Zeki Öngen

Circulating miR-21 and eNOS in subclinical atherosclerosis in patients with hypertension

Abstract Objectives: The aim of this study is to evaluate the relationship of miR-21, nitric oxide (NOx) and endothelial nitric oxide synthase (eNOS) with subclinical atherosclerosis in carotid arteries by measuring carotid intima media thickness (CIMT) in patients with hypertension and healthy controls. Design and Methods: A total of 28 hypertensive and 28 healthy controls were enrolled. MiR-21 expression was analyzed by quantitative reverse transcription-PCR and NOx, and eNOS levels were measured by ELISA assay. CIMT was evaluated by ultrasonography and CIMT ≥ 0.8 mm was accepted as increased CIMT (iCIMT). Results: C-reactive protein (CRP) level, plasma miR-21 expression level and CIMT were found to be significantly higher in the hypertension group when compared to the control group (p = 0.009, p = 0.002 and p < 0.001, respectively). NOx and eNOS levels were significantly lower in the hypertension group compared to the control group (p < 0.001, both). MiR-21 level was positively correlated with the clinical systolic blood pressure, clinical diastolic blood pressure, CRP and CIMT. MiR-21 was also negatively correlated with NOx and eNOS. Eighteen patients with hypertension had iCIMT. MiR-21 and CRP levels were significantly higher (p < 0.001 and p = 0.001), whereas NOx and eNOS levels were significantly lower in patients with iCIMT (p < 0.001, both). Conclusion: The decreased levels of NOx and eNOS found in this study indicate the co-existence of endothelial dysfunction and hypertension once more. In the absence of microalbuminuria, the increased miR-21 expression in patients with iCIMT made us conclude that this miRNA might be involved in the early stages of atherosclerotic process in hypertensive patients.

Circulating miR-221-3p as a novel marker for early prediction of acute myocardial infarction.

Recent studies have reported circulating microRNAs (miRNAs) as novel biomarkers for cardiovascular diseases including acute myocardial infarction, heart failure, diabetes mellitus, stroke, and acute pulmonary embolism. The aims of this study were 1) to compare the plasma expression levels of miRNAs in patients with acute coronary syndrome (ACS) and control subjects and in ST-elevation myocardial infarction (STEMI) and non-STEMI 2) to evaluate miRNAs potential to be used as novel diagnostic biomarkers for ACS. Twenty seven consecutive patients, admitted to emergency department of a training and research hospital between January-December 2013 with acute chest pain and/or dyspnea and diagnosed with ACS, and 16 non-ACS control subjects were included in this study. miRNA profiling was performed by using real time polymerase chain reaction. Functions of dysregulated miRNAs were evaluated by computerized-pathways analysis. miR-221-3p was one of the two most dysregulated miRNAs with a fold regulation of 3.89. It was significantly positively correlated with both Troponin and GRACE and Synthax Score. Moreover, miR221-3p was found to be significantly inversely correlated with left ventricular ejection fraction. miR-221-3p was the most prominent biomarker candidate with an area under curve (AUC) level of 0.881 (95% confidence interval: 0.774-0.987; p=0.002). The present study is the first to report an increased expression levels of miR-221-3p in AMI. Since miR-221-3p has a high discriminative value and significant relations with Troponin, GRACE and Synthax score and left ventricular systolic function, it may be a potential biomarker for early prediction of AMI.

Effectiveness of a lead cap in radiation protection of the head in the cardiac catheterisation laboratory

Introduction During the past 30 years, interventional cardiology has advanced dramatically resulting in outstanding increases in occupational radiation exposure of interventional cardiologists. Despite the remarkable changes in fluoroscopic procedures, radiation protection technology is not much different from how it was decades ago. Moreover, new evidence on occupational radiation suggests that low doses of ionising radiation exposure may be associated with the development of cancer in interventional cardiologists and radiologists1-6. The brain is of particular interest, because it is one of the least protected organs during interventional procedures2. The trunk and the thyroid are protected with lead aprons, and the eyes are protected by lead glasses; however the head is completely exposed. The annual head dose sustained by a cardiologist generally ranges between 20 and 30 mSv, and in some cases may reach up to 60 mSv per year7. This indicates a dose 10 times higher than whole body exposure8. Ceiling-suspended lead shields reduce radiation doses to the brain but they are designed to protect the face and head from primary scatter radiation from the patient. Therefore, a significant amount of secondary radiation scattered from the laboratory walls may reach the operator’s head, despite the presence of a ceilingmounted glass shield. Until now, operators have not used protective garments to protect their head from radiation.

Serum myeloperoxidase level predicts reperfusion in patients with myocardial infarction receiving thrombolytic therapy

Polymorphonuclear leukocytes play a central role in all stages of the atherothrombotic inflammatory process. The atherothrombotic activity of polymorphonuclear leukocytes is exerted by mediators such as myeloperoxidase (MPO). Although the role of MPO has been studied with respect to the development of adverse cardiac events in acute coronary syndromes (ACS), the association of this molecule with effectiveness of reperfusion in patients receiving thrombolysis is not yet known. The study population consisted of a total of 158 patients with acute coronary syndromes. Final diagnosis was ST-segment elevation myocardial infarction in 86 patients, 80 of whom received thrombolysis. Blood samples were drawn at presentation of the patients and serum myeloperoxidase levels were measured. Reperfusion was defined in terms of electrocardiographic ST-segment resolution. The serum levels of MPO were found to be correlated with rates of in-hospital adverse events including death (P < 0.001), reinfarction (P < 0.001), recurrent ischemia (P < 0.001), arrhythmias (P < 0.001), clinical heart failure (P < 0.001), and cardiogenic shock (P < 0.001). There was a significant difference in serum MPO levels between subjects with three-vessel disease and two- or one-vessel disease (P < 0.001). Pre-lytic serum high-sensitivity C-reactive protein levels in patients with successful reperfusion were lower than in patients with failed reperfusion (P < 0.001). Analysis of patients with ST segment elevation myocardial infarction receiving thrombolytic therapy revealed that pre-lytic serum MPO levels in patients with successful reperfusion were significantly lower than those of patients with failed reperfusion (P < 0.001). In the present study, serum MPO levels were found to be a strong predictor of response to thrombolytic treatment in patients with ST-segment elevation myocardial infarction. Therefore the level of inflammatory activity in acute coronary syndromes seems to influence the effectiveness of fibrinolysis.

Takayasu disease with prominent pulmonary artery involvement: confusion with pulmonary disease leading to delayed diagnosis

Pulmonary artery involvement as the initial predominant clinical manifestation in Takayasu arteritis (TA) is rare. We describe a young adult female who presented with life-threatening complications of proximal pulmonary arterial involvement of Takayasu arteritis. In our case, atypical presentation of TA with pulmonary symptoms due to pulmonary artery involvement resulted in an erroneous initial diagnosis of sarcoidosis and then tuberculosis. The frequency of such a clinical form could be underestimated given the difficulties involved in its diagnosis and because its features are similar to those of pulmonary disease.

The effect of genetic polymorphisms of TLR2 and TLR4 in Turkish patients with coronary artery disease.

Coronary artery disease (CAD), being a multifactorial disease process, has been suggested to be associated by the interaction of both environmental and genetic risk factors. Toll-like receptors (TLRs) are related to the receptors of the innate immune system which serves as the recognition of the conserved pathogen motifs and the activation of the signals that stimulate inflammatory genes. In this study, we investigated the relationship between the polymorphisms in the TLR2-Arg753Gly, TLR4-Asp299Gly and Thr399Ile gene and CAD. The study population consisted of 300 patients (149 men, 151 women) with angiographically documented CAD. The polymorphisms were genotyped by real time PCR. No association between TLR2-Arg677Trp or TLR4-Asp299Gly and -Thr399Ile gene polymorphisms and the presence or the severity of CAD was observed. On the other hand, the TLR2-Arg753Arg genotype seemed to have a protective effect against development of CAD (OR=0.17; 95% CI=0.04-0.83). Our findings suggest that TLR2-Arg753Gly polymorphism is associated with CAD susceptibility in Turkish patients.

The Trends in Utilizing Nonvitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation: A Real-Life Experience.

Dabigatran and rivaroxaban are novel nonvitamin K antagonist oral anticoagulants (NOACs) approved for thromboprophylaxis in atrial fibrillation (AF). In Turkey, like other countries, the efficacy of translation of the clinical trial results and current guideline recommendations into daily clinical practice is yet to be discovered. Using data from medical records of three tertiary care cardiology centers, we identified patients with nonvalvular AF on dabigatran or rivaroxaban treatment. Baseline characteristics and utilization trends were compared between dabigatran and rivaroxaban groups. Secondarily, clinical events including ischemic stroke and/or transient ischemic attack, systemic embolism, and bleeding were evaluated. Among 294 patients with AF included, dabigatran was utilized in 177 (60.2%) and rivaroxaban in 117 (39.8%). Overall, 76% of patients had received long-term warfarin therapy. The use of 110 mg twice a day (55.4%) was the prevailing strategy in dabigatran group, whereas in rivaroxaban group 20 mg every day (67.5%) was the preferred option. Of the patients, 37.3% had severe valvular disease in which mitral regurgitation was the predominant valve abnormality. Scores of CHADS2, CHA2DS2VASc, and HAS-BLED were similar in both the groups. Of the patients, 24% in dabigatran group and 13.7% in rivaroxaban group were prescribed the lower dose inappropriately. The two NOACs did not differ significantly in terms of clinical events. The results of this study indicate that in daily practice, the physicians’ behavior in utilizing the NOACs is shaped by the clinical trials and the guideline recommendations. On the other hand, in dose selection, this adherence is not of high quality.

Development of chylothorax and chylous ascites in a patient with congestive heart failure

Chylothorax and chylous ascites are very rare clinical entities generally caused by obstruction and disruption of the thoracic duct. A 60-year-old man presented with exertional dyspnea, fatigue, and chest discomfort of 18-month history. Physical examination revealed S4, bilateral pretibial edema, and moderate amount of ascites. Computed tomography and X-ray of the thorax showed left-sided pleural effusion. Abdominal imaging showed normal liver and spleen structure with intraperitoneal effusion and periportal edema. Thoracentesis and paracentesis yielded a milky, lipemic fluid of exudative nature. Biochemical analysis of the fluids showed a high triglyceride content and elevated lymphocyte count, typical of chylous fluid. All laboratory analyses for possible etiologies including neoplasms, tuberculosis, and cirrhosis were negative. Positron-emission tomography did not show any pathological uptake. Transthoracic echocardiographic examination showed bilateral atrial enlargement, left ventricular hypertrophy, anteroseptal hypokinesia and akinesia, and moderate mitral and tricuspid regurgitation, with an ejection fraction of 25%. Coronary arteries were normal on angiography. The patient was diagnosed with severe congestive heart failure accompanied by chylothorax and chylous ascites. Despite appropriate treatment, there was little change in congestion and no change in symptoms. He died during ultrafiltration therapy due to hemodynamic collapse and asystole.

Antihypertensive Drugs and Inflammation in Acute Ischemic Stroke as a Predictor Factor of Future Cardiovascular Mortality

The beneficial effects of antihypertensive drugs in secondary stroke prevention could not be based on their effects on lowering hypertension only.In this prospective study, the status of blood pressure, treatment regimens, new atherothrombotic event, blood sampling for hs-CRP and fibrinogen were asked at initial visit, 6th, and 12th months in 226 patients with atherothrombotic stroke.Eighty-seven percent of patients had an antihypertensive regimen, but hypertension control was achieved in 34.1% of patients.Neither use of six different antihypertensive drug regimens nor the change in blood pressure levels showed any difference on new atherothrombotic events, outcomes or survival rates.On the other hand, the higher levels of hs-CRP at baseline were found to be associated with higher mortality rates(p = 0.020).Our findings emphasize the predictive role of inflammation in future cardiovascular mortality in patients with acute ischemic stroke, indicating that inflammatory mediators underlying the atherothrombotic process play a more important role than it is assumed.

An unusual adverse effect of sildenafil citrate: acute myocardial infarction in a nitrate-free patient.

Myocardial infarction (MI) associated with sildenafil citrate is seen rarely in patients without any history of coronary artery disease. We report a nitrate-free patient with a history of cardiovascular risk factors who developed acute MI after taking sildenafil. A 44-year-old man diagnosed with acute anterior ST segment elevation MI 120 min after self-administration of 150 mg sildenafil was admitted before attempting any sexual intercourse. The coronary angiography revealed 99% occlusion of the left anterior descending artery (LAD) and a bare-metal stent was implanted. He was discharged after 5 days without any complication. Sildenafil may cause coronary steal or may lead to vasodilation causing hypotension in patient with pre-existing cardiovascular disease, especially in patients on nitrate therapy. Our patient was nitrate free, with normal blood pressure values. Emotional stimulation associated with anticipated sexual activity may have been a triggering factor for vulnerable coronary plaque rupture.