Mehmet Gungor Kaya

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.

Red cell distribution width as a novel prognostic marker in patients undergoing primary angioplasty for acute myocardial infarction.

ObjectivesRed cell distribution width (RDW), a measure of red blood cell size heterogeneity, was evaluated in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BackgroundHigher RDW is associated with mortality in patients with symptomatic cardiovascular disease, heart failure, and also in the general population. We hypothesized that admission RDW would be predictive of adverse outcomes in patients after primary PCI. MethodsTwo thousand five hundred and six consecutive STEMI patients (mean age 56.6±11.8 years; 2075 males, 431 females) undergoing primary PCI were retrospectively enrolled into this study. Admission RDW was measured as part of the automated complete blood count. Patients were grouped as elevated or nonelevated RDW using the upper limit of normal value of 14.8% and were followed for in-hospital and long-term outcomes for a mean period of 1.8±1.3 years (median 21 months). ResultsA higher in-hospital mortality rate was observed among patients with elevated admission RDW (mean 16.1±1.6%) compared with those with nonelevated RDW (mean 13.4±0.8%) (7.6 vs. 3.6%, P<0.001). The long-term cardiovascular prognosis was worse for patients with elevated admission RDW (Kaplan–Meier, log-rank P<0.001). We used Cox proportional hazard models to examine the association between RDW and adverse clinical outcomes. After discharge, there were 129 deaths during follow-up. A significant association was noted between elevated admission RDW level and the adjusted risk of cardiovascular mortality (hazard ratio: 1.831, 95% confidence interval: 1.034–3.24, P=0.03). In addition, elevated admission RDW was also an independent predictor of cardiovascular mortality in the nonanemic subpopulation of patients (hazard ratio: 2.703, 95% confidence interval: 1.208–6.048, P=0.016). ConclusionA high admission RDW level in patients with STEMI undergoing primary PCI was associated with increased risk for in-hospital and long-term cardiovascular mortality.

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.

Long-term safety, tolerability and efficacy of bosentan in adults with pulmonary arterial hypertension associated with congenital heart disease

Objective: To examine long-term safety and efficacy of bosentan—an oral dual endothelin receptor antagonist—in patients with pulmonary hypertension associated with congenital heart disease or Eisenmenger’s syndrome. Design: Retrospective study. Setting: Tertiary cardiology referral centre. Patients: All adult patients with pulmonary arterial hypertension associated with congenital heart disease treated with bosentan at the Royal Brompton Adult Congenital Heart Centre were included. Main outcome measures: Oxygen saturation, functional (WHO) class, 6-minute walk test distance and liver enzymes were analysed. Results: Eighteen patients (14 female) with pulmonary arterial hypertension associated with congenital heart disease (15 patients with Eisenmenger’s syndrome) with a mean (SD) age of 41 (9) years (range 23–69) were included. Median follow-up was 29 months (range 1–39). One patient died during follow-up. Patients tolerated bosentan well and no significant rise in liver transaminases was seen. Arterial oxygen saturation remained stable throughout follow-up. Mean (SD) functional class (p = 0.001) and the 6-minute walk test distance improved compared with baseline (284 (144) vs 363 (124) m, 380 (91) m and 408 (114) m at baseline, 0–6 months, 6–12 months and 1–2 years of treatment, respectively; p<0.05 for each). Conclusions: Bosentan appears to be safe and well tolerated in adults with pulmonary arterial hypertension associated with congenital heart disease or Eisenmenger’s syndrome during mid- to long-term follow-up. In addition, functional class and the 6-minute walk test distance improved and this effect was maintained for up to 2 years of bosentan treatment.

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.