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Elevated plasma levels of lipoprotein(a) [Lp(a)] have been associated with an increased risk of cardiovascular disease. The aim of the present study was to investigate whether Lp(a) plasma levels were associated with subsequent ischemic events and with fibrinolytic variables in patients with established atherosclerotic disease enrolled in the prospective PLAT study. Lp(a) levels and fibrinolytic variables in 37 atherosclerotic patients who subsequently developed an atherothrombotic event during the first year of follow-up (cases) were compared with those in paired controls, matched for age, sex, diagnosis at enrollment and lipid pattern, who remained free from vascular events during the same time frame. Median and mean Lp(a) levels were similar in cases (6.05 mg/dl; 13.8 +/- 19.4 mg/dl) and controls (6.05 mg/dl; 17.1 +/- 21.6 mg/dl). In the whole group plasma Lp(a) levels correlated significantly with the increase of t-PA antigen (r = 0.368; p = 0.002) and fibrinolytic activity (r = 0.410; p = 0.001) induced by venous stasis but not with baseline fibrinolytic variables. These findings indicate that in patients with established atherosclerotic disease Lp(a) may interfere in vivo with the fibrinolytic process but is not predictive of subsequent ischemic events.

Patients with peripheral arterial disease have a high risk of death from cardiovascular events. As defective fibrinolysis associated with leg atherosclerosis has been suggested as a predisposing factor, we sought a relation among decreased fibrinolysis, the presence of leg atherosclerosis and the incidence of thrombotic events in a case-control study nested in the PLAT. Fifty-eight patients with coronary and/or cerebral atherothrombotic disease, free of leg atherosclerosis at Doppler examination, were compared with 50 atherosclerotic patients with leg involvement. High D-dimer (153.0 vs 81.3 ng/ml, p < 0.001) and tPA antigen before venous stasis (14.4 vs 11.8 ng/ml, p < 0.03), and low tPA antigen (6.7 vs 15.6 ng/ml, p < 0.01) and fibrinolytic activity released after venous stasis (fibrinolytic capacity: 113.2 vs 281.4 mm2, p < 0.001) were found in patients with leg atherosclerosis. D-dimer and fibrinolytic capacity, in addition to age, were selected by stepwise discriminant analysis as characterizing patients with leg atherosclerosis. Moreover, higher D-dimer and tPA inhibitor characterized patients with leg atherosclerosis who subsequently experienced thrombotic events. These findings constitute evidence of high fibrin turnover and impaired fibrinolytic potential in patients with leg atherosclerosis. Thus impaired fibrinolysis may contribute to the prothrombotic state in these patients.

A case-control comparison within the framework of the prospective, multidisciplinary PLAT Study was performed to assess whether altered baseline fibrinolytic variables were associated with an elevated risk of ischemic thrombotic events in patients with documented coronary, cerebral, and/or peripheral atherosclerotic disease. Fibrinogen, D-dimer, tissue plasminogen activator (t-PA) antigen, and fibrinolytic activity before and after venous stasis (delta = difference between the two values), t-PA inhibitor, and lipid levels in 60 atherosclerotic patients with a thrombotic event during the first year of follow-up were compared with those in 94 atherosclerotic patients without such events, who were matched for age, sex, and diagnosis at enrollment. Events were associated with a higher release of delta t-PA antigen (P = .047), higher D-dimer (P = .024), and higher t-PA inhibitor (P = .001) levels. delta Fibrinolytic activity was correlated inversely with t-PA inhibitor (P < .01) and triglycerides (P < .05). D-Dimer was also correlated with systolic blood pressure (P < .01). Atherosclerotic patients at higher risk of thrombotic ischemic events are characterized by increased fibrin turnover and impaired fibrinolytic activity due to high t-PA inhibitor levels. This hemostatic disequilibrium may participate with conventional risk factors such as elevated triglyceride levels and systolic blood pressure in the multifactorial mechanism of ischemic sequelae in patients with preexisting vascular atherothrombotic disease.

The Progetto Lombardo Atero-Trombosi (PLAT) Study was a prospective, multicenter, multidisciplinary study of the association among hemostatic variables, conventional risk factors, and atherothrombotic events in four groups of patients with preexisting vascular ischemic disease (335 myocardial infarction survivors, 123 patients with stable angina pectoris, 160 with transient ischemic attacks, and 335 with peripheral vascular disease). In the myocardial infarction group, univariate analysis showed that atherothrombotic events were associated with high fibrinogen (p = 0.001), factor VIII:C (p less than 0.001), and von Willebrand factor antigen (vWF:Ag) (p = 0.004) levels and with low high density lipoprotein cholesterol (p = 0.043), factor VII (p = 0.019), and protein C (p = 0.044) levels; multivariate analysis produced associations with high fibrinogen and factor VIII:C levels and low protein C levels. By both univariate and multivariate analysis, events in the angina pectoris group were associated with high vWF:Ag (p = 0.026) and leukocyte (p = 0.033) levels and the presence of carotid arterial stenosis (p = 0.063); associations with high leukocyte (p = 0.037) and factor VIII:C (p = 0.186) levels, family history (p = 0.031), and diabetes (p = 0.061) were also found in the group with transient ischemic attacks. In those with peripheral vascular disease, events were associated with Fontaine stage greater than or equal to IIB (p = 0.024), high factor VIII:C levels (p = 0.073), and low protein C (p = 0.028), fibrinogen (p = 0.030), antithrombin III (p = 0.054), and factor VII (p = 0.057) levels by univariate analysis and with Fontaine stage and low fibrinogen levels by multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

In this paper are reported the basal results of a multidisciplinary, multicenter study designed to explore in a population with ischemic disease the relation between hemostatic variables, conventional risk factors and atherothrombotic sequelae. 953 patients less than or equal to 69 yrs with documented coronary, cerebral or peripheral atherosclerotic disease were studied and followed-up for 24 months. Examinations included hemostatic and lipid laboratory assays, arterial Doppler examination, cerebral computerized tomography and nuclear magnetic resonance, exercise electrocardiogram and coronary angiography. Fibrinogen (301.4 +/- 71.52 mg/dl) correlated positively with antithrombin III (r = 0.27) and leukocytes (r = 0.25), negatively with HDL-cholesterol (r = 0.18) and tended to increase with smoking. Heavy smokers had higher leukocyte counts than non-smokers (8.0 +/- 2.0 vs. 7.2 +/- 2.1 x 10(3)/microliters), higher triglycerides (1.87 +/- 1.12 vs. 1.53 +/- 1.35 mmol/l) and lower HDL-cholesterol (0.93 +/- 0.27 vs. 1.00 +/- 0.25 mmol/l). FVII correlated positively with triglycerides (r = 0.16) and protein C (r = 0.45). vWF:Ag (145.4 +/- 70.58%) ad FVII:C (139.7 +/- 59.10%) were positively correlated (r = 0.44). FVIII:C correlated positively with fibrinogen (r = 0.21). Myocardial infarction survivors with associated cerebral and peripheral vascular lesions had higher FVIII:C, FVII, fibronogen and vWF:Ag. These findings suggest that hemostatic factors may enhance and/or mediate the effects of conventional risk factors in atherothrombotic ischemic events.