Background: The aim of this study was to assess whether plasma homocysteine is a risk factor for stroke and other thrombotic events in patients with systemic lupus erythematosus (SLE)--a condition known to be associated with premature atherothrombotic complications.
Methods: In this prospective study, we investigated the association between homocysteine and risk of stroke and thrombotic events in 337 SLE patients in the Hopkins Lupus Cohort Study, with follow-up of 1619 person-years (mean 4.8 [SD 1.7] years). Each patient had four follow-up assessments per year to obtain information about established risk factors for thrombosis and coronary artery disease. The prospectively defined endpoints were occurrence of stroke and arterial or venous thrombotic events between 1987 and 1995. Blood samples were taken at study entry from fasting patients. Plasma homocysteine, folate, vitamin B12, and pyridoxal 5'-phosphate (PLP) concentrations were measured. Raised homocysteine concentrations were defined as more than 14.1 mumol/L.
Findings: 93% of the study population were women, 54% African American, and 45% white. The mean age of participants was 34.9 (SD 11.7) years. During follow-up there were 29 cases of stroke and 31 arterial thrombotic events. Raised homocysteine concentrations were found in 51 (15%) SLE patients. The log-transformed total homocysteine concentrations correlated with serum folate (r = 0.31, p = 0.0001). In univariate analyses, raised homocysteine concentrations were significantly associated with stroke (odds ratio 2.24 [95% CI 1.22-4.13], p = 0.01) and arterial thrombotic events (3.74 [1.96-7.13], p = 0.0001). After adjustment for established risk factors, total plasma homocysteine concentrations remained an independent risk factor for stroke (2.44 [1.04-5.75], p = 0.04) and arterial thromboses (3.49 [0.97-12.54], p = 0.05).
Interpretation: Homocysteine is a potentially modifiable, independent risk factor for stroke and thrombotic events in patients with SLE.