The number of people attending this subcommittee meeting was estimated at 75.

Hyperhomocysteinemia.

Dr. M. Cattaneo discussed the topic of hyperhomocysteinemia with special emphasis on methodologic issues. He first presented data regarding comparing the two- and four-hour methionine loading tests for the diagnosis of hyperhomocysteinemia. Based on results in 371 patients, he concluded that there was good concordance between the two tests. However they were not equivalent in that the four-hour test was more sensitive to methionine intolerance. It was therefore suggested that the two hour protocol should not replace the four hour protocol. He next presented data from a study of 628 healthy controls which determined that the methionine loading test does not only explore the trans-sulfuration pathway in homocysteine metabolism. Finally, he discussed results in 200 healthy controls and 52 patients with previous thrombotic episodes comparing an ELISA assay to standard HPLC methodology for plasma total homocysteine measurements. A good correlation was found for total homocysteine concentrations less than 30-35 micromolar; thus the diagnostic accuracy of the ELISA assay was considered excellent for the diagnosis of fasting hyperhomocysteinemia and good for methionine loading tests.

Dr. L. Iacoviello presented an update from the recent ETRO working party meeting on "Population Genetics of Hemostatic Risk Factors for Arterial Disease." She discussed meta-analyses of studies examining the role of the 4G/5G polymorphism in the PAI-1 promoter, the Bcl 1 polymorphism in the beta-fibrinogen gene, the repeat polymorphism in the tissue plasminogen activator gene, and the PLAII polymorphism in the platelet glycoprotein IIIA as risk factors for myocardial infarction. Plans will be made to formalize interactions between the ETRO working party and the activities of this subcommittee.

Dr. G. Lowe reviewed data from a recently published metaanalysis of fibrinogen as a risk factor for ischemic heart disease (Danesh et al., JAMA May 1998) indicating a two-fold increased risk with a tighter confidence interval in patients with fibrinogen levels in the top tertile. He reviewed the various methodologies for fibrinogen assays and emphasized the need for attention to this issue in the interpretation of the metaanalyses. He next presented results of a study in 1,661 healthy subjects (aged 25-74) comparing results of fibrinogen assays performed by Clauss assay, a prothrombin time-derived method, and immunonephelometry. Correlations between the three assays ranged between 0.69 and 0.85. Dr. Lowe is preparing an overview article on the topic of predictive variables and cardiovascular disease for submission by this subcommittee for submission to Thrombosis and Haemostasis.

Dr. L. Iacoviello presented her results on factor VII polymorphisms as a risk factor for ischemic heart disease in patients with a positive family history and young patients. Potential reasons for different results (i.e., patient selection, ethnic differences in polymorphism frequency, as well as environmental factors) were discussed. Further discussion of this topic will be presented at the SSC meeting in Washington next year along with discussion of other genetic risk factors including factor V Leiden, prothrombin 20210A, and factor XIII-Val34Leu polymorphisms.