Mikail Yarlioglues

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.

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.

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.

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.

Association of platelet-to-lymphocyte ratio with severity and complexity of coronary artery disease in patients with acute coronary syndromes.

The SYNTAX score (SXscore) is an anatomic scoring system based on coronary angiography (CA) that not only quantifies lesion severity and complexity but also predicts poor cardiovascular outcomes, including mortality, in patients with acute coronary syndromes (ACS). Recent studies have shown that platelet-to-lymphocyte ratio (PLR) is associated with worse outcomes in many cardiovascular diseases. The aim of this study was to investigate the association of PLR with the severity and complexity of coronary atherosclerosis as assessed by the SXscore in patients with ACS who underwent urgent CA. A total of 1,016 patients with ACS who underwent urgent CA were included in the study from August 2012 to March 2014. Admission PLR values were calculated before CA was performed. The SXscore was determined from baseline CA. The patients were divided into 2 groups, those with low SXscores (≤22) and those with intermediate to high SXscores (≥23). PLRs were significantly higher in patients with intermediate to high SXscores compared with those with low SXscores (p<0.001). In-hospital mortality was significantly higher in the groups with high PLR and intermediate to high SXscores. In multivariate analysis, the independent predictors of intermediate to high SXscore were PLR (odds ratio 1.018, 95% confidence interval 1.013 to 1.023, p<0.001) together with the left ventricular ejection fraction (odds ratio 0.935, 95% confidence interval 0.910 to 0.960, p<0.001), and age (odds ratio 1.029, 95% confidence interval 1.029 to 1.054, p=0.02). A PLR≥116 had 71% sensitivity and 66% specificity in predicting intermediate to high SXscore. In conclusion, the PLR at admission is significantly associated with the severity and complexity of coronary atherosclerosis in patients with ACS. Increased PLR is an independent predictor of higher SXscore in patients with ACS who undergo urgent CA.

Relation of Left Atrial Spontaneous Echocardiographic Contrast in Patients With Mitral Stenosis to Inflammatory Markers

Spontaneous echocardiographic contrast (SEC) is the presence of smoke-like echoes with a characteristic swirling motion of blood in echocardiography. Previous clinical studies have demonstrated that SEC is a risk factor for left atrial thrombus formation and an important indicator of potential systemic embolism originated from heart. An established relation exists between the inflammatory status and the prothrombotic state. Therefore, we investigated the role of inflammatory status on SEC in patients with mitral stenosis (MS). A total of 62 consecutive patients with MS who undergoing mitral balloon valvuloplasty were enrolled in the present study. The patients were divided into 2 groups according to the formation of SEC in the left atrium. Of the 62 patients, 32 (mean age 45 ± 12 years; 75% women) were in the SEC-negative group and 30 patients (mean age 45 ± 11 years; 63% women) were in the SEC-positive group. The high-sensitive C-reactive protein levels were significantly greater in the SEC-positive group than in the SEC-negative group (3.9 ± 2.2 vs 10.6 ± 6.3, p = 0.024). The neutrophil levels (64.6 ± 9.4 vs 72.6 ± 8.6) were significantly greater in the SEC-positive group, and the lymphocyte levels (24.4 ± 6.9 vs 18.3 ± 6.0) were significantly greater in the SEC-negative group (p = 0.001 for each). The neutrophil/lymphocyte (N/L) ratio was also significantly greater in the SEC-positive group (3.0 ± 1.8 vs 4.5 ± 1.8, p = 0.003). In the receiver operating characteristics curve analysis, a N/L ratio > 3.1 mg/dl had a 80% sensitivity and 72% specificity in predicting SEC in patients with MS. On multivariate analysis, high-sensitive C-reactive protein (odds ratio [OR] 1.235, 95% confidence interval [CI] 1.040 to 1.466; p = 0.016), N/L ratio (OR 1.461, 95% CI 0.977 to 2.184; p = 0.02), left atrial volume (OR 3.012, 95% CI 1.501 to 5.611; p = 0.001), and mitral valve area (OR 0.135, 95% CI 0.020 to 0.503; p = 0.017) were independent risk factors of SEC in patients with MS. In conclusion, the high-sensitive C-reactive protein and N/L ratio were independently associated with SEC in patients with MS.

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.