Hyperhomocysteinemia as a thrombotic risk factor in systemic lupus erythematosus

Abstract EN

Objective: The aim of the present work was to assess serum total homocysteine (t-Hcy), vitamin Bl2, folate and anticardiolipin antibody levels in systemic lupus erythematosus (SLE) patients and to clarify the possible role of t-Hcy as a thrombotic risk factor for the development of cerebrovascular stroke (CVS) in cases of SLE.

Methods: Thirty female patients suffering from SLE with a mean age of 26.0 ±9.81 years were included in the study.

Twelve of them had lupus nephritis (nephritis positive subgroup) and nine had CVS (CVS positive subgroup).

All patients were subjected to thorough clinical assessment, radiological evaluation and laboratory investigations, including serum creatinine, lipid profile (total cholesterol, triglycerides, low density lipoprotein- cholesterol "LDL-Chol", high density lipoprotein-cholesterol "HDL-Chol" and atherosclerotic risk ratio "T-Chol/HDL- Chol"), complete hemogram (CBC and ESR) in addition to assessment of t-Hcy, vitamin Bl2, folate and anticardiolipin antibodies.

Fifteen healthy age-matched females served as a control group and underwent the same procedures.

Results: Serum t-Hcy level was significantly elevated in SLE patients than controls (12.69 ± 4.4 Vs 9.83 ± 3.5 ?mol/L respectively, p < 0.05).

CVS positive subgroup of patients exhibited higher t-Hcy level than the CVS negative subgroup (16.57±4.48 Vs11.03±3.36 ?mol/L respectively, p<0.01).

Moreover, serum t-Hcy level was significantly higher among SLE patients with nephritis as compared to those without nephritis (15.06±4.

72 Vs 11 .11±3.

62 ?mol/L respectively, p < 0.01) and a statistically significant positive correlation was found between t-Hcy and serum creatinine (p<0.05).

Hyperhomocysteinemia was associated with a statistically significant decrease in serum vitamin B12 (258.5±98.1 pg/mL) and folate levels (5.37±3.05 ng/ml) as compared to controls (682.1±295.8 pg/mL and 9.27±3.54 ng/ml respectively, with p values <0.001and <0.01 respectively).

Moreover, serum folate level of the CVS positive subgroup was significantly lower than the CVS negative subgroup (p<0.0l).

A significant negative correlation was recorded between serum t-Hcy and each of vitamin B12 and folate levels (p < 0.05 respectively).

In spite of a statistically significant increase in anticardiolipin antibodies in SLE patients collectively as compared to controls (16.59±2.47 and 8.68±1.99 MPL respectively, p<0.001), no statistically significant difference was recorded between CVS positive and CVS negative subgroups (p > 0.05).

A closer look at t-Hcy levels in CVS positive and negative subgroups revealed that t-Hcy at a cut-off 16.0 ?mol/L (95th.

Percentile in the CVS negative subgroup) had a diagnostic sensitivity of 67%.

Conclusion: Hyperhomocysteinemia is an inevitable, metabolic disturbance in cases of SLE due to the underlying derangement in vitamin B12 and folate metabolism.

The condition is further augmented by the presence of an associated lupus nephritis that leads to its decreased clearance.

Hyperhomocysteinemia appears to be a prominent but hopefully a modifiable risk factor for the thrombotic cerebrovascular complications of the disease.