Introduction
The formation of a coronary thrombus is generally the
underlying cause of a myocardial infarction and therefore
factors related to coagulation and fibrinolysis may be
involved in this pathophysiological process. Results of
prospective studies have suggested that levels of
fibrinogen and von Willebrand factor are predictors of
cardiovascular events in certain populations [1–3]. Others
have found that a decrease in fibrinolytic capacity
increases the risk of myocardial infarction [4–6]. Cross-
sectional studies have also shown that levels of
prothrombin fragment 1+2 and thrombin–antithrombin
complex are associated with cardiovascular disease [7–9].
It is therefore possible that an increase in activity of the
coagulation system or a decrease in fibrinolytic activity
contributes to the development of myocardial infarction
and that detection of a state of hypercoagulability in
patients might be of clinical interest. Most of these
studies have concerned either patients with coronary
disease or healthy subjects. Data on hypertensive patients
are sparse. In a study of elderly men at high and low risks
of cardiovascular disease, we found that high levels of
fibrinogen, von Willebrand factor, prothrombin fragment
1+2, thrombin–antithrombin complex and plasminogen
activator inhibitor activity were associated with cardio-
vascular disease [9]. Now that these patients have been
followed up for more than 3 years, we wanted to examine,
in a hypothesis-seeking study, whether these factors
predicted major coronary events (fatal and non-fatal
myocardial infarctions and sudden death).
Methods
Subjects
Five hundred and eight male patients with treated
primary hypertension were included in a risk factor inter-
vention study [10]. The inclusion criteria for the inter-
vention study were, apart from treated hypertension and
male sex, one or more of the following: hypercholestero-
laemia (serum cholesterol level > 6.5 mmol/l), tobacco
smoking (one or more cigarettes per day) and diabetes
mellitus (fasting blood glucose level > 7 mmol/l) [11]. The
patients were representative of high-risk hypertensives in
Göteborg insofar as most of them (over 90%) were
recruited by screening a random third of all men in their
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Original article 537
0263-6352 © 1998 Lippincott-Raven Publishers
Prothrombin fragment 1+2 is a risk factor for myocardial
infarction in treated hypertensive men
Stefan Agewall
a
, John Wikstrand
b
and Björn Fagerberg
a
Background Haemostatic factors may play a part in the
development of acute coronary heart disease.
Objective To evaluate as predictors of major coronary
events (fatal and non-fatal myocardial infarctions and
sudden death) levels of fibrinogen, von Willebrand factor,
prothrombin fragment 1+2, thrombin–antithrombin
complex, plasminogen activator inhibitor activity and
C-reactive protein.
Methods We studied 131 men, aged 56–77 years, with
treated hypertension and at least one additional
cardiovascular risk factor (hypercholesterolaemia,
diabetes mellitus or smoking). These patients were
recruited from a continuing risk factor intervention study.
The mean observation time was 3.0 years.
Results Fourteen patients died and 16 had a major
coronary event during the follow-up period. After
adjustments for other risk factors, levels of prothrombin
fragment 1+2 and C-reactive protein were independent
predictors of major coronary events. The other measured
haemostatic variables were not significantly associated
with major coronary events during follow-up. Fibrinogen
and prothrombin fragment 1+2 levels were independent
predictors for mortality.
Conclusions Among treated hypertensive men, levels
of prothrombin fragment 1+2 and C-reactive protein
were independent predictors of major coronary events.
J Hypertens 16:537–541 © 1998 Lippincott-Raven
Publishers.
Journal of Hypertension 1998, 16:537–541
Keywords: C-reactive protein, coagulation, coronary, fibrinolysis,
hypertension, myocardial infarction
a
Department of Medicine and
b
Wallenberg Laboratory for Cardiovascular
Research, Sahlgrenska University Hospital, Göteborg University, Göteborg,
Sweden.
Sponsorship: This study was supported by grants from the Swedish Medical
Research Council (B92-19X-009937-01Aa, B93-19X-09937-02B, B94-19X
09937-02B, B95-19X-09937-04B), the Swedish Heart and Lung Foundation,
Göteborg Medical Society, Swedish Medical Society and King Gustaf V and
Queen Viktoria Foundation.
Correspondence and requests for reprints to Stefan Agewall, MD, PhD,
Department of Medicine, Sahlgrenska University Hospital, Göteborg
University, S-413 45 Göteborg, Sweden.
Received 8 October 1997 Revised 11 December 1997
Accepted 23 December 1997