Association of sleep apnea with coronary slow-flow phenomenon.

BACKGROUND: Both obstructive sleep apnea (OSA) and coronary slow-flow phenomenon (CSFP) are known to share similar etiopathogenic mechanisms, such as chronic sympathetic activation, upregulation of inflammatory pathways, oxidative stress and, finally, endothelial dysfunction. OBJECTIVE: We evaluated whether there is an association between OSA and coronary flow rates. METHOD: We retrospectively reviewed medical records of all patients who underwent diagnostic nocturnal polysomnography for suspected OSA. Those who had coronary angiography performed within the same year of polysomnography were divided into two main groups: those with (group 1) and without (group 2) OSA; also, angiographic coronary TIMI (thrombolysis in myocardial infarction) frame counts (TFC) were compared between the groups. Patients with coronary arterial stenosis and angiograms with inadequate filling of the coronary arteries or visualization of the distal landmarks for frame counting were excluded from the study. RESULTS: There was a statistically significant difference between the groups regarding TFCs. We found a significant positive correlation between mean TFC and apnea-hypopnea index (r=0.611, P<0.001). CONCLUSION: The current study demonstrated that sleep apnea impairs coronary flow rates and is associated with CSFP.

Safety of clopidogrel in older patients: a nonrandomized, parallel-group, controlled, two-centre study.

BACKGROUND: The safety and efficacy of clopidogrel therapy in patients with stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention (PCI) have been demonstrated. OBJECTIVES: To evaluate the safety (primary outcome, defined as any bleeding complication or thrombocytopenia) and adverse outcomes (secondary outcomes, defined as death from cardiovascular causes, myocardial infarction or stroke) of clopidogrel therapy in patients aged ≥75 years with stable or unstable coronary artery disease undergoing PCI, and to compare these outcomes with those in younger controls. METHODS: Patients with both stable coronary heart disease and acute coronary syndromes undergoing PCI were included in the study. Two groups were formed according to age at the time of admission. Patients aged ≥75 years (the study group, n = 149) formed one group; the other group included patients aged <75 years (the control group, n = 298). During an ad hoc PCI procedure, a 600 mg loading and 75 mg/day maintenance dose of clopidogrel in addition to aspirin (acetylsalicylic acid) therapy (300 mg/day) were administrated to both treatment groups. In-hospital outcomes were investigated during a mean ± SD follow-up period of 5.3 ± 3.9 days. RESULTS: The first safety (primary) outcome of any bleeding event occurred in 16.1% of the patients in the study (older) group and 6.0% of the patients in the control (younger) group (odds ratio [OR] 2.987; 95% CI 1.565, 5.701; p = 0.001). The second safety outcome of TIMI (Thrombolysis in Myocardial Infarction) major bleeding occurred in 4.0% of the patients in the study group and 0.7% of the patients in the control group (OR 6.210; 95% CI 1.238, 31.151; p = 0.012). Other safety outcomes of TIMI minor/minimal bleeding and thrombocytopenia were not different between the two groups. The rate of the first adverse (secondary) outcome of the composite of death from cardiovascular causes, myocardial infarction or stroke was higher in older patients (12.1% vs 5.4%) [OR 2.422; 95% CI 1.197, 4.899; p = 0.012], primarily driven by stroke events (2.0% vs 0%; p = 0.014). CONCLUSIONS: Any bleeding and TIMI major bleeding complications increase in patients aged ≥75 years treated with clopidogrel in addition to aspirin.

Association between plasma asymmetrical dimethylarginine activity and severity of aortic valve stenosis.

OBJECTIVES: Aortic valve stenosis is the most common valvular heart disease in the Western world. The most common cause of aortic valve stenosis in adults is calcification of a normal trileaflet or congenital bicuspid valve. Calcific aortic valve stenosis is an active disease process characterized by mechanical stress, endothelial damage, lipid accumulation, inflammation, synthesis of extracellular matrix proteins, and calcification, reminiscent of atherosclerosis in many aspects. Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase which reduces the bioavailability of nitric oxide and begets endothelial dysfunction. The goal of this study was to examine the association between ADMA activity and severity of aortic valve stenosis. METHODS: One hundred and nine patients were included in this study. Patients were grouped as those with mild aortic stenosis (42 patients, group 1), moderate aortic stenosis (36 patients, group 2), and severe aortic stenosis (31 patients, group 3). ADMA activity was measured by ELISA kit. RESULTS: Mean ADMA activity in group 3 was significantly higher than that in groups 1 and 2 (1.94 ± 0.45 vs. 0.87 ± 0.37 micromol/l, P < 0.001 and 1.94 ± 0.45 vs. 1.34 ± 0.52 micromol/l, P < 0.001, respectively). Serum ADMA activity was positively correlated with mean aortic gradient and maximum aortic gradient and negatively correlated with aortic valve area. CONCLUSION: Our results showed that serum ADMA activity is higher in patients with severe aortic valve stenosis. ADMA activity is positively correlated with aortic valve stenosis severity. Serum ADMA level may be used as a precious marker to evaluate and follow up the severity of aortic valve stenosis.

Relationship between elevated serum gamma-glutamyltransferase activity and slow coronary flow.

OBJECTIVES: We evaluated the relationship between coronary blood flow and serum gamma-glutamyltransferase (GGT) activity in patients with slow coronary flow (SCF). STUDY DESIGN: The study included 90 patients (47 men, 43 women; mean age 50.8+/-9.4 years) with SCF and 88 patients (45 men, 43 women; mean age 51.4+/-8.8 years) with coronary artery disease (CAD), whose diagnoses were made by coronary angiography. Patients with CAD had normal coronary flow. Coronary flow was quantified using the corrected TIMI frame count (TFC) method and serum levels of gamma-glutamyltransferase were measured. The results were compared with those of a control group consisting of 86 age- and sex-matched patients who had normal coronary arteries and normal coronary flow. RESULTS: The three groups were similar with respect to body mass index, presence of hypertension and diabetes mellitus, lipid profiles, and fasting glucose. The use of medications was significantly more common in the CAD group (p<0.01). Compared to the control group, serum GGT activity was significantly increased in both SCF and CAD groups (p<0.01), but these two groups did not differ significantly in this respect (p=0.71). The TFCs for all the epicardial coronary arteries and the mean TFC were significantly higher in the SCF group (p<0.01). Patients with CAD and the controls had similar TFC parameters. The mean TFC showed a positive and moderate correlation with serum GGT activity (r=0.326; p<0.001). In regression analysis, serum GGT activity was found as the only independent predictor of the mean TFC (beta=0.309; p<0.001). CONCLUSION: We have shown for the first time an association between increased serum GGT activity and SCF. Further clinical studies are needed to clarify the physiopathologic role of serum GGT activity in SCF.

Serum gamma-glutamyl transferase activity increased in patients with coronary artery ectasia.

BACKGROUND: Serum gamma-glutamyl transferase (GGT) activity, an enzyme responsible for the extracellular catabolism of antioxidant glutathione, may directly take part in atherogenesis and evolve as a potential biochemical risk indicator of cardiovascular morbidity and mortality. An important characteristic of coronary artery ectasia (CAE) is the fact that in 85% of the cases, atherosclerotic coronary disease accompanies it. The relation between CAE and serum GGT activity has not been studied so far. Hence, we decided to investigate the serum GGT level in patients with CAE. METHODS: We measured serum GGT activity in 88 consecutive patients (48 males) with isolated CAE and 86 patients with coronary artery disease (CAD) and 84 controls. CAE was defined as being without any stenotic lesions with a visual assessment of the coronary arteries showing a luminal dilatation 1.5-fold or more of the adjacent normal coronary segments. Four subgroups were created in accordance with the CAE extension in coronary arteries. RESULTS: There were no statistically significant differences in serum GGT activity among CAE and CAD groups. Serum GGT activity was found significantly increased in patients in both CAE and CAD groups, compared with those in control group (P<0.001, P<0.001, respectively). According to the CAE severity, there were no statistically significant differences in CAE among these subgroups. CONCLUSION: We have shown for the first time that patients with CAE have higher serum GGT activity compared with controls with normal coronary angiograms. Hence, serum GGT activity can be used as a follow-up marker in patients with CAE.

Evaluation of serum levels of solubilized adhesion molecules in patients with aortocoronary saphenous vein grafts.

OBJECTIVE: To assess the diagnostic importance of serum-solubilized adhesion molecules, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, sE-selectin and sP-selectin in aortocoronary saphenous vein graft disease. METHODS: The study population was composed of two groups consisting of 41 patients with saphenous vein graft stenosis (stenosis group) and 43 patients without saphenous vein graft stenosis (no-stenosis group) based on the results of coronary angiography. All patients underwent coronary artery bypass graft operation involving the use of at least one saphenous vein graft for bypass. At the time of cardiac catheterization, it had been more than 1 year since the operation. RESULTS: Serum level of sP-selectin was significantly higher in the stenosis group than in the no-stenosis group (72.9+/-21.7 versus 48.7+/-18.6 ng/ml, P<0.001). No differences were found between the two groups with respect to serum levels of sE-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Multivariate analysis revealed that only serum levels of sP-selectin, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were independently correlated with the stenosis of saphenous vein grafts. A cutoff value of serum sP-selectin >57.5 ng/ml yields a specificity of 79.5%, a sensitivity of 73.3% and a positive predictive value of 80.5% for saphenous vein graft stenosis. CONCLUSION: In this study, sP-selectin level was found to be significantly higher in the group that had late aortocoronary saphenous vein bypass graft disease. This result suggests that platelet activation may play a causal role in late graft disease.

Regional left atrial coagulation and fibrinolytic activities in patients with mitral stenosis.

Systemic thromboembolism is a major complication of mitral stenosis (MS), especially in those patients having atrial fibrillation (AF). Recent evidence has suggested that regional left atrial coagulation activity may be increased in MS and may contribute to the pathophysiology of left atrial thrombus. However, the relation of left atrial coagulation activity to factors that predispose to left atrial thrombus formation is unknown. Also, the relations between left atrial and systemic coagulation activity, fibrinolysis, and platelet activation remain unresolved. Left atrial and peripheral venous levels of fibrinogen, antithrombin III, factor VII and factor VIII for coagulation, D-dimer, tPA and PAI-I, plasmin and antiplasmin for fibrinolysis, and platelet factor 4 and vWF for platelet activation, and endothelial dysfunction were measured in 46 patients with MS and normal clotting times who were undergoing percutaneous mitral valvuloplasty. Left atrial tPA, plasmin, PAI-I, antiplasmin, PF4, and vWF levels exceeded the corresponding peripheral venous levels (P < 0.05) in patients with MS, being more significant in the AF subgroup. There were no significant differences between left atrial and peripheral venous levels of fibrinogen, D-dimer, factor VII, and factor VIII within the patient group (P > 0.05). The results suggest that there are significant variations in the indices of coagulation, fibrinolytic system and platelet activation, and endothelial dysfunction between left atrial and peripheral venous blood samples of patients with MS that may be due to limited spillover from the left atrium to the systemic circulation.