), B-type natriuretic peptide (BNP), C reactive protein, and high sensitivity cardiac troponin I, were collected at all study points. In this study, we included subjects with a left ventricular ejection fraction of <40%. RESULTS: At baseline, circulating miR-22 levels were 1.9-fold higher (p<0.001), miR-92a levels were 1.25-fold higher (p=0.003), and miR-499 were 5-times lower (p<0.001) in AHF compared to CHF. Interestingly, circulating miR-499 was found to be associated with BNP levels (r=0.47, p=0.01). At follow-up, there was a stepwise increase in the levels of all three examined microRNAs (miR-22, p=0.001, miR-92a, p=0.001, and miR-499, p<0.001) for AHF but not for CHF subjects. CONCLUSION: MicroRNAs -22, -92a, and -499 are differentially expressed in chronic and acute HF subjects. MicroRNA signatures are also differentially expressed up to the discharge of the patients. These findings may have important implications for diagnosis, progression, and treatment of patients with chronic and acute heart failure.

The association of T786C and G894T polymorphisms of eNOS gene with diabetic retinopathy in Greece.

PURPOSE: To investigate whether eNOS T786C (rs2070744) and G894T (rs1799983) gene polymorphisms are associated with diabetic retinopathy in Greek diabetic patients. MATERIALS: 271 patients with type-2 diabetes mellitus participated in our study; 130 suffered from diabetic retinopathy and 141 not. All the patients underwent a complete ophthalmological examination, while clinical and demographic data were assessed. Furthermore, they were genotyped for rs2070744 and rs1799983 single nucleotide polymorphisms of eNOS gene. RESULTS: Regarding the clinical and demographic data, no significant differences were detected between the studied groups, except for hemoglobin A1c levels and the frequency of insulin treatment (higher in patients with diabetic retinopathy). The frequency of rs1799983 GT genotype was significantly elevated in patients with diabetic retinopathy (55% vs. 40%, P = 0.011) and was associated with a 2-fold increased risk of developing retinopathy (OR 1.92, 95% CI 1.16-3.17). Furthermore, we demonstrated that the aforementioned genotype was significantly and independently associated with increased odds for retinopathy onset in diabetic subjects (OR 2.23, 95% CI 1.28-3.90, P = 0.005), regardless of the impact of other confounders. CONCLUSIONS: We documented that rs1799983 GT genotype could be recognized as an independent risk factor of retinopathy in Greek patients with type-2 diabetes mellitus, while no role for rs2070744 polymorphism was identified. Further research in different ethnic groups will clarify the exact association of these polymorphisms with the risk for diabetic retinopathy development.

Galectin-3 and Arterial Stiffness in Patients with Heart Failure: A Pilot Study.

BACKGROUND: Cardiac performance depends on optimum ventriculoarterial coupling which is impaired in patients with heart failure (HF). Galectin-3 is a mediator of myocardial fibrosis and remodeling, and is associated with clinical status in patients with chronic HF. We examined the association of arterial stiffness with galectin-3 levels in patients with HF of ischemic etiology. METHODS: We consecutively enrolled 40 patients with stable ischemic HF and reduced ejection fraction. Central aortic stiffness was evaluated non-invasively by measuring carotid femoral pulse wave velocity (PWV). Among other factors, serum levels of galectin-3 and b-type natriuretic peptide (BNP) were measured. RESULTS: The median galectin-3 levels in our study population were 12.9 (10.8-18.7) ng/ml and the mean PWV was 9.31±2.79 m/sec. There was significant association of galectin-3 levels with age (r=0.48, p=0.003), creatinine clearance (r=-0.66, p<0.001) and BNP levels (r=0.36, p=0.05). There was a significant association of galectin-3 levels with PWV (r=0.37, p=0.03) and patients with PWV above median also had significantly increased levels of galectin-3 compared with patients with lower values of PWV [16.1(11.8-25.2) vs. 12.1(10.5-14) ng/ml, p=0.03]. CONCLUSION: We found an association of arterial stiffness and PWV with galectin-3 levels in patients with chronic HF of ischemic etiology. These findings suggest a pathway driving arterial stiffening and myocardial remodelling in HF. This may provide insight into the mechanism determining prognosis and clinical status of patients with HF.

The association among biomarkers of renal and heart function in patients with heart failure: the role of NGAL.

AIM: The NGAL is a biomarker of renal injury associated with the progression of heart failure (HF). We examine the association of NGAL with galectin-3 in patients with chronic HF. METHODS: We consecutively enrolled 115 subjects with stable ischemic HF of reduced ejection fraction. Serum levels of galectin-3, b-type natriuretic peptide and NGAL were measured. RESULTS: NGAL levels were positively correlated with galectin-3 (rho = 0.26; p = 0.04) and b-type natriuretic peptide levels (rho = 0.30; p = 0.005) and inversely correlated with ejection fraction (rho = -0.31; p = 0.02) and creatinine clearance levels. The NGAL was independently associated with galectin-3 levels. CONCLUSION: A positive correlation between NGAL and galectin-3 in HF patients was found, revealing a potential association between renal injury and myocardial fibrosis and remodeling in HF.

The Role of Endothelial Dysfunction in Aortic Aneurysms.

Abdominal aortic aneurysm is a vascular disease which, despite the fact that it shares common risk factors with atherosclerosis, develops in parallel but as a partly independent process, through different pathogenic mechanisms. The pathogenic mechanisms involve metalloproteinase and collagenase activation, median and adventitial degradation, elastin lysis, vascular smooth cells transformation and apoptosis, collagen production and lysis imbalance combined with excessive inflammatory infiltration. Endothelial cells respond to a number of stimulating factors, including smoking, hypertension and AT1 receptor stimulation and non-uniform distribution of wall stress. Their ability to produce NO is crucial in order to adapt. Endothelial cells contribute to AAA development due to increased oxidative stress which is partly mediated by impaired NO bioavailability due to endothelial dysfunction and NADPH oxidase overexpression. In addition, they express several molecules among which adherence molecules, selectins, endothelin-1, regulating inflammatory infiltration and oxidative stress. Inflammatory cells consist of monocytes, polymorphonuclear neutrophils and lymphocytes and they are involved in the degrading process in the aortic wall by secreting proteolytic enzymes or by releasing interleukins which mediate the inflammation response. Endothelial dysfunction and arterial stiffness reflect on indices like FMD, carotid-femoral PWV and augmentation index, sometimes with controversial results. At present, surgical treatment is the only option provided in patients with large AAA, in particular. Focusing on the emerging role of endothelial cells in AAA pathology may contribute in creating new therapeutic options in a disease which has not yet a well-accepted, implemented pharmaceutical treatment.

Effects of CYP2C19 Polymorphism on Endothelial Function, Arterial Stiffness and Inflammation in Coronary Artery Disease Patients Under Clopidogrel Treatment.

BACKGROUND: Clopidogrel's ability to inhibit platelet function determined its clinical usefulness. The role of CYP2C19*2 genotype on antiplatelet treatment is recently under question. Arterial wall properties and inflammation are key players in atherosclerosis development. Hence, we evaluated the impact of CYP2C19*2 genetic polymorphism on endothelial function, arterial stiffness and inflammation in coronary artery disease (CAD) patients receiving clopidogrel treatment. METHODS AND RESULTS: In this study we enrolled 408 consecutive patients with stable CAD under dual antiplatelet therapy (clopidogrel 75mg/day, aspirin 100mg/day), 30 days after percutaneous coronary intervention. Measurement of flow-mediated dilation (FMD) of the brachial artery was used to evaluate endothelial function. Carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) was measured to estimate arterial stiffness. Real time polymerase chain reaction was used for the genotyping of CYP2C19*2. Levels of tumor necrosis factor alpha (TNF-a) and interleukin 6 (IL-6) were measured with ELISA. We found no difference in basic clinical and demographic characteristics nor in FMD, PWV, AIx and inflammatory status (p=NS for all) between CYP2C19 homozygotes for the wild type; carriers of reduced function allele and homozygotes for the reduced function allele. CONCLUSION: CYP2C19*2 loss of action polymorphism causes no impact on vascular function and inflammatory status in stable CAD patients receiving clopidogrel treatment.

Novel Inflammatory Biomarkers in Cardiovascular Therapeutics.

Inflammation has been established as an important determinant of cardiovascular disease progression. Currently, clinical examination, laboratory and imaging tests are invaluable for the diagnosis, prognosis and disease monitoring. Novel inflammatory biomarkers are also used to better restratify patients in risk groups but their potential to guide treatment decisions and management of patients has not been extensively evaluated. Therefore, in this review article we present the most recent data concerning the use of inflammatory biomarkers in cardiovascular therapeutics.