Mahmut Akpek

Protective effects of nebivolol against anthracycline-induced cardiomyopathy: A randomized control study

BACKGROUND We aimed to evaluate the effect of prophylactic nebivolol use on prevention of antracycline-induced cardiotoxicity in breast cancer patients. METHODS In this small, prospective, double-blind study, we randomly assigned 45 consecutive patients with breast cancer and planned chemotheraphy to receive nebivolol 5mg daily (n=27) or placebo (n=18). Echocardiographic measurements and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels were obtained at baseline and at 6-month of chemotherapy. RESULTS Both studied groups had comparable echocardiographic variables and NT-pro-BNP levels at baseline. At 6-month, the left ventricular (LV) end-systolic and end-diastolic diameters increased in the placebo group (LVESD: 29.7 ± 3.4 to 33.4 ± 4.5mm; LVEDD: 47.2 ± 3.8 to 52.0 ± 4.6mm, p=0.01 for both) but remained unchanged in the nebivolol group (LVESD: 30.4 ± 3.5 to 31.0 ± 3.6mm, p=0.20; LVEDD: 47.0 ± 4.4 to 47.1 ± 4.0mm, p=0.93). The placebo group also had lower LVEF than the nebivolol group (57.5 ± 5.6% vs. 63.8 ± 3.9%, p=0.01) at 6-month. NT-pro-BNP level remained static in the nebivolol group (147 ± 57 to 152 ± 69 pmol/l, p=0.77) while it increased in the placebo group (144 ± 66 to 204 ± 73 pmol/l, p=0.01). CONCLUSIONS Prophylactic use of nebivolol treatment may protect the myocardium against antracycline-induced cardiotoxicity in breast cancer patients.

Relation of Neutrophil/Lymphocyte Ratio to Coronary Flow to In-Hospital Major Adverse Cardiac Events in Patients With ST-Elevated Myocardial Infarction Undergoing Primary Coronary Intervention

With the growing understanding of the role of inflammation in patients with atherosclerotic disease, studies have focused on high-sensitivity C-reactive protein (hs-CRP) and other inflammatory markers in their association with outcomes in ST-segment elevation myocardial infarction. The goal of this study was to investigate the association of the neutrophil/lymphocyte (N/L) ratio and in-hospital major adverse cardiac events (MACEs) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). The association of hs-CRP and N/L ratio on admission with Thrombolysis In Myocardial Infarction (TIMI) flow grade after PCI was assessed in 418 consecutive primary patients with PCI. The N/L ratio was significantly higher in the no-reflow group (TIMI grade 0/1/2 flow, n = 158) compared to that of the normal-flow group (TIMI grade 3 flow, n = 260, 4.6 ± 1.7 vs 3.1 ± 1.9, p <0.001). In-hospital MACEs were significantly higher in patients with no reflow (23% vs 7%, p <0.001). There was a significant and positive correlation between hs-CRP and N/L ratio (r = 0.657, p <0.001). In receiver operating characteristic analysis, N/L ratio >3.3 predicted no reflow with 74% sensitivity and 83% specificity. In a multivariate regression model, N/L ratio remained an independent correlate of no reflow (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.34 to 1.76, p <0.001) and in-hospital MACEs (OR 1.14, 95% CI 0.98 to 1.32, p = 0.043). The N/L ratio, an inexpensive and easily measurable laboratory variable, is independently associated with the development of no reflow and in-hospital MACEs in patients with ST-segment elevation myocardial infarction undergoing primary PCI.

Hematologic Parameters and Angiographic Progression of Coronary Atherosclerosis

Hematologic parameters have prognostic importance in cardiovascular disease. However, the relation between atherosclerosis progression and hematologic parameters is not well defined. A total of 394 patients requiring repeat coronary angiography were included in the study. According to angiography, patients were divided into 2 groups, progressive (n = 196) and nonprogressive (n = 198) diseases. Hematologic parameters including mean platelet volume (MPV) and neutrophil/lymphocyte (N/L) ratio were measured. Glucose, creatinine, and cholesterol were significantly higher in the progressive group. Mean platelet volume count was similar in both groups. The N/L ratio was significantly higher in the progressive group (5.0 ± 5.1 vs 3.2 ± 3; P = .001). In multivariate analysis, the N/L ratio was significantly related with progression (relative risk [RR]: 2.267, 95% CI: 1.068-4.815, P = .03). Progression rate was significantly high in patients with high N/L ratio (39% vs 56%). Our results suggest that the N/L ratio is a predictor of progression of atherosclerosis.

Prognostic value of neutrophil/lymphocyte ratio in patients with ST-elevated myocardial infarction undergoing primary coronary intervention: A prospective, multicenter study

OBJECTIVE The pre-procedural neutrophil to lymphocyte ratio (N/L) is associated with adverse outcomes among patients with coronary artery disease but its prognostic value in ST-segment elevation myocardial infarction (STEMI) has not been fully investigated. This study evaluated the relations between pre-procedural N/L ratio and the in-hospital and long-term outcomes in STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHODS A total of 682 STEMI patients presented within the first 6h of symptom onset were enrolled and stratified according to tertiles of N/L ratio based on the blood samples obtained in the emergency room upon admission. RESULTS The mean follow-up period was 43.3 months (1-131 months). In-hospital in-stent thrombosis, non-fatal myocardial infarction, and cardiovascular mortality increased as the N/L tertile ratio increased (p<0.001, p<0.001, p=0.003, respectively). Long-term in-stent thrombosis, non-fatal myocardial infarction and cardiovascular mortality also increased as the N/L ratio increased (p<0.001, p<0.001, p=0.002, respectively). On multivariate analysis, N/L ratio remained an independent predictor for both in-hospital (OR 1.189, 95% CI 1.000-1.339; p<0.001) and long-term major (OR 1.228, 95% CI 1.136-1.328; p<0.001) adverse cardiac events. CONCLUSION The N/L ratio was an independent predictor of both in-hospital and long-term adverse outcomes among STEMI patients undergoing primary PCI. Our findings suggest that this inexpensive, universally available hematological marker may be incorporated into the current established risk assessment model for STEMI.

Usefulness of the Neutrophil-to-Lymphocyte Ratio to Predict Bare-Metal Stent Restenosis

Inflammation plays a crucial role in the pathogenesis of in-stent restenosis (ISR). Neutrophil-to-lymphocyte ratio (NLR) provides a simple method for assessment of inflammatory status and prognosis in patients with coronary artery disease. The aim of the present study was to investigate the predictive value of preprocedural NLR on development of ISR in patients undergoing coronary stent implantation. We retrospectively analyzed clinical, hematologic, and angiographic data of 624 patients (mean age 60.5 ± 10.2 years, 71.8% men) who had undergone coronary stent implantation and a further control coronary angiography owing to stable or unstable angina pectoris. Patients were divided into 3 tertiles based on preprocedural NLR. Restenosis occurred in 21 patients (10.1%) in the lowest tertile, in 62 (29.8%) in the middle tertile, and in 107 (51.4%) in the highest NLR tertile (p <0.001). Serum C-reactive protein levels were also significantly higher in patients in tertile 3 than in those in tertiles 1 and 2 (p <0.001). Using multiple logistic regression analysis, smoking, diabetes mellitus, stent length, preprocedural NLR, and C-reactive protein levels emerged as independent predictors of ISR. In receiver operating characteristics curve analysis, NLR >2.73 had 80% sensitivity and 75% specificity in predicting ISR. In conclusion, high preprocedural NLR is a powerful and independent predictor of bare-metal stent restenosis in patients with stable and unstable angina pectoris.

The association of serum uric acid levels on coronary flow in patients with STEMI undergoing primary PCI

OBJECTIVE Uric acid has been shown as a predictor and an independent risk factor for coronary heart disease, but little is known regarding the association of uric acid levels with coronary blood flow in STEMI. We hypothesized that elevated uric acid levels would be associated with impaired flow and perfusion in the setting of STEMI treated with primary PCI. METHODS Two hundred and eighty nine patients with STEMI who treated primary PCI were enrolled to study. Patients were divided into two groups based upon the TIMI flow grade. No-reflow was defined as TIMI Grade 0, 1 and 2 flows (group 1). Angiographic success was defined as TIMI 3 flow (group 2). Uric acid, MPV and high sensitive CRP were measured. Major adverse cardiac events (MACE) were defined as in stent thrombosis, non-fatal myocardial infarction and in-hospital mortality. RESULTS There were 126 patients (mean age 63±11 and 71% male) in group 1 and 163 patients (mean age 58±12 and 80% male) in group 2. Uric acid, MPV, and hs-CRP levels on admission were higher in group 1 (p=0.0001 for each). A uric acid level ≥5.4 mg/dl measured on admission had a 77% sensitivity and 70% specificity in predicting no-reflow at ROC curve analysis. In-hospital MACE was significantly higher in group 1 (29% vs. 7%, p=0.0001). At multivariate analyses, high plasma uric acid (odds ratio (OR) 2.05, <95% confidence interval(CI) 1.49-2.81; p<0.0001), hs-CRP (OR 1.02, <95% CI 1.01-1.03; p=0.0007) and MPV (OR 3.09, <95% CI 1.95-4.89; p<0.0001) levels were independent predictors of no-reflow post primary PCI and uric acid (OR 2.75, <95% CI 1.93-3.94; p<0.0001), hs-CRP (OR 1.01, <95% CI 1-1.02; p=0.006) levels, but not MPV, were independent predictors of in-hospital MACE. CONCLUSION Plasma uric acid level on admission is a strong and independent predictor of poor coronary blood flow following primary PCI and in hospital MACE among patients with STEMI. Except for predictive value, uric acid levels may be a useful biomarker for stratification of risk in patients with STEMI and may also lead to carry further therapeutic implications.

Prognostic Value of Uric Acid in Patients With ST-Elevated Myocardial Infarction Undergoing Primary Coronary Intervention

Elevated uric acid (UA) levels have been associated with cardiovascular disease in epidemiologic studies. The relation between UA levels and long-term outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention is not known. Data from 2,249 consecutive patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention were evaluated. Patients were divided into 2 groups with high or low UA using upper limits of normal of 6 mg/dl for women and 7 mg/dl for men. There were 1,643 patients in the low-UA group (mean age 55.9 ± 11.6 years, 85% men) and 606 patients in the high-UA group (mean age 60.5 ± 12.6 years, 76% men). Serum UA levels were 8.0 ± 1.5 mg/dl in the high-UA group and 5.2 ± 1.0 mg/dl in the low-UA group (p <0.001). The in-hospital mortality rate was significantly higher in patients with high UA levels (9% vs 2%, p <0.001), as was the rate of adverse outcomes in patients with high UA. The mean follow-up time was 24.3 months. Cardiovascular mortality, reinfarction, target vessel revascularization, heart failure, and major adverse cardiac events were all significantly higher in the high-UA group. In a multivariate analyses, high plasma UA levels were an independent predictor of major adverse cardiac events in the hospital (odds ratio 2.03, 95% confidence interval 1.25 to 3.75, p = 0.006) and during long-term follow-up (odds ratio 1.64, 95% confidence interval 1.05 to 2.56, p = 0.03). In conclusion, high UA levels on admission are independently associated with in-hospital and long-term adverse outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention.

Protective effects of spironolactone against anthracycline-induced cardiomyopathy

The protective effect of beta‐blockers, ACE inhibitors, and ARBs on anthracycline cardiotoxicity has already been demonstrated, but the effect of aldosterone antagonism, which inhibits the last step of the renin–angiotensin–aldosterone system (RAAS), was questioned. This study sought to investigate whether spironolactone protects the heart against anthracycline‐induced cardiotoxicity.

Effect of long-term and high-dose allopurinol therapy on endothelial function in normotensive diabetic patients

Abstract Objectives. Endothelial dysfunction is a well known risk factor for atherosclerosis. Uric acid levels are associated with endothelial dysfunction and atherosclerosis even if in physiological range. Xanthine oxidase inhibition with allopurinol decreases uric acid levels and oxidative stress and improves endothelial function. We have investigated the effect of high-dose and long-term allopurinol therapy on endothelial function in diabetic normotensive patients. Methods. This study is a randomized, single-blind, placebo-controlled trial. Both treatment and placebo groups consisted of 50 patients. In the treatment group, daily oral 900 mg allopurinol was started after randomization and maintained for 12 weeks. Brachial artery flow-mediated dilatation (FMD) and nitrate-induced dilatation (NID) were measured at baseline and after the allopurinol therapy to evaluate endothelial function. Results. HbA1c and uric acid levels decreased after allopurinol therapy (6.1 ± 2.1 vs 5.5 ± 1.0%, 5.0 ± 0.8 vs 3.3 ± 0.5 mg/dl, respectively, p = 0.01) but no change was observed in the placebo group (7.7 ± 1.9% vs 7.6 ± 2.0%, 5.3±2.1 vs 5.6 ± 0.8 mg/dl, respectively, p > 0.05). FMD and NID increased significantly in the treatment group (5.6 ± 2.1% vs 8.5 ± 1.2%, 10 ± 7.4% vs 14 ± 4.0%, 10 ± 7.4% vs 14 ± 4.0%, respectively, p = 0.01), whereas no change was observed in the placebo group (5.8 ± 1.8% vs 6.1 ± 0.8%, 12 ± 9.5 vs 10 ± 3.8%, respectively, p > 0.05). Conclusion. Long-term and high-dose allopurinol therapy significantly improved endothelial function in diabetic normotensive patients. In addition, allopurinol therapy contributes to the lower HbA1c levels.

Relationship between mean platelet volume levels and subclinical target organ damage in newly diagnosed hypertensive patients

Abstract Background. Significant numbers of asymptomatic hypertensive patients are attacked by subclinical target organ damage (TOD) such as proteinuria, left ventricular hypertrophy and carotid atherosclerosis. Platelets become activated in uncontrolled hypertension and play a crucial role in increased thrombotic tendency. Mean platelet volume (MPV) is one of the markers that correlate closely with platelet activity. We aimed to investigate the relationship between MPV levels and subclinical TOD in newly diagnosed hypertensive patients. Methods. 80 newly diagnosed hypertensive patients were enrolled to this cross-sectional study. Ambulatory blood pressure monitoring was performed for all patients. Left ventricular mass index (LVMI), carotid intima-media thickness (IMT) and urine albumin/creatinine ratio (UACR) were measured as indices of cardiac, vascular and renal damage, respectively. MPV was measured from blood samples collected in EDTA tubes and high-sensitivity C reactive protein (hs-CRP) was measured by using nephlometer. Results. MPV was significantly correlated with 24-h systolic–diastolic blood pressure (r = 0.52 and r = 0.55, respectively). Correlation analysis indicated that MPV was moderately related with UACR, LVMI, carotid IMT and hs-CRP (r = 0.50, r = 0.55, r = 0.60 and r = 0.69, respectively, p = 0.0001). Multivariable analysis identified that MPV levels were independently associated with severity of proteinuria, carotid IMT and LVMI (p = 0.001). Conclusion. Our findings suggested that MPV levels were associated with severity of subclinical TOD including; carotid atherosclerosis, left ventricular hypertrophy and renal damage, in hypertensive patients. In addition to this, MPV levels were significantly correlated with hs-CRP levels and 24-h ambulatory blood pressure measurements.