Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus

Petri, Michelle; Roubenoff, Ronenn; Dallal, Gerard E.; Nadeau, Marie; Selhub, Jacob; Rosenberg, Irwin H.

doi:10.1016/s0140-6736(96)03032-2

Cited by 377 publications

(218 citation statements)

References 26 publications

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“…However, we were only able to examine this variable in the incident cases; thus, some caution in the interpretation of these data is in order. Glucocorticoids have been considered to contribute to accelerated atherosclerosis in SLE (36)(37)(38)(39). Although venous and arterial thrombosis may share some clotting abnormalities, atherogenic factors, which are very important in the arterial system, are less important in the venous compartment.…”

Section: Discussionmentioning

confidence: 99%

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients

Calvo‐Alén

Toloza

Fernández

et al. 2005

Arthritis & Rheumatism

127

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Objective. Venous thrombosis is a relatively frequent and serious complication in systemic lupus erythematosus (SLE) that has been associated with the presence of antiphospholipid antibodies (aPL). However, venous thrombotic events can also be seen in patients without aPL, and only a few patients with aPL develop venous thrombosis. This study was carried out to ascertain other factors contributing to the development of venous thrombosis in SLE.Methods. Patients with SLE, ages >16 years with <5 years disease duration and of Hispanic, African American, or Caucasian ethnicity, from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Selected socioeconomic/demographic, clinical, laboratory, and treatment-exposure variables were compared between patients who developed and those who did not develop venous thrombotic events. Significant and clinically relevant variables were then entered into different multivariable models (Cox proportional hazards and unconditional stepwise logistic regression) to identify independent risk factors associated with the primary outcome. In another model, only patients who developed an event after enrollment (time 0) in the cohort were included.Results. Of 570 LUMINA patients, 51 developed at least 1 venous thrombotic event after SLE diagnosis. In univariable analyses, smoking (P ‫؍‬ 0.020), shorter disease duration at time 0 (P ‫؍‬ 0.017), serum levels of total cholesterol, low-density lipoprotein, and triglycerides (all P < 0.0001), and presence of lupus anticoagulant (LAC) (P ‫؍‬ 0.045) were associated with venous thrombotic events. Survival analyses showed a timedependent significant association of the primary outcome with smoking (P ‫؍‬ 0.008) and a borderline significant association with the presence of LAC (P ‫؍‬ 0.070). Multivariable models showed an independent association with smoking, age at time 0, disease activity over time, LAC, mean dose of glucocorticoids, and shorter disease duration at time 0.Conclusion. Venous thrombotic events occur early in the course of SLE. Our data confirm the association between LAC and venous thrombotic events. Smoking, shorter disease duration, older age, disease activity over

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Section: Discussionmentioning

confidence: 99%

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients

Calvo‐Alén

Toloza

Fernández

et al. 2005

Arthritis & Rheumatism

127

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“…4 Hyperhomocysteinaemia has also been linked with deep venous thrombosis, 7 vascular disease in SLE 8 and tentatively with a number of other conditions including dementia 9,10 and pre-eclampsia. 11,12 There are however problems with the current data.…”

Section: Thcy and Cardiovascular Diseasementioning

confidence: 99%

Homocysteine, hypertension and stroke

Perry

1999

J Hum Hypertens

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The balance of evidence from observational studies suggests that elevated homocysteine levels are associated with increased risk of carotid artery disease and stroke. There is however a paucity of prospective studies. There are also concerns regarding confounding due to factors associated with hyperhomocysteinemia, including renal impairment, an atherogenic diet and cigarette smoking. Homozygosity for a defective thermolabile variant of MTHFR, a common genetic polymorphism which results in hyperhomocysteinemia, has not been consistently linked with stroke or other vascular disease. There is a need for additional prospective studies with data on relevant confounders, sufficient power to characterise the form of the association between homocysteine concentrations and stroke risk, whether linear or threshold, and power to study interactions between homocysteine, other dietary markers and established stroke risk factors such as smoking and

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“…Folate supplementation has been shown to normalize increased HCY blood levels (Homocysteine Lowering Trialists' Collaboration, 1998). Observations of altered HCY metabolism related to chronic vascular disease (McCully and Wilson, 1975) and some prospective studies have suggested that there is a relationship between elevated HCY levels and chronic vascular disease (Perry et al, 1995;Petri et al, 1996). Two other studies found a positive correlation between plasma HCY and thickening of the intimal layer of the carotid artery (Malinow et al, 1993) and its narrowing (Selhub et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study

Akoglu

Schrott²,

Bolouri

et al. 2007

Eur J Clin Nutr

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Objective: Hyperhomocysteinemia is a described risk factor of cardiovascular diseases. The aim of this study was the treatment of hyperhomocysteinemia in liver transplant recipients with L-5-methyltetrahydrofolate (L-5-MTHF; 1 mg) vs folic acid (1 mg) vs placebo in a double-blind placebo-controlled study and to compare the relative responsiveness of these patients to L-5-MTHF and folic acid. Subjects/Methods: Patients were recruited from Hepatology-Transplantation-Unit at Johann Wolfgang Goethe-University, Frankfurt. Sixty patients were included in this study and 12 patients dropped out for different reasons. The patients were treated over 8 weeks with supplemental L-5-MTHF or folic acid or placebo. Serum homocysteine (HCY) was analyzed with highperformance liquid chromatography (HPLC) beside routine lab tests. Results: We observed only a significant decrease of total serum HCY in the L-5-MTHF group during the study period (at week 0: 1577.7 mM; after 8 weeks treatment: 9.4172.6 mM, Po0.001). There was no significant decrease of total serum HCY neither in the folic acid group nor in the placebo group. Conclusion: The effects of L-5-MTHF are significantly more potent than folic acid itself. Therefore, lowering serum HCY in liver transplant recipients is effective with L-5-MTHF.

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Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus

Cited by 377 publications

References 26 publications

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients

Homocysteine, hypertension and stroke

The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study

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