Sukru Celik

The effects of lipid-lowering therapy on low-density lipoprotein auto-antibodies: relationship with low-density lipoprotein oxidation and plasma total antioxidant status

BackgroundOxidized low-density lipoprotein (Ox-LDL) is believed to play an important role in the progression of atherosclerosis. Oxidative modification of low-density lipoprotein (LDL) is a prerequisite for rapid accumulation of LDL in macrophages and for the formation of foam cells. Because of high antioxidant levels in plasma, LDL oxidation is suggested to occur mainly in the subendothelial space of the arterial wall, where there is the concomitant presence of large amounts of reactive oxygen species generated by endothelial cells and activated leukocytes. After Ox-LDL formation, antibodies against this form of LDL may occur. Auto-antibodies against Ox-LDL (AuAb-Ox-LDL) show directly in in-vivo LDL oxidation. Many studies have indicated that the amount of antibodies in serum is positively correlated to the rate of progression of atherosclerotic plaques. Design and methodsIn this study the effect of lipid-lowering therapy on the levels of AuAb-Ox-LDL in patients with dyslipidemia was determined using atorvastatin (10 mg/day), and the relationship between the antibodies and plasma total antioxidant status (TAS) and LDL oxidation capacity was also investigated. Serum levels of AuAb-Ox-LDL, lipids, lipoproteins, TAS and susceptibility of LDL to oxidation were determined using lag time in 44 patients with dyslipidemia (29 with hypercholesterolemia and 15 with mixed-type hyperlipidemia). ResultsAfter lipid-lowering therapy, serum levels of AuAb-Ox-LDL were found to be significantly decreased, by 18.7%, while lag time and plasma TAS were increased (31.3% and 7.6% respectively) in patients with dyslipidemia. The percentage change in lag time was found to be negatively correlated to the percentage change in AuAb-Ox-LDL (r  = −0.31, P  < 0.05). The percentage change in lag time also showed a positive correlation with the percentage change in TAS (r  = 0.58, P  < 0.01). AuAb-Ox-LDL levels decreased by 21.7% in patients with hypercholesterolemia and by 12.6% in patients with mixed-type hyperlipidemia. Also AuAb-Ox-LDL levels in patients with hypercholesterolemia were higher than in those with mixed-type hyperlipidemia (367 ± 294 compared with 300 ± 176 mU/l). ConclusionIt was concluded that lipid-lowering therapy may contribute to the reduction in levels of AuAb-Ox-LDL and the increase in the antioxidant capacity of plasma LDL and TAS. It was also suggested that the measurement of antibodies against Ox-LDL during lipid-lowering therapy may be used as an important marker for representing in-vivo LDL oxidation and atherosclerotic processes.

Effects of Prehypertension on Arterial Stiffness and Wave Reflections

The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classifies blood pressure (BP) as normal, prehypertension, and hypertension. Although it has been shown that there is a relationship between hypertension and arterial stiffness, there is not sufficient data about arterial stiffness in patients with prehypertension. The present study was designed to evaluate arterial stiffness and wave reflections in subjects with prehypertension. We evaluated arterial stiffness and wave reflections of 45 subjects with prehypertension and an age-matched control group of 40 normotensive individuals, using applanation tonometry (Sphygmocor, AtCor Medical, Sydney, Australia). Aortic pulse wave velocity (PWV) was measured as indices of elastic-type aortic stiffness. The heart rate-corrected augmentation index (AIx@75) was estimated as a composite marker of wave reflections and arterial stiffness. Aortic PWV (10 ± 2.5 vs. 8.6 ± 1.7, m/s, p  =  0.004) and AIx@75 (21 ± 8.3 vs. 10 ± 9.1, %, p = 0.0001) were significantly higher in subjects with prehypertension than in the control group. In multiple linear regression analysis, we found that the presence of the prehypertension was a significant predictor of aortic PWV (β  =  0.26, p  =  0.009) and AIx@75 (β  =  0.46, p  =  0.0001). Our results suggest that arterial functions were impaired even at the prehypertensive stage.

Immediate procedural and long-term clinical outcomes following drug-eluting stent implantation to ostial saphenous vein graft lesions

Background: Ostial saphenous vein graft (OSVG) lesions were excluded from all the clinical trials demonstrating significantly lower restenosis rates with drug-eluting stents (DES) compared to bare metal stents (BMS). This study aimed to evaluate the efficacy of DES in OSVG lesions by assessing angiographic and 12-month clinical outcomes. Methods: 70 consecutive patients (70 OSVG lesions) underwent coronary stent implantation between May 2003 and April 2006: 37 lesions received DES and 33 lesions BMS. Endpoints were all cause and cardiovascular mortality, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), examined separately and as a combined end-point (major adverse cardiac events, MACE). Results: Procedural (94.6% for DES and 87.9% for BMS) and angiographic (100% for DES and 100% for BMS) success did not differ between the two groups. The only in-hospital events were non-Q wave MI (DES 8.1% versus BMS 12.1%, P=0.69). At 30-day follow-up, there were no other events. Overall, at 1-year follow-up, the BMS group had a higher TLR (30.3% versus 5.4%, P=0.015), TVR (33.3% versus 10.8%, P=0.045) and MACE rate (36.4% versus 10.8%, P=0.024) compared to the DES group. Conclusions: Drug-eluting stent implantation to OSVG lesions achieves better clinical results than BMS but is still associated with a relatively high incidence (10.8%) of revascularization at 1-year follow-up.

Assessment of left ventricular diastolic function and the Tei index by tissue Doppler imaging in patients with primary hyperparathyroidism

Background  The aim of this study was to assess left ventricular (LV) systolic and diastolic function and myocardial performance (the Tei index) by tissue Doppler imaging (TDI) in patients with primary hyperparathyroidism (PHPT).

Relationship Between Arterial Stiffness and Myocardial Damage in Patients With Newly Diagnosed Essential Hypertension

BACKGROUND Arterial stiffness increases in hypertensive individuals. Arterial stiffness is associated with impairment of systolic and diastolic myocardial function in hypertension (HT). However, the relationship between arterial stiffness and serum heart-type fatty acid-binding protein (H-FABP) levels, a sensitive marker of myocardial damage, has not been previously examined in patients with HT. We investigate the relationship between serum H-FABP levels and arterial stiffness in patients with newly diagnosed HT. METHODS We studied 46 (48.5 +/- 10.6, years) never-treated patients with HT and age-matched control group of 40 (47 +/- 8.6, years) normotensive individuals. H-FABP levels were determined in all subjects. We evaluated arterial stiffness and wave reflections of study population, using applanation tonometry (Sphygmocor). Carotid-femoral pulse wave velocity (PWV) was measured as indices of elastic-type, aortic stiffness. The heart rate-corrected augmentation index (AIx@75) was estimated as a marker of wave reflections. RESULTS Carotid-femoral PWV (10.5 +/- 2.2 vs. 8.7 +/- 1.6, m/s, P = 0.0001) and AIx@75 (22.7 +/- 9.5 vs. 15 +/- 11, %, P = 0.001) were significantly higher in patients with HT than control group. H-FABP levels were increased in hypertensive patients compared with control group (21.1 +/- 14.8 vs. 12.9 +/- 8.5, ng/ml, P = 0.002). In multiple linear regression analysis, we found that the body mass index (beta = 0.42, P = 0.0001) and carotid-femoral PWV (beta = 0.23, P = 0.03) were significant determinants of H-FABP levels. CONCLUSION Arterial stiffness is associated with serum H-FABP levels, a sensitive marker of myocardial damage, in patients with newly diagnosed HT.

Relation of Epicardial Fat Thickness and Cardio-Ankle Vascular Index to Complexity of Coronary Artery Disease in Nondiabetic Patients

Objectives: Arterial stiffness and epicardial fat thickness (EFT) are associated with coronary artery disease (CAD). The cardio-ankle vascular index (CAVI) is a novel marker of arterial stiffness. The SYNTAX score (SS) reflects the complexity of CAD. We aimed to evaluate the relation of EFT and CAVI with CAD complexity in nondiabetic patients. Method: We enrolled 121 patients undergoing coronary angiography. In all patients, CAVI and EFT were determined. SS were calculated. The relationship between EFT, CAVI and SS was analyzed. Results: CAVI and EFT were significantly correlated with SS (r = 0.537, p < 0.001, and r = 0.629, p < 0.001, respectively) and found to be independent predictors of intermediate-high SS. For the prediction of intermediate-high SS, receiver-operating characteristic curve analysis revealed a cutoff value of 5 mm for EFT (area under the curve, AUC = 0.851, 95% confidence interval, CI, 0.775–0.910) with a specificity of 92.2% and a sensitivity of 77.4% and 8.6 for CAVI (AUC = 0.877, 95% CI 0.805–0.929) with a specificity of 68.9% and a sensitivity of 93.5%. Conclusion: CAD complexity is associated with adverse cardiovascular events. It can be predicted noninvasively with EFT and CAVI in nondiabetic patients with suspected CAD. Thus, patients at high risk for cardiovascular events may be detected early and managed with appropriate treatment strategies.

Circulating levels of relaxin and its relation to cardiovascular function in patients with hypertension

Background. The role of endogenous relaxin on hypertensive cardiovascular damage remains unknown. We investigated the relaxin level and its relation to cardiovascular function in patients with never treated hypertension (HT). Methods. We studied 42 (47.8±10 years) never treated patients with HT and 40 age‐matched (47±8.6 years) normotensive individuals. Serum relaxin levels were determined in all subjects using enzyme‐linked immunosorbent assay. Left ventricular (LV) diameters were evaluated by transthoracic echocardiography. Ejection fraction and LV mass index were measured. Diastolic functions were evaluated with both conventional and tissue Doppler echocardiography. We evaluated central aortic pressures, heart rate‐corrected augmentation index (AIx@75), a marker of wave reflections, and aortic pulse wave velocity (PWV) as indices of elastic‐type aortic stiffness of the study population using applanation tonometry (SphygmoCor). Results. Relaxin levels were significantly lower in hypertensive patients as compared with controls (36.5±7.3 vs 49.7±39.8 pg/ml, p=0.03). The relaxin level was negatively correlated with brachial and central aortic pressure. However, serum relaxin was not significantly associated with LV diameters, ejection fraction, LV mass index, LV diastolic function, AIx@75 or aortic PWV in our study. Conclusion. Serum relaxin is decreased in patients with HT. However, low endogenous relaxin is not related to cardiovascular function.

Increased frequency of fragmented QRS in patients with severe aortic valve stenosis.

Objective: To investigate the presence of myocardial fibrosis determined by fragmented QRS in patients with severe aortic valve stenosis. Subjects and Methods: Eighty-seven consecutive patients with severe aortic valve stenosis and 83 age- and gender-matched control subjects were enrolled into this study. Severe aortic valve stenosis was defined as an aortic valve area <1 cm2, a Vmax >4 m/s, or a mean gradient ≥40 mm Hg. Fragmented QRS was assessed using a 12-lead electrocardiogram. Results: Fragmented QRS was detected in 40 (46%) patients in the aortic valve stenosis group and in 15 (18%) control subjects (p < 0.001). In multivariate binary logistic regression analysis, the presence of aortic valve stenosis was the only independent factor associated with fragmented QRS (OR = 3.69; 95% CI 1.81-7.55, p < 0.001). Conclusion: A higher frequency of fragmented QRS was detected in patients with severe aortic valve stenosis compared to controls.

Atherosclerosis burden and coronary artery lesion complexity in acute coronary syndrome patients

BACKGROUND Syntax score (SS) is a prognostic marker in patients with acute coronary sydromes (ACS). Carotid intima media thickness (CIMT) and cardio ankle vascular index (CAVI) are well known surrogate marker of atherosclerosis burden. But association between atherosclerosis burden and coronary artery disease (CAD) complexity in ACS patients has not been investigated yet. METHODS AND RESULTS Consecutive patients with first time diagnosis of ACS (n = 172) were enrolled. SS, a marker of CAD complexity, was assessed by dedicated computer software. CIMT was examined by B-mode ultrasound. CAVI was assessed by VaSera VS-1000 cavi instrument. SS for low, intermediate and high tertiles of CIMT value were 10.1 ± 8.2 vs 11.4 ± ± 7.9 and 15.2 ± 8.8; p = 0.02). SS for normal, borderline and abnormal CAVI values were 4 ± 3.7 vs 11.1 ± 7.2 and 14.1 ± 9.1, respectively p = 0.009). Also, there was independent association between SS and CIMT (95% coinfidence interval [CI] 2.1-19, p = 0.014) and CAVI (95% CI 15-29, p = 0.021]. Neither traditional cardiovascular risk factor nor thrombolysis in myocardial infarction (TIMI) risk score was independent determinant of SS. CONCLUSIONS We have shown that patients with higher atherosclerosis burden have more complex coronary artery lesions. Also these patients may be identified early by using surrogate markers of atherosclerosis. Its clinical significance requires further research.

Factor V Leiden and its relation to left ventricular thrombus in acute myocardial infarction.

Objective — The genetic defect of coagulation factor V, known as factor V Leiden, produces a resistance to degradation by activated protein C (APC) and increases the risk of venous thrombosis. However, the role of factor V Leiden in the formation of left ventricular (LV) thrombus has not been studied.We investigated whether factor V Leiden is a risk factor for LV thrombus in patients with acute myocardial infarction (AMI). Methods and results — We have analyzed clinical, echocardiographic and biochemical data in 135 consecutive patients (aged 58 ± 13 years; 31 women) with first anterior AMI. Two-dimensional echocardiographic examination was performed on days I, 3, 7, 15 and 30; LV thrombus was detected in 33 (24.4%) of 135 patients with AMI. The study also included 95 control subjects. Healthy age and sex-matched subjects without a personal or family history of ischaemic heart disease, stroke or thromboembolic disease served as a control group. Blood samples from the patients and controls were analyzed for the factor V Leiden mutation by DNA analysis, using the polymerase chain reaction. In addition, concentrations of fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-I (PAI-1) and D-dimer were measured in 135 patients. There was no significant difference in the prevalence of factor V Leiden between patients and control subjects. The prevalence of the factor V mutation was 9% (3/33) in patients with thrombus, and 7.7% (8/103) in patients without thrombus. The prevalence of factor V Leiden was 7.3% (7/95) in control subjects. No significant differences in plasma fibrinogen (480 ± 195 vs. 444 ± 179 mg/dl, p = 0.6), D-dimer (471 ± 256 vs. 497 ± 293 ng/dl, p = 0.7), vWF (112 ± 18 vs. 103 ± 15%, p = 0.5), PAI-I (26.7 ± 9.8 vs. 28.1 ± 10.2 ng/dl, p = 0.6), and t-PA (19.8 ± 8.7 vs. 17.2 ± 9.1 ng/dl, p = 0.7), levels are found in patients with LV thrombus when compared with those without LV thrombus. Multivariate analyses showed that peak creatine kinase level (p = 0.002) and LV wall motion score index (p = 0.003) were independent predictors of LV thrombus formation. Conclusion — Factor V Leiden mutation is not a risk factor for LV thrombus formation in patients with AMI. (Acta Cardiol 2001; 56(1 ): 1-6)