Plasma histamine concentrations are elevated in patients with diabetes mellitus and peripheral vascular disease

Previous work has shown that plasma and tissue concentrations of histamine are elevated in rats with experimental diabetes mellitus and that leucocytes and platelets from patients with peripheral vascular disease have a higher histamine content than those from controls. In the present study, we have measured: (a) plasma histamine concentrations; (b) leucocyte and platelet histidine decarboxylase (the enzyme responsible for the biosynthesis of histamine) in patients with diabetes mellitus (Types I and II) and peripheral vascular disease; and (c) platelet and leucocyte histamine content. Plasma histamine concentration was significantly higher in patients with diabetes and peripheral vascular disease respectively than that in age-matched controls. Leucocyte histidine decarboxylase activity in diabetic and peripheral vascular disease patients was similar to that in controls, while platelets had no histidine decarboxylase activity. The leucocyte and platelet content of histamine were greater in patients with peripheral vascular disease than those in controls, but they were not altered in diabetic patients. There was no correlation between plasma histamine concentration, leucocyte and platelet histamine content, and histidine decarboxylase activity. We conclude that plasma histamine is elevated in diabetics and in patients with peripheral vascular disease and that platelet and leucocyte histamine content is increased in the latter. This increase in platelet and leucocyte histamine content is not due to an increase in histidine decarboxylase activity of these cells. The increase in plasma and cellular histamine content may contribute to the pathogenesis of increased endothelial permeability in diabetes and to the pathogenesis of intimal damage in atherosclerosis.     

Evidence for local platelet activation in pulmonary vessels in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease.

To investigate the relationships between local platelet activation in pulmonary vessels and pulmonary artery pressure circulating platelet aggregates and plasma beta-thromboglobulin (beta-TG) levels were evaluated in peripheral venous blood and blood from different sites of pulmonary circulation (right ventricle, pulmonary artery and arteriolo-capillary bed) in 29 patients with COPD. Fifteen had pulmonary hypertension and 14 normal pulmonary artery pressure. In normotensive COPD no significant differences could be found in platelet aggregation and beta-TG levels among different sampling sites. On the contrary in patients with pulmonary hypertension a significant increase of platelet aggregates and beta-TG levels was found in blood withdrawn from the arteriolo-capillary bed. A significant correlation was demonstrated between platelet aggregation and both mean pulmonary artery pressure and pulmonary vascular resistance. These results indicate that in patients with pulmonary hypertension secondary to COPD a local platelet activation in pulmonary vessels does occur and may contribute to the maintainance of elevated pulmonary vascular resistance.     

Relation of lipid peroxides to macrovascular disease in type 2 diabetes.

Lipid peroxides are thought to be formed by free radicals and may play an important role in the development of atheromatous vascular disease. We have investigated the relationship between lipids, lipoproteins, coagulation factors, and lipid peroxides (measured as thiobarbituric acid reacting species (TBARS) in Type 2 diabetic patients with macrovascular disease. Eighteen diabetic and 20 non-diabetic subjects with clinical evidence of ischaemic heart disease and/or peripheral vascular disease were investigated, together with 28 healthy subjects without evidence of vascular disease. TBARS concentrations in non-diabetic (mean 5.0 (95% Cl 4.5-5.7) mumol l-1) and diabetic groups (5.6 (5.1-6.0) mumol l-1) with macrovascular disease were not significantly different although values were higher in both groups of patients with vascular disease by comparison with control subjects (2.7 (2.4-3.1) mumol l-1, p less than 0.001). Significant univariate correlations between TBARS concentrations and measures of blood glucose control (fructosamine, blood glucose and HbA1) were found for all 66 subjects (r = 0.35-0.42, p less than 0.01-p less than 0.001), although no independent association between these parameters and TBARS was demonstrated in multiple regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Beta-thromboglobulin and platelets in unstable angina

BACKGROUND. Atheromatous plaque rupture is the main cause of platelet activation in ischaemic heart disease (IHD). Platelet activation is manifested by a release into circulation of the components of granules, including beta-thromboglobulin (beta-TG) - a marker of platelet activation in vivo. The platelet count (PLT), mean platelet volume (MPV) and the proportion of large platelets (L(PLT)) are indirect platelet activation markers. Data in literature on the role of these markers in patients with unstable angina are discordant. AIM. To assess plasma concentration of beta-TG, PLT, MPV and LPLT in patients with unstable angina before and during standard pharmacological therapy. METHODS. The study group consisted of 54 patients (19 females and 35 males) with unstable angina who were divided into two groups: Group A - 45 patients with a history of angina, and group B - nine patients with a new onset unstable angina. beta-TG and platelet activation markers were measured at baseline (groups A and B) and after 8-10 days of standard medical therapy for unstable angina (group B). The control group consisted of 26 healthy subjects (13 females and 13 males). RESULTS. The mean beta-TG concentration in groups A (16.2 IU/ml) and B (19.7 IU/ml - before and 21.8 IU/ml - after treatment) was significantly (p<0.05) higher than in controls (10.6 IU/ml). In patients with unstable angina, the PLT and MPV values were not affected by therapy and were similar to those obtained in controls, whereas the LPLT value was significantly higher than in controls. CONCLUSIONS. Concentrations of beta-TG and L(PLT) are increased in patients with unstable angina due to platelet activation. The introduction of standard medical treatment for unstable angina did not significantly change beta-TG and platelet activation markers.     

Plasma levels of beta-thromboglobulin and platelet factor 4 in relation to the venous platelet concentration

The plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) were determined in patients with various hematologic malignancies, and the results were related to simultaneously determined venous platelet counts. All studied patients were in a steady state. The plasma beta-TG concentrations were determined on 69 occasions and the values ranged from 0 to 82 ng/ml. In 33 instances, the venous platelet count was <25 x 10 (9/1) and in two thirds of these samples beta-TG was undedectable. The highest values for plasma beta-TG were found in patients with the highest venous platelet counts. A highly significant correlation (r=0.77, p <0.001) between the values for plasma beta-TG and venous platelet count was present. The plasma concentrations for PF-4 ranged from 0 to 50 ng/ml. Similarly, there was a highly significant relationship (r=0.78, p<0.001) between the values for PF-4 and venous platelet concentration. We conclude, if the plasma levels of beta-TG and PF-4 are used as markers of platelet activation in vivo, it is necessary to simultaneously consider the platelet concentration in the collected blood.     

Effects of antihypertensive treatment on platelet function in essential hypertension.

To evaluate the effect of antihypertensive therapy on platelet activation in essential hypertension, the plasma levels of beta-thromboglobulin (beta-TG) were examined in 45 patients with essential hypertension and 20 age-matched normotensive control subjects. Hypertensive patients were assigned to monotherapy with one of five different antihypertensive drugs for 6 months, and the change of plasma levels of beta-TG was reexamined after the completion of the monotherapy. The plasma beta-TG increased in hypertensive patients compared with levels in normotensive control subjects. Monotherapy with each drug resulted in sufficient blood pressure control in all hypertensive patients. The plasma beta-TG decreased significantly after monotherapy with an alpha-blocker or an angiotensin-converting enzyme inhibitor (ACEI). The plasma beta-TG increased with the use of a diuretic but did not change with the use of a beta-blocker or calcium antagonist. The platelet activation observed in patients with essential hypertension is reversed by monotherapy with an alpha-blocker or an ACEI. It is possible that these drugs reduce the development of hypertensive vascular complications due to suppression of platelet activation in patients with essential hypertension.     

Platelet function and interferon alpha-2a treatment in essential thrombocythaemia.

The effects of interferon (IFN) alpha-2a treatment on platelet function were evaluated in 20 patients affected by essential thrombocythaemia (ET). Baseline data documented the well-known abnormalities of in vitro platelet aggregation and the constant presence of a delta-storage pool deficiency. The therapy in all patients reduced the platelet count, and in the majority of them caused a partial improvement of in vitro platelet aggregation. Although the mean intraplatelet ADP level improved during treatment, it always remained below the normal range documenting persistence of the delta-storage pool deficiency. The plasma beta-TG levels, which initially were high, significantly decreased during treatment, but the beta-TG ratio and the platelet beta-TG values always remained within the normal range--this suggests an absence of platelet activation either before or during therapy. Our results demonstrate that, despite significantly reducing the platelet count, IFN alpha-2a treatment only partially corrects the qualitative platelet abnormalities in ET.     

P-Selectin expression, platelet aggregates, and platelet-derived microparticle formation are increased in peripheral arterial disease.

Platelet volume has been reported to be increased in vascular disease. Therefore, we studied the relationship of mean platelet volume and platelet count as well as flow cytometrically measured platelet size and platelet function in 50 patients with peripheral arterial disease and 50 healthy volunteers. Platelet activation was measured by P-selectin expression analysis on resting and on stimulated platelets, and the determination of platelet aggregates and platelet-derived microparticles using flow cytometry. P-Selectin expression on platelets was significantly elevated in patients suffering from peripheral arterial disease (all P<0.0001). Platelet aggregates (P<0.0001) and platelet-derived microparticles (P<0.0001) were significantly higher in the patient group compared with controls, whereas mean platelet volume and platelet count showed no significant differences. Platelet count was inversely related to mean platelet volume in patients and controls (r = -0.43, P<0.001). The present study supports the hypothesis of platelet hyperreactivity and circulating activated platelets in peripheral arterial disease. Mean platelet volume, and platelet count cannot be used as predictive markers for platelet activation in peripheral arterial disease patients.     

Plasma beta-thromboglobulin and platelet factor 4 concentrations in patients with atrial fibrillation

The clinical significance of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) levels were evaluated in 26 patients with atrial fibrillation (af) complicated by valvular heart disease (VHD), 73 patients with af but without valvular heart disease and 57 normal subjects. The beta-TG level was significantly higher in af patients without VHD than in normal subjects (49.4 +/- 35.8 ng/ml vs 31.2 +/- 14.0 ng/ml, p less than 0.01) and in af patients with VHD than in normals (64.1 +/- 52.8 ng/ml vs 31.2 +/- 14.0 ng/ml, p less than 0.01). Af patients with or without VHD tended to show high levels of PF4 compared with normals (af patients without VHD: 34.1 +/- 45.5 ng/ml, af patients with VHD: 18.6 +/- 27.2 ng/ml, normals: 11.6 +/- 8.2 ng/ml). There was no correlation between beta-TG levels and age in af patients without VHD or in normals. There was also no correlation between beta-TG levels and heart rate in af patients without VHD. The activation of platelets was suggested in patients with atrial fibrillation on the basis of increased levels of platelet releasing substances, especially in those with VHD. The high levels of beta-TG and PF4 in patients with atrial fibrillation may be one explanation for the high incidence of thromboembolism in these patients, indicating the necessity of antiplatelet therapy.     

Platelet activation during thrombolysis and percutaneous transluminal coronary angioplasty in the acute phase of myocardial infarction

To clarify the mechanism of recanalization and reocclusion in thrombolysis and percutaneous transluminal coronary angioplasty (PTCA), the plasma concentrations of beta-thromboglobulin (beta-TG), thromboxane B2 (TXB2) and platelet aggregation adenosine diphosphate (ADP) (2 microM/ml, collagen 2 micrograms/ml) were assessed in 11 normal subjects and in 19 patients with acute myocardial infarction whose infarct-related vessels were recanalized by thrombolysis and/or PTCA. In patients with acute myocardial infarction, the plasma concentrations of beta-TG and TXB2 were significantly higher than those in normal subjects (beta-TG: 128 +/- 132 ng/ml vs 38 +/- 17 ng/ml, TXB2: 131 +/- 154 pg/ml vs 36 +/- 18 pg/ml). Collagen-induced platelet aggregation decreased significantly in patients with acute myocardial infarction; whereas, ADP-induced platelet aggregation showed no significant difference. Infarct-related vessels recanalized by thrombolysis (seven patients: group 1) and PTCA (seven patients: group 2) were patent on the follow-up angiograms. Infarct-related vessels were reoccluded in five patients immediately after PTCA or during the follow-up angiography (group 3). Beta-TG and TXB2 did not change before and after recanalization in groups 1 and 2, but increased significantly after recanalization in group 3 (beta-TG: 155 +/- 185 ng/ml----269 +/- 233 ng/ml, TXB2: 104 +/- 87 pg/ml----169 +/- 91 pg/ml). Platelet aggregation did not differ significantly among the three groups. We concluded that platelets are not activated during thrombolysis and/or PTCA in cases without reocclusion, while platelets are markedly activated during PTCA in cases with reocclusion. Thus, it is suggested that platelet activation plays an important role in the mechanism of reocclusion.     

Endothelial dysfunction in type 2 diabetes mellitus subjects with peripheral artery disease

We strived to characterize the endothelial function status in type 2 diabetic patients with peripheral artery disease which was detected by ankle-brachial index by utilizing high frequency ultrasounds. Predictors of endothelial dysfunction were investigated. We chose 23 type 2 diabetic patients had ankle-brachial index <0.97 (0.15-0.95; mean=0.74+/-0.20), 31 diabetic patients had ankle-brachial index >/=1.0 and 28 non-diabetic subjects for study. Older age, a longer duration of diabetes, higher systolic blood pressure, higher prevalence of history of hypertension were observed in patients with peripheral vascular disease. Type 2 diabetic patients showed impaired flow-mediated dilatation than non-diabetic and it showed more impaired in patients with peripheral vascular disease. Nitroglyerin-induced dilatation showed a trend of impairment in patients with peripheral vascular disease but did not reach statistical significance. Age (r=-0.259, P=0.019), baseline brachial artery diameter (r=-0.321, P=0.003), ankle-brachial index (r=0.259, P=0.002) and hypertension history (P=0.01) were significantly associated with flow-mediated dilatation. However, after adjusting for age, only baseline diameter and ankle-brachial index were independent predictors of flow-mediated dilatation. In conclusion, we demonstrated flow-mediated dilatation was impaired in type 2 diabetic patients and it was further impaired in patients with peripheral vascular disease. Nitroglycerin-induced dilatation showed a trend of impairment but did not reach statistical significance.     

Plasma beta-thromboglobulin values in thrombocytopenic patients with acute leukemia

Plasma beta-thromboglobulin (beta-TG) levels were measured in 14 healthy subjects and in 20 acute leukemia (AL) patients, newly diagnosed, with highly variable values for venous platelet counts. For healthy subjects the plasma beta-TG levels ranged 12-38 (mean 17) ng/ml. In this group of patients with AL, a highly significant positive correlation (P < 0.001) between the values for plasma beta-TG and venous platelet count was present. During a thrombocytopenic period, the plasma beta-TG concentraton was measured in nine of the AL patients immediately before and 10 to 12 hours after platelet transfusion therapy. Fourteen platelet transfusions were administered when the patient's highest temperature of the day was < 38.5 degrees C, and 18 when the highest temperature of the day was greater than or equal to 38.5 degrees C. The mean pre-transfusion and post-transfusion beta-TG values for the 14 platelet transfusions were 7 +/- 2 and 20 +/- 5 ng/ml, respectively. The corresponding means for the 18 transfusions given to febrile patients were 5 +/- 2 ng/ml and 11 +/- 2 ng/ml, respectively. Of the pretransfusion values, 11/14 and 14/18 were below the control range. We conclude that the plasma beta-TG values are considerably lower in thrombocytopenic patients than in subjects with normal platelet counts. Further work should provide reference values for plasma beta-TG over a wide range of venous platelet counts.     

Characterization of five marker levels of the hemostatic system and endothelial status in normotensive pregnancy and pre-eclampsia

OBJECTIVES: Pre-eclampsia is associated with changes in the hemostatic system and endothelial status. Urinary 11-dehydrothromboxane B2/creatinine (11-DTXB2/Cr) is a marker for platelet activation and vascular constriction, thrombin-antithrombin complex (TAT) for thrombin formation, serum thrombomodulin (TM) for endothelial damage, and beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) for platelet activation and releasing reaction. The present study attempted to evaluate these five markers in normotensive pregnancy and pre-eclampsia. METHODS: These five markers were simultaneously measured in urine and blood samples from 25 women who were not pregnant (group 1, controls), 31 women with normotensive pregnancy (group 2, second controls), 22 women with mild pre-eclampsia (group 3), and 21 women with severe pre-eclampsia (group 4). The average gestational age was 36 wk. RESULTS: The 11-DTXB2/Cr, TAT, and beta-TG levels were significantly higher (P < 0.01) in groups 2, 3, and 4 than in group 1. The TM and beta-TG levels were significantly higher (P < 0.05) in group 3 than in group 2. The TM, beta-TG, and PF-4 levels were increased significantly (P < 0.05-0.01) in group 4 compared to those in groups 1, 2, and 3. CONCLUSION: Platelet aggregation, vascular constriction, and thrombin formation (detected by 11-DTXB2/Cr and TAT) may be markedly enhanced even in group 2, but further enhancement may be relatively slight in groups 3 and 4. In contrast, endothelial damage (determined by TM) and platelet release of PF-4 may not increase significantly in group 2, but they may increase in group 4. Platelet-release of beta-TG may be enhanced in groups 2, 3, and 4. Endothelial damage and platelet-releasing reaction (detected by PF-4 and beta-TG) may be significantly more enhanced in group 4 than in group 3.     

Tissue concentrations of ofloxacin in necrotic foot lesions of diabetic and non-diabetic patients with peripheral arterial occlusive disease

Six diabetic patients with infected foot lesions (mean age 64 years) and six male patients (mean age 71 years) with ischemic acral ulceration due to advanced peripheral arterial occlusive disease were treated with 200 mg ofloxacin b.i.d. The necrotic margin tissue concentrations of ofloxacin determined by HPLC and confirmed by microbiological assay were in the same range (1.6 to 6.4 mg/kg) as plasma levels (1.6 to 5.9 mg/l). No difference of plasma and tissue concentrations was found between patients with peripheral vascular disease and diabetics, respectively. After three weeks treatment bacterial wound pathogens disappeared in 7 subjects, changed in 4 patients and were resistant in one patient. Clinical improvement appeared in 9 of 12 patients after three weeks of therapy. Satisfactory tissue levels of orally administered ofloxacin were achieved in the infected necrotic tissue area of diabetic and non-diabetic patients with impaired peripheral arterial circulation.     

Measurement of platelet life-span in normal subjects and patients with myeloproliferative disease with indium oxine labelled platelets

The use of 111Indium oxine as a platelet label for the performance of platelet life-span studies has been examined. Platelet life-span in normal subjects varied between 8 X 10 and 10 X 36 d. Patients with primary thrombocythaemia had clearly reduced platelet life-span whether or not they presented with vascular occlusion and this abnormality persisted after reduction of the platelet count to normal by busulphan therapy. Patients with similarly elevate platelet counts due to chronic granulocytic leukaemia or after splenectomy had platelet life-span values in the normal range. Plasma beta-TG levels could not be used to predict platelet life-span in these groups of patients. Measurement of platelet life-span using 111Indium labelled platelets is a useful technique in the examination of platelet function in occlusive vascular disease.     

Fibrinogen and von Willebrand factor in type II diabetes mellitus

A hypercoagulable state may contribute to the formation of early vascular lesions in diabetes. The von Willebrand factor is required for the attachment of platelets to the subendothelium; fibrinogen is required for platelet aggregation. This study was designed to assess in type II diabetic patients plasma levels of fibrinogen and von Willebrand factor to see if these variables are associated with platelet aggregation responses to adenosine diphosphate (ADP). Fibrinogen and the von Willebrand factor were significantly increased in diabetics but only fibrinogen was significantly related to platelet aggregation for ADP. Strict metabolic control does not reduce the increased concentrations of these two proteins. Hyperfibrinogenaemia was related to the presence of macrovascular disease. Therefore measurements of plasma fibrinogen could be added to the cardiovascular risk factor profile of diabetic patients. Intervention studies are also needed to reduce the increased incidence of thrombotic diseases in patients with diabetes mellitus.     

Procoagulant membranous microparticles and atherothrombotic complications in diabetics

Endothelial apoptosis and platelet activation play a key role in atherothrombotic event. These two mechanisms resulting membrane thickening leading to procoagulant microparticle (MP) liberation into the blood stream. In the vascular compartment, MP contribute to increased thrombin formation, to platelet activation, and prolong inflammation of the arterial wall by inducing the synthesis of cytokines and adhesion of glycoproteins by the endothelial cells. In diabetic patients, increased endothelial apoptosis associated with intense platelet and monocytic activation could contribute to accelerated atherothrombosis. Endothelial, platelet and monocytic derived MP, found in high concentrations in these patients, induce a prothrombotic, proadhesive and proinflammatory tendency in the vascular comportment which could directly impact on the vascular prognosis. In diabetes, increased platelet or monocytic MP is a marker for microvascular disease. Likewise, in acute coronary syndromes of diabetic patients, high concentrations of procoagulant MP could be associated with a poor cardiovascular prognosis. In these diabetic patients, many treatments (antioxidant, antiplatelet, lipid lowering, antihypertensive) significantly reduce the levels of MP and parameters associated with inflammation. MP are one of the key factors linking inflammation, oxidative stress, apoptosis and thrombosis in accelerated atherothrombotic disease of the diabetic. In future, the measurement of MP should help evaluate the efficacy of antioxidant and antiplatelet therapy, especially in diabetic patients.     

Evidence for the Platelet Specificity of β-Thromboglobulin and Studies on its Plasma Concentration in Healthy Individuals

The concentration of normal human platelet beta-thromboglobulin (beta-TG) was measured in various washed organ samples by a radioimmunoassay. As only trace amounts were detected, beta-TG appears to be a platelet specific protein. Assay of beta-thromboglobulin in plasma samples from 180 normal individuals gave a range of 10--65 mg/ml. In the 10 subjects studied, plasma beta-TG concentration was related to platelet lifespan but not to turnover. The plasma beta-TG concentration rose with increasing age but did not correlate with the whole blood platelet count or the percentage of megathrombocytes. These results provide further substantial evidence that measurement of plasma beta-TG concentration is useful for assessing the participation of platelets in various disease processes.     

Elevated plasma procoagulant and fibrinolytic markers in patients with chronic obstructive pulmonary disease

OBJECTIVE: There is clinical and pathological evidence of thrombosis in pulmonary vessels of patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate the presence of hypercoagulability and determine the extent of this abnormality in COPD patients. PATIENTS AND METHODS: We measured plasma levels of thrombin antithrombin III complex (TAT), fibrinopeptide A (FPA), tissue plasminogen activator-plasminogen activator inhibitor (tPA-PAI): markers of coagulation-fibrinolysis-system, and also beta-thromboglobulin (beta-TG): a marker of platelet activation, in 40 COPD patients and in 20 control subjects. Measurements were also repeated 12 months after entry in all patients. RESULTS: TAT, FPA, tPA-PAI, and beta-TG concentrations were significantly higher in COPD than in control subjects. At 12 months follow-up, deltaA-aDO2 and delta%FEV1 were significantly higher in patients with high TAT or tPA-PAI levels than in patients with low levels and TAT, FPA and tPA-PAI levels remained elevated, although beta-TG levels decreased after domiciliary O2 therapy. CONCLUSION: Our results showed an enhanced prothrombotic process in COPD patients, which could potentially account for the increased thrombosis in pulmonary vessels in these patients.     

Aortic spontaneous echocardiographic contrast and hemostatic markers in patients with nonrheumatic atrial fibrillation

OBJECTIVES: To determine the relationship between spontaneous echocardiographic contrast (SEC) in the descending thoracic aorta and plasma levels of hemostatic markers in patients with nonrheumatic atrial fibrillation (AF). DESIGN AND SETTINGS: A cross-sectional study at a university hospital. PATIENTS AND MEASUREMENTS: In 91 consecutive patients (mean +/- SE age, 70 +/- 1 years; 68 men) with nonrheumatic AF who underwent transesophageal echocardiography, plasma levels of markers for platelet activity (platelet factor 4 [PF4] and beta-thromboglobulin [beta-TG]), thrombotic status (thrombin-antithrombin III complex [TAT]), and fibrinolytic status (D-dimer and plasmin-alpha(2)-plasmin inhibitor complex [PIC]) were determined. RESULTS: Forty-three patients who had aortic SEC (AoSEC) were older (72 years vs 68 years; p < 0.05) and had a higher prevalence of chronic AF (88% vs 52%; p < 0.05) than 48 patients without AoSEC. TAT, PIC, and D-dimer levels were significantly higher in patients with AoSEC than in those without AoSEC, whereas PF4 and beta-TG levels were not different between the two groups. Although the prevalence of cerebral embolism did not differ between the two groups (23% vs 29%), the prevalence of peripheral embolism was higher in patients with AoSEC than in those without AoSEC (10% vs 0%; p < 0.05). Multivariate analysis revealed mitral regurgitation (odds ratio, 7.53; p < 0.02), SEC in the left atrium (odds ratio, 2.14; p < 0.02), and aortic atherosclerosis (odds ratio, 1.87; p < 0.04) emerged as independent predictors of AoSEC. CONCLUSIONS: Patients with nonrheumatic AF who have AoSEC appear to have enhanced coagulation activity but not platelet activity. Intensive anticoagulation treatment might be required for these patients.