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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cancer, Heart, and Sleep Epidemiology B Study Section (CHSB)
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Wright, Jacqueline
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University of Minnesota Twin Cities
Public Health & Prev Medicine
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United States
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Mahmoodi, Bakhtawar K; Cushman, Mary; Anne Næss, Inger et al. (2017) Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism: An Individual Participant Data Meta-Analysis of Prospective Studies. Circulation 135:7-16
Chatterjee, Neal A; Giulianini, Franco; Geelhoed, Bastiaan et al. (2017) Genetic Obesity and the Risk of Atrial Fibrillation: Causal Estimates from Mendelian Randomization. Circulation 135:741-754
Arenas de Larriva, Antonio P; Norby, Faye L; Chen, Lin Y et al. (2017) Circulating ceruloplasmin, ceruloplasmin-associated genes, and the incidence of atrial fibrillation in the atherosclerosis risk in communities study. Int J Cardiol 241:223-228
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Noordam, Raymond; Sitlani, Colleen M; Avery, Christy L et al. (2017) A genome-wide interaction analysis of tricyclic/tetracyclic antidepressants and RR and QT intervals: a pharmacogenomics study from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. J Med Genet 54:313-323
Fashanu, Oluwaseun E; Heckbert, Susan R; Aguilar, David et al. (2017) Galectin-3 and Venous Thromboembolism Incidence: the Atherosclerosis Risk in Communities (ARIC) Study. Res Pract Thromb Haemost 1:223-230
Justice, Anne E (see original citation for additional authors) (2017) Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun 8:14977
Kulkarni, Manjusha; Foraker, Randi E; McNeill, Ann M et al. (2017) Evaluation of the modified FINDRISC to identify individuals at high risk for diabetes among middle-aged white and black ARIC study participants. Diabetes Obes Metab 19:1260-1266
Sarnowski, Chloé; Kavousi, Maryam; Isaacs, Steve et al. (2017) Genetic variants associated with earlier age at menopause increase the risk of cardiovascular events in women. Menopause :
Scott, Robert A; Scott, Laura J; Mägi, Reedik et al. (2017) An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. Diabetes 66:2888-2902

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