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Etiology

Concentrations of fibrinogen, von Willebrand factor antigen, and tPA antigen were associated with an increased risk for coronary events

ACP J Club. 1995 Sept-Oct;123:54. doi:10.7326/ACPJC-1995-123-2-054


Source Citation

Thompson SG, Kienast J, Pyke SD, Haverkate F, van de Loo JC. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med. 1995 Mar 9;332:635-41.


Abstract

Objective

To determine whether baseline measurements of hemostatic factors are associated with the occurrence of coronary events within 2 years in patients with suspected coronary artery disease.

Design

Cohort analytic study with 2-year follow-up.

Setting

18 European centers.

Participants

3043 patients (85% between age 45 and 69 y, 85% men) who had coronary angiography because of suspected coronary artery disease. Exclusion criteria were myocardial infarction (MI) within the previous 2 years or severe right-heart failure or noncardiac diseases likely to cause death within 1 year. 97% of patients were followed for 2 years.

Assessment of risk factors

At baseline, various measures of platelet function and the states of the coagulation and fibrinolytic systems were assessed to detect a prothrombotic state or evidence of endothelial injury. In addition to fibrinogen and fibrinopeptide A, tissue plasminogen activator (tPA) antigen and activity, the euglobulin clot-lysis time, ABO blood type, total cholesterol and triglyceride concentrations, and C-reactive protein levels were measured. Technicians from the 18 centers were trained at the central laboratory.

Main outcome measures

Fatal and nonfatal MI and sudden coronary death.

Main results

106 patients had a definite coronary event during follow-up. After adjustment for the extent of coronary artery disease and other risk factors, an increased incidence of MI or sudden coronary death was associated with higher baseline concentrations of fibrinogen (standardized relative risk [RR] 1.31, 95% CI 1.07 to 1.61), tPA antigen (RR 1.29, CI 1.04 to 1.60), and von Willebrand factor antigen (RR 1.24, CI 1.00 to 1.53). The C-reactive protein level (RR 1.24, CI 1.00 to 1.55) was also associated with the incidence of coronary events, but not after adjustment for fibrinogen concentration.

Conclusion

Concentrations of fibrinogen, von Willebrand factor antigen, and tissue plasminogen activator antigen were directly and independently associated with the risk for subsequent coronary events in patients having coronary angiography because of suspected coronary artery disease.

Source of funding: European Community.

For article reprint: Not available.


Commentary

Previous studies established an association between plasma fibrinogen levels and factor VII activity and decreased fibrinolytic activity with increased coronary events in healthy persons (1, 2). Associations between decreased fibrinolytic activity (tPA inhibitor type I) (3) and inflammation (C-reactive protein) (4) and subsequent coronary events have also been observed in patients with MI or unstable angina. The study by Thompson and colleagues extends the study of circulating hemostatic factors to patients with stable angina who have had coronary arteriography without a recent cardiac event. After adjustment for the extent of coronary artery disease and other risk factors, there was still a significant association between fibrinogen, von Willebrand factor antigen, and tPA antigen levels and the development of sudden cardiac death or MI during a 2-year follow-up. In addition, the combination of a high fibrinogen and C-reactive protein level with a high serum cholesterol value identified patients at particularly high risk.

Unresolved issues include the following: Does inclusion of patients without substantial coronary stenoses dilute or intensify the observed association? Would these same associations remain significant in a large population of postmenopausal women? Factor VII was not evaluated in this study.

On the basis of these observations, relatively simple "blood tests" could identify patients at higher risk. This could result in more efficient use of complex invasive procedures. The effects of risk factor reduction (especially smoking) or treatment with warfarin or aspirin (which can directly reduce the circulating levels of fibrinogen and factor VII) remain to be determined (5). Until such studies are completed, we will not know whether the associations observed by Thompson and colleagues are causal.

Marc Cohen, MD
Hahnemann University HospitalPhiladelphia, Pennsylvania, USA


References

1. Meade TW, Mellows S, Brozovic M, et al. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet. 1986;2:533-7.

2. Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet. 1993;342:1076-9.

3. Cortellaro M, Boschetti C, Cofrancesco E, et al. The PLAT Study: hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients. Principal results. PLAT Study Group. Progetto Lombardo Atero-Trombosi (PLAT) Study Group. Arterioscler Thromb. 1992;12:1063-70.

4. Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med. 1994;331:417-24.

5. Meade TW. Low-dose warfarin and low-dose aspirin in the primary prevention of ischemic heart disease. Am J Cardiol. 1990;65:7C-11C.