Prospective study of plasma D-dimer and incident venous thromboembolism: The Atherosclerosis Risk in Communities (ARIC) Study.
BACKGROUND
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.
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.
Aaron R
AR
Folsom
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, United States.
Alvaro
A
Alonso
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, United States.
Kristen M
KM
George
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, United States.
Nicholas S
NS
Roetker
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, United States.
Weihong
W
Tang
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.
Mary
M
Cushman
D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000276:immunology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000097:blood / Q000453:epidemiology*
D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D
D-dimer; Deep vein thrombosis; Prospective studies; Pulmonary embolism; Risk factors