Hemostatic markers in patients at risk of cerebral ischemia.
BACKGROUND
Increased levels of markers of hemostasis may assist in the determination of the extent of carotid occlusive disease and the identification of neurologically intact individuals at increased risk of ischemic events.


METHODS
We conducted a prospective study of 304 subjects, including 82 with a recent (< or =7 days) transient ischemic attack (TIA), 157 asymptomatic individuals with a cervical bruit, and 65 control subjects. Baseline evaluation included a neurological assessment, ECG, cervical ultrasonography, and cerebral CT and/or MRI. Levels of markers of coagulation and fibrinolytic activity were also determined. Results were analyzed in relation to the degree of carotid disease and the subsequent occurrence of cerebral and cardiac ischemic events.


RESULTS
Over a mean follow-up period of 2.8 years (SD, 1.3 years), 114 ischemic events occurred. Survival analyses showed that prothrombin fragment 1.2 (F(1.2)) was a predictor of time to cerebral and cardiac ischemic events in the combined TIA and asymptomatic bruit group (relative risk [RR], 1.46; 95% CI, 1.18 to 1.81) as well as in the asymptomatic bruit group separately (RR, 1.70; 95% CI, 1.14 to 2.53). In the TIA group, both F(1.2) (RR, 2.36; 95% CI, 1.19 to 4.68) and severe (> or =80%) carotid stenosis (RR, 3.53; 95% CI, 1.19 to 10.51) were predictive of time to ischemic stroke, myocardial infarction, or vascular death.


CONCLUSIONS
In patients with TIAs and in asymptomatic individuals with cervical bruits, F(1.2) levels were found to be independent predictors of subsequent cerebral and cardiac ischemic events. Our results are consistent with an active role of the coagulation system through upregulation of thrombin in carotid disease progression and in the pathogenesis of ischemic events in patients at risk.
Divisions of Neurology, and Hematology, Montreal General Hospital, McGill University, Canada. rcmd239@aol.com
R
R
Côté
C
C
Wolfson
S
S
Solymoss
A
A
Mackey
J R
JR
Leclerc
D
D
Simard
F
F
Rouah
F
F
Bourque
B
B
Léger
D000368:Aged; D000933:Antifibrinolytic Agents; D000990:Antithrombin III / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016893:Carotid Stenosis / Q000097:blood / Q000150:complications; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000378:metabolism*; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D015994:Incidence; D002546:Ischemic Attack, Transient / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications; D010446:Peptide Fragments / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011516:Prothrombin / Q000378:metabolism*; D011792:Quebec / Q000453:epidemiology; D012307:Risk Factors; D015996:Survival Rate; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
D000933:Antifibrinolytic Agents; D015415:Biomarkers; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; C037742:plasmin-plasmin inhibitor complex; C045879:prothrombin fragment 1.2; D005344:Fibrinopeptide A; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases; D005341:Fibrinolysin