Clinical trial NCT00005504: Epidemiology of Venous Thrombosis and Pulmonary Embolism
Official title: Longitudinal Investigation of Thromboembolism Etiology
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Cardiovascular Diseases
Pulmonary Embolism
Venous Thrombosis
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2000-05-26
Enrollment: 21680
Sex: ALL
Minimum age (years): 45
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: ARIC and CHS cohorts

Brief summary: To investigate venous thromboembolism in two carefully conducted prospective epidemiologic studies of African American and white adults -- the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS).

Detailed description: BACKGROUND:

Venous thromboembolism, comprising deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major contributor to morbidity and mortality in the United States. Nevertheless, no comprehensive, prospective, population-based epidemiologic studies have simultaneously examined lifestyle, molecular, and biochemical risk factors for this important disease.

DESIGN NARRATIVE:

Deep venous thrombosis and pulmonary embolism cases were identified and verified in order to estimate incident rates of hospitalized venous thromboembolism in the combined ARIC and CHS cohorts. The association of venous thromboembolism was determined prospectively with demographic and lifestyle factors, plasma lipids, medical history, and hemostatic components (including fibrinogen, platelet count, factors VIIc and VIIIc) using existing ARIC and CHS data. A nested case control study was conducted using stored pre-diagnosis blood and DNA specimens to determine the prospective associations of venous thromboembolism with the following: levels of procoagulant or anticoagulant factors and related genetic variants (including factor V Leiden), fibrinolytic factors (e.g., plasminogen activator inhibitor-1) and related genetic variants, markers of thrombin activation, and other potentially important biochemical or related genetic factors (e.g., homocysteine).

The study was renewed in 2003 to extend event follow-up for four more years and to conduct longitudinal analyses of incidence and potential risk factors not fully explored such as diet, frailty, hormone replace therapy and obesity interactions. It was renewed in 2008 to conduct a genome wide association study. It was again renewed in 2013 and 2017.

Eligibility criteria: Inclusion: in the ARIC or CHS cohorts already

Exclusion: not in the ARIC or CHS cohorts

Primary outcomes:
measure: Venous thrombosis and pulmonary embolism
timeFrame: Yearly Follow up
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Minnesota
name: Aaron Folsom, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Folsom AR, Aleksic N, Wang L, Cushman M, Wu KK, White RH. Protein C, antithrombin, and venous thromboembolism incidence: a prospective population-based study. Arterioscler Thromb Vasc Biol. 2002 Jun 1;22(6):1018-22. doi: 10.1161/01.atv.0000017470.08363.ab.
citation: Folsom AR, Cushman M, Tsai MY, Aleksic N, Heckbert SR, Boland LL, Tsai AW, Yanez ND, Rosamond WD. A prospective study of venous thromboembolism in relation to factor V Leiden and related factors. Blood. 2002 Apr 15;99(8):2720-5. doi: 10.1182/blood.v99.8.2720.
citation: Folsom AR, Cushman M, Tsai MY, Heckbert SR, Aleksic N. Prospective study of the G20210A polymorphism in the prothrombin gene, plasma prothrombin concentration, and incidence of venous thromboembolism. Am J Hematol. 2002 Dec;71(4):285-90. doi: 10.1002/ajh.10229.
citation: Folsom AR, Cushman M, Heckbert SR, Rosamond WD, Aleksic N. Prospective study of fibrinolytic markers and venous thromboembolism. J Clin Epidemiol. 2003 Jun;56(6):598-603. doi: 10.1016/s0895-4356(03)00052-0.
citation: Aleksic N, Folsom AR, Cushman M, Heckbert SR, Tsai MY, Wu KK. Prospective study of the A455V polymorphism in the thrombomodulin gene, plasma thrombomodulin, and incidence of venous thromboembolism: the LITE Study. J Thromb Haemost. 2003 Jan;1(1):88-94. doi: 10.1046/j.1538-7836.2003.00029.x.
citation: Tsai AW, Cushman M, Tsai MY, Heckbert SR, Rosamond WD, Aleksic N, Yanez ND, Psaty BM, Folsom AR. Serum homocysteine, thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE). Am J Hematol. 2003 Mar;72(3):192-200. doi: 10.1002/ajh.10287.
citation: Tsai AW, Cushman M, Rosamond WD, Heckbert SR, Tracy RP, Aleksic N, Folsom AR. Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE). Am J Med. 2002 Dec 1;113(8):636-42. doi: 10.1016/s0002-9343(02)01345-1.
citation: Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright P, Folsom AR. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004 Jul 1;117(1):19-25. doi: 10.1016/j.amjmed.2004.01.018.
citation: Fashanu OE, Heckbert SR, Aguilar D, Jensen PN, Ballantyne CM, Basu S, Hoogeveen RC, deFilippi C, Cushman M, Folsom AR. Galectin-3 and Venous Thromboembolism Incidence: the Atherosclerosis Risk in Communities (ARIC) Study. Res Pract Thromb Haemost. 2017 Oct;1(2):223-230. doi: 10.1002/rth2.12038. Epub 2017 Sep 4.
citation: Folsom AR, Tang W, George KM, Heckbert SR, MacLehose RF, Cushman M, Pankow JS. Prospective study of gamma' fibrinogen and incident venous thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE). Thromb Res. 2016 Mar;139:44-9. doi: 10.1016/j.thromres.2016.01.008. Epub 2016 Jan 12.
citation: Folsom AR, Tang W, Weng LC, Roetker NS, Cushman M, Basu S, Pankow JS. Replication of a genetic risk score for venous thromboembolism in whites but not in African Americans. J Thromb Haemost. 2016 Jan;14(1):83-8. doi: 10.1111/jth.13193. Epub 2015 Dec 29.