Berrin Umman

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.

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.

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.

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.

Androgenic anabolic steroids also impair right ventricular function

Chronic anabolic steroid use suppresses left ventricular functions. However, there is no information regarding the chronic effects of anabolic steroids on right ventricular function which also plays a key role in global cardiac function. The main objective of the present study was to investigate the effects of androgenic anabolic steroids usage among athletes on remodeling the right part of the heart. Androgenic-anabolic steroids-using bodybuilders had smaller diastolic velocities of both ventricles than drug-free bodybuilders and sedentary counterparts. This study shows that androgenic anabolic steroids-using bodybuilders exhibited depressed diastolic functions of both ventricles.

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).

Left ventricular remodeling and aortic distensibility in elite power athletes

The aim of this study was to determine left ventricular (LV) morphology and aortic function in power athletes and to compare them with normal subjects. Thirty-two elite male wrestlers and 15 age-matched healthy male controls were included. All subjects underwent echocardiographic examination. Measurements included LV cavity dimension at systole and diastole, wall thickness, diastolic parameters, and aortic diameter, 3 cm above aortic valve, at systole and diastole. Left ventricular mass and mass index were found to be higher in the athletes than in control subjects. The aortic distensibility index was found to be reduced in the athletes compared with controls (2.53 ± 0.91 vs 3.94 ± 1.77 cm2 dyne−1 10−6, P = 0.003), while the aortic stiffness index was significantly higher in the athletes than in controls (9.12 ± 3.23 vs 6.65 ± 2.35, P = 0.02). However, LV end-systolic wall stress was lower in the athletes than in controls. Furthermore, transmitral early (E) and late (A) peak velocity, peak velocity of the myocardial systolic wave (Sm), and early (Em) and atrial (Am) diastolic waves at the inferior wall were higher in the athletes than in controls. Reduced aortic distensibility in elite power athletes may be one of the cardiovascular adaptation factors which affect LV hypertrophy.

Association of genetic variants in Methylenetetrahydrofolate Reductase and Paraoxonase-1 genes with homocysteine, folate and vitamin B12 in coronary artery disease

Background The aim of the present study was to investigate the association between genetic variants in metylenetetrahydrofolate reductase (MTHFR) and Paraoxonase-1 (PON1) 55/192 genes and total homocysteine (tHcy), folate, B12 vitamin, and PON1 levels in patients with coronary artery disease (CAD). Methods The study included 235 patients with CAD and 268 healthy control subjects. Results LL and LM genotypes and L allele of PON1 55 were over-represented in patients. In contrast, MM genotype and M allele were more frequent in controls. QQ genotype and Q allele of PON1 192 and CT genotype of MTHFR were significantly diminished and QR genotype and R allele were significantly elevated in CAD patients compared with controls. The plasma tHcy were elevated but B12 levels were diminished in patients. PON1 55 and 192 genetic variants were significantly associated with PON1 activity, triglyceride, total cholesterol, tHcy and, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol in patients, respectively. Conclusion Genetic variants of PON1 55/192 and MTHFR were associated with CAD.

Left ventricular geometric patterns and QT dispersion in untreated essential hypertension.

The spectrum of left ventricular adaptation to hypertension, different types of hypertrophy patterns, and QT dispersion in different types of hypertrophy was investigated in 107 patients with untreated essential hypertension and 30 age- and gender-matched normal adults studied by 12-derivation electrocardiogram (ECG), two-dimensional, and M-mode echocardiography. Left ventricular mass (LVM), body mass index, total peripheral resistance (TPR), relative wall thickness (RWT), and QT dispersion were found to be statistically significantly higher in the hypertension group (P < .001 for all). Among hypertensive patients, 41.1% had both normal LVM and RWT, here called normal left ventricle in hypertension; 10.3% had concentric hypertrophy with increased LVM and RWT; 14.95% had eccentric hypertrophy with increased LVM and normal RWT; and 32.7% had concentric remodeling with normal LVM and increased RWT. Echocardiographically derived cardiac index was higher in the concentric hypertrophy and eccentric hypertrophy patterns (P = .002 and P < .0001, respectively), whereas TPR was higher in the concentric hypertrophy and concentric remodeling patterns (P = .017 and .02, respectively). QT dispersion values were found to be increased in the hypertensive group (P = .001), whereas similar values were calculated for different types of hypertrophy patterns. We conclude that the more common types of ventricular adaptation to essential hypertension are eccentric hypertrophy and concentric remodeling. Concentric hypertrophy is found to be associated with both volume and pressure overload, whereas eccentric hypertrophy is associated with volume overload only and concentric remodeling is associated with pressure overload. But different left ventricular geometric patterns seem to have similar effects on QT dispersion.