Hyperhomocysteinemia and other inherited prothrombotic conditions in young adults with a history of ischemic stroke

Background and Purpose-The mechanisms of ischemic stroke in young adults are poorly understood. During the last years, several studies suggested a role for genetic factors predisposing to thrombophilia and for moderate hyperhomocysteinemia in this setting. Methods-We evaluated in 132 consecutive patients (66 males, 66 females; mean +/- SD age, 38.4 +/- 11.7 years; mean +/- SD age at first event, 34.8 +/- 10.9 years; range, 6 months to 50 years) referred to our center between January 1997 and December 1999 for a history of young adult ischemic stroke (age at first event, <51 years) the prevalence of factor V (FV) Leiden, prothrombin (FII) G20210A, and C677T and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene mutations and fasting serum total homocysteine levels. Two hundred sixty-two apparently healthy subjects (117 males, 145 females; mean +/- SD age, 36 +/- 13.2 years) served as controls. Results-Total homocysteine levels differed significantly (P=0.004, t test) between patients and controls: 13.03 +/- 18.61 versus 10.75 +/- 6.24 mu mol/L (mean +/- SD), respectively. In contrast, homozygosity for the TT mutation of the MTHFR gene was 30 of 132 (22.7%) in patients and 45 of 262 (17.2%) in controls; this difference was not statistically significant (P>0.05, chi(2) test). However, when we stratified the whole population according, to genotype, fasting serum homocysteine levels were significantly higher in TT patients than in TT controls (25.3 +/- 36.8 versus 15 +/- 11.6 mumol/L; P=0.02, t test). Mutations of FV Leiden and of FII G20210A gene are currently reported to be associated with a tendency toward ischemic stroke. Their frequencies were not statistically significantly different between patients and controls in this setting: 7 of 132 (5.3%) versus 17 of 262 (6.5%) for FV Leiden and 10 of 132 (7.6%) versus 16 of 262 (6.1%) for FII G20210A, respectively (all P>0.05, chi(2) test). Conclusions-In the present cohort of patients, moderate hyperhomocysteinemia is the only variable that helps to identify young adults with a history of ischemic stroke.