Plasma d-dimer and incident ischemic stroke and coronary heart disease: The atherosclerosis risk in communities study

Background and Purpose - Epidemiological studies have documented that plasma d-dimer, a fibrin degradation product, is a risk marker for coronary heart disease, but there is limited prospective evidence for stroke. Given that thrombosis is a key mechanism for many strokes, we studied whether d-dimer is a risk marker for ischemic stroke incidence in the Atherosclerosis Risk in Communities (ARIC) Study. Methods - We measured d-dimer in 11 415 ARIC participants free of stroke and coronary heart disease in 1992 to 1995. We followed them for stroke, stroke subtype, and coronary heart disease events through 2012. Results - Over a median of 18 years of follow-up, 719 participants had incident strokes (628 ischemic and 91 hemorrhagic). d-dimer was associated positively with risk of total, ischemic, and cardioembolic strokes, with risk elevated primarily for the highest quintile of d-dimer. After adjustment for other cardiovascular risk factors, the hazard ratio for the highest versus lowest quintile of d-dimer was 1.30 (95% confidence interval, 1.02-1.67) for total stroke, 1.33 (95% confidence interval, 1.02-1.73) for ischemic stroke, and 1.79 (95% confidence interval, 1.08-2.95) for cardioembolic stroke. There was no association with hemorrhagic, lacunar, or nonlacunar stroke categories. d-dimer was positively but weakly associated with coronary heart disease incidence. Conclusions - A higher basal plasma d-dimer concentration in the general population is a risk marker for ischemic stroke, especially cardioembolic stroke.