Coronary thrombosis is regarded as the final occlusive event in the progress of coronary heart disease (CHD). Disturbances of the hemostatic system may favor this process and thus may indicate increased risk of myocardial infarction. Coagulation and lipid factors were measured in 2116 healthy male participants of the Prospective Cardiovascular Miinster (PROCAM) study. After 6 years of follow-up, 82 coronary events (9 sudden cardiac deaths and 14 fatal and 59 nonfatal myocardial infarctions) were observed. The mean plasma fibrinogen levels of the event and nonevent groups differed by 0.25 g/L (2.88 [SD, 0.68] versus 2.63 [SD, 0.63] g/L, respectively; P=.OO1). The incidence of coronary events in the upper tertile of the plasma fibrinogen distribution was 2.4-fold higher than in the lower tertile. By multiple logistic function analysis, plasma fibrinogen was found to be an independent risk indicator for CHD (P<.05). Individuals in the high serum low-density lipoprotein (LDL) cholesterol tertile who also showed high plasma fibrinogen concentrations had a 6.1-fold increase in coronary risk. Unexpectedly, individuals with low plasma fibrinogen had a low incidence of coronary events even when serum LDL cholesterol was high. The mean factor VIIc activities in the event and nonevent groups did not differ significantly (112.3% [SD, 19.9] and cardiac death appear to be associated with the occurrence of occlusive coronary thrombi.1 -3 One reason favoring or even precipitating thrombus formation might be a thrombogenic state in the patient's blood. Long-term epidemiological studies 410 in healthy persons report increased levels of plasma fibrinogen and factor VIIc in those individuals who develop a coronary event. This might suggest an increase in coagulation activity. To evaluate the possible role of the hemostatic system, plasma fibrinogen and factor VIIc were measured in the Prospective Cardiovascular Miinster (PROCAM) study. 1112 Since that time, plasma fibrinogen and factor VIIc have been determined in more than 10 000 persons who had not suffered from MI or stroke at the time of entry. The results from 2116 men who completed an observation period of 6 years are reported here. Methods Study DesignIn the PROCAM study, apparently healthy employees of Westphalian companies were examined deliberately for car- 11 The examination at onset included each patient's history, physical examination, electrocardiogram (ECG) at rest, and a laboratory blood analysis.The study began in 1979. Two years later the determination of plasma fibrinogen and factor VIIc was included, and 10 581 individuals (7540 men and 3041 women) were recruited ( Table 1). As expected, relevant numbers of MI or coronary heart disease (CHD) death occurred only in men aged 40 years and over. The analysis described below was therefore confined to the 2116 male participants between 40 and 65 years of age without a prior history of MI or stroke who had completed their 6-year follow-up.Diagnostic criteria and the definition of the end points have been p...

SummaryWe investigated the vessel status of coronary and peripheral arteries and those arteries supplying the brain in 929 consecutive male patients admitted to a coronary rehabilitation unit. The severity of coronary atherosclerosis was scored using coronary angiography. Changes in extracranial brain vessels and manifest cerebrovascular disease (CVD) were determined by B-mode ultrasound and Doppler examination. Peripheral arterial disease (PAD) was diagnosed using base-line and stress oscillography. We assessed variables of coagulation, fibrinolysis, and the acute phase response.There was a significant increase in plasma fibrinogen, plasminogen, d-dimer and C-reactive protein (CRP) with increasing severity of coronary heart disease. Compared to men with unaffected arteries, men with 3 diseased coronary arteries had 58% greater d-dimer concentrations. Patients with CVD and PAD, respectively, also had significantly higher fibrinogen, d-dimer and CRP concentrations. We did not find an association between plasminogen activator inhibitor activity and the severity of coronary atherosclerosis.In conclusion, plasma fibrinogen, d-dimer and CRP concentrations were significantly related to atherosclerosis in the coronary, peripheral and extracranial brain arteries.

Numerous investigations have demonstrated the role of thrombus formation in the pathogenesis of coronary heart disease (CHD). A tendency to thrombosis may also be indicated by elevated levels of coagulation factor VII clotting activity (FVIIc). Significant associations of FVIIc with increased coronary risk, however, have been found only in the Northwick Park Heart Study. Here we present the results of the 8-year follow-up of FVIIc measurements in 2780 healthy men of the Prospective Cardiovascular Münster study. In the study population (age at entry, 49.3 +/- 6.1 years, mean +/- SD), 130 CHD events occurred during follow-up. FVIIc was significantly higher in subjects with coronary events than in those without (112.4 +/- 20.1% vs 108.7 +/- 21.4%, P = .023). Compared with individuals without coronary events, FVIIc was not significantly higher in men with nonfatal events (111.7 +/- 20.4%; P = .196, n = 93), but there was a tendency toward higher FVIIc activity in subjects with fatal events (114.6 +/- 19.5%; P = .076, n = 37). In the multiple logistic regression analysis, we did not find FVIIc to be an independent risk factor for CHD, and the significance of FVIIc disappeared after total cholesterol, LDL-cholesterol, and triglycerides were taken into account. The increase in the number of CHD events through higher levels of FVIIc was more pronounced in the presence of additional cardiovascular risk factors: smoking; myocardial infarction events in family; angina pectoris; high levels of fibrinogen, total cholesterol, LDL cholesterol, and triglycerides; and a low level of HDL cholesterol. We conclude that FVIIc is a risk factor for CHD, especially in the presence of additional risk factors, and must be taken into account when assessing cardiovascular risk in men.

Background Recent findings provide evidence for the importance of inflammatory processes in the pathogenesis of atherosclerosis. C-reactive protein was elevated in patients with peripheral artery disease, coronary heart disease and myocardial infarction compared to normal subjects. MethodsIn 1112 male and 299 female survivors of myocardial infarction (mean age SD, men, 50·4 9·5, women, 56·1 9·3), we investigated whether plasma C-reactive protein concentration is associated with the severity of coronary heart disease and generalized pre-clinical or clinically manifest arteriopathy. The control group consisted of 326 male and 138 female individuals matched for age without clinical symptoms of coronary disease. The severity of arteriosclerotic changes was determined for the extra-cranial brain-supplying arteries, abdominal aorta, pelvis and leg arteries. In myocardial infarction patients coronary angiography was performed. Laboratory analyses included determination of C-reactive protein, fibrinogen, D-dimer, HDL-cholesterol, LDL-cholesterol and triglycerides. ResultsThe following ranking of C-reactive protein concentrations was found: controlscpatients after myocardial infarction without atherosclerosiscpatients with myocardial infarction and pre-clinical atherosclerosiscpatients with myocardial infarction and clinically manifest atherosclerosis. Additionally, our data showed a significant association between C-reactive protein concentrations and the angiographically detected degree of coronary heart disease.Conclusions As C-reactive protein is a marker of inflammatory processes, our results in patients with clinically manifest and early pre-clinical atherosclerosis support the hypothesis that inflammatory processes in the vessel wall participate in atherogenesis. Moreover, they support the hypothesis of a causal relationship between an acute phase reaction and the pathogenesis of atherosclerosis in coronary arteries and other parts of the arterial vessel system.