Sabahattin Umman

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 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.

The use of human heart-type fatty acid-binding protein as an early diagnostic biochemical marker of myocardial necrosis in patients with acute coronary syndrome, and its comparison with troponin-T and creatine kinase–myocardial band

Heart-type fatty acid-binding protein (H-FABP), a new biochemical marker of sarcolemmal injury due to acute myocardial ischemia, can be used as a tool in early diagnosis and management of patients at high risk. The aim of this study was to determine the early diagnostic value of H-FABP in acute coronary syndrome (within 6–24 h of chest pain) and to compare it with troponin-T (TnT) and creatine kinase–myocardial band (CK-MB) for accuracy. The study consisted of 40 consecutive patients with chest pain admitted to the coronary care unit with the diagnosis of suspected acute coronary syndrome. The patient population consisted of two groups according to the time of admission; the first group (26 patients) included patients admitted within 6 h of chest pain, and the second group (14 patients) included patients admitted within 6–24 h of chest pain. The blood samples for H-FABP, TnT, and CK-MB were obtained at admittance, at the 6th, and at the 24th hours for the first group, and at admittance and at the 24th hours for the second. Statistical analysis was performed among the 26 patients for the first 6 h values, and among all 40 patients for the values obtained within 6–24 h and at the 24th hour. The patients were then divided into groups according to the changes in the electrocardiogram (ECG) and cardiac enzymes as unstable angina pectoris, non-ST elevation myocardial infarction (MI), and ST-elevation MI. Coronary angiography was performed in 38 (95%) patients. Sensitivity of TnT, CK-MB, and H-FABP in the first group (within 6 h of chest pain) were 38%, 76%, and 95% respectively. The sensitivity of H-FABP was significantly higher than TnT (P = 0.014). Sensitivity of TnT, CK-MB, and H-FABP tests in the second time period (within 6–24 h of chest pain) were 100%, 90%, and 91% respectively. In this time period, the sensitivity of TnT was higher than H-FABP, but it was statistically insignificant. At the 24th hour, sensitivity of TnT was 100%, CK-MB 90%, and H-FABP 27.3%, and TnT and CK-MB were more sensitive than H-FABP for the whole group (P = 0.002). In the first group (within 6 h of chest pain) H-FABP positivity was slightly but insignificantly higher in patients with two- and three-vessel disease compared with those with one-vessel disease (60.7% and 33.3%, P = 0.19) and in the same group, patients who underwent primary coronary intervention had a significantly higher H-FABP positivity than others (80%, 32%, P = 0.02). Within 6–24 h of chest pain, H-FABP positivity was 80% in patients with one-vessel disease and 71.4% in patients with two- and three-vessel disease (P = 0.69). Within 6–24 h, positivity of H-FABP reached a peak value of 100% in patients who underwent primary coronary intervention, while H-FABP was positive in 60% of the others (P < 0.001). We conclude that within the 6 h of acute coronary syndrome, H-FABP seems to be a more sensitive biochemical marker than TnT in the early detection of ischemic myocardial necrosis. But after the first 6 h of the onset of chest pain the sensitivity of H-FABP decreases, and this marker should not be used alone in patients admitted 24 h after the onset of chest pain.

The role of exercise on platelet aggregation in patients with stable coronary artery disease: exercise induces aspirin resistant platelet activation.

Objectives: The aim of our study was to determine the relation between exercise stress test and aspirin resistance in patients with stable coronary artery disease.Background: Clinically aspirin resistance is defined as having thrombotic and embolic cardiovascular events despite regular aspirin therapy.Methods: We studied platelet functions of 62 patients with stable coronary artery disease and 20 subjects with normal coronary arteries by Platelet Function Analyzer (PFA-100, Dade Behring, Germany) at rest and after exertion with collagen and/or epinephrine (Col/Epi) and collagen and/or ADP cartridges. Closure time (CT) < 186 seconds was defined as aspirin resistance with Col/Epi cartridges of PFA-100. Symptom limited treadmill stress test (protocol of Bruce) was performed with Oxford Streslink TD-1 system.Results: 8 (12.9%) patients were aspirin resistant by PFA-100 (CT < 186s despite regular aspirin therapy) at rest. At the first minute of the recovery period of exercise stress test 14 (22.5%) patients were aspirin resistant by PFA-100. CTs with Col/ADP were respectively 89 ± 6 s (83–100s) and 89 ± 5 s (82–104s) at rest and after exercise (p = 0.107). 20.3% (11/54) of patients known as in vitro aspirin sensitives at rest had shorter CTs and 11.1% (6/54) had aspirin resistance after exercise (p = 0.004). There was no statistically significiant difference in platelet functions in the control group after exertion.Conclusion: We conclude that 11.1% of in vitro aspirin sensitive subjects at rest had aspirin resistance after exercise by PFA-100. In some individuals, exercise induced platelet activation is aspirin insensitive at usual antiplatelet doses. We need further clinical trials to optimize antiplatelet therapy in patients with coronary artery disease.

Effect of intracoronary streptokinase administered immediately after primary percutaneous coronary intervention on long-term left ventricular infarct size, volumes, and function.

OBJECTIVES The purpose of this study was to investigate the reflections of the improvement in microvascular perfusion provided by adjuvant intracoronary streptokinase (ICSK) on late-phase infarct size and left ventricular volumes and functions. BACKGROUND It has been shown that ICSK given immediately after primary percutaneous coronary intervention (PCI) improves myocardial perfusion in the early days of ST-segment elevation acute myocardial infarction. METHODS Ninety-five patients undergoing primary PCI were randomized to ICSK 250 kU (n = 51) or no additional therapy (n = 44). Two days later, coronary hemodynamic indexes were measured to evaluate tissue-level perfusion. After 6 months, angiography, echocardiography, and technetium-99m single-photon emission computed tomography (SPECT) were performed. RESULTS At 2 days, all indexes of microvascular function were significantly better in the ICSK group than in the control group, including coronary flow reserve (2.5 vs. 1.7, p < 0.001) and index of microvascular resistance (20.2 vs. 34.2, p < 0.001). At 6 months, infarct size (22.7% vs. 32.9%; p = 0.003) and left ventricular end-systolic (41.1 ml vs. 60.9 ml; p = 0.009) and end-diastolic volumes (95.5 ml vs. 118.3 ml; p = 0.006) were significantly smaller, and the ejection fraction was significantly higher (57.2% vs. 51.8%; p = 0.018) in the ICSK group compared with the control group. CONCLUSIONS In this study, it has been demonstrated that low-dose ICSK given immediately after primary PCI significantly limits long-term infarct size and preserves left ventricular volumes and functions. (Effect of Complementary Intracoronary Streptokinase Administration Immediately After Primary Percutaneous Coronary Intervention on Microvascular Perfusion and Late Term Infarct Size in Patients With Acute Myocardial Infarction; NCT00302419).

Multiple coronary thrombosis and stent implantation to the subtotally occluded right renal artery in a patient with essential thrombocytosis: a case report with review.

Essential thrombocytosis is a myeloproliferative disorder of unknown etiology manifested clinically by the overproduction of platelets in the absence of a definable cause. Platelet dysfunction in essential thrombocytosis results in both hemorrhage and thrombosis. It is one of the rare causes of ischemic cardiovascular events. Fewer than 20 cases of essential thrombocytosis with involvement of coronary arteries leading to acute coronary syndromes or myocardial infarction have been reported. We report a case of multiple coronary thrombosis involving the left anterior descending artery and circumflex artery and stent implantation to the subtotally stenotic right renal artery in a women with unstable angina pectoris, essential thrombocytosis and previous history of renal artery trombosis.

Acute anterior myocardial infarction after chemotherapy for testicular seminoma in a young patient.

Testicular cancer is the most common solid tumor among young men aged 15 to 35 years. Combination chemotherapy with cisplatin, etoposide, and bleomycin remains the mainstay of treatment. We present a 27-year-old man who presented with an acute anterior myocardial infarction during the second course of chemotherapy for seminoma. Because the patient had no significant risk factors for coronary heart disease, the infarction was likely caused by the chemotherapy regimen.

Concurrent Microvascular and Infarct Remodeling After Successful Reperfusion of ST-Elevation Acute Myocardial Infarction

Background—Connection between the course of microvascular and infarct remodeling processes over time after reperfused ST-elevation acute myocardial infarction has not been fully elucidated. The aim of this study is to investigate the association of temporal changes in hemodynamics of microcirculation in the infarcted territory and infarct size (IS) after primary percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction. Methods and Results—Thirty-five patients admitted with ST-elevation acute myocardial infarction undergoing primary percutaneous coronary intervention were enrolled in the study. Coronary flow reserve (CFR), index of microvascular resistance (IMR), and IS were assessed 2 days after primary percutaneous coronary intervention and at the 5-month follow-up. The predictors of the 5-month IS were the baseline values of IS (&bgr;=0.6, P<0.001), IMR (&bgr;=0.280, P=0.013), and CFR (&bgr;=−0.276, P=0.017). There were significant correlations between relative change in IS and relative change in measures of microvascular function (IS and CFR [r=−0.51, P=0.002]); IS and IMR ([r=0.55, P=0.001]). In multivariate model, relative changes in IMR (&bgr;=0.552, P=0.001) and CFR (&bgr;=−0.511, P=0.002) were the only predictors of relative change in IS. In patients with an improvement in IMR >33%, the mean IS decreased from 32.3±16.9% to 19.3±14% (P=0.001) in the follow-up. Similarly, in patients with an improvement in CFR >41%, the mean IS significantly decreased from 29.9±20% to 15.8±12.4% (P=0.003). But in patients with an improvement in IMR and CFR, which were below than the mean values, IS did not significantly decrease during the follow-up. Conclusions—Improvement in microvascular function in the infarcted territory is associated with reduction in IS after reperfused ST-elevation acute myocardial infarction. This link suggests that further investigations are warranted to determine whether therapeutic protection of microvascular integrity results in augmentation of infarct healing.

Changes in endothelial function before and after renal transplantation

Endothelial dysfunction is an early key event in the development of atherosclerotic cardiovascular disease observed in chronic renal failure patients. The role of renal transplantation (RTx) on endothelial dysfunction is still unclear. The aim of this study was to evaluate the endothelial function of chronic renal failure patients before RTx (while they were on hemodialysis, HD), and after RTx (at the 6th and 12th months) by a noninvasive method, brachial arterial ultrasound. A total of 22 (17 male, mean age: 33.9 ± 11.6 years) RTx recipients were enrolled in the study. Endothelium‐dependent vasodilation (EDD) was assessed by establishing reactive hyperemia. EDD prior to transplantation was significantly lower when compared with EDD measured at the 6th and 12th months after RTx (EDD pretransplantation: 6 ± 3.7%, EDD at the 6th month of RTx: 8.3 ± 2.3% and EDD at the 12th month of RTx: 12.1 ± 3.6%, P < 0.001). When the EDD values measured at the 6th and 12th months of RTx were compared, measurements of the 12th month were found significantly higher than those of the 6th month (P < 0.001). Our results also showed that RTx has provided improvement in endothelial function by eliminating the uremic environment although not in the early post‐RTx period.