Homocysteine, antiphospholipid antibodies and risk of thrombosis in patients with systemic lupus erythematosus

Abstract

Cardiovascular disease is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Antiphospholipid syndrome (APS) is one of the most important causes of thrombosis in SLE. In addition, an association between hyperhomocysteinemia and increased cardiovascular risk has also been reported. Our aim is to analyse the association of thrombosis with plasma total homocysteine (ptHcy), antiphospholipid antibodies (aPL) and other vascular risk factors in SLE patients. Fasting plasma levels of ptHcy, vitamin B12, folate, total cholesterol and creatinine were measured in 117 SLE patients. Clinical and immunological data were obtained from our prospective computerized database. aPL-positivity was defined according to Sapporo criteria. There was no association between aPL and ptHcy. ptHcy was higher in patients with arterial (median 13.02 versus 10.16 micromol/L, P = 0.010) but not venous thrombosis. In the subgroup analysis, this association was only seen in aPL-negative patients. In logistic regression, aPL (OR 6.60, 95% CI 1.86-23.34) and ptHcy (OR 1.10, 95% CI 1.01-1.19) were independently associated with arterial thrombosis. However, when hypertension, smoking and plasma total cholesterol were added to the model, only aPL (OR 7.38, 95% CI 2.02-26.91) and hypertension (OR 7.70, 95% CI 2.33-25.39), but not ptHcy, remained independently related to arterial events. aPL was the only variable independently related to venous thrombosis (OR 7.68, 95% CI 1.60-36.86). ptHcy concentrations are higher in SLE patients with arterial thrombosis. No interaction between homocysteine and aPL was found. Raised ptHcy may be a marker of increased vascular risk in aPL-negative SLE patients. The role of homocysteine as a marker of vascular risk may depend on the presence of traditional risk factors, although a modest intrinsic effect cannot be entirely excluded.

Factors Associated with Arterial Vascular Events in PROFILE: A Multiethnic Lupus Cohort

“…Similarly, previous smoking history and other important risk factors for arterial vascular events such as dyslipidemia (10), diabetes mellitus, and serial high-sensitivity C-reactive protein levels (24;40) were not available uniformly in all patients. Systematic evaluation of these factors and thrombophilic risk factors such as hyperhomocysteinemia (15;21;23), antiprothrombin antibodies (17;58) and other inherited and acquired thrombophilic conditions (59) is an important future goal. Nonetheless, we have identified important factors contributing to the development of arterial vascular events.…”

Prevalence of LDL atherogenic phenotype in patients with systemic lupus erythematosus

“…Patri et al2 reported that patients with SLE were more likely to have a sedentary lifestyle, obesity, and hypercholesterolemia, while Borha et al7,8 found that, compared with controls, patients with SLE had lower high-density lipoprotein (HDL) cholesterol as well as higher very low-density lipoprotein (VLDL) cholesterol, triglycerides, and lipoprotein (a) concentrations. Increased carotid intima thickness, increased plasma concentrations of circulating oxidized LDL and homocysteine, as well as endothelial defects, have all been incriminated in the premature coronary heart disease seen in patients with SLE 9–11…”

The relationship between plasma homocysteine level and HLA‐B51 in patients with Behcet's disease: a case‐control study

“…Generally, homocysteine is considered as a prothrombotic factor in other rheumatologic diseases, but there are still some controversial reports. 32 Due to the above limitations in our study, we recommend longitudinal studies on hyperhomocysteinemia and clinical thrombosis stratified by presence or absence of HLA-B51 and on other ethnic populations with larger case groups to confirm the finding. 28 Other studies reported that high serum homocysteine level is an independent risk factor for thrombosis in patients with systemic lupus erythematous, 29,30 but some other studies have reported that even severe hyperhomocysteinemia, in itself, is not sufficient to promote thrombosis and rather, other factors associated with abnormal homocysteine metabolism may be responsible for the propensity to thrombosis observed in individuals with severe hyperhomocysteinemia 31 and suggested that the role of homocysteine as a marker of vascular risk may depend on the presence of traditional risk factors of thrombosis, although a modest intrinsic effect cannot be entirely excluded.…”

“…28 Other studies reported that high serum homocysteine level is an independent risk factor for thrombosis in patients with systemic lupus erythematous, 29,30 but some other studies have reported that even severe hyperhomocysteinemia, in itself, is not sufficient to promote thrombosis and rather, other factors associated with abnormal homocysteine metabolism may be responsible for the propensity to thrombosis observed in individuals with severe hyperhomocysteinemia 31 and suggested that the role of homocysteine as a marker of vascular risk may depend on the presence of traditional risk factors of thrombosis, although a modest intrinsic effect cannot be entirely excluded. 32 Due to the above limitations in our study, we recommend longitudinal studies on hyperhomocysteinemia and clinical thrombosis stratified by presence or absence of HLA-B51 and on other ethnic populations with larger case groups to confirm the finding. It also would be worthwhile to study other genotypes involved in the pathway of homocysteine metabolism which has been reported to be associated with hyperhomocysteinemia in other populations.…”