Huseyin Oflaz

Evaluation of Endothelial Function in Subclinical Hypothyroidism and Subclinical Hyperthyroidism

Subclinical hypothyroidism and subclinical hyperthyroidism are two frequently occurring conditions for which exact therapeutic approaches have not yet been established. The aim of this study was to compare the endothelial function and carotid artery intimae-media thickness (IMT) of these two groups of patients to euthyroid subjects and to assess the effects of these conditions on endothelial function. Study groups comprised of 25 subclinical hypothyroid patients (mean age, 32.28 +/- 9.67 years), 13 subclinical hyperthyroid patients (mean age, 35.69 +/- 9.67 years), and 23 euthyroid subjects (mean age, 35.87 +/- 7.93 years). They were evaluated for flow-mediated dilatation (FMD), and carotid artery IMT. The groups were matched strictly for atherosclerotic risk factors. The subclinical hypothyroid group was found to have significantly lower FMD values. No significant differences were observed between the groups with respect to other vascular parameters. The only discriminative factor between the groups was the state of their thyroid function. Therefore, subclinical hypothyroidism may have adverse effects on endothelial function independent from other well-known atherosclerotic risk factors.

The role of aspirin resistance on outcome in patients with acute coronary syndrome and the effect of clopidogrel therapy in the prevention of major cardiovascular events.

AbstractBackground: Aspirin resistance may increase up to more then threefold the risk of major cardiovascular events (MACE) in patients with stable coronary artery disease. Aim:The aim of our study was to determine; the prevalence of aspirin resistance in patients with acute coronary syndromes, the role of aspirin resistance on outcome in the follow-up and the effect of clopidogrel therapy in the prevention of MACE in aspirin resistant subjects. Material and methods: We detected the prevelance of aspirin resistance in 105 patients with acute coronary syndrome. Platelet functions were analyzed in Platelet Function Analyzer (PFA)-100 (Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and collagen and/or ADP (Col/ADP) cartridges. Primary end points of the study were myocardial infarction, unstable angina, cardiac death. Results: 19% (n = 20) of patients were aspirin resistant by PFA-100. In the follow-up, MACE occured in 9 patients (45%) with aspirin resistance and in 10 patients (11.7%) with aspirin sensitive platelet aggregation (p = 0.001). Multivariate analysis showed that aspirin resistance was an independant predictor of MACE. The prevalence of MACE in patients who were on clopidogrel treatment for 12 months were lower compared to those who were on a clopidogrel treatment for the first six months (p = 0.040). Conclusions: We determined that the MACE risk in patients with acute coronary syndromes having detected aspirin resistance, was higher at statistically significant levels compared to patients having aspirin sensitive platelet aggregation. Our results showed that aspirin resistance, was an independant predictor of MACE in patients with acute coronary syndrome.

Endothelial Function in Patients with Obstructive Sleep Apnea Syndrome but without Hypertension

Background: Obstructive sleep apnea syndrome (OSAS) influences endothelial function and causes hypertension. Objectives: Our aim was to evaluate the role of endothelial dysfunction in the pathogenesis of hypertension in OSAS. Methods: Twenty-three patients with OSAS but without hypertension and 15 healthy normotensive subjects were investigated. The presence or absence of OSAS was evaluated with a sleep study. Endothelial function was investigated with brachial artery ultrasound examination. Results: Baseline characteristics were equivalent between the two groups. Minimal oxygen saturation and apnea-hypopnea indexes in the OSAS and control groups were 62.9 ± 16.5 versus 94.9 ± 1.1% (p < 0.0001) and 53.1 ± 20.3 versus 3.8 ± 0.9 (p < 0.0001), respectively. There was not statistically significant difference between basal brachial artery diameters measured in the morning and in the evening in all groups. Flow-mediated dilation (FMD) values measured in the morning were lower than those measured in the evening in both OSAS patients and the control group: FMD of OSAS patients was 6.04 ± 3.18% in the morning and 10.38 ± 4.23% in the evening hours (p = 0.001), and FMD of control subjects was 10.9 ± 2.6% in the morning and 13.9 ± 2.32 in the evening hours (p = 0.002). Differences in FMD values measured both in the morning and evening hours in OSAS patients were lower compared with those in control subjects (p < 0.0001 in the morning hours and p = 0.003 in the evening hours). Conclusions: We detected a prominent diurnal deterioration in endothelial function in normotensive OSAS patients compared with healthy subjects. This deterioration may occur due to ongoing hypoxemia during the night and it may be a possible cause of hypertension and atherosclerotic cardiovascular diseases in patients with OSAS.

The effect of calcineurin inhibitors on endothelial function in renal transplant recipients.

Abstract:  Endothelial dysfunction is of vital importance, as it may cause ischemia and dysfunction in various organs. Despite, this problem has been well documented in patients with end‐stage renal disease (ESRD), there is not enough data considering this issue following renal transplantation. One of the potential causes of endothelial dysfunction in renal transplant recipients may be administration of calcineurin inhibitors. The aim of this study is to evaluate the effects of two different calcineurin inhibitors [cyclosporin A (CsA) and tacrolimus (FK506)] on endothelial function in renal transplant patients. Forty‐four renal transplant recipients [22 on FK506 (group I) and 22 on CsA (group II)] were studied. Endothelial functions of the brachial artery were evaluated by using high resolution vascular ultrasound. Endothelium‐dependent and ‐independent vasodilations were assessed by establishing reactive hyperemia and using sublingual nitroglycerine (NTG), respectively. Results are presented as percentage change from baseline values. Significant endothelial dysfunction was noted in renal transplant patients treated with CsA. While endothelium‐dependent vasodilation was 12.1 ± 5.1% in group I and it was 6.5 ± 3.7% in group II (p < 0.001). The increase in brachial artery diameter after sublingual NTG was 20.1 ± 6.3 and 12.7 ± 5.6% in groups I and II, respectively. This indicates that the endothelium‐dependent and ‐independent vasodilation of the patients on FK506 is better preserved than the patients on CsA therapy. Besides, blood flow volume (BFV) increase was 51.2 ± 39.4 and 43.9 ± 24.3%, in groups I and II, respectively, in reactive hyperemia period (p > 0.05). Post‐transplant course of renal transplant recipients is complicated by endothelial dysfunction. This problem is more prominent in patients on CsA therapy, which can predispose these patients to more frequent cardiac complications.

Association of haematological indices with the degree of microvascular injury in patients with acute anterior wall myocardial infarction treated with primary percutaneous coronary intervention

Background: In acute myocardial infarction (AMI), increased neutrophil count has been associated with more severe coronary artery disease and larger infarct size. Increased mean platelet volume (MPV) is also associated with poor clinical outcome and impaired angiographic reperfusion in patients with AMI. However, the associations of neutrophil count and MPV with the indices of tissue level reperfusion were not fully elucidated. Aim: To elucidate the relationship between baseline neutrophil count and MPV on presentation and microvascular injury in patients with anterior AMI treated with primary percutaneous coronary intervention (pPCI). Methods: 41 patients with anterior wall AMI treated successfully with pPCI were included. The leucocyte count, neutrophil count and MPV were obtained on admission, and the percentage of neutrophils was calculated. After PCI thrombolysis in myocardial infarction, grade 3 flow was established in all patients. The coronary flow velocity pattern (diastolic deceleration time (DDT)) was examined with transthoracic echocardiography and measured intracoronary pressures with fibreoptic pressure–temperature sensor-tipped guidewire in the left anterior descending artery within 48 h after pPCI. Thermodilution-derived coronary flow reserve (CFR) was calculated. Index of microvascular resistance (IMR) was defined as simultaneously measured distal coronary pressure divided by the inverse of the thermodilution-derived hyperaemic mean transit time. Subsequently, a short compliant balloon was placed in the stented segment and inflated to measure coronary wedge pressure (CWP). Results: Higher neutrophil counts were strongly associated with higher IMR (r = 0.86, p<0.001), lower CFR (r = −0.60, p<0.001), shorter DDT (r = −0.73, p<0.001) and higher CWP (r = 0.73, p<0.001). Likewise, there were significant correlations among the percentage of neutrophils and CFR (r = −0.34, p = 0.02), IMR (r = 0.46, p = 0.002), DDT (r = −0.36, p = 0.01) and CWP (r = 0.49, p = 0.001). Relationships among leucocyte count and IMR (r = 0.38, p = 0.01), CFR (r = −0.33, p =  0.03), DDT (r = −0.36, p = 0.01) and CWP (r = 0.32, p = 0.026) were slightly significant. Higher neutrophil count remained independently associated with indices of microvascular perfusion in multivariable models controlling for age, smoking habits and time to treatment. Also, higher MPV on admission was strongly associated with higher IMR (r = 0.89, p<0.001), steeper DDT (r = −0.64, p<0.001), lower CFR (r = −0.43, p = 0.004) and higher CWP (r = 0.77, p<0.001). Conclusion: Absolute and relative neutrophilia and higher MPV on admission were independently associated with impaired microvascular perfusion in patients with anterior AMI treated with pPCI. It is possible that neutrophilia and high MPV are simple surrogate markers of worse microvascular injury in patients with AMI.

MR imaging features of ventricular noncompaction: Emphasis on distribution and pattern of fibrosis

OBJECTIVE The purpose of this study is to describe morphologic features and delayed contrast-enhancement pattern of the noncompaction of the left ventricle in cardiac magnetic resonance (MR) imaging. METHODS We retrospectively reviewed morphological cardiac MR imaging findings of ventricular noncompaction in 15 patients (eight men, seven women, and ages 6 months to 73 years old, mean 22 year). In 10 patients delayed contrast enhanced images were obtained after the morphological examination. RESULTS In all patients, noncompaction was seen in the apical and midventricular-lateral segment. Basal-septal segment involvement was not determined in any patients. Noncompacted/compacted ratio was 2-4.5 (mean 3). In nine patients, right ventricular involvement was observed in addition to left ventricular noncompaction. Delayed contrast-enhancement was seen in eight out of 10 patients not only involved segments but also normal segments of the heart. CONCLUSION Cardiac MR imaging is a valuable imaging method in patients with suspected ventricular noncompaction by showing increased trabeculations, deep intertrabecular recesses and fibrosis. Fibrosis is a common finding in ventricular noncompaction.

Coronary flow reserve is impaired in patients with nonalcoholic fatty liver disease: Association with liver fibrosis

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. Coronary flow reserve (CFR) is widely used to examine the integrity of coronary microvascular circulation. We evaluated the prevalence of impaired CFR in patients with biopsy-proven NAFLD. We also investigated the independent clinical, biochemical, and liver histology predictors of CFR in the setting of NAFLD. METHODS Fifty-nine consecutive patients with NAFLD and 77 age- and gender-matched controls were evaluated. CFR recordings were performed by transthoracic Doppler harmonic echocardiography. CFR>or=2.0 was considered normal. RESULTS CFR was significantly lower in patients with NAFLD than in controls (2.11+/-0.45 vs. 2.52+/-0.62, P<0.001). An impaired CFR (i.e. <2) was found in 25 NAFLD patients (42.4%) whereas all controls had normal CFR values (P<0.001). A stepwise linear regression analysis in NAFLD patients identified liver fibrosis scores as the only independent predictor of CFR values (beta=-0.60; t=-2.44, P=0.021). CONCLUSION Our findings indicate that in patients with biopsy-proven NAFLD: (a) an abnormal CFR is found in approximately 42.4% of cases, and (b) liver fibrosis scores are an independent predictor of depressed CFR.

Clinical relevance of aspirin resistance in patients with stable coronary artery disease: a prospective follow-up study (PROSPECTAR).

Aspirin resistance may increase the risk of major adverse cardiac events (MACE) more than threefold in patients with stable coronary artery disease (CAD). This study aimed to determine the prevalence of aspirin resistance in patients with stable CAD, the role of aspirin resistance on outcome in the follow-up, and the effect of clopidogrel therapy in MACE prevention in aspirin-resistant individuals. We detected the prevalence of aspirin resistance in 234 patients with stable CAD. Platelet function was determined by PFA-100 with collagen and/or epinephrine and collagen and/or ADP cartridges. The mean follow-up time was 20.6 ± 6.9 months. The primary endpoints of the study were occurrence of myocardial infarction, unstable angina, stroke and cardiac death. Of patients, 22.2% (n = 52) were aspirin resistant by PFA-100. During follow-up, MACE occurred in eight patients (15.4%) with aspirin resistance and in 20 patients (11.0%) with aspirin-sensitive platelet aggregation (P = 0.269). MACE increased in aspirin-resistant patients after termination of clopidogrel therapy. Eleven patients experienced MACE after cessation of clopidogrel therapy (P < 0.001). The MACE risk in patients with stable CAD having detected aspirin resistance was similar compared with patients having aspirin-sensitive platelet aggregation by PFA-100. The MACE prevalence increased during follow-up, however, just after cessation of clopidogrel therapy.

Traditional and “new” cardiovascular risk markers and factors in pediatric dialysis patients

Cardiovascular disease (CVD) is the principal cause of mortality in patients with end-stage renal disease (ESRD). The aim of this study was to analyze carotid intima-media thickness (cIMT), endothelium-dependent dilatation (EDD), and left ventricular mass index (LVMI) as the cardiovascular risk markers and to investigate the independent risk factors of these markers in pediatric dialysis patients. This study included 39 children and adolescents undergoing dialysis (15 hemodialysis and 24 peritoneal dialysis) and 15 age- and gender-matched healthy subjects. The cIMT and EDD were assessed by high-resolution ultrasound, and LVMI was calculated from standard echocardiographic measurements. Compared with control subjects, cIMT standard deviation scores (SDS), LVMI, total homocysteine (tHcy), and high-sensitivity C-reactive protein (hs-CRP) values were significantly higher in patients, but EDD values did not differ. The mean hs-CRP level was significantly higher in hemodialysis (HD) patients than in peritoneal dialysis (PD) patients. The cIMT-SDS and LVMI were associated with several variables in univariate analysis. Stepwise linear regression analysis, indexed SBP (p = 0.017), and hemoglobin (p = 0.001) turned out to be independent variables for predicting LVMI, and a significant predictor of cIMT was indexed diastolic blood pressure (DBP) (p = 0.035). The causes of atherosclerosis and left ventricular hypertrophy are multifactorial in children and adolescents with ESRD. Better management of hypertension and anemia may be priorities for preventing or improving CVD in these patients.

Reduction of uric acid levels with allopurinol treatment improves endothelial function in patients with chronic kidney disease.

BACKGROUND Endothelial dysfunction (ED) is a key event in the development of atherosclerotic cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Association of hyperuricemia with CVD has been previously reported in the nonuremic population. In this prospective study, we aimed to evaluate the effects of treatment of hyperuricemia with allopurinol on ED and changes in the serum reactive oxygen species in patients with CKD. METHODS In this study, 19 (13 male) hyperuricemic (UA > 7 mg/dl) nondiabetic CKD patients without any comorbidity, aged < 60 years with creatinine clearance (CrCl) between 20 and 60 ml/min were evaluated. Endothelial functions were assessed by ischemia-induced forearm vasodilatation method (EDD). Oxidative stress was evaluated by measuring the serum oxidized LDL (ox-LDL), advanced oxidation protein products (AOPP) and nitrotyrosine (NT) levels. After measuring all these tests at baseline, allopurinol therapy was commenced for 8 weeks. After 8 weeks of allopurinol treatment, all measurements were repeated. Then, allopurinol treatment was ceased and same measurements were also repeated 8 weeks after ceasing of the treatment. RESULTS Serum creatinine, total cholesterol, albumin, hs-CRP, CrCl and proteinuria levels of the patients were similar among three study periods. After allopurinol therapy, the mean serum UA and NT levels significantly reduced as compared to baseline. At the 8th week after cessation of allopurinol treatment, serum UA levels were significantly increased. After allopurinol therapy, EDD value increased from 5.42 ± 8.3% at baseline to 11.37 ± 9% (p < 0.001). At the 8th week after ceasing allopurinol treatment, EDD returned to baseline values (5.96 ± 8%, p < 0.001). CONCLUSION Treatment of hyperuricemia with allopurinol improve ED in patients with CKD. However, mechanism responsible for this beneficial effect seems to be apart from antioxidant effects of allopurinol.