Markers of coagulation activation, endothelial stimulation and inflammation in patients with peripheral arterial disease.
OBJECTIVE
Patients with peripheral arterial disease have a significantly increased risk of cardiovascular and cerebrovascular mortality. Studies have shown that some haemostatic and inflammatory markers are elevated in these patients but the effect of the severity of the disease has not been fully documented. The aim of this study was to assess the level of coagulation activation, endothelial stimulation and inflammation in patients with claudication and critical limb ischaemia (CLI) compared to healthy controls.


METHODS
A prospective observational study was conducted amongst 202 subjects: 132 claudicants, 30 patients with critical ischaemia, and 40 controls. D-dimer (DD) and thrombin-antithrombin III (TAT) levels measured using ELISA as markers of coagulation activation. von Willebrand factor (vWF) and high-sensitivity C-reactive protein (CRP) levels were measured as markers of endothelial and inflammatory stimulation.


RESULTS
vWF and CRP levels were significantly higher in patients with intermittent claudication (1.9 U/ml, range 0.78-4.05; p < 0.001; 3.4 mg/l, range 0.15-24; p > 0.001, respectively) and critical ischaemia (2.36 U/ml; range 1.03-5.69; p < 0.001; 7.17 mg/ml, range 0.15-174; p < 0.001, respectively) compared to controls (1.28 U/ml, range 0.62-3.13; 1.04, range 0.15-7.59 mg/l). DD was also significantly higher in claudicants (48.6 microg/ml; range 2-1741; p < 0.001) and in patients with CLI (61.1 microg/ml, range 3.65-1963; p < 0.001) compared to controls (26.1 microg/ml, range 9.65-203.1). TAT levels were significantly higher in CLI (3.14 mg/l, range 2.09-58.11), compared to controls (2.36 mg/l, range 1.49-7.38; p = 0.004). Patients with CLI had significantly higher levels of CRP, vWF, and TAT than claudicants.


CONCLUSIONS
Coagulation activation and endothelial stimulation are significantly increased in patients with peripheral arterial disease compared to healthy controls. Coagulation and endothelial activation increases with the severity of the arterial disease.
Cassar
K
K
Department of Vascular Surgery, University of Aberdeen, Aberdeen, Scotland. k.cassar@abdn.ac.uk
Bachoo
P
P
Ford
I
I
Greaves
M
M
Brittenden
J
J
D000368:Aged; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007383:Intermittent Claudication / Q000097:blood*; D007511:Ischemia / Q000097:blood*; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D011446:Prospective Studies; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D014841:von Willebrand Factor; D000990:Antithrombin III; D002097:C-Reactive Protein; D010447:Peptide Hydrolases