Homocysteine in Sickle Cell Disease: Relationship to Stroke

PURPOSE: The risk factors and pathophysiology of stroke and other serious complications of sickle cell disease (SCD) are poorly defined. Hyperhomocysteinemia has recently been identified as a risk factor for stroke and other vascular diseases in the general population, however its role in SCD has not been investigated. PATIENTS AND METHODS: We measured serum homocysteine and red cell folate levels in 100 patients with SCD, including 16 patients with stroke. A disease severity score was determined for all patients and those without stroke were classified into mild (44 patients) or severe (40 patients) disease groups. RESULTS: Homocysteine levels for the stroke group (median 13.3 μmol/L, mean 13.1 ± 4.3 μmol/L) were significantly higher than those in patients without stroke (median 9.7 μmol/L, mean 10.7 μmol/L) (P<0.02), and on multiple regression analysis homocysteine level was independently correlated with stroke (P<0.026). Homocysteine and folate levels were inversely correlated (r = −0.41, P<0.00005). Using logistic regression, the odds ratio for stroke in patients with homocysteine levels above the median (10.1 μmol/L) was 3.5 in this group of patients (95% confidence interval 1.1 to 11.9). CONCLUSION: High homocysteine levels may be a risk factor for development of stroke in SCD patients. The role of homocysteine in the pathogenesis of stroke in SCD needs to be examined in a longitudinal, prospective study.