Cerebrovascular events in patients with significant stenosis of the carotid artery are associated with hyperhomocysteinemia and platelet antigen-1 (Leu33Pro) polymorphism.
OBJECTIVE
Although risk factors for carotid artery stenosis caused by atherosclerosis are known, it is unclear what triggers "activation" of the atherosclerotic plaques and the ensuing thromboembolic cerebral events. The aim of this study was to evaluate whether thrombophilic factors, platelet glycoprotein (GP) polymorphisms, and homocysteine are associated with a risk of ischemic events in patients with significant carotid stenosis.


METHODS
Consecutive patients with >/=50% carotid stenosis, whether symptomatic (with ipsilateral ischemic events) or asymptomatic, who were evaluated and followed in a neurovascular clinic were tested for plasma levels of homocysteine, C677T mutation in methylenetetrahydrofolate reductase, G20210A mutation of factor II, factor V Leiden, antiphospholipid antibodies, and polymorphisms of platelet membrane GP: human platelet antigen (HPA)-1, GP Ia (C807T), and GP Ib (variable number of tandem repeats, Kozak, and HPA-2).


RESULTS
Eighty-six asymptomatic and 67 symptomatic patients were evaluated. The former group was older (73.7+/-6.9 versus 69.5+/-9.1 years, P=0.02). Major risk factors for stroke were similar in both groups. In symptomatic patients versus asymptomatic patients, hyperhomocysteinemia was 3-fold more frequent (34.3% versus 12.8%, respectively; P=0.002) and HPA-1a/b was almost 2-fold more common (38.8% versus 20.9%, respectively; P=0.01). All other thrombophilic factors and platelet polymorphisms studied did not differ significantly between the 2 groups. Multivariate analysis revealed that hyperhomocysteinemia and the HPA-1a/b genotype conferred a significant risk of cerebral ischemic events, with odds ratios (95% CI) of 4.07 (1.7 to 9.7) and 3.4 (1.5 to 7.8), respectively.


CONCLUSIONS
Hyperhomocysteinemia and HPA-1a/b are independent risk factors for ischemic events in patients with significant carotid stenosis.
Streifler
J Y
JY
Neurology Unit, Rabin Medical Center, Golda Campus, Petach-Tikva, Israel. jonathans@clalit.org.il
Rosenberg
N
N
Chetrit
A
A
Eskaraev
R
R
Sela
B A
BA
Dardik
R
R
Zivelin
A
A
Ravid
B
B
Davidson
J
J
Seligsohn
U
U
Inbal
A
A
D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D017152:Antibodies, Antiphospholipid / Q000097:blood; D016824:Antigens, Human Platelet / Q000235:genetics*; D016893:Carotid Stenosis / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015897:Comorbidity; D005165:Factor V / Q000235:genetics; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D039661:Integrin beta3; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D015999:Multivariate Analysis; D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology
D017152:Antibodies, Antiphospholipid; D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins; C095381:factor V Leiden; C083451:human platelet antigen 1b; D006710:Homocysteine; D005165:Factor V; D011516:Prothrombin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)