Atherosclerosis 142 (1999) 403 – 407

Symptoms of chronic bronchitis, haemostatic factors, and coronary

heart disease risk

Pekka Jousilahti a,*, Veikko Salomaa a, Vesa Rasi b, Elina Vahtera b

a
National Public Health Institute, Department of Epidemiology and Health Promotion, Mannerheimintie 166, FIN-00300 Helsinki, Finland
b
Finnish Red Cross Blood Transfusion Ser6ice, Department of Haemostasis, Helsinki, Finland

Received 22 January 1998; received in revised form 23 July 1998; accepted 19 August 1998

Abstract

Positive association has been suggested between a variety of infections and coronary heart disease. Disturbances in blood
coagulation system may form a link between infections and coronary heart disease. The aim of this study was to analyze whether
chronic bronchitis, defined by the occurrence of symptoms, is associated with selected haemostatic factors in a cross-sectional
population study of 2379 Finnish men and women aged between 45 and 64 years. Plasma fibrinogen level was significantly higher,
3.70 versus 3.35 g/l (PB0.001) in men and 3.64 versus 3.44 g/l (PB 0.001) in women, among subjects with symptoms of chronic
bronchitis than among those without symptoms. The association was independent of age, smoking, body mass index, physical
exercise, and alcohol consumption. Also plasminogen was higher among men with symptoms than among those without but the
difference disappeared after adjustment for age and smoking. Factor VII coagulant activity and factor VII antigen level did not
differ between subjects with and without symptoms. Thus, fibrinogen may be associated with a possible mechanism to link chronic
bronchitis to coronary heart disease risk, even though the causality of the association cannot be verified in a cross-sectional study.
© 1999 Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Chronic bronchitis; Coronary heart disease; Fibrinogen; Haemostatic factors

1. Introduction heart disease death has been shown to associate also

Experimental and epidemiological studies have sug-
gested a positive association between a variety of infec-
tions and coronary heart disease [1 – 5]. These include
infections in different organs, both of viral and bacte-
rial origin, and both acute and chronic in nature. Most
attention has been paid to dental, gastric, and respira-
tory tract infections.
There is also growing evidence that haemostatic ac-
tivity plays a role in coronary heart disease risk [6,7].
The association between plasma fibrinogen level and
the risk of coronary heart disease has been demon-
strated in several studies. Increased risk of coronary
* Corresponding author. Tel.: +358-9-47448623; fax: + 358-9-
47448338; e-mail: pekka.jousilahti@ktl.fi.
with factor VII coagulant activity. Further, increased
levels of haemostatic factors, particularly high plasma
fibrinogen levels, have been shown to be associated
with the occurrence of respiratory infections [8]. There-
fore, haemostatic factors may form a biologically plau-
sible mechanism to link infections to coronary heart
disease risk. Several life style factors, such as smoking,
obesity, physical exercise, and socio-economic status
have also been shown to affect the levels of haemostatic
factors [9,10].
The aim of this study was to analyze whether chronic
bronchitis, defined by the occurrence of symptoms, is
associated with the following haemostatic factors,
plasma fibrinogen, coagulation factor VII antigen (F
VII:Ag), factor VII coagulant activity (F VII:C), and
plasminogen.

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404 P. Jousilahti et al. / Atherosclerosis 142 (1999) 403–407

Table 1
Plasma levels of fibrinogen, factor VII coagulant activity (F VII:C), factor VII antigen (F VII:Ag) and plasminogen among subjects with and
without symptoms of chronic bronchitis

Men (number) Symptoms of chronic bronchitis P-valuea Women (number) Symptoms of chronic bronchitis P-valuea

No Yes No Yes

Mean SD Mean SD Mean SD Mean SD

Fibrinogen (g/l) 1095 3.35 0.78 3.70 0.90 B0.001 1182 3.44 0.76 3.64 0.83 B0.001
F VII:C (%) 1100 125.2 25.2 124.7 24.7 0.778 1189 126.8 25.7 129.6 25.3 0.116
F VII:Ag (%) 1100 104.9 23.2 104.0 23.9 0.549 1189 107.9 24.6 108.8 22.9 0.622
Plasminogn (%) 1100 113.1 14.0 115.3 14.1 0.022 1176 114.2 14.7 115.8 14.9 0.107

a
Standard t-test between subjects with and without symptoms of chronic bronchitis.

2. Material and method
The participants of the Finrisk haemostasis study are
a sub-sample of the FINMONICA (The Finnish part of
the WHO MONICA study) risk factor survey carried
out in 1992 [11]. A random sample of 3000 people aged
45 – 64 years living in three geographical areas was
drawn from the Finnish population register. The sam-
pling was stratified so that the sample size was 250 men
and 250 women per area and 10-year age group. Ten
people were excluded from the sample because of death
or emigration from the study area prior the survey,
leaving 2990 who were eligible. Of these 2379 (79.6%)
participated. For different reasons such as unacceptable
sample or use of anticoagulant medication, some sam-
ples were later deemed unsuitable for the analyses for
one or several parameters [11]. The number of subjects
in each analysis is given in Table 1.
Symptoms of chronic bronchitis and smoking status
were assessed in the survey using a set of standardized
questions in a self-administered questionnaire. Symp-
toms of chronic bronchitis were assessed by using a set
of three questions, modified from the respiratory ques-
tionnaire of Rose and Blackburn: (i) do you usually
have cough with phlegm in the mornings in the winter;
(ii) do you usually have cough with phlegm during the
day or at night in the winter; and (iii) do you cough like
this on most days or nights as much as 3 months each
year [12]. In the analysis, positive answers in either or
both of the two first questions were classified as grade
one-symptoms, and positive answers in the third ques-
tion were classified as grade two-symptoms. Based on
the responses for smoking questions, the participants
were classified as current smokers — persons who had
smoked during the preceding month, and as current
non-smokers. The non-smokers were further divided to
never-smokers and ex-smokers. The usual amount of
cigarettes smoked daily was also recorded.
Body mass index (kg/m2) was used as the indicator of
obesity. Weight was measured in light clothing and
height without shoes. Data on physical exercise was
obtained by the questionnaire. Physical activity both in
work and at leisure time was assessed by using a four
level scale. Weekly consumption of alcohol (in g) was
assessed by using a set of standardized questions on the
questionnaire.
A detailed description of the laboratory methods
used in determination of plasma fibrinogen, F VII:C, F
VII:Ag, and plasminogen has been published earlier
[11]. Standard t-test was used to compare the levels of
haemostatic factors between subjects with and without
symptoms of chronic bronchitis. The effect of age,
smoking, body mass index, physical activity, and alco-
hol consumption on fibrinogen levels was assessed by
analysis of covariance’s. The effect of smoking was also
analyzed by stratification.
3. Results
Plasma fibrinogen levels were significantly higher
among subjects with symptoms of chronic bronchitis, as
compared with those without the symptoms (Table 1).
In men the mean fibrinogen levels were 3.70 and 3.35
g/l (PB 0.001), and in women 3.64 and 3.44 g/l (P B
0.001), among subjects with and without the symptoms,
respectively. Also plasminogen levels were slightly
higher, 115.3 versus 113.1% (P= 0.022), among men
with symptoms of chronic bronchitis than among men
without the symptoms. This difference disappeared,
however, after adjustment for age and smoking.
Subjects with symptoms were only slightly older than
those without, 54.6 versus 54.1 years in men and 55.2
versus 54.1 years in women, respectively. 50% of men
with symptoms of chronic bronchitis and 23% of men
without the symptoms were current smokers. Among
women the proportions were 29 and 13%, respectively.
In both genders, however, fibrinogen levels remained
significantly higher among subjects with symptoms of
chronic bronchitis, as compared with those without
Table 2
Plasma fibrinogen (g/l) levels by symptoms of chronic bronchitisa

Men Women

Symptoms of chronic bronchitis P-valueb Symptoms of chronic bronchitis P-valueb

No symptoms Grade 1 symptoms Grade 2 symptoms No symtoms Grade 1 symptoms Grade 2 symptoms
(n= 785) (n=75) (n = 225) (n =900) (n = 85) (n= 192)

Non-adjusted 3.35 3.64 3.72 B0.001 3.44 3.61 3.65 B0.001

Adjusted for age 3.35 3.64 3.70 B0.001 3.45 3.58 3.63 0.001
Adjusted for age and smok- 3.40 3.57 3.58 B0.001 3.46 3.55 3.58 0.037
ing
Multifactorial adjustedc 3.40 3.55 3.59 B0.001 3.47 3.53 3.58 0.049

a
Data of ten men and five women excluded because of incomplete data on one or more variables.
b
Analyses of variance, fibrinogen levels of subjects without symptoms of chronic bronchitis versus subjects with grade one- and two-symptoms.
c
Adjusted for age, smoking, body mass index, leisure time physical exercise, physical exercise in work and alcohol consumption.
P. Jousilahti et al. / Atherosclerosis 142 (1999) 403–407
405
406 P. Jousilahti et al. / Atherosclerosis 142 (1999) 403–407
Table 3
Plasma fibrinogen (g/l) levels by symptoms of chronic bronchitis and smoking status (number of subjectsa)
Men
Symptoms of chronic bronchitis
No Yes
Non-smokersc 3.25 (608) 3.39 (150)
Smokersd 3.72 (182) 3.93 (150)
a
Five men and three women excluded because of incomplete data on smoking status.
b
Analyses of variance.
c
Adjusted for previous smoking status (never-smokers vs. ex-smokers).
d
Adjusted for number of cigarettes smoked daily.
symptoms, also after adjustment for age and smoking
(Table 2). There was a small difference in fibrinogen
levels between subjects with grade one- and grade two-
symptoms but this difference disappeared after adjust-
ment for smoking. Further adjustment for body mass
index, physical activity and consumption of alcohol
affected the results only marginally.
In both genders, and among subjects with and with-
out symptoms of chronic bronchitis, fibrinogen levels
were markedly higher among smokers than non-smok-
ers (Table 3). When stratified by smoking status, ad-
justed for the previous smoking history among
non-smokers and for average number of cigarettes
smoked daily among smokers, fibrinogen levels were
significantly higher among subjects with symptoms of
chronic bronchitis, as compared with subjects without
symptoms, in both smoking and non-smoking men and
in non-smoking women.
4. Discussion
Symptoms of chronic bronchitis associated with
plasma fibrinogen levels but not with the other mea-
sured haemostatic factors. The mean fibrinogen level of
men was about 11% higher and of women about 6%
higher among subjects with symptoms of chronic bron-
chitis than among subjects without the symptoms. Part
of that difference was due to the difference in smoking
prevalence between the groups but a significant differ-
ence remained also after adjustment for smoking. It has
been estimated that the association of fibrinogen level
with coronary heart disease risk is even stronger than
that of serum cholesterol [6]. This means that 1%
increase in fibrinogen level is associated with approxi-
mately 2–3% increase in coronary heart disease risk.
We have shown previously in a prospective study of
our earlier study cohorts that the symptoms of chronic
bronchitis, as measured by using the same set of ques-
tions as in the present study, were a significant predic-
tor of coronary heart disease risk [4]. In men the risk of
first coronary event was about 50% higher and in
Women
P-valueb Symptoms of chronic bronchitis P-valueb
No Yes
0.035 3.42 (792) 3.53 (198) 0.049
0.044 3.75 (110) 3.79 (79) 0.743
women about 40% higher among subjects with symp-
toms as compared with those without the symptoms.
Adjustment for the major cardiovascular risk factors
decreased the risk ratio somewhat but the risk of first
coronary event of subjects with symptoms remained
about 35% higher as compared with the subjects with-
out the symptoms, also after adjustment for smoking,
serum cholesterol and blood pressure.
Even though several of studies have reported an
association between infections and coronary heart dis-
ease, it is still debated whether an infection is a causal
factor for the disease and whether its role is indepen-
dent of other risk factors [5]. Besides smoking, also
other confounding factors, such as low socio-economic
status, may lie behind both infections and coronary
heart disease. The association between infections and
coronary heart disease may also be mediated through
other risk factors, such as disturbances in lipid and
glucose metabolism and haemostatic system [13–16].
During infections serum lipid profile becomes more
atherogenic and glucose and insulin levels tend to in-
crease. Fibrinogen acts as an acute phase reactant and
increases during acute infections. It has also seasonal
variation which is consistent with the variation in the
occurrence of respiratory infections [17].
Several mechanisms have been suggested through
which an elevated fibrinogen concentration may be
linked to coronary heart disease. It can be involved in
the atheromatous plaque building through fibrin depo-
sition and lysis, and with generation of fragments pos-
sessing mitogenic and chemotactic properties. High
fibrinogen levels increase also platelet aggregability [7].
Fibrinogen concentration has a strong impact on blood
viscosity, which, in turn, is related to the risk of throm-
bosis. Interestingly, a recent study found increased
plasma viscosity during an air pollution episode [18].
The authors speculate that inflammation in the airways,
caused by the pollutants, may lead to increased blood
viscosity and increased coronary heart disease morbid-
ity and mortality presumably through the increased
plasma fibrinogen concentration.
 P. Jousilahti et al. / Atherosclerosis 142 (1999) 403–407
In conclusion, plasma fibrinogen levels were
markedly higher among subjects with symptoms of
chronic bronchitis than among those without the symp-
toms. Part of the increased coronary heart disease risk
associated with chronic bronchitis may be mediated
through fibrinogen. However, the causality of the asso-
ciation cannot be verified in a cross-sectional study.
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