Cihan Örem

Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects

BACKGROUND Tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. However, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. METHODS The antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. Twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. These were control diet I (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18%-20% of the total daily energy intake), and control diet period II (4 weeks). The cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (FMD) technique, low-density lipoprotein (LDL) oxidation products and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as lipids and lipoprotein levels were monitored. RESULTS Consumption of a hazelnut-enriched diet significantly improved FMD (56.6%), total cholesterol (-7.8%), triacylglycerol (-7.3%), LDL-cholesterol (-6.17%), and high-density lipoprotein cholesterol (6.07%) compared with the control diet I. Oxidized-LDL, hs-CRP, and sVCAM-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets I and II. Modest correlations between sVCAM-1 and FMD and between sVCAM-1 and hs-CRP were observed (r = -0.49, P < .025; r = 0.66, P < .001, respectively). CONCLUSION Hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing LDL oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. These beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. Therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit.

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.

Plasma fibronectin level and its association with coronary artery disease and carotid intima-media thickness.

Background The exact relation of fibronectin with coronary atherosclerosis is unknown. The aim of the present study was to examine the association of fibronectin level with presence and extent of coronary artery disease (CAD) and intima‐media thickness (IMT) of common carotid artery (CCA). Design The IMTs of CCA of 86 patients who underwent coronary angiography were measured; traditional vascular risk factors were also evaluated in these patients. Fibronectin, lipids, C‐reactive protein (CRP) and fibrinogen levels were determined. Results Plasma fibronectin levels of the patients with CAD were found to be significantly elevated compared to patients with normal vessels (0.46 ±0.11 and 0.36± 0.12 mg/dl respectively, P = 0.001). Fibronectin levels were not associated with extent of CAD. No significant association was observed between fibronectin level and traditional risk factors. IMTs of right and left CCA in patients with CAD were found to be elevated compared to patients with normal vessels (0.89 ± 0.1mm compared with 0.76 ± 0.1 mm, P = 0.001 and 0.93 ± 0.2 mm compared with 0.71 ± 0.1 mm, respectively P < 0.001). Fibronectin levels were positively correlated with CRP (r = 0.45, P < 0.001), low‐density lipoprotein‐cholesterol (r = 0.23, P = 0.03) and total cholesterol (r = 0.21, P = 0.04) levels and negatively correlated with high‐density lipoprotein‐cholesterol (HDLC) levels (r = ‐ 0.24, P = 0.02). IMT of left CCA was positively correlated with CRP levels (r = 0.23, P = 0.04) and negatively correlated with HDL‐C levels (r = 0.2, P = 0.04). Logistic regression analysis showed that age (P < 0.01) and fibronectin levels (P = 0.01) were independent predictors for the existence of CAD. Conclusions The results suggest that fibronectin levels may be a significant predictor of CAD. However, it was shown that fibronectin levels were not associated with extent of CAD and IMT of CCA. Coron Artery Dis 14:219‐224

Iron status and its relationship with lipid peroxidation in patients with acute myocardial infarction.

Aim — The aim of this study was to investigate iron status and its relationships with lipid peroxidation in patients with acute myocardial infarction (MI). Methods — The study included 30 male patients aged between 32 and 73 years (mean 55 ± 6) with acute MI.We measured the levels of plasma iron, transferrin (TF), ferritin (FER), ceruloplasmin (CER), cardiac enzymes, and erythrocyte malondialdehyde (e-MDA) in patients with acute MI on the admission and 1st, 3rd, 5th, 7th, 15th, 45th post MI day and investigated the variations of these parameters in acute MI. Results — The e-MDA level started to increase on the admission day and showed a peak value on the post MI 1st day (88 ± 23 and 98 ± 26 nmol/g Hb, respectively). Afterwards, the e-MDA level minimally changed until post MI 45th day, which showed a minimum level (57 ± 13 nmol/g Hb) (p < 0.05). In addition, the iron concentration of serum reached its maximum level on the 1st post MI day (99 ± 30 mg/dl, p < 0.05) and relatively decreased after the 3rd day. Courses of MDA and iron levels were similar. The FER level started to increase from the admission day of the patients (230 ± 375 mg/dl), showed a mean peak value on the 3rd day (296 ± 568 mg/dl) and decreased to a minimum level on the 45th day (121 ± 85 mg/dl) (p <0.05). Contrarily, the TF level started to decrease on the 1st day (221 ± 44 mg/dl), decreased minimum level on the 3rd day (211 ± 37 mg/dl) and continued approximately the same level until the 45th day (244 ± 45 mg/dl) (p < 0.05). The CER level started to increase from the first day of admission of the patients (43 ± 12 mg/dl), reached a maximum level on the 7th day (59 ± 12 mg/dl) and similar levels were observed until the 15th day. On the 45th day, the CER level was higher than on the first day (52 ± 13 mg/dl) (p < 0.05). Conclusion — There was an association of higher iron status with increased lipid peroxidation in patients with myocardial infarction.

The significance of autoantibodies against oxidatively modified low-density lipoprotein (LDL) in patients with psoriasis.

Psoriasis is associated with changes in plasma lipid and lipoproteins, which may play a role in the development of occlusive vascular disease. The oxidation of low-density lipoprotein (LDL) is considered a key event in the development and progression of atherosclerosis. Autoantibodies against oxidized LDL (auAb-oxLDL) may contribute to understanding the relationship between oxidative processes and development of atherosclerosis. Thirty-three patients with psoriasis and 30 matched control subjects were investigated. LDL oxidation was evaluated as the presence of autoantibodies against LDL oxidatively modified with Cu++, by an ELISA system in the patients and control sera. AuAb-ox LDL levels of the patients were found to be significantly increased compared with a control group. 42% of the patients and 3.3% of the control subjects had higher auAb-ox LDL levels than the cut-off point (352 mU/ml). The levels of auAb-ox LDL were found to be correlated with PASI score (r = 0.67, p < 0.01). Also, The antibody level was found to be correlated with polymorphonuclear elastase and alpha-1 antitrypsin levels (r = 0.58, p < 0.05; r = 0.51, p < 0.05, respectively). It was concluded that increased levels of auAb-oxLDL in the psoriatic patients may be a consequence of the interaction between imbalance of oxidant-antioxidant system and lipoproteins, and the measurement of auAb-oxLDL in the patients may mirror in vivo occurrence of oxidative processes.

Increased plasma fibronectin levels in patients with acute myocardial infarction complicated with left ventricular thrombus

Fibronectin is a polymorphic and multifunctional glycoprotein that plays a wide-ranging role in hemostasis. In this study, it was aimed to determine plasma fibronectin levels and evaluate its possible role in left ventricular (LV) thrombus formation following acute myocardial infarction (AMI). We have determined clinical, echocardiographic, and biochemical parameters in 97 consecutive patients (aged 59 +/- 13; 87 men/10 women) with first anterior AMI. Two-dimensional echocardiography was performed on Days 1, 3, 7, 15, and 30. Blood samples were obtained within 24-48 h after the onset of symptoms. The study also included 30 healthy control subjects. Plasma fibronectin levels were significantly higher in patients with AMI than control subjects (38 +/- 13 vs. 25.2 +/- 8.7 mg/dl, P=.0001). LV thrombus was detected in 20 (20.6%) of 97 patients. Plasma fibronectin levels were significantly higher in patients with LV thrombus (Group 2) than in patients without LV thrombus (Group 1) (44.5 +/- 11 vs. 36.1 +/-13.4 mg/dl, P=.01). Although univariate analysis showed that plasma fibronectin levels were higher in patients with thrombus, multivariate analysis showed that plasma fibronectin levels were not an independent predictor of LV thrombus formation (P=.059). In multivariate analyses, only peak creatine phosphokinase (CPK) level and LV wall motion score index (WMSI) were independent predictors of thrombus formation (P=.007 and P=.0001, respectively). These results suggest the increased plasma fibronectin levels may be one of the risk factors for LV thrombus formation after AMI. However, further studies concerning the relation between plasma fibronectin levels and LV thrombus formation are necessary.

Plasma fibronectin level and its relationships with lipids, lipoproteins and C-reactive protein in patients with dyslipidaemia during lipid-lowering therapy

Objectives — The purpose of this study is to determine plasma fibronectin level and its relationships with plasma lipids, lipoproteins and C-reactive protein (CRP) levels in patients with dyslipidaemia during lipid-lowering therapy. Methods — Plasma levels of fibronectin, CRP, fibrinogen, lipids and lipoproteins in 38 patients with dyslipidaemia were determined before and after lipid-lowering therapy by using atorvastatin, 10 mg/day. Results — After lipid-lowering therapy, serum levels of fibronectin and CRP were found to be significantly decreased by 30.4% and 43,6%, respectively, while fibrinogen levels were increased 11.7% in patients with dyslipidaemia. Before the treatment, fibronectin was found to be positively correlated with CRP and total cholesterol (r=0.38, p<0.05 and r=0.33, p<0.05, respectively) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r=–0.42, p<0.01) in patients with dyslipidaemia. High fibronectin levels (0.57±0.17 g/l) were found in patients with HDL-C below 35 mg/dl (0.57±0.09 g/l), compared to patients with HDL-C above 35 mg/dl (0.45±0.11 g/l). During the lipidlowering therapy, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and apo B levels were reduced while HDL-C and apo AI levels were increased. Conclusions — It was found that plasma fibronectin and CRP levels were decreased by lipid lowering therapy. Plasma fibronectin levels were associated with lipids, lipoproteins, CRP levels before treatment and these relationships disappeared after treatment. Consequently, it was suggested that reduction of plasma fibronectin levels, together with lipids and loss of its relationship with CRP, may play a role on the antiatherogenic effects of lipid-lowering therapy.OBJECTIVES The purpose of this study is to determine plasma fibronectin level and its relationships with plasma lipids, lipoproteins and C-reactive protein (CRP) levels in patients with dyslipidaemia during lipid-lowering therapy. METHODS Plasma levels of fibronectin, CRP, fibrinogen, lipids and lipoproteins in 38 patients with dyslipidaemia were determined before and after lipid-lowering therapy by using atorvastatin, 10 mg/day. RESULTS After lipid-lowering therapy, serum levels of fibronectin and CRP were found to be significantly decreased by 30.4% and 43.6%, respectively, while fibrinogen levels were increased 11.7% in patients with dyslipidaemia. Before the treatment, fibronectin was found to be positively correlated with CRP and total cholesterol (r=0.38, p<0.05 and r=0.33, p<0.05, respectively) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r=-0.42, p<0.01) in patients with dyslipidaemia. High fibronectin levels (0.57 +/- 0.17 g/l) were found in patients with HDL-C below 35 mg/dl (0.57 +/- 0.09 g/l), compared to patients with HDL-C above 35 mg/dl (0.45 +/- 0.11 g/l). During the lipid-lowering therapy, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and apo B levels were reduced while HDL-C and apo AI levels were increased. CONCLUSIONS It was found that plasma fibronectin and CRP levels were decreased by lipid lowering therapy. Plasma fibronectin levels were associated with lipids, lipoproteins, CRP levels before treatment and these relationships disappeared after treatment. Consequently, it was suggested that reduction of plasma fibronectin levels, together with lipids and loss of its relationship with CRP, may play a role on the antiatherogenic effects of lipid-lowering therapy.

Assessment of left ventricular systolic and diastolic function by Doppler tissue imaging in patients with preinfarction angina

BACKGROUND The aim of this study was assessment of left ventricular (LV) systolic and diastolic function by pulsed wave Doppler tissue imaging (DTI) in patients with or without preinfarction angina in acute myocardial infarction. METHODS We prospectively evaluated 31 consecutive patients (4 women, 27 men; age 58 +/- 10 years) with a first acute myocardial infarction. LV systolic and diastolic function was assessed by classic methods and DTI on the third day during acute myocardial infarction. Patients were divided into 2 groups according to the presence (group 1; n = 10) or absence (group 2; n = 21) of preinfarction angina. Mitral inflow velocities and early diastolic mitral annular velocity (Em), late diastolic mitral annular velocity (Am), peak systolic mitral annular velocity, Em/Am, the ratio of early diastolic mitral inflow velocity (E) to Em, and myocardial performance index were calculated by DTI. RESULTS Group 1 had significantly higher Em and Em/Am than group 2 (11.3 +/- 3.34 cm/s vs 7.4 +/- 2.07 cm/s, P <.0001; 1.01 +/- 0.38 cm/s vs 0.6 +/- 0.2 cm/s, P =.001, respectively). The E/Em ratio and myocardial performance index were significantly lower in group 1 than in group 2 (5.1 +/- 2.92 vs 8.10 +/- 3.15, P=.018; 0.49 +/- 0.15 vs 0.65 +/- 0.24, P =.042, respectively). Wall-motion score index was lower in those with preinfarction angina than in those without (1.6 +/- 0.36 vs 1.9 +/- 0.39; P =.04, respectively). Peak systolic mitral annular velocity and Am were not statistically different between groups (9.4 +/- 1.84 vs 8.3 +/- 2.03, P =.172; 11.7 +/- 3.07 vs 12.1 +/- 3.34, P =.72, respectively). There were no significant differences between the 2 groups regarding transmitral E velocity, atrial contraction mitral inflow velocity (A), E/A ratio, isovolumetric relaxation time, and deceleration time of the mitral E wave (P =.91, P =.08, P =.58, P =.81, and P =.71, respectively). CONCLUSION LV diastolic function was better in patients with preinfarction angina than in patients without. This condition could not be detected by conventional mitral inflow Doppler velocities, but could be detected by DTI. This preliminary evidence shows that DTI is better than conventional mitral Doppler indices in the assessment of a favorable LV diastolic function in patients with preinfarction angina.

Effect of coronary angiography on plasma endothelin-1 and nitric oxide concentrations.

Endothelium takes part in the regulation of vascular tone through the production of endothe lium-derived relaxing factor, nitric oxide (NO), and the contracting factor endothelin-1 (ET-1). Induction of ET-1 and NO is influenced by many stimuli including hypoxia and shear stress. Some of these stimuli may arise during coronary angiography (CAG). In this study, the authors aimed to show endothelial response in patients undergoing CAG by evaluating plasma ET-1 and NO end-products including nitrite and nitrate concentrations. Twenty-four male patients with a mean age of 54.3 years (age range: 37-70) were included in the study. The patients had no coronary atherosclerotic lesions established by CAG. The mean time of the CAG procedures was 24.8 minutes, with a range of 19-33 minutes. Immediately before blood sampling, systolic and diastolic blood pressures were recorded. The mean blood pressures before and after CAG were 140/90 and 150/95, respectively. End products of NO radical, nitrite and nitrate (NOx), in plasma were used as a marker for the production of NO radical. ET-1 concentrations were measured by ELISA method. Significant increases in ET-1 concentrations were observed during CAG while no change observed in NOx concentrations. Duration of the CAG procedure was found to be correlated with the percent increase of the plasma ET-1 concentrations during CAG (r = 0.45, p<0.05, Figure 1), but not with NOx concentrations. Plasma ET-1 concentrations in patients who were cigarette smoking were found higher than those of patients who were nonsmokers (1.26 ±0.38 and 2.97 ±0.87 fmol/L, respectively). It was concluded that endothe lial cells show increased ET-1 production as a response of some mechanical or emotional stimuli during CAG procedure that may play an important role in the regulation of vascular tonicity and some pathological processes. The authors suggest that duration and manipulation of CAG may be an important factor in plasma ET-1 concentrations.

Association Between Serum C-reactive Protein Elevation and Atrial Fibrillation After First Anterior Myocardial Infarction

Elevated inflammatory markers have been found to correlate with higher risk for cardiac events in patients with acute myocardial infarction (AMI). It has been suggested that C‐reactive protein (CRP) may be involved in the initiation process of atrial fibrillation (AF). However, the role of CRP levels in the occurence of AF in patients with AMI has not been studied. This study investigated whether CRP is a risk factor for AF in patients with acute anterior MI.