Does exercise-induced myocardial ischaemia cause enhanced platelet activation and fibrin formation in patients with stable angina and severe coronary artery disease? (original) (raw)
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2010
Background-Platelet reactivity is increased by exercise in patients with obstructive coronary artery disease (CAD) but not in patients with syndrome X. In this study, we prospectively investigated whether the platelet response to exercise might help distinguish, among patients with angina, those with obstructive CAD from those with normal coronary arteries (NCAs). Methods and Results-Venous blood samples were collected before and 5 minutes after exercise from 194 consecutive patients with stable angina. Platelet reactivity was measured by the platelet function analyzer (PFA)-100 system as the time for flowing whole blood to occlude a collagen-adenosine diphosphate ring (closure time). Coronary angiography showed CAD in 163 patients (84%) and NCA in 31 patients (16%). Baseline closure time was shorter in NCA patients (78.0Ϯ16 versus 95.5Ϯ23 seconds, PϽ0.0001). With exercise, closure time decreased in CAD patients (Ϫ15.5 seconds; 95% confidence limits [CL], Ϫ13.0 to Ϫ18.0 seconds; PϽ0.0001), but increased in NCA patients (12.5 seconds; 95% CL, 7.4 to 17.7 seconds; Pϭ0.0004). An increase in closure time with exercise Ն10 seconds had 100% specificity and positive predictive value for NCAs. Similarly, a decrease Ն10 seconds had 100% specificity and positive predictive value for CAD. A closure time change (increase or decrease) Ն10 seconds allowed a correct classification of 55% of all patients. Conclusions-Among patients with stable angina, the response of platelet reactivity to exercise was predictive of normal or stenosed coronary arteries at angiography. Specifically, an increase in closure time with exercise Ն10 seconds was invariably associated with the presence of NCA. (Circulation. 2003;107:1378-1382.)
American Heart Journal, 1987
Thirty-seven patients affected by spontaneous angina and 15 comparable control subjects were enrolled in a 12-month prospective study to evaluate the relatIonship between blood clotting activation (assessed by tlbtlnopeptlda A [WA] plasma concentration) and the occurfanca of myocardlal ischamk attacks. FPA measurements and cllnlcai axamhmtions In patients were performed every 2 weeks. In control sublects blood sampling was performed every 4 weeks. Data from 28 patients who completed the study and from the 15 control subjects were analyzed. The clinical activity of anglna was divided into three classes (asymptomatlo, mildly symptomatic, and severely symptomatic) on the basis of the number and time-concentration of the ischemic attacks and ECG changes during the 15 days preceding each cltnlcal axamtnatlon. In all but one patient, a cyclic pattern of activtty of coronary artery disease was observed. During follow-up studies, 824 FPA measurements were performed In pattents and 173 in control subjects. Mean values were 4.88 ? 4.53 and 1.32 f 0.80 rig/ml, respectively (p < 0.001). FPA levels dlffered markedly In relation to the activity of angina. A ralatlonship between FPA levels and activity of disease (r = 0.54, p < 0.01) was found in time course. Bohr8 heparhi admlnlstratton (100 IU/kg) during the active phase of angina sharply but incompletely lowered FPA plasma levels, indicating thrombin formation both intravascularly and extravascularly. Present results indkata that a marked blood clotting activation occurs simultaneously with the outbursts of clinical activity of spontaneous angina.
Predictors of exercise-induced platelet reactivity in patients with chronic stable angina
Journal of Cardiovascular Medicine, 2009
Objective Previous studies have shown that exercise increases platelet reactivity in patients with coronary artery disease (CAD). However, the response of platelet reactivity to exercise is considerably variable and its predictors are poorly known. Methods We studied 214 consecutive patients (age 61.9 W 9 years, 167 men) with stable angina and obstructive coronary artery disease. All patients underwent a symptomlimited treadmill exercise stress test. Venous blood samples were collected before and at peak exercise. Platelet reactivity was assessed by the platelet function analyzer system as the time for flowing whole blood to occlude a collagen-adenosine diphosphate ring (closure time: shorter times U higher reactivity). Both closure time at peak exercise and the exercise-induced change in closure time from rest were assessed as an expression of exerciserelated platelet reactivity. Results Closure time decreased significantly with exercise in the whole population (from 95.9 W 22 to 81.2 W 18 s, P < 0.001). The only variable significantly associated with closure time at peak exercise was hematocrit (P U 0.003). Basal systolic blood pressure (P U 0.023) and lack of nitrate use (P U 0.03), on the contrary, were the only variables significantly associated with increased exercise-induced closure time change. Peak hematocrit maintained an independent association with peak closure time in multivariable analysis, although the correlation was mild. No variable, on the contrary, was associated with exercise-induced platelet reactivity after correction for basal closure time values at multivariable analyses. Conclusion Among stable coronary artery disease patients, platelet reactivity after exercise cannot be reliably predicted by several common clinical and laboratory variables.
Subclinical activation of fibrinolysis in atherosclerotic disease detected by Bβ 15–42 assay
La Ricerca in Clinica e in Laboratorio, 1989
Blood coagulation and fibrinolysis are involved in the pathogenesis of atherosclerosis 3. It has been suggested that the decrease in plasmin activity may lead to a continuous fibrin deposition on atherosclerotic plaques ~. In order to detect Whether a subclinical activation of fibrinolysis may occur in the atherosclerotic disease, we measured the peptides containing the B~3 15-42 sequence derived from fibrinogen or fibrin in a group of patients with ischemic arterial disease. Since the B[3 15-42 sequence is part of a B~ chain fragment released during the earliest stage of plasmin proteolysis, this assay is a sensitive test of in vivo plasmin activity 5. The second aim of this study was to investigate whether a subclinical plasmin activity was related to thrombin activity. For this purpose we concomitantly measured the concentrations of plasma fibrinopeptide A (FPA). FPA is cleaved from the A~ chain of fibrinogen by thrombin action. This reaction is the initial step in the conversion of fibrinogen to fibrin and its measurement is a sensitive test of in vivo thrombin activity 7. Moreover, the B[5 15-42/FPA ratio was used as an index of relative plasmin to thrombin action on flbrin(ogen). MATERIALS AND METHODS Patients-A total of 46 patients (36 men and 10 women, ranging in age from 40 to 77 years, mean 58 years) were studied. They were suffering from myocardial infarction (n-° = 17), unstable angina (n ° = 11), stroke (n ° = 9) and transitory ischemic attacks (TIA) (n ° = 9). All patients were investigated at least 3 months after their last thrombotic episode: Myocardial infarction or unstable angina were diagnosed according to clinical, electrocardiographic and enzy
Impaired Fibrinolysis in Angiographically Documented Coronary Artery Disease
Advances in Hematology, 2015
Impaired fibrinolysis may predispose to coronary artery disease (CAD). Hypofibrinolysis due to high levels of plasminogen activator inhibitor-1 (PAI-1) has been reported in CAD. A novel regulator of fibrinolytic activity, thrombin activatable fibrinolysis inhibitor (TAFI), has attracted attention in recent years. It acts by blocking the formation of a ternary complex of plasminogen, fibrin, and tissue plasminogen activator (t-PA). Previously ambiguous results regarding TAFI levels have been reported in CAD. We measured plasma levels of PAI-1 and TAFI antigen in 123 patients with age ranging from 40 to 65 years who had been submitted to coronary angiography and assessed the association of these markers with the extent of stenosis in three groups: angiographically normal artery (NAn), mild to moderate atheromatosis (MA), and severe atheromatosis (SA). Plasma levels of PAI-1 were increased in patients with severe atheromatosis compared to mild/moderate atheromatosis or to normal patients (66.60, 40.50, and 34.90 ng/mL, resp.; P < 0.001). For TAFI no difference was found between different groups. When patients were grouped in only two groups based on clinical cut-off point for intervention (stenosis less than or above 70%) we found increased plasma levels for PAI-1 (37.55 and 66.60 ng/mL, resp.; P < 0.001) and decreased plasma levels for TAFI (5.20 and 4.53 g/mL, resp.; P = 0.04) in patients with stenosis above 70%. No difference was found in PAI-1 or TAFI levels comparing the number of affected vessels. Conclusion. As evidenced by a raised level of PAI-1 antigen, one can suggest an impaired fibrinolysis in stable CAD, although no correlation with the number of affected vessels was found. Curiously, a decreased plasma level of total TAFI levels was observed in patients with stenosis above 70%. Further studies measuring functional TAFI are required in order to elucidate its association with the extent of degree of atheromatosis.
Thrombosis Research, 1999
cantly diminished in patients with CAD after physical exercise and their platelets were significantly Generalized atherosclerosis and coronary artery more sensitive towards the inhibitory effects of disease (CAD) are associated with endothelial dysiloprost and SIN-1. These data demonstrate a sigfunction and during acute myocardial ischemia nificant reduction in platelet activation in response platelet activation has been reported. Activated to physical exercise in patients with CAD and adplatelets exert activated fibrinogen receptors (GP vanced atherosclerosis. Despite exercise induced IIb/IIIa) and express CD 62p being regarded as myocardial ischemia as evidenced by angina and reliable marker for platelet activation. Patients ECG-changes, the platelets are not generally actiwith angiographically proven CAD performed a vated, as it could be expected. Thus, patients with bicycle exercise test until the onset of angina or myocardial ischemia experienced a reduced plate-ST-segment depression. We studied the ischemialet activity and enhanced sensitivity towards prosinduced alterations in fibrinogen binding to actitacyclin (PGI 2) and nitric oxide, probably due to vated platelet GP IIb/IIIa receptors and CD 62p an augmented release of endogenous platelet inexpression. Therefore, the basal fibrinogen binding hibitory mediators.
American Heart Journal, 1998
Several atherogenic, hemostatic, inflammatory, and genetic parameters and markers have been implicated as risk factors in coronary artery disease, although whether they are risk factors for acute as opposed to chronic coronary disease is unclear. Fifty subjects with an isolated myocardial infarction >3 months previously were compared with 50 subjects with a minimum 3-year history of stable angina, documented coronary artery disease, normal electrocardiogram and normal ventricular wall motion, and no episode suggesting infarction or unstable angina. Biologic variables analyzed included apolipoprotein B (apo B), lipoprotein (a), C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (TPA) and inhibitor (PAI-1), thrombin-antithrombin (TAT), fragment 1+2 (F1+2), von Willebrand factor (vWF), activated protein C resistance, homocyst(e)ine, anticardiolipin antibodies, blood group, and the angiotensin-converting enzyme insertion/deletion (I/D) and angiotensin II receptor gene polymorphisms. There were no significant differences between the 2 groups for any of the variables studied, although fibrinogen and F 1+2 tended to be slightly higher in the angina group (P = .09 for each). These significant correlations were present: age with fibrinogen, homocyst(e)ine, and vWF; factor VII with apo B, homocyst(e)ine, and TPA; apo B with TPA and CRP; CRP with fibrinogen, TPA, PAI-1, and factor VII; fibrinogen with vWF. Examination of atherogenic, hemostatic, inflammation, and genetic variables in the clinically quiescent state permitted no distinction between subjects with a previous isolated myocardial infarction in contrast to those with long-standing uncomplicated stable angina, favoring the notion that acute coronary events occur at random on a varying background of atherosclerosis. The multiple correlations found among these variables also underscore their complex interaction in the atherosclerotic process.
Increased levels of endothelial haemostatic markers in patients with coronary heart disease
Thrombosis Research, 2002
von Willebrand factor (vWF), thrombomodulin and tissue plasminogen activator antigen (tPAag) are regarded as markers of endothelial activation and/or damage. Elevated levels have been associated with atherosclerotic disease states. The aim of the present study was to compare the levels of vWF, thrombomodulin and tPAag in patients with coronary heart disease (CHD) and matched healthy individuals to see if they discriminated significantly between the study groups also after adjustment for established CHD risk factors. Patients (n = 193) in various stages of CHD and matched controls (n = 193) were included. To evaluate possible influence of acute phase reaction, reinvestigation was performed after 6 months. We observed elevated levels of vWF ( P < .001) and tPAag ( P < .001) but not thrombomodulin ( P =.082) in CHD patients when compared to controls, still statistically significant after 6 months and also after adjustment for established risk factors.
Experimental Biology and Medicine, 2016
Peripheral arterial disease is a widely prevalent atherosclerotic occlusive disorder. Symptoms commence with exercise-induced pain in the lower extremities, known as claudication. Despite the fact that exercise has been shown to improve fibrinolytic profile some patients, the effect of exercise on coagulation and fibrinolysis cascades in claudicants has not been comprehensively defined. Literature search in English language yielded 13 studies of exercise on claudicants, including 420 patients. Claudicants tend to have a higher coagulation activity at rest compared to healthy individuals, a trend that persists even after exercise. Post-exercise coagulation activity of claudicants is increased when compared to their respective baseline levels, but it is so in a non-consistent manner. From the available data, it has been suggested that claudicants have a functional and effective fibrinolytic mechanism in place, operating continuously at a relatively higher activity level compared to he...