[Show abstract][Hide abstract] ABSTRACT: To evaluate functional and compositional properties of high-density lipoprotein (HDL) in subjects from a kindred of genetic apolipoprotein (apo) A-I deficiency, two homozygotes and six heterozygotes, with a nonsense mutation at APOA1 codon -2, Q[-2]X, were recruited together with age- and sex-matched healthy controls (n=11). Homozygotes displayed undetectable plasma levels of apoA-I and reduced levels of HDL-cholesterol and apoC-III (5.4% and 42.6% of controls, respectively). Heterozygotes displayed low HDL-cholesterol (21+/-9 mg/dl), low apoA-I (79+/-24 mg/dl), normal low-density lipoprotein-cholesterol (132+/-25 mg/dl) and elevated triglyceride (130+/-45 mg/dl) levels. Cholesterol efflux capacity of ultracentrigufally-isolated HDL subpopulations was reduced (up to -25%, p<0.01, on a phospholipid basis) in heterozygotes vs. controls. Small, dense HDL3 and total HDL from heterozygotes exhibited diminished antioxidative activity (up to -48%, p<0.001 on a total mass basis) vs. controls. HDL subpopulations from both homozygotes and heterozygotes displayed altered chemical composition, with depletion in apoA-I, phospholipid and cholesteryl ester, enrichment in apoA-II, free cholesterol and triglyceride, and altered phosphosphingolipidome. The defective atheroprotective activities of HDL were correlated with altered lipid and apolipoprotein composition. These data reveal that atheroprotective activities of HDL particles are impaired in homozygous and heterozygous apoA-I deficiency and are intimately related to marked alterations in protein and lipid composition.
[Show abstract][Hide abstract] ABSTRACT: Assuming that coronary interventions, both coronary bypass surgery (CABG) and percutaneous coronary intervention (PCI), are directed to preserve left ventricular function, it is not known whether medical therapy alone (MT) can achieve this protection. Thus, we evaluated the evolution of LV ejection fraction (LVEF) in patients with stable coronary artery disease (CAD) treated by CABG, PCI, or MT as a post hoc analysis of a randomized controlled trial with a follow-up of 10 years.
Left ventricle ejection fraction was assessed with transthoracic echocardiography in patients with multivessel CAD, participants of the MASS II trial before randomization to CABG, PCI, or MT, and re-evaluated after 10 years of follow-up.
Of the 611 patients, 422 were alive after 10.32 ± 1.43 years. Three hundred and fifty had LVEF reassessed: 108 patients from MT, 111 from CABG, and 131 from PCI. There was no difference in LVEF at the beginning (0.61 ± 0.07, 0.61 ± 0.08, 0.61 ± 0.09, respectively, for PCI, CABG, and MT, P = 0.675) or at the end of follow-up (0.56 ± 0.11, 0.55 ± 0.11, 0.55 ± 0.12, P = 0.675), or in the decline of LVEF (reduction delta of -7.2 ± 17.13, -9.08 ± 18.77, and -7.54 ± 22.74). Acute myocardial infarction (AMI) during the follow-up was associated with greater reduction in LVEF. The presence of previous AMI (OR: 2.50, 95% CI: 1.40-4.45; P = 0.0007) and during the follow-up (OR: 2.73, 95% CI: 1.25-5.92; P = 0.005) was associated with development of LVEF <45%.
Regardless of the therapeutic option applied, LVEF remains preserved in the absence of a major adverse cardiac event after 10 years of follow-up.
http://www.controlled-trials.com. Registration number ISRCTN66068876.
European Heart Journal 07/2013; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Patients with coronary artery disease (CAD) should be treated with statins to attain very low cholesterol levels, in order to reduce cardiovascular adverse events. More than 70% of these patients do not reach the appropriate cholesterol goal despite moderate statin doses. However, it is not known whether therapeutic uptitration with different lipid-lowering strategies has a similar "pleiotropic" effect on atherosclerotic endothelial dysfunction evaluated by measurement of endothelial progenitor cells (EPCs).Objective
We sought to compare, in patients with stable CAD and with a low-density lipoprotein cholesterol (LDL-C) >70 mg/dL on treatment with simvastatin 20 mg, the effects on EPCs by increasing simvastatin to 80 mg versus adding ezetimibe 10 mg.Methods
Patients (n = 68, 63 ± 9 years, 39% men) were randomly allocated to receive ezetimibe 10/simvastatin 20 mg or simvastatin 80 mg for 6 weeks. Circulating EPCs were measured by flow cytometry before and after the treatment.ResultsBoth strategies presented similar effects on metabolic parameters. The LDLs were equally reduced by ezetimibe 10/simvastatin 20 mg and simvastatin 80 mg (28.9% ± 13% vs 21.1% ± 33%; P = .46, respectively). The levels of EPCs were unaffected by ezetimibe 10/simvastatin 20 mg (median [25th, 75th]: pre- vs posttreatment, 7.0 [2.3; 13.3] vs 3.1 [0.1; 13.2] EPCs/10(4) mononuclear cells; P = .43) or simvastatin 80 mg (pre- vs posttreatment, 6.1 [2.9; 15.2] vs 4.0 [1.4; 10.7] EPCs/10(4) mononuclear cells; P = .5) ,and there were no differences between the groups on treatment effects (P = .9).Conclusions
Among stable patients with CAD and with an LDL-C >70 mg/dL on simvastatin 20 mg, increasing simvastatin dose to 80 mg or adding ezetimibe 10 mg promoted similar further cholesterol reduction but did not have incremental effects on circulating EPCs. These data suggest that the effects of simvastatin moderate doses on EPCs are not increased by intensive lipid-lowering strategies (clinicaltrials.gov: NCT00474123).
Journal of Cardiovascular Pharmacology and Therapeutics 06/2013; · 3.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Monitoring of disease activity and the best therapeutic approach are a challenge in Takayasu arteritis (TA). When associated with acute coronary syndromes (ACS), the best interventional treatment has not been established. The objective of this study was to describe the baseline characteristics, clinical manifestations, treatment and long-term outcome of patients with TA and ACS. METHODS: We retrospectively analyzed eight patients between 2004 and 2010. The following data were obtained: age, gender, clinical and electrocardiographic manifestations, Killip class, risk factors for ACS, markers of myocardial necrosis (CK-MB and troponin), creatinine clearance, left ventricular ejection fraction, inflammatory markers (C-reactive protein and erythrocyte sedimentation rate [ESR]), medication during hospital stay, angiographic findings, treatment (medical, percutaneous or surgical) and long-term outcome. Statistical data were expressed as percentages and absolute values. RESULTS: All eight patients were women, median age 49 years. Typical chest pain was present in 37.5%. Elevated ESR was observed in 85.7%. Three patients underwent coronary artery bypass grafting, three underwent percutaneous coronary angioplasty (two with bare-metal stents and one with a drug-eluting stent) and two were treated medically. In-hospital mortality was 25%. There were no deaths during a mean follow-up of 30 months. CONCLUSIONS: In our study, patients who were discharged home had good outcomes in long-term follow-up with medical, percutaneous or surgical treatment. ESR appears to be associated with ACS in TA.
Revista portuguesa de cardiologia: orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology: an official journal of the Portuguese Society of Cardiology 03/2013; · 0.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. METHODS/DESIGN: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. DISCUSSION: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.
[Show abstract][Hide abstract] ABSTRACT: Systemic Lupus Erythematosus (SLE) is the most common systemic autoimmune disease, occurring more frequently in women, usually aged between 16 and 55 years1,2. Although classically the kidneys are the organs most affected in SLE, cardiopulmonary circulation and the heart may also be affected significantly3. In this context, the occurrence of acute pulmonary edema associated with lupus myocarditis is rare and specific immunosuppressive therapy remains unclear.
Arquivos brasileiros de cardiologia 05/2012; 98(5):e78-81. · 1.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report on a 30-year-old female patient, with biological mitral valve prosthesis due to symptomatic mitral stenosis and a history of acute myocardial infarction and generalized tonic-clonic seizure episodes, visual hallucinations, cerebral thromboembolic events and, at present, chorea and acute carditis. The patient was diagnosed with active rheumatic fever (RF), systemic lupus erythematosus (SLE) and Antiphospholipid syndrome (APS). The combination of three unusual diagnoses in the same patient makes this a unique case, modifying patient treatment and prognosis.
Arquivos brasileiros de cardiologia 02/2012; 98(2):e28-31. · 1.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is increasing interest in autoimmune diseases, especially their relationship with cardiovascular disease. Rheumatoid arthritis in particular has been considered an independent risk factor for coronary artery disease in recent years. Various studies have aimed to clarify important aspects of risk stratification and treatment options in patients with rheumatoid arthritis, and specific therapies are being studied that promise to reduce their long-term cardiovascular risk. We performed a wide-ranging review of the literature to highlight the importance of atherosclerotic and inflammatory mechanisms in coronary artery disease. We also suggest strategies for risk stratification and treatment of cardiovascular disease in patients with rheumatoid arthritis.
Revista portuguesa de cardiologia: orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology: an official journal of the Portuguese Society of Cardiology 01/2012; 31(3):225-32. · 0.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the impact of hyperglycemia in different age-groups of patients with acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS :A total of 2,027 patients with AMI were categorized into one of five age-groups: <50 years (n = 301), ≥50 and <60 (n = 477), ≥60 and <70 (n = 545), ≥70 and <80 (n = 495), and ≥80 years (n = 209). Hyperglycemia was defined as initial glucose ≥115 mg/dL.
The adjusted odds ratios for hyperglycemia predicting hospital mortality in groups 1-5 were, respectively, 7.57 (P = 0.004), 3.21 (P = 0.046), 3.50 (P = 0.003), 3.20 (P < 0.001), and 2.16 (P = 0.021). The adjusted P values for correlation between glucose level (as a continuous variable) and mortality were 0.007, <0.001, 0.043, <0.001, and 0.064. The areas under the ROC curves (AUCs) were 0.785, 0.709, 0.657, 0.648, and 0.613. The AUC in group 1 was significantly higher than those in groups 3-5.
The impact of hyperglycemia as a risk factor for hospital mortality in AMI is more pronounced in younger patients.
Diabetes care 01/2012; 35(1):150-2. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute respiratory failure is present in 5% of patients with acute myocardial infarction and is responsible for 20% to 30% of the fatal post-acute myocardial infarction. The role of inflammation associated with pulmonary edema as a cause of acute respiratory failure post-acute myocardial infarction remains to be determined. We aimed to describe the demographics, etiologic data and histological pulmonary findings obtained through autopsies of patients who died during the period from 1990 to 2008 due to acute respiratory failure with no diagnosis of acute myocardial infarction during life.
This study considers 4,223 autopsies of patients who died of acute respiratory failure that was not preceded by any particular diagnosis while they were alive. The diagnosis of acute myocardial infarction was given in 218 (4.63%) patients. The age, sex and major associated diseases were recorded for each patient. Pulmonary histopathology was categorized as follows: diffuse alveolar damage, pulmonary edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds ratio of acute myocardial infarction associated with specific histopathology was determined by logistic regression.
In total, 147 men were included in the study. The mean age at the time of death was 64 years. Pulmonary histopathology revealed pulmonary edema as well as the presence of diffuse alveolar damage in 72.9% of patients. Bacterial bronchopneumonia was present in 11.9% of patients, systemic arterial hypertension in 10.1% and dilated cardiomyopathy in 6.9%. A multivariate analysis demonstrated a significant positive association between acute myocardial infarction with diffuse alveolar damage and pulmonary edema.
For the first time, we demonstrated that in autopsies of patients with acute respiratory failure as the cause of death, 5% were diagnosed with acute myocardial infarction. Pulmonary histology revealed a significant inflammatory response, which has not previously been reported.
Clinics (São Paulo, Brazil) 01/2012; 67(3):213-7. · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the setting of stable coronary artery disease (CAD), it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone.
We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10mg/simvastatin 20mg (E10/S20) with simvastatin 80 mg (S80).
CAD patients (n=83, 63 ± 9 years, 57% men) receiving S20, were randomly allocated to receive E10/S20 or S80, for 6 weeks. Lipids, inflammatory markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, soluble CD40 ligand and oxidized LDL), and platelet aggregation (platelet function analyzer [PFA]-100) changes were determined. Baseline lipids, inflammatory markers and PFA-100 were similar between groups. After treatment, E10/S20 and S80 patients presented, respectively: (1) similar reduction in LDL-C (29 ± 13% vs. 28 ± 30%, p=0.46), apo-B (18 ± 17% vs. 22 ± 15%, p=0.22) and oxidized LDL (15 ± 33% vs. 18 ± 47%, p=0.30); (2) no changes in inflammatory markers; and, (3) a higher increase of the PFA-100 with E10/S20 than with S80 (27 ± 43% vs. 8 ± 33%, p=0.02).
These data suggest that among stable CAD patients treated with S20, (1) both E10/S20 and S80 were equally effective in further reducing LDL-C; (2) neither treatment had any further significant anti-inflammatory effects; and (3) E10/S20 was more effective than S80 in inhibiting platelet aggregation. Thus, despite similar lipid lowering and doses 4× less of simvastatin, E10/S20 induced a greater platelet inhibitory effect than S80.
International journal of cardiology 02/2011; 158(3):400-4. · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: B-type natriuretic peptide (BNP) and inflammatory markers are implicated in the pathophysiology of both ischemic cardiomyopathy and complications after cardiac surgery with cardiopulmonary bypass (CPB). The purpose of this study was to assess preoperative and postoperative levels of BNP, interleukin-6 (IL-6), interleukin-8 (IL-8), P-selectin, intercellular adhesion molecule (ICAM), C-reactive protein (CRP) in patients undergoing cardiac surgery with CPB and investigate their variation and ability to correlate with immediate outcome.
Plasma levels of these markers were measured preoperatively, 6 and 24 h after CBP in 62 patients. Main endpoints were requirements for intra-aortic balloon pump, intensive care unit (ICU) stay longer than five days, ventilator dependence >24 h, requirement for dobutamine, hospital stay >10 days, clinical complications (infection, myocardial infarction, renal failure, stroke and ventricular arrhythmias) and in-hospital mortality.
Preoperative BNP levels correlate with longer ICU stay (P = 0.003), longer ventilator use (P = 0.018) and duration of dobutamine use (P < 0.001). The receiver-operating characteristic curve demonstrated BNP levels >190 pg/ml as predictor of ICU >5 days and BNP levels >20.5 pg/ml correlated with dobutamine use, with areas under the curve of 0.712 and 0.842, respectively. Preoperative levels of ICAM-1 were associated with in-hospital mortality (P = 0.042). In the postoperative period, was found association between CRP, IL-6 and P-selectin with ventilation duration (P = 0.013, P = 0.006, P < 0.001, respectively) and P-selectin with ICU stay (P = 0.009).
BNP correlates with clinical endpoints more than inflammatory markers and can be used as a predictor of early outcome after heart surgery.
Interactive Cardiovascular and Thoracic Surgery 02/2011; 12(5):778-83. · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of calcification in coronary artery disease is gaining importance, both in research studies and in clinical application. Calcified plaque has long been considered to be the most important atherosclerotic plaque within the arterial tree and frequently presents a challenge for percutaneous intervention. Current investigations have shown that plaque calcification has a dynamic course that is closely related to the magnitude of vascular inflammation. Numerous inflammatory factors synthesized during the early stages of atherosclerosis induce the expression and activation of osteoblast-like cells localized in the arterial wall that produce calcium. There is no doubt that the role of these factors in calcification associated with coronary artery disease could be a crucial strategic point in prevention and treatment. A number of diagnostic imaging methods have been developed in recent years, but their performance needs to be improved. In this context, we undertook an update on coronary calcification, focusing on physiopathology, clinical implications, and imaging techniques.
Vascular Health and Risk Management 01/2011; 7:143-51.
[Show abstract][Hide abstract] ABSTRACT: Depression and coronary artery disease (CAD) are both extremely prevalent diseases. In addition, compromised quality of life and life expectancy are characteristics of both situations. There are several conditions that aggravate depression and facilitate the development of CAD, as well as provoke a worse prognosis in patients with already established CAD: inferior adherence to medical orientations (medications and life style modifications), greater platelet activation and aggregation, endothelial dysfunction, and impaired autonomic dysfunction (lowered heart rate variability). Recent literature has shown that depression alone is becoming an independent risk factor for cardiac events both in primary and secondary prevention. As the diagnosis of depression in patients with heart disease is difficult, due to similarities of symptoms, the health professional should perform a careful evaluation to differentiate the clinical signs of depression from those related with general heart diseases. After a myocardial infarction, depression is an independent risk factor for mortality. Successful therapy of depression has been shown to improve patients' quality of life and cardiovascular outcome. However, multicentric clinical trials are needed to support this inference. A practical liaison between qualified professionals is necessary for the better management of depressed patients with excess risk in developing CAD. Accordingly, pathophysiological and clinical implications between depression and CAD are discussed in this article.
Vascular Health and Risk Management 01/2011; 7:159-64.
[Show abstract][Hide abstract] ABSTRACT: Few studies have prospectively addressed the effects of exercise in the inflammatory activity of patients with coronary artery disease (CAD). We sought to evaluate the consequences of an acute bout of exercise on inflammatory markers and BNP in untrained CAD patients before and after randomization to a training program.
34 CAD patients underwent a 50-min acute exercise session on a cycle-ergometer at 65% peak oxygen uptake before and after blood sampling. They were then randomized to a 4-month chronic exercise program (15 patients) or general lifestyle recommendations (19 patients), undergoing a new acute session of exercise after that.
In the overall population, acute exercise caused a significant increase in C-reactive protein [CRP; 1.79 (4.49) vs. 1.94 (4.89) mg/L, P < 0.001], monokine induced by interferon-γ [Mig; 351 (324) vs. 373 (330) pg/mL, P = 0.027] and vascular adhesion molecule-1 [VCAM-1; 226 (82) vs. 252 (110) pg/mL, P = 0.02]. After 4-months, in exercise-trained patients, there was a significant decrease in the inflammatory response provoked by the acute exercise compared to patients in the control group reflected by a significant decrease in the differences between rest and post-exercise levels of CRP [-0.29 (0.84) mg/L vs. -0.11 (0.21) mg/L, P = 0.05]. Resting BNP was also significantly lower in exercise-trained patients when compared to untrained controls [15.6 (16.2) vs. 9.7 (11.4) pg/mL, P = 0.04 and 19.2 (27.8) vs. 23.2 (27.5) pg/mL, P = 0.76; respectively].
Chronic exercise training might partially reverse the inflammatory response caused by acute exercise in CAD patients. These results suggest that regular exercise is an important nonpharmacological strategy to the improvement in inflammation in CAD patients.
Clinical Research in Cardiology 01/2011; 100(1):77-84. · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prostate adenocarcinoma is the most common cancer type in the male sex after skin cancer. Among the several types of treatment for prostate cancer, the androgen deprivation therapy has been highly recommended in patients with metastatic or locally advanced disease, which probably results in increased survival. However, the androgen deprivation is the cause of several adverse effects. Complications such as osteoporosis, sexual dysfunction, gynecomastia, anemia and body composition alterations are well-known effects of the therapy. Recently, a number of metabolic complications have been described, such as increase in the abdominal circumference, insulin resistance, hyperglycemia, diabetes, dyslipidemia and metabolic syndrome, with a consequent increase in the risk of coronary events and cardiovascular mortality in this specific population. This update article presents a literature review carried out at MEDLINE database of all literature published in English from 1966 to June 2009, using the following key words: androgen deprivation therapy, androgen suppression therapy, hormone treatment, prostate cancer, metabolic syndrome and cardiovascular disease, with the objective of analyzing which would be the actual cardiovascular risks of androgen deprivation therapy, also called androgen suppression, in patients with prostate cancer.
Arquivos brasileiros de cardiologia 09/2010; 95(3):412-5. · 1.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oral beta-blockers improve the prognosis of patients with acute myocardial infarction, while atrial fibrillation worsens the prognosis of this population. The reduction of atrial fibrillation incidence in patients treated with beta-blockers could at least in part explain the benefits of this drug.
To investigate the effect of beta-blockers on the incidence of atrial fibrillation in patients with acute myocardial infarction.
We analyzed 1401 patients with acute myocardial infarction and evaluated the occurrence or absence of atrial fibrillation, the use of oral beta-blockers and mortality during the first 24 hours.
a) The use of beta-blockers was inversely correlated with the presence of atrial fibrillation (rho = 0.004; OR = 0.54). b) Correlations with mortality were as follows: 31.5% in patients with atrial fibrillation, 9.2% in those without atrial fibrillation (rho < 0.001; Odds Ratio = 4.52), and 17.5% in patients not treated with beta-blockers and 6.7% in those who received the drug (rho < 0.001; OR = 0.34). c) Adjusted Models: The presence of atrial fibrillation was independently correlated with mortality (OR = 2.48, rho = 0.002). The use of beta-blockers was inversely and independently correlated with mortality (OR = 0.53; rho = 0.002). The patients who used beta-blockers showed a lower risk of atrial fibrillation (OR = 0.59; rho = 0.029) in the adjusted model.
The presence of atrial fibrillation and the absence of oral beta-blockers increased in-hospital mortality in patients with acute myocardial infarction. Oral beta-blockers reduced the incidence of atrial fibrillation, which might be at least partially responsible for the drug's benefit.
Clinics (São Paulo, Brazil) 03/2010; 65(3):265-70. · 1.59 Impact Factor