Urotensin-II, oxidative stress, and inflammation increase in hypertensive and resistant hypertensive patients.

Objective: Hypertension is a multi-factorial process prevalent in developed as well as in developing countries. Urotensin-II, different antioxidants, free radicals, and inflammatory biomarkers play an essential role in the cardiovascular system. The aim of this study is to investigate Urotensin-II, oxidative stress, and inflammation markers in normotensive, hypertensive, and resistant hypertensive patients. Methods: Fifty resistance hypertensive (rHT) patients, 50 hypertensive patients, and 50 age gender matched normotensive controls (NT-control) were enrolled. Urotensin-II (UII), total oxidant status (TOS), total antioxidant status (TAS), native thiol (NT), total thiol (TT), disulfide (DIS), interleukin 1 beta (IL1ß), interleukin 6 (IL6), tumor necrosis factor-alpha (TNFα), high sensitive c reactive protein (hsCRP), high-density lipoprotein (HDL) low-density lipoprotein (LDL), and total cholesterol (TC) were evaluated. Results: Serum levels of UII, IL1ß, IL6, TNFα, DIS, TOS, and OSI were found higher in rHT and HT as compared to NT-control (p < .001). On the contrary, serum levels of TT, TAS, and NT were lower in rHT and HT as compared to NT-control (p < .001). While TC, hsCRP, TOS, OSI, UII, IL1ß, IL6, and TNFα levels increase from HT to rHT group (p < .001); TAS and NT levels decrease from HT to rHT group (p < .001). Conclusions: UII levels, oxidative stress, and inflammation are higher in rHT and HT, while antioxidants and thiol levels are lower than the NT-control. Our study clearly showed that rHT and HT are more susceptible to impaired states of antioxidants, oxidative stress, and free radicals.

Premature Myocardial Infarction: Genetic Variations in SIRT1 Affect Disease Susceptibility.

OBJECTIVES: Premature myocardial infarction (PMI) is an uncommon disease, and its incidence varies between 2% and 10%, rising, depending on genetic susceptibility under the influence of lifestyle. The purpose of this study was to investigate the association between SIRT1 single nucleotide polymorphisms (SNPs), SIRT1, and eNOS (endothelial nitric oxide synthase) protein expressions, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) in young patients with premature ST-elevation myocardial infarction (STEMI). METHODS: Genotyping of the three single-nucleotide polymorphisms (rs7895833 A > G in the promoter region, rs7069102 C > G in intron 4, and rs2273773 C > T in exon 5) in SIRT1 gene was performed in 108 consecutive patients (87.0% were men with a mean age of 40.74 ± 3.82 years) suffering from ST-elevation myocardial infarction at the age of ≤45 and 91 control subjects. RESULTS: The risk for myocardial infarction was increased by 2.31 times in carriers of CC or CG genotypes. SIRT1 protein levels were enhanced and endothelial nitric oxide synthase levels were diminished in ST-elevation myocardial infarction patients regardless of the underlying gene variant. There was no correlation between SIRT1 expression and the amount of endothelial nitric oxide synthase, total antioxidant status, total oxidant status, and oxidative stress index levels in patients and in the control group either. CONCLUSIONS: SIRT1 single-nucleotide polymorphisms were associated with premature myocardial infarction, which affected the SIRT1 and endothelial nitric oxide synthase protein expression, irrespective of the underlying SIRT1 genotype.

MicroRNA 199a Is Downregulated in Patients After Coronary Artery Bypass Graft Surgery and Is Associated with Increased Levels of Sirtuin 1 (SIRT 1) Protein and Major Adverse Cardiovascular Events at 3-Year Follow-Up.

BACKGROUND The cardioprotective protein SIRT1 is elevated in patients with coronary artery disease (CAD) to compensate for the disease-related adverse effects, but less is known about the prognostic role of SIRT 1 regulating microRNAs in patients after coronary artery bypass graft (CABG) surgery. MATERIAL AND METHODS The expression of the SIRT 1-specific microRNAs miR-199a and miR-195 was analyzed using real-time PCR in 68 patients referred for CABG surgery and 34 control patients undergoing heart valve surgery. In CABG patients, major adverse cardiac and cerebrovascular events (MACCEs), including all-cause death, myocardial infarction (MI), re-vascularization, heart failure symptoms ≥NYHA II, re-hospitalization for any cardiovascular reason, and stroke, were analyzed at a median follow-up (FU) of 3.2 years (range: 3.0-3.6). RESULTS The level of miR-199a in patients with CAD was significantly reduced compared to the control group (relative expression: 0.89±0.49 vs. 1.90±0.90, p=0.001), while SIRT 1 protein was markedly enhanced (p<0.001). In patients undergoing CABG who had MACCEs, miR-199a was significantly lower compared to patients with an uneventful FU (0.71±0.25 vs. 0.98±0.53, p=0.007). Heart failure status, death, and total MACCEs rate were inversely correlated with the amount of miR-199a (p=0.039) at 3-year FU. CONCLUSIONS Altered expression of miR-199a in myocardial tissue was found to be associated with SIRT 1 upregulation in patients with CAD undergoing CABG and was associated with an increased MACCEs rate at mid-term follow-up.

Valve sparing surgery in an adult patient with dextrocardia and annuloaortic ectasia.

We report the case of a patient with situs inversus totalis, annuloaortic ectasia complicated by aortic insufficiency and mitral regurgitation which induced congestive heart failure. Both valvular lesions were repaired physiologically using aortic root sparing Yacoub 'remodeling' technique and mitral ring annuloplasty. Valve sparing techniques can be used effectively even in patients with complicated clinical scenarios (like dextrocardia and annuloaortic ectasia) to avoid the potential risks related to prosthetic valve implantation and lifelong anticoagulation therapy.

Role of cathepsin D activation in major adverse cardiovascular events and new-onset heart failure after STEMI.

AIM: Increased serum levels of the activated aspartic lysosomal endopeptidase cathepsin D (CatD) have been found in patients with acute myocardial infarction (AMI). However, to date there have been no analyses of clinical follow-up data measuring the enzyme course and its role in the development of post-MI heart failure. This study aimed to evaluate the role of serum CatD activity in the development of heart failure in patients with ST-segment elevation acute myocardial infarction (STEMI). PATIENTS AND METHODS: Eighty-eight consecutive patients (79.5 % men, mean age 57.4 ± 10.2 years) with STEMI were included in this study. Serum CatD activity was measured directly after primary percutaneous coronary intervention (PCI), before discharge, and at the 6-month follow-up. Patients were monitored for major adverse cardiovascular events (MACE), defined as hospitalization due to cardiovascular causes, recurrent nonfatal myocardial infarction, unplanned PCI, new-onset heart failure, and cardiovascular mortality. RESULTS: Serum CatD activity was significantly higher in patients with AMI after PCI and during follow-up (FU) than that in age-matched controls (16.2 ± 7.5 and 29.8 ± 8.9 vs. 8.5 ± 4.2 RFU; p < 0.001 for each time point). At the 6-month follow-up, serum CatD activity in these patients was inversely related to new-onset cardiac dysfunction compared with patients with preserved and improved LVEF after treatment (23.1 ± 3.2 vs. 28.8 ± 7.0 and 29.7 ± 5.0 RFU respectively, p < 0.01). Patients suffering from MACE during a follow-up period of 6 months had lower serum levels of activated CatD than those without any MACE (23.8 ± 4.6 vs 29.6 ± 6.9 RFU; p < 0.001). CONCLUSIONS: Serum CatD activity as a marker of healthy endogenous phagocytosis and remodeling was impaired in patients with new-onset cardiac dysfunction, and lower levels of serum CatD were associated with MACE at the 6-month post-MI follow-up.

Atrial conduction abnormalities in patients with psoriasis vulgaris.

BACKGROUND: Psoriasis vulgaris is one of the most common chronic inflammatory skin disorders. Patients with psoriasis are at risk of developing atrial fibrillation (AF). The electromechanical delay (EMD) is the time interval from the onset of the P wave on surface electrocardiography (ECG) to the beginning of the A wave. Prolonged atrial EMD is an independent risk factor for the development of AF. AIM: This study investigated the intra- and interatrial EMD in patients with psoriasis. METHODS: This study included 85 adults with psoriasis vulgaris (Group 1) and 46 age- and sex-matched healthy individuals (Group 2). ECGs were obtained from all subjects, and atrial EMD variables were calculated. Results are reported as means ± standard deviations and percentages. Continuous variables were analysed using Student's t-test. A p-value < 0.05 was considered statistically significant. RESULTS: Interatrial electromechanical delay (IA-EMD) and intra-left atrial electromechanical delay (ILA-EMD) were significantly longer in the psoriasis group compared with controls. A correlation analysis between psoriasis severity (PASI score) and the atrial conduction parameters revealed a significant positive correlation between PASI and IA-EMD (r = 0.261, p < 0.001). In addition, there was a positive correlation between high-sensitivity C-reactive protein (hsCRP) and IA-EMD (p = 0.022). CONCLUSIONS: The atrial conduction time was longer in patients with psoriasis vulgaris and it correlated with the severity of disease and hsCRP. Since the association between delayed conduction and AF is known, the measurement of intra-atrial conduction times could be a practical tool to estimate the AF risk in these patients.

Efficacy of statins on sirtuin 1 and endothelial nitric oxide synthase expression: the role of sirtuin 1 gene variants in human coronary atherosclerosis.

Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and are used to reduce the risk of coronary artery disease (CAD) due to their pleiotropic effects. Recently, greater focus has been placed on the role of sirtuin 1 (SIRT1) in cardiovascular disease research. However, insufficient data exist on the relationships between statins, SIRT1 protein levels, and SIRT1 gene variants. In the present study, we investigated the effects of statins, atorvastatin and rosuvastatin, in CAD patients by analysing the associations between SIRT1 gene variants, rs7069102C>G and rs2273773C>T, and SIRT1/endothelial nitric oxide (eNOS) expression, as well as total antioxidant and oxidant status, and the oxidative stress index. SIRT1 expression was significantly higher, and eNOS expression was significantly lower in CAD patients when compared with controls. Statin treatment reduced SIRT1 expression and increased eNOS expression, similar to the levels found in the control population, independent from the studied SIRT1 gene variants. Oxidative stress parameters were significantly increased in CAD patients, and were decreased by statin treatment, demonstrating the antioxidative effects of statins on atherosclerosis. These results indicate that statin treatment could produce its protective effect on cardiovascular disease through the inhibition of SIRT1 expression. This is the first study reporting on the effect of statins, specifically atorvastatin and rosuvastatin, on SIRT1 expression in CAD patients.

The effect of the SIRT1 2827 A>G polymorphism, resveratrol, exercise, age and occupation in Turkish population with cardiovascular disease.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in Europe. One of the candidate molecule affecting epigenetic mechanisms of CVD is the SIRT1, a subclass of sirtuins, is located on the long arm of chromosome 10 (10q21.3). Particularly, the relation between 2827 A>G polymorphism of the SIRT1 positioned on exon 2, leading to conversion of histidine to arginine, and the formation of CVD is not known yet. One of the activator of SIRT1, resveratrol, is also known as a cardioprotective molecule. On the other hand, the parameters including exercise, occupation and age affect CVD. The aim of the present study was to investigate the effect of the rs144124002 (2827 A>G) single nucleotide polymorphisms (SNP) of SIRT1 and exercise-occupation-age parameters on CVD. METHODS: SNP of SIRT1 were analyzed using DNA isolation, the polymerase chain reaction (PCR) and restriction fragment length polymorphism. To do so, large cohorts of CVD patients (n=293) and healthy controls (n=117) who directed Cardiology Department of Bezmialem Vakif University, Bezmialem Vakif University Hospital were used. RESULTS: In this study, when we assessed CVD and control groups about 2827 A>G polymorphism, all individuals were determined as homozygous genotype. We found a positive effect between the modifications of resveratrol, exercise, age and occupation and CVD (OR=0.17; CI 95%, 0.1-0.2; p ≤ 0.001). CONCLUSION: This is the first study demonstrating the correlation between the SIRT1 rs144124002 polymorphism and CVD in Turkish population.

Implication of plasma intermedin levels in patients who underwent first-time diagnostic coronary angiography: a single centre, cross-sectional study.

BACKGROUND: Intermedin (IMD) is involved in the prevention of atherosclerotic plaque progression, possessing cardioprotective effects from hypertrophy, fibrosis and ischemia-reperfusion injury. Elevated plasma IMD levels have been demonstrated in patients with acute coronary syndromes. No human study has examined the role of IMD in stable patients who underwent diagnostic coronary angiography with suspicion of coronary artery disease (CAD). Thus we investigated the role of IMD as a biomarker to discriminate patients with CAD and predict those with severe disease who require early and intensive therapeutic intervention before presenting with acute coronary syndrome. METHODS: Eligible two hundred and thirty-eight consecutive patients (123 males, mean age 58.4 ± 10.0 years) who underwent first-time diagnostic coronary angiography were included in this study. Plasma concentrations of IMD were measured from arterial blood samples by the enzyme-linked immunosorbent assay. Patients were divided into three groups according to the presence and degree of CAD, consisting of 48 patients with normal coronary anatomy (Group 1), 111 patients with < 50% coronary stenosis (Group 2), and 79 patients with ≥ 50% stenosis in at least one of the major coronary arteries (group 3). The severity and extent of CAD was evaluated by calculations of the vessel, Gensini, and SYNTAX scores. RESULTS: Circulating plasma IMD levels in patients with CAD were significantly higher than those in patients without CAD (157.7 ± 9.6, 134.8 ± 11.9, and 117.6 ± 7.9 pg/mL in groups 3, 2 and 1 respectively; p < 0.001). Besides, plasma IMD levels were correlated with Gensini and SYNTAX scores (rs = 0.742, and rs = 0.296, respectively; p < 0.05). The presence of ≥50% coronary artery stenosis could be predicted if a cut-off value of 147.7 pg/mL for plasma IMD was used with 88.6% sensitivity and 88.7% specificity. Moreover, a plasma IMD level of <126.6 pg/mL could discriminate a patient with normal coronary arteries from patients with angiographically proven CAD with a sensitivity and specificity of 84.7%, and 83.3% respectively. CONCLUSIONS: We demonstrated that IMD might be used as a biomarker to predict CAD and its severity in patients who underwent first time diagnostic coronary angiography.

Successful transcatheter closure of bilateral multiple coronary arterial fistulae in one session.

Coronary artery fistulae represent the most frequent congenital anomalies of the coronary arteries, but multiple bilateral fistulae are a rare condition. Current therapeutic options for symptomatic patients are percutaneous closure and cardiac surgery. Transcatheter closure of fistulae using coils is preferred as an effective and safe alternative to surgery. Here we report the case of a patient with congenital coronary artery fistulae arising from both the left and right coronary arteries draining individually into the right pulmonary artery treated successfully with a transcatheter approach.

SIRT1 gene polymorphisms affect the protein expression in cardiovascular diseases.

Cardiovascular disease (CVD), the leading cause of death worldwide, is related to gene-environment interactions due to epigenetic factors. SIRT1 protein and its downstream pathways are critical for both normal homeostasis and protection from CVD-induced defects. The aim of this study was to investigate the association between SIRT1 single nucleotide polymorphisms (SNPs) (rs7895833 A>G in the promoter region, rs7069102 C>G in intron 4 and rs2273773 C>T in exon 5 silent mutation) and SIRT1 and eNOS (endothelial nitric oxide synthase) protein expression as well as total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) in CVD patients as compared to controls. The frequencies of mutant genotypes and alleles for rs7069102 and rs2273773 were significantly higher in patients with CVD compared to control group. The risk for CVD was increased by 2.4 times for rs7069102 and 1.9 times for rs2273773 in carriers of mutant allele compared with carriers of wild-type allele pointing the protective role of C allele for both SNPs against CVD. For rs7895833, there was no significant difference in genotype and allele distributions between groups. SIRT1 protein, TAS, TOS and OSI levels significantly increased in patients as compared to control group. In contrast, level of eNOS protein was considerably low in the CVD patients. An increase in the SIRT1 expression in the CVD patients carrying mutant genotype for rs7069102 and heterozygote genotype for all three SNPs was observed. This is the first study reporting an association between SIRT1 gene polymorphisms and the levels of SIRT1 and eNOS expressions as well as TAS, TOS and OSI.

Neutrophil-to-lymphocyte ratio and in-hospital mortality in patients with acute heart failure.

OBJECTIVES: Previous studies have demonstrated the role of inflammation in acute heart failure. The neutrophil-to-lymphocyte ratio was found to be a useful inflammatory marker for predicting adverse outcomes. We hypothesized that an elevated neutrophil-to-lymphocyte ratio would be associated with increased mortality in acute heart failure patients. METHODS: The study cohort consisted of 167 acute heart failure patients with an ejection fraction <50%. The primary endpoint was in-hospital mortality, and the patients were divided into two groups according to in-hospital mortality. RESULTS: In a multivariate regression analysis, including baseline demographic, clinical, and biochemical covariates, the neutrophil to lymphocyte ratio remained an independent predictor of mortality (OR 1.156, 95% CI 1.001 - 1.334, p = 0.048). CONCLUSION: In conclusion, an elevated neutrophil-to-lymphocyte ratio seems to be a predictor of short-term mortality in patients with acute heart failure and a reduced left ventricular ejection fraction.

A giant right atrial villous myxoma with simultaneous pulmonary embolism.

INTRODUCTION: Primary cardiac tumors are rare and approximately three quarters of them are benign and up to half of the benign tumors are myxomas. Right atrial villous myxoma with pulmonary embolism is an unusual apparition. PRESENTATION OF CASE: A 29 year-old male was admitted to our outpatient clinic with progressive exertional dyspnea, chest pain and intermittent feeling faint. A giant right atrial villous mobile mass was detected by means of transthoracic echocardiography. To exclude possible pulmonary embolism, chest computed tomography scan was performed and showed filling defects in the branch of the pulmonary artery. The mass was totally resected. DISCUSSION: RA villous myxoma is a rare subtype in an unusual location with high potential of pulmonary embolism. Early surgery for villous myxoma has a great importance in order to reduce the risk of pulmonary embolism. CONCLUSION: 3D TEE should be a sufficient technique for diagnosis and evoluation of shape, size and origin of the cardiac mass an adequate guide to surgical treatment.

Serum gamma-glutamyl transferase levels and in-hospital mortality in patients with acute heart failure.

BACKGROUND: Acute heart failure (AHF) is a major cause of hospitalisation, morbidity and mortality worldwide. Gamma-glutamyl transferase (GGT) is an enzyme responsible for the extracellular catabolism of antioxidant glutathione and a potential risk indicator of cardiac mortality. Limited data exists on the prognostic value of circulating levels of GGT in patients hospitalized due to AHF. AIM: To study the association between baseline GGT activity and in-hospital mortality in AHF patients. METHODS: The study cohort consisted of 183 AHF patients with left ventricular ejection fraction (LVEF) < 50%. The primary endpoint was in-hospital mortality. Patients were divided into two groups according to in-hospital mortality. The relationship between GGT activity and in-hospital mortality was tested using logistic regression models, adjusting for clinical characteristics and echocardiographic findings. RESULTS: After adjustment for possible confounders, GGT level was significantly related (OR 1.056, 95% CI 1.018-1.096, p = 0.04) to in-hospital mortality. CONCLUSIONS: Elevated GGT activity is an independent predictor of short-term mortality in patients with AHF and reduced LVEF.

Comparison of single-dose and repeated levosimendan infusion in patients with acute exacerbation of advanced heart failure.

BACKGROUND: Levosimendan (LS) is a novel inodilator that improves cardiac performance, central hemodynamics, and symptoms of patients with decompensated chronic heart failure. The aim of this study was to compare the effects of single and repeated LS infusion on left ventricular performance, biomarkers, and neurohormonal activation in patients with acute heart failure. MATERIAL AND METHODS: Twenty-nine consecutive patients with acute exacerbation of advanced heart failure were included in this study. LS was initiated as a bolus of 6 µg/kg followed by a continuous infusion of 0.1 µg/kg/min for 24 hours in both groups who received intravenous single and repeated (baseline and at 1 and 3 months) treatment. Physical examination, echocardiography, and biochemical tests (brain natriuretic peptide, tumour necrosis factor-alpha, interleukin-1beta, 2, and 6) were performed before treatment and on 3 day of the treatment. The last evaluation was performed at 6 month after the baseline treatment. RESULTS: Twenty male and 9 female patients with mean age of 60.2 ± 7.4 years were included in this study. A significant improvement in New York Heart Association functional status and myocardial performance index was detected only in the repeated LS treated patients at 6 month compared to the pretreatment status (p=0.03 and p<0.001; respectively). In addition, a significant decrease in brain natriuretic peptide (p<0.01) and plasma interleukin-6 (p=0.05) levels were also achieved only in patients who were given repeated LS. CONCLUSIONS: Our study showed that repeated LS treatment is more effective compared to the single dose LS treatment in improving clinical status, hemodynamic and laboratory parameters in patients with acute exacerbation of advanced heart failure.

Epicardial fat thickness in patients with psoriasis vulgaris.

OBJECTIVES: Psoriasis vulgaris is one of the most common skin disorders. Patients with psoriasis carry an excessive risk of coronary artery disease. Visceral adipose tissue around the heart affects the heart and coronaries by secreting proatherogenic mediators. It can be evaluated easily by measurement of epicardial fat thickness (EFT). The aim of this study was to investigate EFT in patients with psoriasis vulgaris. STUDY DESIGN: One hundred and fifteen adult patients (62 male; mean age 33.6±6.0 years) with psoriasis vulgaris (Group 1) and 60 age- and sex-matched healthy individuals (28 male; mean age, 32.5±8.3 years) (Group 2) were included in this study. EFT was obtained by transthoracic echocardiography. Disease-specific characteristics of the patients were recorded. Serum glucose, lipid profile and high-sensitive C-reactive protein (hs-CRP) levels were measured. RESULTS: EFT and hs-CRP were significantly higher in Group 1 than in Group 2 (5.7±1.2 vs. 4.1±1.0 mm, p<0.001 and 0.52±0.45 mg/dl vs. 0.19±0.17 mg/dl, p<0.001, respectively). The psoriasis disease activity score and hs-CRP were found to be independent predictors of EFT in patients with psoriasis vulgaris (ß=0.21, t=2.67, p=0.01 and ß=0.62, t=7.72, p=0.001, respectively). CONCLUSION: Our findings indicate that EFT was significantly higher in patients with psoriasis vulgaris compared with the controls. It was more prominent in patients with severe disease.

A new parameter predicting chronic total occlusion of coronary arteries: platelet distribution width.

Platelet distribution width (PDW) measures the variability in platelet size and is a marker of platelet activation. We investigated whether PDW is associated with the extent of coronary artery disease (CAD) and coronary total occlusions (CTOs). We studied 162 patients: 108 had a coronary lesion with a diameter stenosis of ≥50%, the CAD(+) group, and 54 patients had normal coronary anatomy, the CAD(-) group. The CAD(+) group was subdivided into CAD(+) CTO(+) and CAD(+) CTO(-) groups. Among patients with CAD, the CTO(+) group had a significantly greater PDW (%) than the CTO(-) group (16.9 ± 2.8, 15.4 ± 3.0, and 15.4 ± 1.9, respectively; P = .008). In a receiver-operating characteristic analysis, a PDW cut point of 15.7% was identified in patients with CTO(+) (area under curve = 0.64, 95% confidence interval 0.54-0.75). A PDW value of more than 15.7% demonstrated a sensitivity of 64% and a specificity of 66%. The PDW is a simple platelet index that may predict the presence of CTO.