Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:499-504
© 1999 American Heart Association, Inc.
Original Contributions |
Relationship of Plasmin Generation to Cardiovascular Disease Risk Factors in Elderly Men and Women
Abstract—Plasmin–
2-antiplasmin
complex (PAP) marks plasmin generation and fibrinolytic balance. We
recently observed that elevated levels of PAP predict acute myocardial
infarction in the elderly, yet little is known about the correlates of
PAP. We measured PAP in 800 elderly subjects who were free of clinical
cardiovascular disease in 2 cohort studies: the
Cardiovascular Health Study and the Honolulu Heart
Program. Median PAP levels did not differ between the
Cardiovascular Health Study (6.05±1.46 nmol/L) and the
Honolulu Heart Program (6.11±1.44 nmol/L), and correlates of PAP were
similar in both cohorts. In CHS, PAP levels increased with age
(r=0.30), procoagulant factors (eg, factor VIIc,
r=0.15), thrombin activity (prothrombin fragment F1+2,
r=0.29), and inflammation-sensitive proteins (eg,
fibrinogen, r=0.44; factor VIIIc,
r=0.37). PAP was associated with increased
atherosclerosis as measured by the ankle-arm index
(AAI) (P for trend, 
0.001). PAP was negatively related
to factors associated with the insulin resistance syndrome (IRS) (eg,
fasting insulin, r=-0.26; body mass index,
r=-0.26), possibly reflecting an association with
plasminogen activator inhibitor-1
(r=-0.29). Although our study did not have sufficient
power to detect a significant interaction, PAP and AAI appeared to be
more weakly associated in subjects with more manifestations of the IRS:
PAP appeared more strongly associated with AAI in the subgroup with 0
or 1 metabolic disorders (P0.001; slope
estimate, -0.14) compared with the subgroup with 2 or more
metabolic disorders (P=0.10; slope estimate,
-0.08) and in those with non–insulin-dependent diabetes mellitus
(P=0.46; slope estimate, -0.04). Although PAP reflects
reactive fibrinolysis and is associated with
subclinical atherosclerosis, this relationship may be
weaker in populations with characteristics of the IRS, possibly
reflecting the inhibitory effects of
plasminogen activator inhibitor-1
on PAP. Decreased fibrinolysis in the presence of
subclinical disease in subjects with
hyperinsulinemia or glucose intolerance is
consistent with the premise that depressed plasmin generation
may enhance the progression of atherosclerosis in
these people.
Key Words: blood coagulation • fibrinolysis • myocardial infarction • elderly • diabetes
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