Venous thromboembolism (VTE), comprising deep venous thrombosis and pulmonary embolism, is a major contributor to morbidity and mortality in the U.S. We propose a 3-year renewal of the Longitudinal Investigation of Thromboembolism Etiology (LITE), a prospective study of VTE in the Atherosclerosis Risk in Communities (ARIC) Study and Cardiovascular Health Study (CHS) cohorts, involving 21,680 participants followed for more than two decades. In the previous four project periods, during which 1,055 VTEs occurred, we successfully identified or clarified, via 91 publications, multiple genetic and non-genetic risk factors for VTE. We plan to build upon these findings during this continuation, by adding VTE cases, addressing new hypotheses related to VTE risk factors or outcomes, and using the information from all project periods to improve understanding of VTE occurrence. LITE renewal aims are to: (1) Extend VTE event follow-up in ARIC for 4 more years, increasing the number of LITE VTE events by 262, to a total of 1,317. (2) Explore in depth possible reasons for the higher rates of VTE incidence in African Americans than whites, and systematically test for clinically relevant race interactions with risk factors for VTE. (3) Test the prospective association of incident VTE with novel biomarkers available at no additional cost: plasma galactin 3, sex hormones, and changes in plasma NT- proBNP, troponin T, and C-reactive protein. (4) Measure plasma high molecular weight kininogen and prekallikrein, components of the contact pathway of coagulation, and determine their association with VTE. (5) Test the prospective association of VTE with blood-based biomarkers of accelerated aging?shorter teleomere length and lower mitochontrial copy number. (6) Study the long-term consequences of VTE on physical functioning and quality of life. LITE is one of the few and most productive US prospective studies on VTE. A 3-year renewal will allow LITE to contribute new information on VTE risk factors and outcomes, with potential implications for VTE prevention and treatment.

Public Health Relevance

This prospective epidemiologic study is identifying novel personal characteristics and genetic variants that contribute to increased risk of venous thromboembolism, i.e., blood clots in veins that may travel and block blood supply to organs. This information will have important implications for the prevention and treatment of this common and significant cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059367-18
Application #
9682497
Study Section
Cancer, Heart, and Sleep Epidemiology B Study Section (CHSB)
Program Officer
Wright, Jacqueline
Project Start
1998-02-01
Project End
2021-03-31
Budget Start
2019-04-01
Budget End
2021-03-31
Support Year
18
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Weng, Lu-Chen; Guan, Weihua; Steffen, Lyn M et al. (2018) Pleiotropic effects of n-6 and n-3 fatty acid-related genetic variants on circulating hemostatic variables. Thromb Res 168:53-59
Lutsey, P L; Norby, F L; Alonso, A et al. (2018) Atrial fibrillation and venous thromboembolism: evidence of bidirectionality in the Atherosclerosis Risk in Communities Study. J Thromb Haemost 16:670-679
Roetker, Nicholas S; MacLehose, Richard F; Hoogeveen, Ron C et al. (2018) Prospective Study of Endogenous Hormones and Incidence of Venous Thromboembolism: The Atherosclerosis Risk in Communities Study. Thromb Haemost 118:1940-1950
Hong, Jaeyoung; Hatchell, Kathryn E; Bradfield, Jonathan P et al. (2018) Transethnic Evaluation Identifies Low-Frequency Loci Associated With 25-Hydroxyvitamin D Concentrations. J Clin Endocrinol Metab 103:1380-1392
Gong, J; Nishimura, K K; Fernandez-Rhodes, L et al. (2018) Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI. Int J Obes (Lond) 42:384-390
Robinson-Cohen, Cassianne; Bartz, Traci M; Lai, Dongbing et al. (2018) Genetic Variants Associated with Circulating Fibroblast Growth Factor 23. J Am Soc Nephrol 29:2583-2592
Cowan, Logan T; Lakshminarayan, Kamakshi; Lutsey, Pamela L et al. (2018) Periodontal disease and incident venous thromboembolism: The Atherosclerosis Risk in Communities study. J Clin Periodontol :
Ward-Caviness, Cavin K; Huffman, Jennifer E; Everett, Karl et al. (2018) DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis. Blood 132:1842-1850
Irvin, Marguerite R; Sitlani, Colleen M; Noordam, Raymond et al. (2018) Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry. Pharmacogenomics J :
Floyd, J S; Sitlani, C M; Avery, C L et al. (2018) Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group. Pharmacogenomics J 18:127-135

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