Saim Sağ

Effect of N-acetylcysteine on oxidative stress and ventricular function in patients with myocardial infarction.

Recent evidence suggests that postischemic myocardial dysfunction (“stunning”) may be mediated by oxygen free radicals. Various studies have reported the beneficial effects of antioxidants in ischemia–reperfusion injury. The aim of this study was to assess the effect of N-acetylcysteine (NAC) treatment on oxidative stress, infarct size, and left ventricular (LV) function, as adjunct therapy in myocardial infarction (MI). Patients with acute MI received either 15 g NAC infused over 24 h (n = 15) or no NAC (n = 15), combined with streptokinase. Peripheral venous blood was serially sampled to measure creatine kinase (CK)-MB levels. Plasma malondialdehyde (MDA) level was measured at admission and after 4 and 24 h. Echocardiography was performed within 3 days of MI and after 3 months. At admission, plasma MDA levels were not different between the groups. In the NAC-treated patients plasma MDA levels decreased, whereas in the nontreated NAC patients MDA levels increased at 4 and 24 h (P < 0.01 and P < 0.001, respectively). Left ventricular ejection fraction was higher (P < 0.05) and LV end-systolic and end-diastolic diameters were lower (P < 0.001 and P < 0.001) in patients receiving NAC on day 3. Left ventricular wall motion score index was significantly lower in patients treated with NAC on day 3 (P < 0.05). Left ventricular diastolic parameters were not different whether patients were treated with NAC or not. No difference in reduction of infarct size was detected between the groups according to CK-MB levels. It was thus demonstrated that administration of NAC in combination with streptokinase significantly diminished oxidative stress and improved LV function in patients with acute MI. These encouraging results would justify the performance of a larger controlled study.

Effects of Origanum onites on Endothelial Function and Serum Biochemical Markers in Hyperlipidaemic Patients

The effects of Origanum onites on endothelial function and antioxidative status were investigated in 48 patients with mild hyperlipidaemia who required no drug therapy. All participants were given lifestyle and low-fat dietary advice, however 32 of the patients (study group) were also prescribed 25 ml of aqueous distillate of Origanum onites to be taken after each meal for 3 months. The remaining 16 patients were the control group. Various biochemical markers and endothelial function parameters were measured at baseline and after 3 months. A significantly greater increase in high density lipoprotein-cholesterol and significantly greater decreases in low density lipoprotein-cholesterol, apolipo-protein B, lipoprotein(a) and high-sensitivity C-reactive protein occurred in the study group compared with the control group over the 3-month study period. Paraoxonase and arylesterase activities, and flow- and nitroglycerine-mediated dilatation of the brachial artery showed significantly greater increases in the study group compared with the changes in the control group. In conclusion, consumption of Origanum onites distillate had beneficial effects on lipid profiles, antioxidant status and endothelial function in patients with mild hyperlipidaemia.

Association of monocyte to HDL cholesterol level with contrast induced nephropathy in STEMI patients treated with primary PCI.

Abstract Background: Contrast induced nephropathy (CIN) has been proven to be a clinical condition related to adverse cardiovascular outcomes. In recent studies, the monocyte to high density lipoprotein ratio (MHR) has been postulated as a novel parameter associated with adverse renal and cardiovascular outcomes. In this study we investigated the association of MHR with CIN in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Methods: Consecutive STEMI patients treated with primary PCI were prospectively recruited. Subjects were categorized into two groups; as patients who developed CIN (CIN+) and patients who did not develop CIN (CIN–) during hospitalization. CIN was defined as either a 25% increase in serum creatinine from baseline or 44.20 µmol/L increase in absolute value, within 72 h of intravenous contrast administration. Results: A total number of 209 patients were included in the study. Thirty-two patients developed CIN (15.3%). In the CIN (+) patients, monocytes were higher [1.02 (0.83–1.39) vs. 0.69 (0.53–0.90) 109/L, p<0.01] and HDL cholesterol levels were lower [0.88 (0.78–1.01) vs. 0.98 (0.88–1.14) mmol/L, p<0.01]. In addition, MHR was significantly higher in the CIN (+) group [1.16 (0.89–2.16) vs. 0.72 (0.53–0.95) 109/mmol, p<0.01]. In multivariate logistic regression analysis, MHR, Mehran score, AGEF score and CV/eGFR were independently correlated with CIN. Conclusions: Higher MHR levels may predict CIN development after primary PCI in STEMI patients.

Serum fetuin-A levels in patients with systolic heart failure

Objective Inflammation and dystrophic calcification have been associated with cardiovascular disease (CVD) and chronic heart failure (CHF). The aim of the present study was to investigate the potential usefulness of fetuin-A as a biomarker in CHF. Methods Serum fetuin-A was measured in 66 CHF patients with left ventricular function < 50% and in 31 healthy controls at baseline. Fetuin-A was evaluated as a diagnostic marker for systolic heart failure and compared with C-reactive protein (CRP) and pro-brain natriuretic peptide (pro-BNP). Results The levels of serum fetuin-A were significantly decreased in the CHF patients compared to the control group (P < 0.01). Although there were significant correlations between fetuin-A and certain parameters in patients and controls, none of these were present consistently in either group. It was found that serum fetuin-A levels could identify patients with systolic heart failure with a high degree of sensitivity and specifi city. Conclusions Serum fetuin-A is decreased in CHF patients, indicating that anti-inflammatory activity is downregulated in CHF and that calcification may be associated with CHF.

A nation-wide survey of patients with homozygous familial hypercholesterolemia phenotype undergoing LDL-apheresis in Turkey (A-HIT 1 registry)

BACKGROUND AND AIMS Homozygous familial hypercholesterolemia (HoFH) is a genetic condition characterized by lethally high levels of low-density lipoprotein cholesterol (LDL-C) from birth, and requires rapid and aggressive intervention to prevent death due to coronary heart disease and/or atherosclerosis. Where available, lipoprotein apheresis (LA) is the mainstay of treatment to promote survival. METHODS A-HIT1 registry was conducted with the aim of providing insight to the real-life management of HoFH patients undergoing LA in Turkey, where LA procedures are fully reimbursed and widely available. Participating centers provided patient information, including family history, treatment patterns and relevant laboratory values, via a standard questionnaire. RESULTS The study evaluated 88 patients (mean age: 27 ± 11 years, 41 women) in 19 centers. All patients were receiving regular LA with a clinical diagnosis of HoFH. Mean age at first symptom disease was 10 ± 10 years, and at diagnosis it was 12 ± 11 years; 74.7% were diagnosed before age 15 years; and only 31% before the age of 7. First referral of most patients was to pediatricians. Early onset coronary artery disease was present in 57.8% of patients. Mean age at first LA was 21 ± 12 years. Only 11 (12.5%) patients were undergoing LA weekly. Mean frequency of apheresis sessions was 19 ± 13 days. For the last four LA sessions, LDL-C levels reached the target in only in 5.7% of patients. CONCLUSIONS Diagnosis of HoFH is delayed, and LDL targets are not reached. LA frequencies are not optimal. Urgent attention is needed to support the survival of patients with HoFH.

Fluvastatin Decreases Oxidative Stress in Kidney Transplant Patients.

OBJECTIVE Oxidative stress has been suggested to have a pivotal role in the development of cardiovascular disease in kidney transplant patients (KTPs). The effects of fluvastatin on oxidative status in KTPs have not been well evaluated. The aim of the present study was to evaluate the effects of fluvastatin on oxidative status by investigating erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPx), serum paraoxonase (PON1), and serum arylesterase (ARE), along with lipid peroxidation products, serum malonldialdehyde, and apolipoprotein B malondialdehyde (ApoB MDA). METHODS Eighteen KTPs were included in the present study. Blood samples were obtained after 1 nights fast. Erythrocyte SOD, erythrocyte GPx, serum PON1, serum ARE, serum MDA, and ApoB MDA were measured using methods described previously. Paired-sample t test was used for comparing the changes from week 0 to week 4 of parameters that might be associated with fluvastatin treatment. RESULTS The present study has shown that erythrocyte SOD and GPx, and serum PON1 and ARE activities increased at the fourth week of the statin treatment. Furthermore an increase in the antioxidant enzymes following fluvastatin may be a clue for the antioxidant effects of this drug. Four weeks of fluvastatin long-acting tablets 80 mg/day led to a decrease in plasma Apo-MDA and MDA levels. CONCLUSION The findings of the present study demonstrate that fluvastatin 80 mg long-acting tablets may be used safely for 4 weeks and decrease atherogenic lipoproteins in KTPs. Furthermore, after 4 weeks of fluvastatin treatment, the levels of antioxidant parameters increased and oxidative parameters decreased. Further placebo-controlled treatment studies would be helpful to evaluate the effects of fluvastatin on oxidant and antioxidant parameters including PON1 in patients with KT.

Treatment with a combination of bosentan and sildenafil allows for successful liver transplantation in a patient with portopulmonary hypertension.

Pulmonary arterial hypertension (PAH) that occurs in the setting of cirrhosis and portal hypertension is referred to as portopulmonary hypertension (PPHTN). Liver transplantation (LTx) is curative, but the presence of moderate-to-severe PPHTN may be a contraindication for transplantation because of the elevated risk of peri- and post-transplantation morbidity and mortality. We report a successful liver transplantation in a patient with liver cirrhosis after treatment of moderate-to-severe PPHTN with a combination of the dual endothelin receptor antagonist bosentan and the specific phosphodiesterase-5 inhibitor sildenafil.

Inappropriate sinus tachycardia-induced cardiomyopathy during pregnancy and successful treatment with ivabradine.

A 32-year-old patient, in the 17th week of her first pregnancy, was admitted to the local hospital with complaints of palpitations and shortness of breath, which progressed over a month. The patient had no prior history of any cardiac disease. At the time of admission, the electrocardiogram (ECG) of the patient revealed that she had supraventricular tachycardia. When the patient did not respond to adenosine and electrical cardioversion, she was transferred to our hospital. ECG revealed IST with a heart rate (HR) of 152 bpm (Fig. 1a). She was continuously monitored, and intravenous esmolol infusion and oral metoprolol were started. Due to the high HR, verapamil (240 mg/day) and digoxin (0.25 mg/ day) were added, and HR decreased to 120 bpm (Fig. 1b). Echocardiography showed normal left ventricular (LV) dimensions, LV ejection fraction (LVEF) at 45%, and mild mitral regurgitation (MR). On the 7th day of hospitalization, LVEF decreased to 40%, followed by a decrease to 30% at the end of the 2nd week. The patient developed severe MR. Furosemide was added to the treatment, but the patient did not experience clinical relief. After receiving the patient’s consent, we began ivabradine treatment (2x5 mg), and the patient’s HR dropped to 90 bpm (Fig. 1c) and remained normal until discharge (Fig. 1d). Prior to ivabradine treatment, fetal echocardiography showed the fetal HR to be 156 bpm (Fig. 2a). After the 1st day of ivabradine treatment, the fetal HR was 150 bpm (Fig. 2b), and on the 7th day, it was 148 bpm (Fig. 2c). However, it did not decline further until delivery. When the patient’s HR returned to normal, LVEF improved each day and reached 50% and MR reduced. Maternal tachycardia and fetal bradycardia were not detected during the monthly follow-ups. A healthy baby boy was delivered. The baby was only fed with breast milk, and on 15th day, ECG showed sinus rhythm with an HR of 180 bpm (Fig. 2d).

Association of Aortic Diameters with Coronary Artery Disease Severity and Albumin Excretion

Introduction. Aortic diameters, aortic distensibility, microalbuminuria, coronary artery disease which are all together related to vascular aging are investigated in this paper. Methods. Eighty consecutive nondiabetic patients undergoing elective coronary angiography were enrolled into the study. Systolic and diastolic aortic diameters, aortic distensibility, CAD severity by angiogram with the use of Gensini scoring, and albumin excretion rates were determined. Results. Cases with CAD had significantly larger systolic (30,72 ± 3,21 mm versus 34,19 ± 4,03 mm for cases without and with CAD, resp.) and diastolic aortic diameters measured 3 cm above aortic valve compared to patients without CAD (33,56 ± 4,07 mm versus 29,75 ± 3,12 mm). The systolic and diastolic diameters were significantly higher in albuminuria positive patients compared to albuminuria negative patients (p = 0.017 and 0.008, resp., for systolic and diastolic diameters). Conclusion. In conclusion aortic diameters are increased in patients with coronary artery disease and in patients with microalbuminuria. In CAD patients, systolic blood pressure, pulse pressure, aortic systolic and diastolic pressure, and albumin excretion rate were higher and aortic distensibility was lower.

What have we learned from Turkish familial hypercholesterolemia registries (A-HIT1 and A-HIT2)?

BACKGROUND AND AIMS Familial hypercholesterolemia (FH) is a common genetic disease of high-level cholesterol leading to premature atherosclerosis. One of the key aspects to overcome FH burden is the generation of large-scale reliable data in terms of registries. This manuscript underlines the important results of nation-wide Turkish FH registries (A-HIT1 and A-HIT2). METHODS A-HIT1 is a survey of homozygous FH patients undergoing low density lipoprotein (LDL) apheresis (LA). A-HIT2 is a registry of adult FH patients (homozygous and heterozygous) admitted to outpatient clinics. Both registries used clinical diagnosis of FH. RESULTS A-HIT1 evaluated 88 patients (27 ± 11 years, 41 women) in 19 centers. All patients were receiving regular LA. There was a 7.37 ± 7.1-year delay between diagnosis and initiation of LA. LDL-cholesterol levels reached the target only in 5 cases. Mean frequency of apheresis sessions was 19 ± 13 days. None of the centers had a standardized approach for LA. Mean frequency of apheresis sessions was every 19 ± 13 (7-90) days. Only 2 centers were aware of the target LDL levels. A-HIT2 enrolled 1071 FH patients (53 ± 8 years, 606 women) from 31 outpatients clinics specialized in cardiology (27), internal medicine (1), and endocrinology (3); 96.4% were heterozygous. 459 patients were on statin treatment. LDL targets were attained in 23 patients (2.1% of the whole population, 5% receiving statin) on treatment. However, 66% of statin-receiving patients were on intense doses of statins. Awareness of FH was 9.5% in the whole patient population. CONCLUSIONS The first nationwide FH registries revealed that FH is still undertreated even in specialized centers in Turkey. Additional effective treatment regiments are urgently needed.