Huseyin Bozbas

Epicardial adipose tissue thickness by echocardiography is a marker for the presence and severity of coronary artery disease

BACKGROUND AND AIM Epicardial adipose tissue (EAT), which is thought to be a component of visceral adiposity, is associated with the metabolic syndrome. We aimed to test the hypothesis that echocardiographic EAT thickness can be a marker for the presence and severity of coronary artery disease (CAD). METHOD AND RESULTS In all, 150 patients (100 patients with CAD and 50 patients with normal coronary arteries by diagnostic coronary angiography; 65 women, 85 men; mean age 55.7+/-7.4 years) were enrolled. EAT thickness was measured using 2-D echocardiographic parasternal long- and short-axis views. EAT thickness measurements were compared with angiographic findings. EAT thickness was significantly higher in patients with CAD in comparison to those with normal coronary arteries (6.9+/-1.5 mm vs. 4.4+/-0.8 mm; P<0.001). Furthermore, EAT thickness increased with the severity of CAD (multivessel disease 7.4+/-1.2 mm vs. single vessel disease 5.7+/-1.7 mm; P<0.001). Gensinis score significantly correlated with EAT thickness (r=0.600, P<0.001). EAT thickness of > or = 5.2 mm had 85% sensitivity and 81% specificity (ROC area 0.914, P<0.001, 95% CI [0.86-0.96]) for predicting CAD. CONCLUSION EAT thickness, which is easily and non-invasively evaluated by transthoracic echocardiography, can be an adjunctive marker to classical risk factors for the prediction of CAD.

Clinical Benefit of Statin Pretreatment in Patients Undergoing Percutaneous Coronary Intervention A Collaborative Patient-Level Meta-Analysis of 13 Randomized Studies

Background— Previous studies suggested that statin pretreatment reduces cardiac events in patients undergoing percutaneous coronary intervention. However, most data were observational, and single randomized trials included limited numbers of patients. Methods and Results— We performed a collaborative meta-analysis using individual patient data from 13 randomized studies in which 3341 patients received either high-dose statin (n=1692) or no statin/low-dose statin (n=1649) before percutaneous coronary intervention, with all patients receiving statin therapy after intervention. Occurrence of periprocedural myocardial infarction, defined as postintervention creatine kinase–MB increase ≥3 times the upper limit of normal, and 30-day major adverse cardiac events (death, myocardial infarction, target-vessel revascularization) was evaluated. Incidence of periprocedural myocardial infarction was 7.0% in the high-dose statin versus 11.9% in the control group, which corresponds to a 44% risk reduction in the active-treatment arm (odds ratio by fixed-effects model 0.56, 95% confidence interval, 0.44 to 0.71, P <0.00001). The rate of major adverse cardiac events at 30 days was significantly lower in the high-dose statin group (7.4% versus 12.6%, a 44% risk reduction; P <0.00001), and 1-month major adverse cardiac events, excluding periprocedural events, were also reduced (0.6% versus 1.4%; P =0.05). The benefit of high-dose statins was realized irrespective of clinical presentation ( P for interaction=0.43) and was maintained across various subgroups but appeared greater in the subgroup with elevated baseline C-reactive protein levels (n=734; 68% risk reduction for periprocedural myocardial infarction versus 31% in those 1861 patients with normal CRP; P for quantitative interaction=0.025). Conclusions— High-dose statin pretreatment leads to a significant reduction in periprocedural myocardial infarction and 30-day adverse events in patients undergoing percutaneous coronary intervention. This strategy should be considered in all patients with planned percutaneous coronary intervention. # Clinical Perspective {#article-title-50}Background— Previous studies suggested that statin pretreatment reduces cardiac events in patients undergoing percutaneous coronary intervention. However, most data were observational, and single randomized trials included limited numbers of patients. Methods and Results— We performed a collaborative meta-analysis using individual patient data from 13 randomized studies in which 3341 patients received either high-dose statin (n=1692) or no statin/low-dose statin (n=1649) before percutaneous coronary intervention, with all patients receiving statin therapy after intervention. Occurrence of periprocedural myocardial infarction, defined as postintervention creatine kinase–MB increase ≥3 times the upper limit of normal, and 30-day major adverse cardiac events (death, myocardial infarction, target-vessel revascularization) was evaluated. Incidence of periprocedural myocardial infarction was 7.0% in the high-dose statin versus 11.9% in the control group, which corresponds to a 44% risk reduction in the active-treatment arm (odds ratio by fixed-effects model 0.56, 95% confidence interval, 0.44 to 0.71, P<0.00001). The rate of major adverse cardiac events at 30 days was significantly lower in the high-dose statin group (7.4% versus 12.6%, a 44% risk reduction; P<0.00001), and 1-month major adverse cardiac events, excluding periprocedural events, were also reduced (0.6% versus 1.4%; P=0.05). The benefit of high-dose statins was realized irrespective of clinical presentation (P for interaction=0.43) and was maintained across various subgroups but appeared greater in the subgroup with elevated baseline C-reactive protein levels (n=734; 68% risk reduction for periprocedural myocardial infarction versus 31% in those 1861 patients with normal CRP; P for quantitative interaction=0.025). Conclusions— High-dose statin pretreatment leads to a significant reduction in periprocedural myocardial infarction and 30-day adverse events in patients undergoing percutaneous coronary intervention. This strategy should be considered in all patients with planned percutaneous coronary intervention.

Relation between epicardial fat thickness and coronary flow reserve in women with chest pain and angiographically normal coronary arteries

OBJECTIVE A significant proportion of women with angina-like chest pain and angiographically normal coronary arteries have microvascular dysfunction as detected by reduced coronary blood flow reserve (CFR). Classical clinical risk factors of atherosclerosis poorly predict this scenario. We sought to assess whether increased epicardial fat tissue, which is a metabolically active organ, could be associated with impaired CFR in these patients. METHODS We enrolled 68 women who underwent coronary angiography and had no obstructive coronary artery disease. Data about classical risk factors, insulin resistance and serum levels of C-reactive protein (CRP) and adiponectin were obtained. Stress tests were evaluated. Coronary flow velocities at baseline and under-induced hyperemia and epicardial fat thickness (EFT) were measured by transthoracic echocardiography within 48 h of angiography. CFR >or=2.0 was considered normal. RESULTS Forty percent of women had reduced CFR suggestive of microvascular dysfunction and 60% had normal CFR. Menopause, hypertension and abnormal stress tests were significantly more prevalent, adiponectin level was significantly decreased, CRP, insulin resistance, and EFT were significantly increased in women with microvascular dysfunction as compared with those without. On multivariate regression analysis EFT emerged as the only independent predictor of microvascular dysfunction (P<0.0001). EFT of >0.45 cm had 85% sensitivity and 75% specificity to detect CFR <2 (P<0.0001). Traditional risk factors for atherosclerosis did not predict women with abnormal microvascular function. CONCLUSIONS EFT has the potential to be an additional and easy diagnostic tool for risk stratification of women with chest pain and angiographically normal coronary arteries.

Pulmonary Hypertension in Patients With End-Stage Renal Disease Undergoing Renal Transplantation

INTRODUCTION Pulmonary hypertension (PHT) has been reported to occur in a considerable proportion of patients with end-stage renal disease (ESRD). It is a progressive condition of the pulmonary circulation that poses prognostic importance. In this study, we sought to investigate the prevalence and the predictors of PHT among ESRD patients undergoing renal transplantation. PATIENTS AND METHODS We retrospectively evaluated the records, clinical and demographic data as well as laboratory results of 500 adult patients who underwent renal transplantation at our institution. A comprehensive Doppler echocardiographic examination was performed in all patients as part of the preoperative assessment. Systolic pulmonary artery pressure (SPAP) was calculated using Bernoulli equation; a value of >30 mm Hg was accepted as PHT. RESULTS The mean age of the study population was 31.6 +/- 10.2 years. The mean duration of dialysis was 40 months; 432 patients (86.4%) were on hemodialysis (HD) and 68 (13.6%) on peritoneal dialysis (PD). PHT was detected in 85 (17%) patients with a mean SPAP of 46.7 +/- 8.7 mm Hg (range = 35-75 mm Hg). The mean age, sex, and laboratory variables were similar between patients with versus without PHT (P > .05 for all). The mean duration of dialysis therapy was longer in the PHT group than those subjects with normal SPAP (50.8 vs 38.5 months; P = .008). Concerning the type of dialysis, the ratio of patients having PHT was higher in the HD compared with the PD group (18.8% vs 5.9%; P = .008). The prevalence of chronic obstructive pulmonary artery disease, asthma, smoking, hypertension, and diabetes mellitus did not differ between patients with versus without PHT (P > .05 for all). CONCLUSION The findings of this study revealed that PHT was a common clinical condition among patients with ESRD evaluated for renal transplantation. The time on renal replacement therapy particularly HD as the treatment was associated with greater prevalences. Since it may be of prognostic importance in patients undergoing renal transplantation, a careful preoperative assessment including a comprehensive Doppler echocardiographic examination is needed to identify PHT.

Impaired coronary flow reserve in patients with metabolic syndrome

BACKGROUND Metabolic syndrome (MetS) is a strong predictor of cardiovascular events. Coronary flow reserve (CFR), as determined by transthoracic echocardiography, is an indicator of microvascular function. In this study, we sought to determine whether CFR is impaired in patients with MetS without clinical coronary heart disease. METHODS Thirty-three patients with MetS (mean age, 67+/-8 years) and 35 age- and sex-matched controls were studied prospectively. Transthoracic two-dimensional and Doppler echocardiography was performed on all patients. Baseline and hyperemic (after dipyridamole infusion) coronary flow rates were measured using pulsed Doppler echocardiography. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. RESULTS There was no difference with regard to baseline systolic and diastolic coronary flow rates in patients with MetS compared with control subjects (19.9+/-3.1cm/s vs. 19.7+/-2.9cm/s, P>.05; and 27.7+/-4.2cm/s vs. 27.1+/-3.6cm/s, P>.05, respectively). Hyperemic diastolic flow and CFR were significantly lower in patients with MetS than in controls (61.7+/-9.4cm/s vs. 70.2+/-9.2cm/s, P<.0001; and 2.2+/-0.5 vs. 2.6+/-0.4, P=.001, respectively). In a logistic regression analysis that included age, sex, body mass index, hypertension, and dyslipidemia and MetS, MetS was the only predictor of a CFR<2.5 (P=.007, OR=6.1, 95% CI: 1.6-23.3). CONCLUSION In conclusion, CFR is impaired in patients with MetS suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is present in this patient population. Metabolic syndrome is associated with a CFR<2.5.

Prevalence and Predictors of Arrhythmia in End Stage Renal Disease Patients on Hemodialysis

Background. Sudden death is common in end-stage renal disease (ESRD). Cardiac arrhythmia is observed frequently in patients with ESRD and is thought to be responsible for this high rate of sudden death. This study investigated the prevalence and the predictors of arrhythmia in patients on maintenance dialysis. Methods. Ninety-four patients on hemodialysis program were enrolled in the study. Routine laboratory results were noted. Arrhythmia, periods of silent ischemia, and heart-rate variability analyses were obtained from 24-hour Holter monitor recordings. Corrected QT (QTc) dispersion was calculated from 12-lead surface EKG. Echocardiographic and tissue Doppler examinations were performed on interdialytic days as well. Ventricular arrhythmia was classified according to Lown classification; classes 3 and above were accepted as complex ventricular arrhythmia (CVA). Results. The mean age was 52.5±13.2 years; 44 (46.8%) were women. Ventricular premature contractions were detected in 80 (85.1%) patients, of whom 35 (37.2%) were classified as complex ventricular arrhythmia (CVA). Coronary artery disease, hypertension, and QTc dispersion appeared as independent factors predictive of CVA development. Atrial premature contractions (APC) were detected in 53 patients (56.4%) and supraventricular arrhythmia in 15 (16%) patients; all were identified as atrial fibrillation. Duration of dialysis therapy was found as an independent predictor of APC. Conclusion. Arrhythmia is frequently observed in ESRD patients receiving hemodialysis and may be responsible for the high rate of sudden mortality. Hypertension, CAD, and QTc dispersion are independent predictors of CVA, and duration of dialysis therapy is an independent factor affecting APC development in these patients.

Serum gamma-glutamyl transferase activity: new high-risk criteria in acute coronary syndrome patients?

In acute coronary syndromes (ACS), oxidation and inflammation have very important roles and in-vitro studies have demonstrated that &ggr;-glutamyl transferase (GGT) participates in such oxidative and inflammatory reactions. We aimed to evaluate the prognostic value of baseline serum GGT activity on the development of major adverse cardiac event (MACE) in the follow-up of the patients with ACS in coronary care unit (CCU), after 1 and 6 month periods. We included 117 patients (mean age: 61.2±11.3 years, 93 males) hospitalized in CCU with the diagnosis of ACS. All had baseline serum GGT activity and were free of systemic and hepatobiliary disease. MACE was defined as the composite of mortality from cardiac causes, recurrent hospitalization with ACS and nonfatal recurrent myocardial infarction diagnoses, to need for coronary revascularization during CCU, over 1 and 6 month follow-up periods. During the follow-up of CCU, MACE occurred in 17 (14.5%) patients (two died). Serum GGT activity was significantly higher in the patients with MACE than those free of MACE (P=0.001) and GGT was found as the independent predictor of the development of MACE-CCU [relative hazard: 1.05, 95% confidence interval (CI): 1.01–1.09, P=0.007]. During the follow-up of 1 month, MACE occurred in 23 (20.0%) patients (five died). Serum GGT activity was significantly higher in patients with MACE than those free of MACE (P=0.021) and GGT was found as the independent predictor of the development of MACE-1 month (relative hazard: 1.04, 95% CI: 1.01–1.08, P=0.039). During the follow-up of 6 months, MACE occurred in 24 (21.8%) patients (two died). Again, GGT was significantly higher in patients who developed MACE than those free of MACE (P=0.001) and GGT was found as the independent predictor of the development of MACE-6 months (relative hazard 1.06, 95% CI: 1.03–1.10, P<0.001). Serum GGT activity was found to be an independent predictor of the development of MACE in the patients with ACS during CCU, over 1 and 6 month follow-up periods.

Association Between Serum Gamma-Glutamyltransferase Activity and Carotid Intima-Media Thickness

Serum gamma-glutamyltransferase (GGT) activity is a marker of oxidative stress and activity is associated with cardiovascular disease. Carotid intima-media thickness (IMT) is a noninvasive predictor of atherosclerosis. We investigated the association between serum GGT activity and carotid IMT. Fifty-five persons who had normal liver function tests were consecutively enrolled. Carotid IMT was evaluated in the right and left common carotid arteries. The averaged values of carotid IMT and serum GGT activity were compared. Serum GGT activity correlated with carotid IMT (r = .396, P = .003). Serum GGT activities were increased in patients with carotid intimal hyperplasia compared with those without intimal hyperplasia (20.3 ± 11.2 vs 34.3 ± 16.1 U/L; P = .001). Serum GGT activity is associated with carotid IMT. This finding supports the concept that elevated serum GGT activity is a marker of atherosclerosis.

Does pravastatin therapy affect cardiac enzyme levels after percutaneous coronary intervention

Serum cardiac enzyme elevation after percutaneous coronary intervention (PCI), a relatively common complication, is a prognostic determinant of long-term outcome in patients who undergo these procedures. Statins are postulated to reduce such complications. This study investigated the short-term effects of pravastatin on serum creatine kinase myocardial isoform (CK-MB) and serum cardiac troponin I (cTpI) levels after elective PCI. Of 93 patients studied, 72 (77.4%) were men, and 21 (22.6%) were women (mean age, 58.9±11.0 y). Patients were randomly divided into 3 groups before they underwent elective PCI. Preoperatively, group 1 patients (n=30) received pravastatin 10 mg/d, and group 2 patients (n=29) received pravastatin 40 mg/d. Control group patients (n=34) received no lipid-lowering medication. Serum CK-MB and serum cTpI levels were measured preoperatively and then again at 6, 24, and 36 h postoperatively. Demographic features of patients and characteristics of the PCI procedure, including number of vessels/lesions and duration and number of inflations, did not differ among groups (P>.05). Mean serum CK-MB and serum cTpI levels were significantly increased after PCI in all patients (P<.001). When compared with control group patients, those given pravastatin did not experience significantly lowered postprocedural serum CK-MB or serum cTpI levels (P>.05). Preprocedural pravastatin therapy at dosages of 10 mg/d and 40 mg/d seems inadequate for preventing serum cardiac enzyme elevations during short-term follow-up after PCI. Additional research on this topic is recommended.

Association of serum adiponectin levels and coronary flow reserve in women with normal coronary angiography

Background Women may have atypical clinical presentations and atypical risk factors of coronary artery disease. Adiponectin has anti-insulin-resistant properties and antiatherogenic effects. We investigated the association between serum adiponectin levels and coronary flow reserve (CFR) in women with normal coronary arteries. Methods CFR was assessed in 45 consecutive women (mean age 54.2 ± 9.2 years) with normal epicardial coronary arteries by coronary angiography. Serum adiponectin, C-reactive protein, insulin, and glucose levels were examined and Homeostasis Model Assessment for Insulin Resistance index was calculated. Peak diastolic coronary flow velocities were measured in distal left anterior descending artery at baseline and after dipyridamole infusion by transthoracic pulsed wave Doppler echocardiography. CFR was calculated as the ratio of hyperemic to baseline peak diastolic velocities. A CFR value ≥ 2 was accepted as normal. Results Adiponectin levels were lower in patients with impaired CFR than those with normal CFR (7.1 ± 2.3 vs. 13.8 ±6.7 μg/ml P < 0.001). Adiponectin levels were correlated with CFR (r =0.531, P < 0.001) and inversely correlated with C-reactive protein (r = −0.308, P = 0.047), insulin (r = −0.426, P = 0.008), and Homeostasis Model Assessment for Insulin Resistance index (r = −0.442, P = 0.004). Adiponectin levels of ≤ 8.5 μU/ml had 83% sensitivity and 93% specificity [receiver operating characteristic area 0.084, P < 0.001, 95% confidence interval (0.56-1.08)] for predicting impaired CFR. Conclusion Decreased adiponectin levels are associated with impaired CFR in women with normal epicardial coronary arteries and hypoadiponectinemia may be a risk factor for impaired CFR in women.