Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article evaluates the prevalence of cardiovascular and thrombophilic risk factors in patients with retinal artery occlusion. Forty-one patients with a first episode of a retinal artery occlusion underwent complete ophthalmic examination, routine blood testing and specific laboratory tests for thrombophilia, such as fasting and postmethionine homocysteine, lipoprotein(a), plasminogen activator inhibitor-1, factor VIII, factor V Leiden, factor II G20210A polymorphism, lupus anticoagulant and anticardiolipin antibodies. The control population consisted of 100 healthy individuals comparable as regards age and sex. At univariate analysis, hypertension, smoking, dyslipidaemia (both high cholesterol and triglyceride levels), antiphospholipid antibodies, hyperhomocysteinaemia, elevated factor VIII and lipoprotein(a) levels were significantly associated with retinal artery occlusion; at multivariate analysis, adjusted for age, sex, traditional and thrombophilic risk factors, smoking, hypercholesterolaemia, elevated homocysteine and lipoprotein(a) levels confirmed their independent role as risk factors for retinal artery occlusion. In conclusion, the results of the present pilot study demonstrate that the prevalence of hypercholesterolaemia and smoking and the 'thrombophilic burden' are increased in patients with retinal artery occlusion. Our findings may have implications for the management of these patients, suggesting the need for an intensive and tailored secondary prevention and new therapeutic approaches.
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PMID:Cardiovascular and thrombophilic risk factors in patients with retinal artery occlusion. 1747 72

Folic acid is a vitamin B essential for the integrity and function of DNA. Relative deficiency of folic acid may occur in conditions such as pregnancy and hyperproliferative or chronic inflammatory disorders. Folic acid supplementation has been proven to be beneficial in the prevention of neural tube defects and in limiting methotrexate side effects, and may reduce the risk of colorectal cancer. Folate is a critical vitamin in determining plasma homocysteine levels, which in turn is a major risk factor for cardiovascular diseases. The results of large clinical trials with dietary supplementation of folic acid, vitamin B12 and vitamin B6 have shown that this homocysteine-lowering therapy is effective in the secondary prevention of non-fatal strokes, but had no effect in the prevention of fatal cardiovascular diseases. Hyperhomocysteinemia has also been reported in age-related neurological conditions with cognitive impairment (e.g. dementia), and psychiatric disorders such as depression. Elevated homocysteine levels are frequent in patients with chronic immune-mediated disorders including rheumatoid arthritis, systemic lupus erythematosus, chronic plaque psoriasis and psoriatic arthritis, which have in common a tendency to an accelerated atherosclerosis leading to increased deaths from cardiovascular events. Folic acid supplementation appears as a reasonable therapeutic option in patients affected by chronic inflammatory skin diseases, such as moderate to severe psoriasis; in particular, those with concomitant hyperhomocysteinemia, low plasma folate and additional cardiovascular risk factors.
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PMID:Folic acid in general medicine and dermatology. 1753 1

The aim of this study was to evaluate traditional risk factors for coronary artery disease (CAD), homocysteine, anti-oxidized low-density lipoprotein (anti-oxLDL), anti-lipoprotein lipase (anti-LPL) and endothelin-1 (ET-1) in patients with primary anti-phospholipid syndrome (APS), furthermore verify possible association among these variables and arterial thrombosis. Thirty-eight women with primary APS and 30 age-and-sex-matched controls were evaluated. Patients presented higher-LDL and triglycerides levels and lower-HDL levels than controls. Anti-LPL antibodies were not detected in both groups. The mean number of risk factors was higher in patients than in controls (P = 0.030). Anti-oxLDL antibodies, homocysteine and ET-1 mean levels were similar between groups, but abnormal homocysteine levels were found only among primary APS patients (P = 0.031). Hypertension and the presence of at least one risk factor for CAD were more prevalent in patients with arterial involvement than those without. Homocysteine levels and mean number of risk factors for CAD were significantly higher in patients with arterial thrombosis than controls. In a multivariate analysis hypertension was the only independently associated with arterial thrombosis (OR 14.8, 95% CI = 2.1-100.0, P = 0.006). This study showed that in primary APS patients other risk factors besides anti-phospholipid antibodies contribute for the occurrence of arterial events and the most important factor was hypertension.
Lupus 2007
PMID:Impact of hypertension and hyperhomocysteinemia on arterial thrombosis in primary antiphospholipid syndrome. 1789

Abnormal increases of antiphospholipid antibody and plasma homocysteine levels are recently emerging as nonlipidic risk factors for cerebral atherogenesis and thrombosis. Both antiphospholipid antibody and homocysteine share many similar bioeffects in hemostasis, but their interaction is still inconsistent. In this study, we examined the relation between the plasma homocysteine level and lupus anticoagulant, anticardiolipin antibody, and anti-beta2-glycoprotein I antibody in patients with noncardiac cerebral ischemia. Systemic lupus erythrematosus patients were excluded. The results showed a higher frequency of moderate hyperhomocysteinemia in patients with an abnormal increase of lupus anticoagulant only. Neither the serum folate and cobalamin levels nor methylenetetrahydrofolate reductase allele mutation contributes to this result. Accordingly, homocysteine interacts with lupus anticoagulant to promote cerebral atherosclerosis and ischemia. The role of vasculopathic or prothrombotic autoantibody generation in response to specific pathological change such as hyperhomocysteinemia warrants further investigation.
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PMID:Hyperhomocysteinemia relates to the subtype of antiphospholipid antibodies in non-SLE patients. 1791 Nov 91

Epidemiological studies conducted over the past 25 years have provided ample support for the association of mild hyperhomocysteinemia (HHcy) with an elevated risk of atherothrombosis. Since autoimmune disorders (AD) are frequently associated with relevant and early signs of atherothrombotic damage not adequately explained by the traditional risk factors involved in the onset of cardiovascular disease (CVD), a large interest has been shown to the putative role of mild HHcy in this setting. On the basis of such considerations, we focused the attention on the relationship between homocysteine (Hcy) and CVD in patients affected with autoimmune diseases, reviewing the most recent literature data and also providing our original experience. Although the large amount of available studies clearly shows that HHcy represents a common finding in patients affected with several autoimmune diseases, the actual role of Hcy in the development of CVD in the course of AD is not clear yet, perhaps, with the only exception of the systemic lupus erythematosus. In the other conditions, the role of Hcy in the pathogenesis of vascular complications is still a matter of debate, as the result of conflicting reports and/or lack of an adequate body of investigation.
Lupus 2007
PMID:Hyperhomocysteinemia: a cardiovascular risk factor in autoimmune diseases? 1797 57

We prospectively assessed associations of thrombophilia- hypofibrinolysis with central retinal vein occlusion (CRVO) (40 patients) and central retinal artery occlusion (CRAO) (9 patients). We used polymerase chain reaction measures for thrombophilia (factor V Leiden, prothrombin, C677T MTHFR, platelet glycoprotein PlA1/A2) and hypofibrinolysis (plasminogen activator inhibitor-1 4G4G). Serologic thrombophilia measures included protein C, protein S (total and free) and antithrombin III, homocysteine, lupus anticoagulant, anticardiolipin antibodies IgG-IgM, and factors VIII and XI. Serologic hypofibrinolysis measures included Lp(a) and plasminogen activator inhibitor activity. For comparison with 40 CRVO and 9 CRAO patients, 80 and 45 race-gender matched controls were studied. The factor V mutation was more common in CRVO (3/40, 8%) than controls (0/79, 0%), P = .036, as was high (>150%) factor VIII (12/40, 30%) versus (4/77, 5%), P = .0002. Low antithrombin III (<80%) was more common in CRVO (5/39, 13%) than in controls (2/73, 3%), P = .049. Homocysteine was high (> or =13.5 micromol/L) in 5/39 (13%) CRVO patients versus 2/78 controls (3%), P = .04. Three of 9 CRAO patients (33%) had low (<73%) protein C versus 2/37 controls (5%), P = .044. Two of 9 CRAO patients (22%) had high (> or =13.5 micromol/L) homocysteine versus 0/42 controls (0%), P =. 028. Four of 9 CRAO patients had the lupus anticoagulant (44%) versus 4/33 (12%) controls (P = .050). CRVO is associated with familial thrombophilia (factor V Leiden, factor VIII, low antithrombin III, homocysteinemia), and CRAO is associated with familial and acquired thrombophilia (low protein C, homocysteinemia, lupus anticoagulant), providing avenues for thromboprophylaxis, and triggering family screening.
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PMID:Ocular vascular thrombotic events: central retinal vein and central retinal artery occlusions. 1816 May 89

Cardiovascular morbidity and mortality in SLE is increased in patient with established disease, and SLE itself has been determined to be an independent risk factor for cardiovascular events. Autopsy studies have demonstrated that the coronary vessels of SLE patients have atherosclerotic plaque, and most cardiovascular events are not attributable to active vasculitis. It is believed that patients with inflammatory disease, including SLE, are more likely to have vulnerable plaque rupture, accounting for more frequent events. Elevated homocysteine levels have been associated with the presence and progression of atherosclerotic plaque. Enzyme polymorphisms involved in the folatehomocysteine pathway do not seem to contribute to differences in homocysteine concentration or atherosclerotic plaque. Recently, endothelial dysfunction has been identified as an early abnormality in ASCVD, and has been demonstrated in the vessels of SLE patients. Premature cardiovascular disease in SLE patients is likely attributable to the consequences of inflammation. There is preliminary evidence that type I interferons maybe the initial stimulation of the cascade of atherosclerotic development, starting with endothelial damage, and abnormal vascular repair.
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PMID:Premature atherosclerotic cardiovascular disease and systemic lupus erythematosus from bedside to bench. 1893 29

The vasculature plays a crucial role in inflammation, angiogenesis, and atherosclerosis associated with the pathogenesis of inflammatory rheumatic diseases, hence the term 'vascular rheumatology'. The endothelium lining the blood vessels becomes activated during the inflammatory process, resulting in the production of several mediators, the expression of endothelial adhesion molecules, and increased vascular permeability (leakage). All of this enables the extravasation of inflammatory cells into the interstitial matrix. The endothelial adhesion and transendothelial migration of leukocytes is a well-regulated sequence of events that involves many adhesion molecules and chemokines. Primarily selectins, integrins, and members of the immunoglobulin family of adhesion receptors are involved in leukocyte 'tethering', 'rolling', activation, and transmigration. There is a perpetuation of angiogenesis, the formation of new capillaries from pre-existing vessels, as well as that of vasculogenesis, the generation of new blood vessels in arthritis and connective tissue diseases. Several soluble and cell-bound angiogenic mediators produced mainly by monocytes/macrophages and endothelial cells stimulate neovascularization. On the other hand, endogenous angiogenesis inhibitors and exogenously administered angiostatic compounds may downregulate the process of capillary formation. Rheumatoid arthritis as well as systemic lupus erythematosus, scleroderma, the antiphospholipid syndrome, and systemic vasculitides have been associated with accelerated atherosclerosis and high cardiovascular risk leading to increased mortality. Apart from traditional risk factors such as smoking, obesity, hypertension, dyslipidemia, and diabetes, inflammatory risk factors, including C-reactive protein, homocysteine, folate deficiency, lipoprotein (a), anti-phospholipid antibodies, antibodies to oxidized low-density lipoprotein, and heat shock proteins, are all involved in atherosclerosis underlying inflammatory rheumatic diseases. Targeting of adhesion molecules, chemokines, and angiogenesis by administering nonspecific immunosuppressive drugs as well as monoclonal antibodies or small molecular compounds inhibiting the action of a single mediator may control inflammation and prevent tissue destruction. Vasoprotective agents may help to prevent premature atherosclerosis and cardiovascular disease.
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PMID:Vascular involvement in rheumatic diseases: 'vascular rheumatology'. 1894 76

Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis. We previously showed that SLE patients have a higher risk of insulin resistance (IR) and abnormal insulin secretion. The present study was to further investigate the relationship between fasting insulin levels and both classic and novel cardiovascular risk factors in patients with SLE. Body mass index (BMI), fasting glucose and insulin, lipid profile, oxidation markers, fibrinolytic factors, vascular function factors, and disease-specific variables were determined in a total of 87 female SLE patients. The homeostasis model assessment (HOMA) was used to evaluate the IR and secretion. SLE patients had significantly higher fasting insulin, HOMA IR, HOMA beta-cell, titers of autoantibodies against oxidized low density lipoprotein, systolic blood pressure, homocysteine, and brachial-ankle pulse wave velocity (baPWV) than age-matched healthy controls. There were no statistical differences in disease duration, anti-dsDNA, C3, C4, disease activity, and medication dosage between SLE patients stratified by fasting insulin levels. However, mean values for BMI, insulin, HOMA IR, HOMA beta-cell, triglyceride (TG), homocysteine, and baPWV were significantly higher in the SLE patients with hyperinsulinemia when compared with those SLE controls. In addition, fasting insulin levels were positively correlated with TG, homocysteine, blood pressure, plasminogen activator inhibitor 1, and baPWV in SLE patients. The elevation of fasting insulin levels in SLE patients is not only associated with IR, but is related to classic and novel cardiovascular risk factors. This study concludes that there is an insulin-related cardiovascular disease risk in SLE.
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PMID:Elevation of fasting insulin and its association with cardiovascular disease risk in women with systemic lupus erythematosus. 1903 7

Antiphospholipid antibodies (aPL) occur in a variety of autoimmune, malignant, and infectious diseases, with or without the thrombotic or obstetric sequelae that characterize the antiphospholipid syndrome. Although many studies have focused on the clinical implications of aPL in systemic lupus erythematosus, few have specifically addressed the questions facing rheumatologists caring for rheumatoid arthritis patients who are concomitantly positive for aPL. Such a clinical scenario requires current knowledge of antiphospholipid syndrome diagnosis criteria, test reliability, conditions causing temporal positivity of aPL, and treatment risks and benefits. Recently researched factors possibly integral to rheumatoid arthritis's increased morbidity and mortality and related to aPL include oxidatively modified low-density lipoprotein antibodies, homocysteine, annexins, infectious agents, beta estradiol, and specific gene polymorphisms. This review presents current scientific research addressing the pathophysiologic mechanisms and clinical implications of aPL in rheumatoid arthritis.
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PMID:Antiphospholipid antibodies in rheumatoid arthritis: identifying the dominoes. 1917 Nov 11


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