Bulent Boyaci

Serum uric acid levels as a predictor of in-hospital death in patients hospitalized for decompensated heart failure

Objectives — The aim of this study was to determine the value of serum uric acid levels in predicting in-hospital mortality of chronic heart failure patients hospitalized for decompensation in spite of appropriate medical therapy. Methods and results — This study was conducted in patients who were admitted to our clinic between January 2003 and April 2004 due to decompensated heart failure. Only patients who had a functional capacity of class IV and who already received loop diuretic and ACE inhibitor therapy before their admission were included. Patients with recurrent admissions during this period were excluded. Eighty-five patients fulfilled these criteria: group I consisted of 25 patients who died during hospitalization whereas group II consisted of 60 patients who were discharged alive after treatment. Age, sex, left ventricular ejection fraction derived from 2-D echocardiography, serum sodium (Na), gamma-glutamyl transpeptidase (GGT), creatinine, uric acid levels, white blood cell counts and drugs used on admission were the selected parameters as predictors of in-hospital mortality in these patients.When stepwise logistic regression analysis was used, female sex and serum uric acid levels at admission appear to be the only predictors of death during that hospitalization independent of other variables. Conclusions — Serum uric acid levels may be used as a predictor of death in hospitalized heart failure patients with class IV symptoms.

Independent relationship of serum uric acid levels with leukocytes and coronary atherosclerotic burden.

BACKGROUND AND AIM Epidemiological studies have shown that increased serum uric acid (SUA) level is associated with coronary artery disease (CAD). Leukocytes have been shown to play an important role in the atherosclerotic process. The aim of the study was to investigate whether there is any relationship among SUA, leukocyte counts and coronary atherosclerotic burden in patients who are suspected of having CAD. METHOD AND RESULTS We enrolled 690 eligible patients who had undergone coronary angiography between October 2005 and June 2006 in a consecutive manner. The relationship of SUA with total and differential leukocyte counts and CAD was investigated. Serum uric acid levels (5.57+/-1.64 vs 4.63+/-1.27 mg/dl, p<0.001) and leukocytes were higher in patients with CAD than those with normal coronary arteries (NCA). When we divided the patients into four groups according to the quartiles of SUA, we found that the monocyte count was prominently related with SUA (478+/-165, 553+/-177, 565+/-199 and 607+/-229 mm(-)(3), Q1-Q4, p<0.001). In multivariate analysis, SUA was an independent predictor of CAD (OR, 1.270; 95% CI, 1.087-1.484, p=0.003). When we performed multiple linear regression analyses to determine the independent predictors of inflammatory cells in blood, we found a strong, positive and independent relationship between SUA with neutrophils (beta+/-SE: 206+/-60, p=0.001) and monocytes (beta+/-SE: 35+/-7, p<0.001). CONCLUSION Our study results demonstrated that neutrophils and monocytes which play an important role in inflammation and atherosclerosis were independently related with SUA. This finding suggests an important epidemiologic relation and may provide a possible causative mechanism of SUA in atherosclerotic process.

Association of Fragmented QRS Complex with Myocardial Reperfusion in Acute ST‐Elevated Myocardial Infarction

In this study, we aimed to evaluate the relationship between TIMI myocardial perfusion (TMP) grade, as an indicator of myocardial reperfusion, and fragmented QRS (fQRS) in standard 12‐lead electrocardiogram. Also, we evaluate fQRS is an additional indicator of myocardial reperfusion. One hundred patients admitted with first STEMI to Coronary Intensive Care Unit and who were used thrombolytic therapy was included in this retrospective study. Standard 12‐lead electrocardiogram records of patients simultaneous with coronary angiography (second day) were assessed and analysed for the presence of fQRS. Also, coronary angiography images were analyzed to identify the infarct related artery, TIMI grade of infarct related artery and TMP grade of infarct related artery. The patients with fQRS demonstrated a significantly lower TMP grade, TIMI grade and ejection fraction compared with the non‐fQRS patients (P = 0.004, P = 0.003, P = 0.02 respectively). The patients with inadequate myocardial reperfusion demonstrated a significantly higher fQRS compared with the adequate myocardial reperfusion patients. (56.9% versus 23.5%, P = 0.002 respectively). On correlation analysis, there was a significant negative correlation between fQRS and left ventricular ejection fraction (r = −232, P = 0.02) TMP grade and adequate myocardial reperfusion (TMP 3) showed significant negative correlation with fQRS (r = −0.370, P = 0.000; r = −0.318, P = 0.001 respectively). Presence of fragmented QRS in STEMI patients was associated with inadequate myocardial reperfusion and it can be used as a simple, noninvasive parameter to evaluate myocardial reperfusion.

Effects of left ventricular systolic dysfunction on left atrial appendage and left atrial functions in patients with chronic nonvalvular atrial fibrillation.

Objective — It has been claimed that left ventricular (LV) systolic dysfunction impairs left atrial (LA) and left atrial appendage (LAA) functions. In this study, we compared the LA and LAA function parameters in patients with chronic nonvalvular atrial fibrillation (AF) with and without LV systolic dysfunction. Methods and results — The study population consisted of 28 patients with chronic nonvalvular AF. Group I consisted of 12 patients with LV systolic dysfunction (mean age: 61 ± 14 years; LV ejection fraction: 44 ± 6%), group II of 16 patients with normal LV systolic function (mean age: 52 ± 15 years; LV ejection fraction: 65 ± 3%). LV ejection fraction (EF) was measured by echocardiography utilizing bi-plane area length method.The following LA and LAA transoesophageal echocardiography parameters were obtained: 1) LA diameter, 2) LAA ejection velocity, 3) LAA filling velocity, 4) LAA ejection fraction, 5) pulmonary venous (PV) systolic velocity, 6) PV diastolic velocity, 7) PV systolic velocity/diastolic velocity ratio.The left atrium diameter was significantly larger in group I than in group II (4.7 ± 0.7 cm vs. 3.8 ± 0.6 cm, p < 0.05). The LAA ejection velocity and LAA ejection fraction were significantly lower in group I than in group II (22.6 ± 15.5 cm/s vs 37.5 ± 11.3 cm/s and 26.9 ± 20.8% vs. 41.3 ± 10.9%, p < 0.05 for both comparisons). The PV systolic velocity and PV systolic velocity/diastolic velocity ratio were significantly smaller in group I than in group II (26.2 ± 14.8 cm/s vs. 51.5 ± 22 cm/s and 0.7 ± 0.6 vs. 1.2 ± 0.5, p < 0.05 for both comparisons). Although decreased LAA filling and PV diastolic velocities were determined in group I, no significant difference existed between groups I and II.Thrombus and/or spontaneous echo contrast (SEC) in the LA and/or LAA were more frequent in group I (75% vs. 18%, p < 0.05). Conclusion — These results indicate that LV systolic dysfunction impairs various LA and LA function parameters and is associated with an increased frequency of SEC and/or LA thrombus in patients with chronic nonvalvular AF.

Plasma osteopontin levels in prediction of prognosis in acute myocardial infarction.

Objective We sought to explain the clinical importance of the osteopontin (OPN) in the setting of acute ST-elevation myocardial infarction (STEMI). Methods Eighty consecutive patients (55 ± 11 years, 12 women and 68 men) and sixty healthy control subjects were included in the study. In all patients, plasma OPN levels were assessed on admission and on the third day (peak value). Creatinine kinase (CK)/CK-myocardial band (MB), troponin I and N-terminal pro-brain natriuretic factor levels and echocardiographic fi ndings were also recorded. Patients were classifi ed into high and low OPN groups according to the median OPN value, and monitored for the occurrence of major adverse cardiovascular events (MACE). Results Patients with STEMI had higher OPN levels (23.8 [16.7-41.3] ng/ml) on admission than the control subjects (18.0 [11.3-31.5] ng/ml, P= 0.004). The third day value of OPN was signifi cantly higher (39.2 [27.2-56.0] ng/ml) than the OPN level on admission (23.8 [16.7-41.3] ng/ml, P < 0.001). Admission and peak OPN levels were not correlated with CK/CK-MB, white blood cell counts, troponin I and the N-terminal pro-brain natriuretic factor. The plasma OPN levels were not correlated with left ventricular wall motion score index either. In the subgroups of infarct localization and reperfusion strategy, plasma OPN levels were similar. When the patients were compared according to the median OPN values, there were no diff erences in the occurrence of MACE between the high and low OPN groups. Conclusion This study suggests, for the fi rst time, that the plasma OPN level increases in the fi rst hours of the acute STEMI; however, it could not be used as a prognostic biomarker of STEMI.

The particular interactions of the traditional cardiovascular risk factors with different circulating specific leukocyte subtype counts in blood: an observational study.

OBJECTIVE The pathogenesis of atherosclerosis is multifactorial, however the impact of inflammatory cells in this process is well known. Different traditional cardiovascular risk factors (CVRFs) may have specifically different effects on leukocyte subtype. Thus, these special interactions may induce different vascular involvement forms due to the altered endothelial damage and vascular repair mechanisms. The aim of the present study was to investigate whether there is any specific relationship between the leukocyte subtypes and the traditional CVRFs and to evaluate the independency of possible relationships. METHODS The study had a cross-sectional observational design. The study population consisted of the patients who underwent coronary angiography with a suspicion of coronary artery disease (CAD) at our institution in an outpatient manner. We enrolled 677 consecutive eligible patients with CAD or normal coronary arteries (NCA) and investigated the associations of traditional CVRFs, demographic properties and biochemical parameters including fasting plasma glucose (FPG), creatinine, serum uric acid level (SUA) and lipids with total circulating inflammatory cell (WBC, leukocytes) and subtype counts including neutrophils (N), lymphocytes (L) and monocytes (M). As a dependent variable, total leukocyte count and subtypes, and neutrophil/lymphocyte ratio (N/L ratio) which has been found to being related with increased vascular risk and events were investigated in the groups determined by the presence or absence of CVRFs and CAD by the univariate analyses and then multiple linear regression analyses. RESULTS When we performed multiple linear regression analyses to determine the independent associations of inflammatory cell subtypes, we have found that FPG had an independent incremental association with WBC (β±SE:4.2±1.4, p=0.004) and N (β±SE:4.2±1.2, p=0.001). Current smoking had an independent incremental association with WBC and all cell subtypes (for WBC, N, L, and M: β±SE: 748±161, p<0.001; β±SE: 556±136, p<0.001; β±SE: 185±69, p=0.007; β±SE: 38±20, p=0.061, respectively) and SUA had an independent incremental association with WBC (β±SE: 115±43, p=0.008), N (β±SE: 107±38, p=0.005) and M (β±SE: 26±6, p<0.001). Hypertension had an independent incremental association with WBC (β±SE: 431±140, p=0.002) and N (β±SE: 315±118, p=0.008). Male gender had an independent incremental association with only M (β±SE: 52±20, p=0.010). Family history of CAD had an independent decremental association with WBC (β±SE: -327±139, p=0.019) and N (β±SE: -326±121, p=0.007). Finally, age had an independent decremental association with WBC (β±SE: -32±7, p<0.001) and L (β±SE: -16±3, p<0.001). The N/L ratio was independently related with increased age (p<0.001), FPG (p=0.003) and SUA (p=0.012). CONCLUSION Our study results demonstrate that leukocyte subtypes have different specific associations with traditional CVRFs. We found that FPG affects specifically N while SUA affects specifically N and M, and current smoking affects nonspecifically on all cell subtypes. While hypertension with N and male gender with M were specifically related, age and family history of CAD were only related to L. These different interactions may lead to different endothelial damage and vascular repair mechanisms.

The Relationship of Serum Erythropoietin Level With Coronary Collateral Grade

BACKGROUND Erythropoietin has been shown to induce neovascularization and protect against ischemic vascular injury. We investigated whether a higher serum erythropoietin (EPO) level is related to better coronary collateral vessel grade. METHODS Ninety-nine patients with stable angina pectoris who have at least 1 coronary stenosis of equal to or greater than 70% at coronary angiography were prospectively enrolled. Serum EPO and vascular endothelial growth factor (VEGF) levels were studied. Coronary collateral degree was graded according to the Rentrop method. Patients with grade 2-3 collateral degree were included in the good collateral group and formed Group I. The patients with grade 0-1 collateral degree were included in the poor collateral group and formed Group II. RESULTS The serum EPO level was significantly higher in the good collateral group (17.3 ± 9.3 mU/mL vs 11.7 ± 5.0 mU/mL; P < 0.001). There was also a positive correlation between serum EPO level and Rentrop score (r = 0.39; P < 0.001). In multivariate analysis, serum EPO level (odds ratio [OR] 1.336; 95% confidence interval [CI], 1.120-1.593; P = 0.001), oxygen saturation (OR 0.638; 95% CI, 0.422-0.963; P = 0.033) and presence of chronic total occlusion (CTO) (OR 26.7; 95% CI, 3.874-184.6; P = 0.001) were independently related to well-developed coronary collaterals. CONCLUSIONS Higher serum EPO level is related to better coronary collateral development. Erythropoietin may have a positive effect on the development of collaterals and may provide a new agent for the treatment strategies to enhance coronary collateral vessel development.

Medium-term follow-up of intermediate coronary stenoses left unrevascularized based on myocardial fractional flow reserve findings.

Objective — Coronary stenoses of intermediate severity create difficulties in decision making when revascularization is concerned. Myocardial fractional flow reserve (mFFR), an accurate tool to identify physiological significance of individual coronary stenoses, may help solve this problem. Methods and results — Fifty-eight intermediate (30-70%) coronary stenoses in 51 patients (mean age 54.4 ± 8.9 years, 9 women) were left unrevascularized because of normal (≥ 0.75) mFFR findings and the patients were prospectively followed with regard to the occurrence of death, myocardial infarction and target vessel revascularization.The mean reference vessel diameter, percent stenosis and mFFR of the intermediate lesions were 3.3 ± 0.3 mm, 46.8 ± 9.2% and 0.86 ± 0.05, respectively. Of the 58 intermediate lesions, 20 (34%) were associated with perfusion defects on thallium scan. Significant (> 70%) disease in addition to the one with the intermediate stenosis was present in 1 coronary artery in 24 (47%), and 2 coronary arteries in 6 (12%) patients and angioplasty of at least one significant stenosis was performed at the initial evaluation in 18 (35%) patients. Follow-up for a mean of 16.6 ± 6.6 months disclosed no death or myocardial infarction.Target vessel revascularization was performed in 3 (6%) patients at a mean of 4 ± 2.6 months. A control angiogram, which was performed in 12 of 18 patients who had undergone angioplasty at the initial evaluation revealed restenosis in 3 (25%) patients with no significant angiographic changes in the target intermediate stenoses. Anginal status was found to be significantly improved at follow-up. Conclusions — In this study, we found that intermediate coronary stenoses with an mFFR ≥ 0.75 have a favourable medium-term clinical outcome with respect to major cardiac adverse events when left unrevascularized based on mFFR findings.

Incremental effects of serum uric acid levels, autonomic dysfunction, and low-grade inflammation on nocturnal blood pressure in untreated hypertensive patients and normotensive individuals.

OBJECTIVES We aimed to evaluate the associations between nocturnal blood pressure (BP) and serum uric acid (SUA) level, low-grade inflammation, and cardiac autonomic function in untreated dipper and nondipper hypertensive patients and normotensive individuals. STUDY DESIGN The study included 92 consecutive patients (44 men, 48 women; mean age 51.6 ± 9.7 years) who presented for initial evaluation of hypertension. All patients underwent 24-hour Holter monitoring to assess heart rate variability (HRV) and ambulatory BP. Serum high-sensitivity C-reactive protein (hs-CRP) and SUA levels were measured. Due to the non-normal distribution of hs-CRP and microalbuminuria (MAU), they were normalized by logarithmic transformation. RESULTS Of the study group, 60 patients (65.2%) were diagnosed as hypertensive (50% nondippers). In univariate correlation analysis, log(MAU) showed a significant correlation with nocturnal BP (r=0.560, p<0.001). Among HRV parameters, SDNN, SDANN, and triangular index were inversely correlated with log(hs-CRP) (r=-0.356, p=0.001; r=-0.350, p=0.001; r=-0.314, p=0.002, respectively) and nighttime BP (r=-0.286, p=0.006; r=-0.251, p=0.02; r=-0.294, p=0.004, respectively). Log(hs-CRP) was positively correlated with nighttime BP (r=0.302, p=0.003). Serum UA levels were correlated with only nocturnal BP; i.e., nocturnal mean (r=0.260, p=0.01), systolic (r=0.249, p=0.016), and diastolic BP (r=0.249, p=0.017). In multiple linear regression analysis, log(hs-CRP) and age were independent predictors of cardiac autonomic dysfunction, and log(hs-CRP), SUA, and HRV parameters were independent predictors of nocturnal BP measurements. CONCLUSION Our findings suggest the role of low-grade inflammation, uric acid levels, and autonomic dysfunction even in the early stages of hypertension.

Atrial Fibrillation Induced by Gemcitabine Treatment in a 65-Year-Old Man

Gemcitabine, a pyrimidine analogue, is a cell cycle-specific antineoplastic agent that is structurally related to cytarabine. Major side effects of the treatment with gemcitabine are hepatic dysfunction, myelosuppression, renal impairment and pulmonary toxicity. Development of atrial fibrillation (AF) during gemcitabine treatment is very rare and was reported in only 2 case reports in the literature. Case Report: We report the case of a 65-year-old man who developed AF under gemcitabine therapy for non-small cell lung cancer (stage IIIB). In this patient, AF was intrinsically associated with chemotherapy administration which triggered arrhythmia. Conclusion: Although AF caused by gemcitabine appears to be rare, patients at risk of developing atrial fibrillation should be closely monitored for this complication.