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.
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.
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).
Homocysteine is a potentially modifiable, independent risk factor for stroke and thrombotic
events in patients with SLE.