Significant correlation coefficients were found between both log-PAI score and predicted O2max (mL · kg−1 · min−1) with blood leukocyte count (r = −0.0998, P = 0.014 and r = −0.1514, P < 0.00005, respectively). These inverse associations remained after age-adjustment (r = −0.0856, P = 0.036, and r = −0.1307, P = 0.001, respectively).
In a final stepwise multiple regression model including all significant age-adjusted correlates of plasma fibrinogen—age, sum of skinfolds, and blood leukocytes were the only significant predictors of plasma fibrinogen (P < 0.00005, P = 0.0002, and P = 0.0229 respectively) (Table 5, Model 3). The trends of lower fibrinogen concentrations with higher PAI categories and quartiles of predicted O2max (mL · kg−1 · min−1) were no longer significant after adjustment for age, sum of skinfolds, and leukocyte count.
Prospective studies have shown plasma fibrinogen concentration to be an independent predictor for acute myocardial infarction (17). A reduction in fibrinogen concentrations may be an important mechanism through which physical activity protects against IHD (8).
The present study has examined cross-sectionally the effects of leisure time physical activity on plasma fibrinogen concentrations. The results showed that among nonsmoking middle-aged men of high social class, higher levels of overall physical activity were associated with lower plasma fibrinogen concentrations after adjustment for the confounding effects of age and subcutaneous adiposity. Total leisure time physical activity classifications have been previously associated with lower fibrinogen concentrations within more representative studies of middle-aged men (16,19). These investigations also showed beneficial effects of high intensity/sports activity. Certain studies have reported only vigorous exercise or the highest category of exercise intensity to be associated with reduced fibrinogen concentrations in middle-aged (8,25) and elderly men (41).
Within several British studies the relationships between physical activity/leisure-time energy expenditure and plasma fibrinogen have been complicated by other social characteristics associated with physical inactivity. Physically inactive groups (particularly those refraining from higher intensity activity) have tended to constitute older men, including a larger prevalance of current smokers, fewer lifelong nonsmokers, fewer nonmanual occupations, and less unemployed (8,16). In the Caerphilly Prospective Heart Disease Study plasma fibrinogen concentration (after standardization for age, smoking, and preexisting IHD) was only significantly lower within the unemployed men (47% of the cohort), who showed greater variation in physical activity habits (16). Within the Scottish Heart Health Survey and Northern Ireland health and activity survey, the inverse relationship between plasma fibrinogen and physical activity was largely explained by age, smoking, and social class (26,27). In contrast to these investigations, vigorous exercise has been associated with reduced fibrinogen concentrations in middle-aged men after adjustment for age, BMI, smoking, and social class variables (8).
The present study is consistent with all epidemiological studies to date reporting the highest plasma fibrinogen concentrations among smokers (28). The prevalence of cigarette smoking within this socioeconomic cohort (9.8%) was substantially lower than that reported in representative British studies (approximately 35–40%) (4,8,16,27,39,47). Social class differences in fibrinogen concentrations have been shown to be almost entirely due to the large social class differences in smoking habits (4). Social network characteristics have also been associated with fibrinogen concentrations within a representative sample of middle-aged men (21). In the above study, men reporting inadequate social participation and low social support had higher fibrinogen levels, mediated by cardiorespiratory fitness and smoking, respectively.
There have been inconsistent findings on the effect of physical activity on fibrinogen concentrations within smokers. The relationship between fibrinogen concentration and social factors (including active physical pursuits) has previously been reported to be evident only in nonsmokers (37), whereas other investigations have confirmed associations between higher levels of physical activity and reduced fibrinogen concentrations in smokers (8). An inverse association between plasma fibrinogen and directly determined O2max has also previously been reported to be stronger for smokers than for nonsmokers (25).
The present study confirms various associations of plasma fibrinogen concentration with other risk indicators for IHD. There is general agreement that plasma fibrinogen concentrations increase with age (23). We found adiposity, as determined by subcutaneous skinfold measurements, to be significantly related to plasma fibrinogen concentrations. Plasma fibrinogen has been previously related to skinfold measurements (31) in addition to other anthropometric measures of obesity (7,18). In middle-aged men, the relation has been reported to be more dependent on abdominal obesity, as estimated by the waist-to-hips circumference ratio, than stature-adjusted weight (14,23,46). Physically active men have been demonstrated to have lower levels of directly determined intra-abdominal adipose fat (22). Studies in middle-aged women have shown that anthropometric estimates of obesity substantially effect the relationship between physical activity and fibrinogen concentrations (20).
In our final multivariate model, the strongest determinants (age, sum of skinfolds, and blood leukocyte count) together explained approximately 8.0% of the variation in plasma fibrinogen concentrations among nonsmokers. Within a random sample of 50- to 60-year-old nonsmoking men (45), blood leukocyte count, and abdominal adiposity (as evaluated by the waist-to-hips circumferences ratio) were also the strongest predictors of fibrinogen levels. In the above study, energy expenditure contributed an additional 2.5% of the fibrinogen variance at baseline examination.
Our findings are consistent with others indicating a significant association between blood leukocytes and plasma fibrinogen among nonsmoking men (19,36,45). Both fibrinogen and blood leukocytes are well-documented indicators of a general acute-phase response and numerous epidemiological studies have reported on associations between “inflammatory” factors and IHD (9). Blood leukocyte count was significantly inversely associated with log-PAI score and predicted O2max (mL · kg−1 · min−1) in the present study. Blood leukocyte count was also inversely related to directly determined O2max in the Kuppio IHD Risk Factor Study (24). In contrast to our findings, the ARIC study showed sporting physical activity to be significantly associated with fibrinogen concentrations after adjustment for BMI and numerous biochemical confounders, including leukocyte count (19). The interrelationships between physical activity/cardiorespiratory fitness, plasma fibrinogen, and acute-phase markers require further investigation.
Despite strong epidemiological associations, there remains no convincing evidence from controlled clinical trials that exercise training reduces plasma fibrinogen concentrations (2,34), except in patients with established IHD (42,44).
In summary, the present study confirms the relationship between both physical activity and predicted O2max (mL · kg−1 · min−1) with age-adjusted plasma fibrinogen concentrations among middle-aged, nonsmoking men of similar social class. These relationships were no longer statistically significant after adjustment for all confounding IHD risk indicators.
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