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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL046696-03
Application #
2223135
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1992-04-13
Project End
1997-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Pathology
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Olson, Nels C; Sallam, Reem; Doyle, Margaret F et al. (2013) T helper cell polarization in healthy people: implications for cardiovascular disease. J Cardiovasc Transl Res 6:772-86
Jenny, Nancy Swords; Yanez, N David; Psaty, Bruce M et al. (2007) Inflammation biomarkers and near-term death in older men. Am J Epidemiol 165:684-95
Jaar, Bernard G; Plantinga, Laura C; Astor, Brad C et al. (2007) Novel and traditional cardiovascular risk factors for peripheral arterial disease in incident-dialysis patients. Adv Chronic Kidney Dis 14:304-13
Liu, Yongmei; Berthier-Schaad, Yvette; Fallin, Margaret D et al. (2006) IL-6 haplotypes, inflammation, and risk for cardiovascular disease in a multiethnic dialysis cohort. J Am Soc Nephrol 17:863-70
Liu, Yongmei; Berthier-Schaad, Yvette; Plantinga, Laura et al. (2006) Functional variants in the lymphotoxin-alpha gene predict cardiovascular disease in dialysis patients. J Am Soc Nephrol 17:3158-66
Liu, Yongmei; Berthier-Schaad, Yvette; Fink, Nancy E et al. (2005) Beta-fibrinogen haplotypes and the risk for cardiovascular disease in a dialysis cohort. Am J Kidney Dis 46:78-85
Zieske, Arthur W; Tracy, Russell P; McMahan, C Alex et al. (2005) Elevated serum C-reactive protein levels and advanced atherosclerosis in youth. Arterioscler Thromb Vasc Biol 25:1237-43
Cushman, Mary; Arnold, Alice M; Psaty, Bruce M et al. (2005) C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study. Circulation 112:25-31
Liu, Yongmei; Coresh, Josef; Eustace, Joseph A et al. (2004) Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. JAMA 291:451-9
Sartini, Danielle; Moussawi, Mohamad; Sallam, Reem et al. (2004) Correlation between serum estradiol in the follicular phase of the ovarian cycle and decay acceleration factor (DAF) expression on red blood cells and coxsackiervirus B-3 induced hemagglutination in young cycling women. Am J Reprod Immunol 51:180-7

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