title: D-dimer as a marker for cardiovascular and arterial thrombotic events in patients with peripheral arterial disease. A systematic review.
abstract: Peripheral artery disease (PAD) is associated with an increased risk for cardiovascular events. D-dimers are a marker for hypercoagulability and are linked with thrombotic events in patients with venous as well as arterial thrombosis. The predictive value of plasma D-dimer levels in relation to cardiovascular events in patients with PAD is not unambiguously established. It was our objective to gather evidence evaluating the value of D-dimer as a predictor of arterial thrombotic events patients with PAD. The Pubmed, Embase, and Cochrane databases were searched (January 1980-November 2012), and 65 abstracts were found. The strategy was supplemented with manual review of reference lists. Case-control, cohort or prospective cohort studies that measured fibrin D-dimer in patients with PAD, were included. Studies were excluded if there was no follow-up for arterial thrombotic events or when no specific information on D-dimer was available. The search yielded 10 studies for our analysis, comprising 2,420 patients with PAD, with a total of 1,036 cardiovascular events in 10,599 patient-years. Two studies with a follow-up of one year showed that fibrin D-dimer predicts both deterioration of PAD and subsequent thrombotic events. Five out of six studies with a median follow-up of 2-4 years revealed that an increased D-dimer is predictive of various arterial thrombotic events including mortality. Two studies with a longer follow-up (over 6 years) did not show an independent association between increased D-dimer levels, arterial thrombotic events and CVD mortality. In conclusion, an increased D-dimer appeared to be independently associated with a two times increased risk of near-term cardiovascular events (relative risk 2.30, 95% confidence interval 1.43-3.68). However formal meta-analysis was only feasible for four out of 10 included studies. Due to the extended heterogeneity of the included studies cautious interpretation of these data is warranted.
authors.affiliation: Maastricht University Medical Center, Maastricht, Limburg 6200, The Netherlands. m-c.kleinegris@maastrichtuniversity.nl.
authors.forename: Marie-Claire F
authors.initials: MC
authors.lastname: Kleinegris
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Arina J
authors.initials: AJ
authors.lastname: ten Cate-Hoek
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000150:complications*; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood* / Q000209:etiology*
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D