Aaron R Folsom1, Alvaro Alonso2, Kristen M George2, Nicholas S Roetker2, Weihong Tang2, Mary Cushman3. 1. Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, United States. Electronic address: folso001@umn.edu. 2. Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, United States. 3. Department of Medicine, University of Vermont, Colchester Research Facility, 360 South Park Dr., 206D, Colchester, VT 05446, United States; Department of Pathology, University of Vermont, Colchester Research Facility, 360 South Park Dr., 206D, Colchester, VT 05446, United States. Electronic address: Mary.Cushman@uvm.edu.
Abstract
INTRODUCTION: Plasma D-dimer is a useful clinical test for acute venous thromboembolism (VTE), and concentrations remain higher in VTE patients after treatment than in controls. Yet, evidence is limited on whether higher basal D-dimer concentrations in the general population are associated with greater risk of first VTE. OBJECTIVE: To assess the prospective association between D-dimer and incident VTE over a long follow-up. METHODS: We measured plasma D-dimer in 12,097 participants, initially free of VTE, in the Atherosclerosis Risk in Communities Study. Over a median follow-up of 17years, we identified 521 VTEs. We calculated hazard ratios of VTE using proportional hazards regression. RESULTS: The age, race, and sex adjusted hazard ratios of VTE across quintiles of D-dimer were 1, 1.5, 1.8, 2.1, and 3.2 (p for trend <0.0001). For the first 10years of follow-up, the hazard ratio for the highest versus lowest quintile was 3.5, and was 2.9 after 10years. In both whites and African Americans, VTE risk remained strongly associated with D-dimer after further adjustment for diabetes, body mass index, kidney function, and several thrombophilia genetic markers. D-dimer was associated with both unprovoked and provoked VTE, but more strongly with unprovoked. CONCLUSIONS: A higher basal level of plasma D-dimer in the general population, presumably reflecting a predisposition to thrombosis, is a strong, long-term risk factor for a first VTE.
INTRODUCTION: Plasma D-dimer is a useful clinical test for acute venous thromboembolism (VTE), and concentrations remain higher in VTEpatients after treatment than in controls. Yet, evidence is limited on whether higher basal D-dimer concentrations in the general population are associated with greater risk of first VTE. OBJECTIVE: To assess the prospective association between D-dimer and incident VTE over a long follow-up. METHODS: We measured plasma D-dimer in 12,097 participants, initially free of VTE, in the Atherosclerosis Risk in Communities Study. Over a median follow-up of 17years, we identified 521 VTEs. We calculated hazard ratios of VTE using proportional hazards regression. RESULTS: The age, race, and sex adjusted hazard ratios of VTE across quintiles of D-dimer were 1, 1.5, 1.8, 2.1, and 3.2 (p for trend <0.0001). For the first 10years of follow-up, the hazard ratio for the highest versus lowest quintile was 3.5, and was 2.9 after 10years. In both whites and African Americans, VTE risk remained strongly associated with D-dimer after further adjustment for diabetes, body mass index, kidney function, and several thrombophilia genetic markers. D-dimer was associated with both unprovoked and provoked VTE, but more strongly with unprovoked. CONCLUSIONS: A higher basal level of plasma D-dimer in the general population, presumably reflecting a predisposition to thrombosis, is a strong, long-term risk factor for a first VTE.
Authors: Vanessa Xanthakis; Danielle M Enserro; Joanne M Murabito; Joseph F Polak; Kai C Wollert; James L Januzzi; Thomas J Wang; Geoffrey Tofler; Ramachandran S Vasan Journal: Circulation Date: 2014-10-01 Impact factor: 29.690
Authors: Mary Cushman; Albert W Tsai; Richard H White; Susan R Heckbert; Wayne D Rosamond; Paul Enright; Aaron R Folsom Journal: Am J Med Date: 2004-07-01 Impact factor: 4.965
Authors: Nels C Olson; Mary Cushman; Suzanne E Judd; Leslie A McClure; Susan G Lakoski; Aaron R Folsom; Monika M Safford; Neil A Zakai Journal: J Am Heart Assoc Date: 2015-02-27 Impact factor: 5.501
Authors: Peter Willeit; Alexander Thompson; Thor Aspelund; Ann Rumley; Gudny Eiriksdottir; Gordon Lowe; Vilmundur Gudnason; Emanuele Di Angelantonio Journal: PLoS One Date: 2013-02-07 Impact factor: 3.240
Authors: Antonio P Arenas de Larriva; Alvaro Alonso; Faye L Norby; Nicholas S Roetker; Aaron R Folsom Journal: J Thromb Haemost Date: 2019-03-18 Impact factor: 5.824
Authors: Jeanney Lew; Monika Sanghavi; Colby R Ayers; Darren K McGuire; Torbjørn Omland; Dorothee Atzler; Maria O Gore; Ian Neeland; Jarett D Berry; Amit Khera; Anand Rohatgi; James A de Lemos Journal: Circulation Date: 2017-02-07 Impact factor: 29.690
Authors: Lindsay Fernández-Rhodes; Kristin L Young; Adam G Lilly; Laura M Raffield; Heather M Highland; Genevieve L Wojcik; Cary Agler; Shelly-Ann M Love; Samson Okello; Lauren E Petty; Mariaelisa Graff; Jennifer E Below; Kimon Divaris; Kari E North Journal: Circ Res Date: 2020-06-04 Impact factor: 17.367
Authors: Aaron R Folsom; Weihong Tang; Saonli Basu; Jeffrey R Misialek; David Couper; Susan R Heckbert; Mary Cushman Journal: Thromb Haemost Date: 2019-02-19 Impact factor: 5.249
Authors: Aaron R Folsom; Saonli Basu; Ching-Ping Hong; Susan R Heckbert; Pamela L Lutsey; Wayne D Rosamond; Mary Cushman Journal: Am J Med Date: 2019-04-04 Impact factor: 4.965
Authors: Nicholas S Roetker; Richard F MacLehose; Ron C Hoogeveen; Christie M Ballantyne; Saonli Basu; Mary Cushman; Aaron R Folsom Journal: Thromb Haemost Date: 2018-10-08 Impact factor: 5.249
Authors: Rakhi P Naik; Kim Smith-Whitley; Kathryn L Hassell; Nkeiruka I Umeh; Mariane de Montalembert; Puneet Sahota; Carlton Haywood; Jean Jenkins; Michele A Lloyd-Puryear; Clinton H Joiner; Vence L Bonham; Gregory J Kato Journal: Ann Intern Med Date: 2018-10-30 Impact factor: 25.391
Authors: Weihong Tang; Mary Rachel Stimson; Saonli Basu; Susan R Heckbert; Mary Cushman; James S Pankow; Aaron R Folsom; Nathan Pankratz Journal: J Thromb Haemost Date: 2019-12-06 Impact factor: 5.824