# Epidemiology of Venous Thrombosis and Pulmonary Embolism

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $817,909

## Abstract

Project Summary
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 4-year renewal of the Longitudinal
Investigation of Thromboembolism Etiology (LITE), a prospective study of VTE over 3+ decades in the
Atherosclerosis Risk in Communities (ARIC) Study and Cardiovascular Health Study (CHS). In the previous
five project periods, we successfully identified or clarified, in 127 publications, multiple genetic and non-genetic
risk factors for VTE. We plan to build upon these findings, by adding VTE cases, addressing new hypotheses
related to VTE proteomic risk markers, and using information from all project periods to improve understanding
of VTE occurrence and possible prevention.
 LITE's 3 renewal aims are to: Aim 1: Extend VTE event follow-up in ARIC for 4 more years, increasing the
total number of LITE VTE events by 140, to a total of 1,224. Aim 2: Leverage a large panel of aptamer-based,
plasma proteomics data (n~5,000 human proteins) available in ARIC to conduct a prospective study of
proteomic risk markers for incident non-cancer VTE (n=552 cases among 11,600 individuals), and add
identical proteomics data from the HUNT3 Study (n=200 incident non-cancer VTEs and 200 random sub-
cohort). We anticipate also being able to add identical proteomics data on 5,000 CHS participants who
developed 150 VTEs. We will independently replicate significant proteins in the MESA study (n=175 non-
cancer VTE cases among 6,500 participants) and an independent portion of HUNT3 (n=500 additional non-
cancer VTE cases and subcohort n=500). We will validate the top 5 novel, replicated, aptameric-based
proteins by either commercial assays or, where non-existent, by developing targeted quantitative protein
assays using liquid chromatography-mass spectrometry. Aim 3: Conduct a GWAS in ARIC of the novel
proteins identified and replicated in Aim 2, and to replicate any significant genetic associations in MESA and
HUNT3. We will also conduct a Mendelian randomization study to elucidate the causal relation between
significant protein biomarkers and VTE, followed by a network analysis to integrate the genomic and proteomic
findings.
 LITE is one of the few and most productive US prospective studies on VTE. A 4-year renewal will offer
unprecedented opportunities to address several significant NHLBI strategic research priorities by relating
~5,000 aptamer-based protein markers to VTE risk in multiple cohorts. We expect to identify undiscovered
and potentially causal pathways leading to VTE, with the aim of providing critical new knowledge about VTE
etiology, methods to identify people at risk of unprovoked VTE, and potential paths to new interventions for the
prevention and treatment of VTE.

## Key facts

- **NIH application ID:** 10117923
- **Project number:** 2R01HL059367-19A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** AARON R FOLSOM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $817,909
- **Award type:** 2
- **Project period:** 1998-02-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117923

## Citation

> US National Institutes of Health, RePORTER application 10117923, Epidemiology of Venous Thrombosis and Pulmonary Embolism (2R01HL059367-19A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10117923. Licensed CC0.

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