Coronary heart disease (CHD) and other thrombosis related disorders are a major source of morbidity and mortality in the United States and the world. To a certain extent they are diseases of the elderly, with the majority of overt CHD occurring in persons over the age of 65. Recently, fibrinogen and factor VII have been implicated as independent CHD risk factors in middle age populations, although causative roles have not been established. We propose to expand the study of thrombosis and CHD by carefully examining selected measures of coagulation and fibrinolysis in individuals 65 years and older: measures of pro-coagulation (factor antigen VII, prothrombin fragment 1.2, fibrinopeptide A and thrombin - antithrombin III complex), measures of coagulation inhibition (protein C and protein S, antithrombin III, and the lipoprotein associated coagulation inhibitor (LACI), and measures of fibrinolysis (plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator-PAI-1 complex, plasmin - alpha-2 antiplasmin complex, and Lp(a). This study is facilitated by our current role as Central Blood Analysis laboratory for the Cardiovascular Health Study (CHS) and the Honolulu Heart Program (HHP). Our major hypothesis is that measures of coagulation and fibrinolysis will correlate to the incidence of CHD and other thrombosis related disorders, and help identify those individuals at greatest risk. The cohort from CHS is made up of a general mainland U.S. population, while the HHP cohort is made up of Japanese-Americans m Hawaii. These two genetically distinct populations have different event rates for CHD, and offer a unique opportunity to test associations that are uncovered by comparing results across populations. Our first specific aim is to determine the relationship between the proposed measures and the incidence of CHD (and other thrombosis related disorders) using a case/control format. The second specific aim is to determine the short and medium term biological variability of the proposed measures, to aid in interpretation of observed differences. Our third specific aim is to establish in both cohorts the distribution of the proposed measures, including relationships to other variables in the extensive CHS and HHP data bases such as established risk factors and prevalent disease. These studies will increase our understanding of the relationship of thrombosis to cardiovascular risk.
Showing the most recent 10 out of 37 publications
