The goal of the proposed research is to determine if serial assessment of novel risk factors for cardiovascular disease (CVD) is an important tool in prediction of clinical CVD events in an elderly cohort, the Cardiovascular Health Study. The researchers have exciting new data showing strong associations of biomarkers of hemostasis and inflammation with increased CVD risk in apparently healthy subjects over 65. These unique results, along with results of the proposed research, may have a major impact on practice of cardiovascular medicine. To define normal longitudinal change, the biomarkers of interest will be measured at two time points three years apart. A nested case-control study with myocardial infarction and CVD death as endpoints, will be completed to study the relationship between longitudinal change of biomarkers and CVD risk. Effect modification by subclinical CVD will be assessed. Levels of biomarkers at the two time points will be used to determine whether proximity of measurement to CVD event is an important determinant of predictive utility of the markers. Prediction models will be developed and validated to identify older individuals at the highest risk of future CVD. The candidate is committed to becoming an independent investigator in cardiovascular epidemiology. Along with her excellent medical background, to accomplish her goal, expertise is required in epidemiology, biostatistics, and molecular biochemistry and physiology. The candidate has begun training in all three areas, pursuing a masters degree in Epidemiology, studying the epidemiology of hemostasis in the elderly, and participating in research with a notable biochemistry group. The goal of this award is to support expanded knowledge and solidification of all three key areas of molecular epidemiology, through an important research project. This will facilitate success of the candidate in molecular cardiovascular epidemiology. The environment for the proposed research is ideal for the candidate's needs. The sponsor, RP Tracy, a clinical chemist, has a significant role as a molecular epidemiologist, having built a large laboratory with a reputation for high-precision biomarker assessment in many epidemiologic studies. He is committed to the candidate, as demonstrated in the application. The cosponsor, LH Kuller, has contributed broadly to the field of cardiovascular epidemiology, and supplements the skills of Dr. Tracy. The expertise of the other advisors is diverse and well matched to the career development plans of the candidate, and to the aims of the research. A critical factor to the success of the applicant is the unequivocal commitment of the institution to her career development.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08HL003618-01
Application #
2027135
Study Section
Special Emphasis Panel (ZHL1-CSR-Y (O1))
Project Start
1997-01-01
Project End
2001-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Kennedy, Margaret; Solomon, Cam; Manolio, Teri A et al. (2005) Risk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study. Arch Intern Med 165:1896-902
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
Cushman, Mary; Costantino, Joseph P; Bovill, Edwin G et al. (2003) Effect of tamoxifen on venous thrombosis risk factors in women without cancer: the Breast Cancer Prevention Trial. Br J Haematol 120:109-16
Van Hylckama Vlieg, A; Callas, P W; Cushman, M et al. (2003) Inter-relation of coagulation factors and d-dimer levels in healthy individuals. J Thromb Haemost 1:516-22
Smiles, Adam M; Jenny, Nancy S; Tang, Zhonghua et al. (2002) No association of plasma prothrombin concentration or the G20210A mutation with incident cardiovascular disease: results from the Cardiovascular Health Study. Thromb Haemost 87:614-21
Andreescu, Astrid C M; Cushman, Mary; Rosendaal, Frits R (2002) D-dimer as a risk factor for deep vein thrombosis: the Leiden Thrombophilia Study. Thromb Haemost 87:47-51
Sites, Cynthia K; Toth, Michael J; Cushman, Mary et al. (2002) Menopause-related differences in inflammation markers and their relationship to body fat distribution and insulin-stimulated glucose disposal. Fertil Steril 77:128-35
Cushman, M; Psaty, B M; Meilahn, E N et al. (2001) Post-menopausal hormone therapy and concentrations of protein C and antithrombin in elderly women. Br J Haematol 114:162-8
Geffken, D F; Cushman, M; Burke, G L et al. (2001) Association between physical activity and markers of inflammation in a healthy elderly population. Am J Epidemiol 153:242-50
Andreescu, A C; Cushman, M; Hammond, J M et al. (2001) Trousseau's syndrome treated with long-term subcutaneous lepirudin (case report and review of the literature). J Thromb Thrombolysis 11:33-7

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