Relationships Between D-Dimer Levels and Stroke Risk as Well as Adverse Clinical Outcomes After Acute Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis

Objective: Abnormal elevation of D-dimer levels is an important indicator of disseminated intravascular clotting. Therefore, we hypothesized that high D-dimer levels were associated with the risk of stroke and adverse clinical outcomes of patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Methods: The present meta-analysis aimed to systematically analyze the associations between D-dimer and the risk of stroke as well as the clinical outcomes of patients with post-stroke or TIA. Meanwhile, dose–response analyses were conducted when there were sufficient data available. Three electronic databases including Pubmed, the Embase database, and the Cochrane Library were searched by two investigators independently. All the pooled results were expressed as risk ratios (RRs). Results: Finally, 22 prospective cohort studies were included into this meta-analysis. The results suggested that high D-dimer levels were associated with increased risks of total stroke (RR 1.4, 95%CI 1.20–1.63), hemorrhagic stroke (RR 1.25, 95%CI 0.69–2.25), and ischemic Stroke (RR 1.55, 95%CI 1.22–1.98), and the dose-dependent relationship was not found upon dose–response analyses. Besides, the high D-dimer levels on admission were correlated with increased risks of all-cause mortality [RR 1.77, 95% confidence interval (CI) 1.26–2.49], 5-day recurrence (RR 2.28, 95%CI 1.32–3.95), and poor functional outcomes (RR 2.01, 95%CI 1.71–2.36) in patients with AIS or TIA. Conclusions: On the whole, high D-dimer levels may be associated with the risks of total stroke and ischemic stroke, but not with hemorrhagic stroke. However, dose–response analyses do not reveal distinct evidence for a dose-dependent association of D-dimer levels with the risk of stroke. Besides, high D-dimer levels on admission may predict adverse clinical outcomes, including all-cause mortality, 5-day recurrence, and 90-day poor functional outcomes, of patients with AIS or TIA. More studies are warranted to quantify the effect of D-dimer levels on the risk of stroke or TIA, so as to verify and substantiate this conclusion in the future.