1997 MINUTES
PREDICTIVE VARIABLES AND CARDIOVASCULAR DISEASE SUBCOMMITTEE
Friday, 6 June, 1997, 13:00-17:00
Tiziano, Fortezza da Basso
Florence, Italy
Chair: K. Bauer, USA
Co-Chairs: R. Hull, Canada; S. Humphries, UK; G. Lowe, UK
The number of people attending this subcommittee meeting was estimated at 450.
Epidemiologic studies:
Dr. George Miller led off the session by presenting an overview of three major prospective epidemiologic studies. These include the ARIC (USA), PROCAM (Münster, Germany) and Second Northwick Park Heart ( NPHS II) Studies (UK). Data were presented from NPHS II indicating a steep decline in coronary event rates, which has been greater than anticipated at its inception in 1989. As compared to NHPS I which was initiated in the 1970s, NPHS II includes fewer current smokers (26% versus 46%) and participants had lower mean diastolic blood pressures at entry. Plasma fibrinogen measurements were also significantly reduced in NPHS II as compared to NPHS I.Genetic Polymorphisms:
Dr. L. Iacoviello presented an update from the ETRO working party on "Population Genetics of Hemostatic Risk Factors for Arterial Vascular Disease." She discussed a meta-analysis of studies examining the role of the 4G/5G polymorphism in the PAI-1 promoter as a risk factor for myocardial infarction. The 4G/4G allele was associated with a 1.24-fold increased risk of coronary heart disease (CHD).Dr. F. Rosendaal reviewed data from the Leiden Thrombophilia Study that the G20210A mutation in the prothrombin gene is a risk factor for venous thrombosis. This mutation is correlated with elevated prothrombin levels. Dr. Michael Laffan (UK) discussed data from a thrombophilia clinic population showing that elevated factor VIII:C is a risk factor for venous thrombosis. These patients also had elevated VIII:Ag levels which correlated with VIII:C. Thus far, it has not been possible to define genetic abnormalities that are associated with these elevations.
Hyperhomocysteinemia:
Dr. M. Cattaneo (Milan) presented an overview of hyperhomocysteinemia as a risk factor for venous thrombosis. He reviewed methodologic issues related to plasma homocysteine measurements including performance of assays post-methionine loading. Dr. A. Tripodi (Milan) presented plans for a multi-center study of plasma homocysteine assays. Dr. Armando D'Angelo discussed his center's experience in evaluating hyperhomocysteinemic patients.Fibrinogen:
Dr. Lowe (UK) reported results from several Scottish epidemiologic studies confirming the predictive value of fibrinogen for CHD events in men and women. He commented that variability of fibrinogen measurements has decreased with use of the international fibrinogen standard. Also improved predictive power of fibrinogen measurements for CHD can be obtained using a heat nephelometry assay.Dr. F. Haverkate (Netherlands) briefly presented results of antithrombin III, protein C, protein S, and APC resistance determinations performed by the ECAT foundation in 70 laboratories.
Parameters of Hemostatic Activation
: Dr. J. Morrissey (USA) described a clot-based assay for measuring free factor VIIa levels in plasma and the results of some clinical investigations using this method. He also presented preliminary data regarding potential explanations for a ten-fold difference in normal levels between the clot-based assay and an immunoenzymatic assay reported by Philippou and Lane.Inflammation and Hemostatic Variables
: Dr. R. Tracy (USA) and F. Haverkate reviewed the topic of inflammation as it relates to hemostatic variables and CHD risk. Recent data were presented regarding elevated levels of C-reactive protein as a coronary risk factor.