1999 MINUTES

PREDICTIVE VARIABLES AND CARDIOVASCULAR DISEASE

Saturday, 14 August 1999

1:00 to 5:00 PM

Room 30/31

Washington Convention Center

Washington, DC

Chair: K. Bauer, USA

Co-Chairs: R. Hull, Canada; L. Iacoviello, Italy; G.D.O. Lowe, UK

The number of people attending this subcommittee meeting was estimated at 200.

Fibrinogen Assays. Dr. Ian Mackie, chair of the British Society of Haematology Working Party on Fibrinogen Assays, reported on a comprehensive evaluation of commercial fibrinogen standards, Clauss fibrinogen assays, and prothrombin-derived methods. These studies were performed on both photo-optical and mechanical coagulation analyzers at several sites in the U.K. In addition to lyophilised plasmas, a large number of plasma samples were analysed from patients with disseminated intravascular coagulation, liver disease, dysfibrinogenaemia, as well as those with elevated fibrinogen levels. The major findings included apparent errors of calibration in some commercial fibrinogen reference preparations, differences in results between Clauss kits, and a variety of discrepancies in prothrombin-derived assays, which were dependent on the thromboplastin and standard preparations used.

Overview of the Results of the Second Northwick Park Heart Study. Dr. George Miller presented an overview of the results of this prospective cardiovascular survey designed to prospectively look for associations between coagulation activation markers and a first episode of myocardial infaction in middle-aged males.

Meta-Analysis of Haemostatic Variables in Prediction of Cardiovascular Disease. Dr. John Danesh presented the results of meta-analyses for fibrinogen, C-reactive protein, albumin, and leucoycte count as markers of coronary risk. Using studies published before 1998 that included 4,000 cases of myocardial infarction, a 1 gram/L increase in fibrinogen was associated with a 1.8-fold increased risk. The analysis of C-reactive protein included 1,053 cases and conferred a 1.7-fold increased risk. Among 3,770 cases of coronary heart disease, the population in the bottom third of the population with respect to serum albumin level had an increased risk as compared to the top third. Among 8,054 cases, the population in the top third of the population for hematocrit had a 1.3-fold increased risk as compared to the bottom third. Data was also presented for plasma viscosity and erythrocyte sedimentation rate.

Overview of Committee Report on "Predictive Variables and Cardiovascular Disease." Dr. Gordon Lowe presented an overview of an article on this topic that is being prepared for submission to Thrombosis and Haemostasis. The variables to be included include Factor VII, tPA, PAI-1, coagulation inhibitors, and fibrinogen. The preparation of this paper has been delayed awaiting more prospective studies and comparative studies of different assays. It is anticipated that a draft manuscript will be circulated by the end of 1999 and hopefully ready for SSC approval at next year’s Annual Business Meeting in Maastricht.

The Genetics of Factor XIII, Fibrinogen, and Platelet Glycoproteins and Vascular Disorders. Drs. Peter Grant and Rashta Anwar presented data regarding the protective role of the Factor XIII-Val34Leu polymorphism for arterial as well as venous thrombosis. Data was presented indicating that the activation peptide of Factor XIII is actually released by a lower concentration of thrombin for the mutant Factor XIII molecule as contrasted with the wild type molecule. Dr. Angela Carter presented data regarding fibrinogen polymorphisms and the PlA2 polymorphism in the platelet glycoprotein IIIA gene as risk factors for myocardial infarction. Dr. Pascal-Goldschmidt also presented data regarding the role of the Pl A2 polymorphism as a risk factor for myocardial infarction.

Report of the ETRO Working Party on "Population Genetics of Hemostatic Risk Factors for Arterial Vascular Disease." Meta-Analysis of Genetic Polymorphisms and the Risk of Myocardial Infarction in the Young. Dr. Licia Iacoviello presented an update from this group which included a meta-analysis of the Pl A2 allele. Among 9,274 cases and 14,675 healthy controls, the polymorphism had a weak effect on the risk of coronary artery disease. The effect however was double in subjects younger than age 60 (odds ratio=1.22) and strongest in restenosis after angioplasty (odds ratio=1.31).

Overview of Activated Protein C Resistance (APCR) and Factor V Leiden in Prediction of Thrombosis. Drs. Gordon Lowe and M. McColl presented data on the role of APCR due to the Factor V-Arg506Gln mutation in venous thrombosis. Recommendations were presented regarding populations warranting screening and the implications of a positive diagnosis with respect to patient management. Dr. Lowe presented a meta-analysis of the role of APCR in deep venous thromobosis following total hip replacement. He concluded that APCR is probably associated with an increased risk of both asymptomatic (venographic) deep venous thrombosis and confirmed clinical thromboembolism after elective total hip arthroplasty despite routine antithrombotic prophylaxis.