Low level of tissue plasminogen activator activity in non‐diabetic patients with a first myocardial infarction

Abstract

Abstract. Lundblad D, Dinesen B, Rautio A, Røder ME, Eliasson M (Sunderby Hospital, Luleå; University of Umeå, Umeå, Sweden; Steno Diabetes Center, Gentofte; and University of Copenhagen, Copenhagen NV, Denmark). Low level of tissue plasminogen activator activity in non-diabetic patients with a first myocardial infarction. J Intern Med 2005; 258: 13-20.Objective. To explore the role of tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor type 1 (PAI-1) in survivors of a first myocardial infarction (MI). Insulin and proinsulin were analysed as potential risk factors. Design. Case-control study in northern Sweden. Subjects. A total of 115 patients under 65 years of age with a first MI were enrolled and recalled for further examination 3 months later. Twenty-seven patients were excluded, 17 with known diabetes and 10 who did not come to the follow-up, giving a final number of 88 patients, 73 men and 15 women. Patients were age-and sex matched with control subjects drawn from the local cohort in the MONICA population survey 1994.Main outcome measures. We compared MI patients and controls using univariate and multiple regression analyses including odds ratios (OR).Results. PAI-1 activity, fibrinogen, postload insulin and -proinsulin were significantly higher and tPA activity significantly lower in MI patients in the univariate analysis. In a multiple regression analysis, including also age, sex and cardiovascular risk factors, these parameters were divided in quartiles. The lowest quartile of tPA activity was significantly associated with MI (OR ¼ 19.1; CI 3.0-123) together with the highest quartiles of fibrinogen (OR ¼ 25; CI 5.2-120) but other variables were not. Conclusion. Low tPA activity, i.e. low fibrinolytic activity, characterized nondiabetic subjects after a first MI which is not explained by concomitant disturbances in metabolic and anthropometric variables.

The Impact of the Fibrinolytic System on the Risk of Venous and Arterial Thrombosis

“…A problem concerning the measurement of both tPA and PAI-1 levels is that the levels have a strong diurnal variation, which could influence the results if measurements are not performed following standardized procedures. 60 Most population-based studies found increased PAI-1 antigen or activity levels to be associated with increased risk of arterial disease in unadjusted models or models only adjusted for age and sex, 37,38,[61][62][63][64][65][66][67][68] as did cohort studies including patients with angina or other preexisting arterial disease. 21,22,69 No association between PAI-1 and arterial events during follow-up was found in two prospective studies on patients with coronary heart disease 70 or severe angina pectoris.…”

“…77 However, two cohort studies and two casecontrol studies have found elevated tPA activity to decrease the risk of arterial disease. 64,66,69,70 In the PLAT study, tPA release after venous stasis at baseline was increased in patients with a major atherothrombotic event, compared with those who remained free of events after 2 years of follow-up. 22 However, in another cohort study on patients with coronary heart disease, patients with a decreased tPA release after venous occlusion had a higher risk of myocardial infarction, ischemic stroke, or unstable angina during follow-up of 42 months.…”

Reduced plasma fibrinolytic capacity as a potential risk factor for a first myocardial infarction in young men

“…Increased plasminogen activator inhibitor‐1 (PAI‐1) activity or antigen has been found to be associated with an increased risk of first and recurrent arterial diseases (Takazoe et al , 2001; Smith et al , 2005). However, other studies found no association (Wiman et al , 2000; Mannucci et al , 2005) or the risk associated with increased PAI‐1 levels disappeared after adjustment for markers of insulin resistance (Ladenvall et al , 2002; Lundblad et al , 2005). Several studies have shown a positive association between tissue‐type plasminogen activator (t‐PA) and the risk of myocardial infarction (Thogersen et al , 1998; Zorio et al , 2003; Mannucci et al , 2005), although this could not be confirmed in the Caerphilly study, a large prospective study (Smith et al , 2005).…”

Die Bedeutung thrombophiler Risikofaktoren bei Patienten mit arteriellen Thrombosen

“…Verschiedene Studien konnten keine Assoziation zwischen PAI-1-Spiegeln und Myokardinfarkt oder ischämischem Hirninfarkt zeigen (10,31,42,62). In anderen Studien war eine Beziehung zwischen erhöhter PAI-1-Konzentration und arteriellen Gefäßverschlüssen nachweisbar, die allerdings in der multivariaten Analyse unter Hinzunahme von Faktoren der Insulinresistenz ihren prädiktiven Wert verloren (2,34,40,46,57,64).…”