Ozgur Gunebakmaz

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.

Platelet activation and inflammatory response in patients with non-dipper hypertension

OBJECTIVE Non-dipper hypertensives had about three times the risk of atherosclerotic events than hypertensives whose blood pressure was >10% lower at night compared to daytime (dippers). Platelet activation and inflammatory response may derive from most atherosclerotic events. Mean platelet volume (MPV) is a determinant of platelet activation and high sensitive C-reactive protein (hs-CRP) is the best candidate assay to identify and monitor the inflammatory response. We aimed to determine whether MPV and hs-CRP levels are elevated in non-dipper patients compared to dippers and healthy controls. In addition, we tried to find out if MPV and CRP are related to each other or not in non-dipper hypertensives. METHOD The total 126 patients study group included 86 patients with hypertension and 40 healthy subjects (16 male, mean age; 51+/-4) as control. Ambulatory blood pressure monitoring was performed for all patients. Hypertensive patients were divided into two groups; 46 dipper patients (18 male, mean age; 50+/-9) and 40 non-dipper patients (17 male, mean age; 53+/-11). Clinical baseline characteristics were similar between groups. We measured mean platelet volume in a blood sample collected in EDTA tubes and high-sensitive CRP was measured by using BN2 model nephlometer. RESULTS Non-dipper patients demonstrated higher levels of MPV compared to dippers and normotensives (9.72+/-0.52 fl vs 9.38+/-0.33 fl and 8.92+/-0.42 fl, p<0.05, respectively). High-sensitive CRP levels were also significantly higher in non-dippers compared to dippers and normotensives (4.9+/-1.7mg/l vs 3.8+/-1.5mg/l and 2.7+/-0.8mg/l, p<0.05, respectively). There was significant positive correlation between MPV and CRP levels (p=0.002, r=0.482) in non-dipper hypertensives. CONCLUSION Our results suggest that patients with non-dipping tend to have increased platelet activation and inflammatory response. Increased platelet activation and inflammatory response could contribute to increase the atherosclerotic risk in non-dipper patients compared to dippers.

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.

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.

Intravenous N-acetylcysteine plus high-dose hydration versus high-dose hydration and standard hydration for the prevention of contrast-induced nephropathy: CASIS—A multicenter prospective controlled trial

BACKGROUND Contrast-induced nephropathy (CIN) is a leading cause of acute renal failure and affects mortality and morbidity. We investigated the efficacy of prophylactic intravenous (IV) N-acetylcysteine (NAC) and hydration for the prevention of CIN in patients with mild to moderate renal dysfunction who are undergoing coronary angiography and/or percutaneous coronary intervention (PCI). METHODS A total of 220 patients who had mild to moderate renal dysfunction with serum creatinine (SCr) ≥ 1.1mg/dL or creatinine clearance ≤ 60 mL/min were randomized in 3 groups: 80 patients were assigned to IV NAC plus high-dose hydration with normal saline, 80 patients to only high-dose hydration with normal saline and 60 patients to standard hydration with normal saline (control group). The primary end point was the alteration of SCr level. The secondary end point was the development of CIN after the procedure. RESULTS SCr levels changed the least in the NAC plus high-hydration group (P=0.004). The rate of the CIN in the NAC plus high-dose hydration group was also lower than the high-dose hydration group (P=0.006). No significant differences in the primary and secondary end points were found between high-dose hydration and control group. CONCLUSION The results of this study suggest that NAC plus high-dose hydration was superior to high-dose hydration alone as well as standard hydration for the protection of renal functions in patients with mild to moderate renal dysfunction who are undergoing coronary angiography and/or PCI. High-dose hydration without NAC was not better than standard hydration alone.

Relation Between Mean Platelet Volume and Severity of Atherosclerosis in Patients With Acute Coronary Syndromes

Platelets play a central role in the pathophysiology of coronary artery disease (CAD). Increased mean platelet volume (MPV) is an indicator of platelet function and associated with poor clinical outcome in patients with acute coronary syndrome (ACS). We evaluated the relationship between MPV and severity of CAD in patients with ACS. A total of 395 patients with ACS were included. Severity of CAD was assessed with the Gensini and Syntax scores. High levels of MPV were associated with the Gensini and Syntax scores, number of diseased vessels (>50%), number of critical lesions (>50% and >70%), and noncritical lesions. After multivariate analysis, high levels of MPV were independent predictors of multivessel CAD together with age. In patients with ACS, high MPV levels were associated with severity of CAD. It is possible that MPV can be a helpful marker in patients with CAD for the severity of coronary atherosclerosis.

Predictive Value of Admission Platelet Volume Indices for In-hospital Major Adverse Cardiovascular Events in Acute ST-Segment Elevation Myocardial Infarction

Although mean platelet volume (MPV) is an independent correlate of impaired angiographic reperfusion and 6-month mortality in ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), there is less data regarding the association between platelet distribution width (PDW) and in-hospital major adverse cardiovascular events (MACEs). A total of 306 patients with STEMI pPCI were evaluated. No reflow was defined as a post-PCI thrombolysis in myocardial infarction (TIMI) flow grade of 0, 1, or 2 (group 1). Angiographic success was defined as TIMI flow grade 3 (group 2). The values of MPV and PDW were higher among patients with no reflow. In-stent thrombosis, nonfatal myocardial infarction, in-hospital mortality, and MACEs were significantly more frequent among patients with no reflow. In multivariate analysis, PDW, MPV, high-sensitivity C-reactive protein, and glucose on admission were independent correlates of in-hospital MACEs. Admission PDW and MPV are independent correlates of no reflow and in-hospital MACEs among patients with STEMI undergoing pPCI.

The mean platelet volume in patients with non-dipper hypertension compared to dippers and normotensives

Abstract Objectives. Increased platelet activation plays an important role in the development of atherosclerosis. Mean platelet volume (MPV) is a determinant of platelet activation. In our study, we aimed to determine whether MPV levels are elevated in non-dipper patients compared with dippers and healthy controls. In addition, we tried to find out if MPV levels are correlated with blood pressure measurements in hypertensive patients. Methods. This cross-sectional study included 56 hypertensive patients; 27 age- and sex-matched healthy volunteers were enrolled to study as a control subjects. Ambulatory blood pressure monitoring was performed for all patients. Hypertensive patients were divided into two groups: 28 dipper patients (10 male, mean age 51 ±8 years) and 28 non-dipper patients (11 male, mean age 53±10 years). MPV was measured in a blood sample collected in EDTA tubes and was also used for whole blood counts in all patients. Results. In non-dipper patients, 24-h systolic blood pressure (141.5±10.21 vs 132.3±7.7 mmHg, p<0.001), 24-h diastolic blood pressure (88.2±8.5 vs 81.0±8.2 mmHg, p<0.01) and 24-h average blood pressure (105.7±8.5 vs 97.7±7.4 mmHg, p<0.001) are significantly higher than dippers. Whereas daytime measurements were similar between dippers and non-dippers, there was a significant difference between each group during night-time measurements (night-time systolic 137.1 ±11.0 vs 120.2±8.0 mmHg, p<0.001; night-time diastolic 85.3±8.0 vs 72.8±7.9 mmHg, p<0.001). Non-dipper patients (9.61 ±0.42 fl) demonstrated higher levels of MPV compared with dippers (9.24±0.35 fl) and normotensives (8.87±0.33 fl) (p<0.001 and p<0.001, respectively). There was significant correlation between MPV and ambulatory diastolic and systolic blood pressure in non-dipper hypertensives. Conclusion. Our results suggest that MPV, a determinant of platelet activation, has a positively correlation with blood pressure and elevated in non-dipper compared with dippers and controls. Increased platelet activation could contribute to increase the atherosclerotic risk in non-dipper patients compared with dippers.

Does Nebivolol Prevent Contrast-Induced Nephropathy in Humans?

An experimental study showed that nebivolol is an effective agent in contrast‐induced nephropathy (CIN) prophylaxis.

Mean platelet volume predicts embolic complications and prognosis in infective endocarditis

OBJECTIVES This study was designed to examine the change in mean platelet volume (MPV) over the course of infective endocarditis (IE) and also the association between MPV and complications including embolic events in IE. METHODS Forty patients (26 male, mean age 46±15 years) who were hospitalized with a diagnosis of IE at the Department of Cardiology, Erciyes University, from March 2005 to August 2008, were retrospectively evaluated. The diagnosis of IE was made clinically and was confirmed with Dukes criteria. The erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), and MPV were measured before treatment and periodically during the follow-up period, until discharge. RESULTS There were 27 cases of native valve endocarditis and 13 of prosthetic valve endocarditis. While 31 patients were treated medically, an operation was performed in nine patients because of unsuccessful medical therapy. On admission, mean MPV was 10.8±1.1 fl, ESR was 82±26mm/h, and hs-CRP was 110±72mg/l. Seven patients died: one intraoperatively, three patients postoperatively, and three patients during medical treatment. With the exception of these seven patients, ESR and hs-CRP were significantly reduced in all patients at discharge compared to levels at hospitalization (ESR 82±26 to 32±22, p=0.001 and hs-CRP 110±72 to 25±15, p=0.001). Similarly, we detected a significant decrease in MPV from hospitalization to discharge, i.e., from the active period of the disease to recovery (10.8±1.1 to 9.7±0.8 fl, p=0.002). In addition, MPV was found to be significantly higher in patients with observed embolic complications (11.5 vs. 10.3 fl, p=0.001), other complications (11.0 vs. 10.2 fl, p=0.001), and death (11.1 vs. 10.4 fl, p=0.005). CONCLUSION MPV can be used as an activity criterion in IE, like ESR and hs-CRP. Also, high MPV is associated with a poor prognosis and adverse outcomes, and predicts complications including embolic events.