Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SLE affects most aspects of cardiac function, and recent studies have reported increasing cardiovascular morbidity and mortality. Pathologically, SLE is characterized by a pancarditis involving pericardium, myocardium, endocardium, and coronary arteries. In autopsy series, pericarditis has been found in 43% to 100% (mean 62%, Table I), and myocarditis was found in 8% to 78% (mean 40%, Table II), but both have been underdiagnosed clinically. Libman-Sacks lesions have been noted in 25% to 100% (mean 43%) and infective endocarditis in 1.1% to 4.9% of clinical and autopsy studies (Table III). Coronary disease may be due to arteritis, which should be treated with high-dose steroids, or it may be due to atherosclerosis, which is amenable to medical or surgical therapy. Valvular disease has been treated surgically, but with a combined surgical mortality as high as 25%. Aortic insufficiency and mitral regurgitation are the most common valvular problems, although aortic and mitral stenosis have also been reported. Hypertension has been noted in 14% to 69%, and heart failure in 5% to 44%. Evidence for a lupus cardiomyopathy, which may be subclinical, is reviewed. While steroids may ameliorate SLE pancarditis, they have also been associated with hypertension, LV hypertrophy, purulent and constrictive pericarditis, mitral regurgitation, and perhaps accelerated atherosclerosis. It remains to be seen if improved diagnosis and treatment of the cardiovascular manifestations of SLE can enhance survival.
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PMID:Cardiovascular manifestations of systemic lupus erythematosus. 390 17

An examination has been carried out of 46 patients (33 females, 13 males, a mean age 40) with Sneddon's syndrome characterized by cerebrovascular disturbances and marked livedo. A clinical spectrum of the syndrome included miscarriage and intrauterine death of the fetus (20 cases), peripheral vein thromboses (12 cases), coronary heart disease (18 cases), thrombocytopenia (8 cases), arterial hypertension (27 cases), headache (39 cases), epileptic seizures (5 cases). Similar manifestations are usually seen in antiphospholipid syndrome (AFLS). Antibodies to phospholipids, those to cardiolipin, lupus anticoagulant were detectable in 78, 50 and 61% of the cases, respectively. Clinical and immunological signs of AFLS in the absence of SLE-typical symptoms provided grounds for considering them primary AFLS. Similar clinical patterns in 36 patients with cardiolipin antibodies and/or lupus anticoagulant and 10 patients without the antibodies and anticoagulant suggest these cases to be AFLS too.
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PMID:[Sneddon's syndrome and the primary antiphospholipid syndrome]. 805 89

Patients with systemic lupus erythematosus (SLE) are at significant risk for premature cardiovascular disease, now a leading cause of death in this population. Most previous studies have used an overt clinical event to identify cardiovascular disease, likely underestimating the actual prevalence in these patients. Although the rates of myocardial infarction in SLE are high, the actual number of coronary events is low, precluding large clinical trials using a coronary event as the sole outcome. The ability to measure atherosclerosis, a known determinant of coronary heart disease, provides investigators with a desirable surrogate for the clinical cardiac event. With the advent of sensitive imaging techniques to identify subclinical atherosclerosis, we are now better equipped to determine the true prevalence and mechanisms of vascular disease in SLE. In this review, we will discuss several vascular imaging techniques and the current trend away from measuring flow-limiting vessel stenosis toward measuring earlier structural and functional aspects of the vascular system.
Lupus 2000
PMID:Vascular imaging: changing the face of cardiovascular research. 1080 84

It has been reported that paraoxonase 1 (PON1) activity inhibits low-density lipoprotein (LDL) oxidation and modulates the risk of coronary heart disease. This study shows that autoantibodies (IgG) directed against modified LDL were increased in 71 patients positive for anticardiolipin antibodies. In a representative subgroup of these patients (n = 36) PON1 activity was dramatically decreased and the prevalence of the RR genotype of this enzyme tended to be increased in patients who had developed arterial thrombosis. This study suggests that PON1 abnormalities play a role in the antiphospholipid syndrome.
Lupus 2000
PMID:Paraoxonase activity is dramatically decreased in patients positive for anticardiolipin antibodies. 1086 1

Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--are more biologically potent than alpha-linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.
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PMID:Omega-3 fatty acids in inflammation and autoimmune diseases. 1248 Jul 95

Anti-phosphatidylethanolamine antibodies (aPE) belong to the group of anti-phospholipid antibodies (aPL) and are directed against neutral phospholipid, connected with co-factor protein, while cardiolipin antibodies (aKL) are directed against negative phospholipid. The paper presents a study of prevalence and clinical significance of IgG aPE in 28 patients (22 women and 6 men, mean age 47.6 +/- 11.6 years) with Sneddon's syndrome (SS), which consists in cerebrovascular disturbances and extensive livedo reticularis. IgG aPE were detected by immune-enzyme assay. The upper normal limit, calculated as mean + 3SD after studying 19 healthy donors, was 0.303 optic density units. aPE were found in 15 (54%), aKL and/or lupus anticoagulant (LA)--in 6 (21%) patients with SS. aPE were found in 10 (46%) out of 22 aKL- and LA-negative patients. Among the aPE-positive patients there was a higher incidence of cortic dementia (53% vs. 8%, p = 0.02), the widening of cortical sulci, detected by means of computed tomography and magnetic resonance imaging (73% vs. 31%, p = 0.05), and mild renal syndrome (73% vs. 16%, p = 0.03). Besides, they displayed a higher rate of headaches (87% vs. 62%), chorea (33% vs. 8%), epilepsy (27% vs. 8%), non-carrying of pregnancy (91% vs. 50%), peripheral venous thrombosis (27% vs. 15%), coronary heart disease (47% vs. 31%), cardiac valvular thickening, detected by means of EchoCG (93% vs. 69%), arterial hypertension (87% vs. 54%), thrombocytopenia (20% vs. 0), anemia (40% vs. 15%); however, the difference was not significant. The results show that aPE detection, performed in addition to detection of classic immunological antiphospholipid syndrome markers (aKL and LA), increases the portion of aPE-positive patients with SS by 33%. aPE are often (in 46% of cases) found in aKL- and LA-negative patients with SS. aPE is likely to be the most significant factor of thrombosis in small arteries of the brain cortex and kidneys, which could explain their association with dementia and renal syndrome.
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PMID:[Anti-phosphatidylethanolamine antibodies in patients with Sneddon's syndrome]. 1598 83

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a strong female predilection. Cardiovascular morbidity and mortality is a frequent complication, particularly in females aged 35-44 years, in whom the risk of myocardial infarction is raised 50-fold. The mechanisms underlying this increased risk are not fully understood. Certain traditional risk factors, such as hypertension and diabetes mellitus, are more common in SLE patients than in the general population. These factors do not, however, completely account for the increased cardiovascular risk; factors such as renal impairment, increased homocysteine levels and early menopause probably have a role. In addition, several factors more specifically related to lupus are proposed to be of importance, including chronic inflammation, antiphospholipid antibodies and therapy, especially corticosteroid use. Thus, we need to be proactive in our approach to risk-factor management in SLE patients. Here, we propose that, like diabetes mellitus, SLE should be considered a coronary heart disease equivalent condition for baseline risk and that assessment of cardiovascular risk should be done routinely. In addition to lifestyle modifications, blood pressure and cholesterol levels should be stringently controlled, and administration of aspirin should be considered in selected patients. The increased use of certain interventions, such as statins, also needs to be more widely investigated in this population.
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PMID:Therapy insight: systemic lupus erythematosus as a risk factor for cardiovascular disease. 1611 5

Systemic autoimmune disorders are frequently associated to cardiac involvement and to a high prevalence of ischemic coronary events, often occurring at a younger age than in the normal population. Large increase in mortality is related to premature atherosclerosis with coronary artery disease and stroke in patients with connective tissue diseases. Coronary heart disease is responsible for 40-50% of the deaths of patients with rheumatoid arthritis. Transesophageal or transthoracic echocardiography are the most useful and noninvasive techniques able to detect not only valvular abnormalities, embolic sources or pulmonary hypertension, but also left ventricular systolic or diastolic dysfunction. Furthermore, the introduction of new indexes, contrast agents and software increased the accuracy of this technique. It is possible now to evaluate coronary flow reserve by transthoracic echocardiography in patients with systemic autoimmune disease in order to detect microvasculature disorder. However, an ischemic response in a symptomatic patient requires, in most cases, further evaluation with cardiac catheterization. Coronary artery imaging allows confirmation of the presence, extent and position of atheromatous lesions. More recently, other imaging modalities including magnetic resonance and computerized tomography angiography have been developed to allow imaging of the coronary arteries.
Lupus 2005
PMID:Cardiac imaging techniques in systemic autoimmune diseases. 1621 76

Premature coronary heart disease (CHD) has emerged as a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Overall SLE patients have a 5-6-fold increased risk of CHD and this excess risk is especially pronounced in younger women where the excess risk may be >50-fold. Studies from our group and others have also demonstrated that SLE patients have a higher prevalence of subclinical atherosclerosis compared with controls, with approximately 30% having evidence of subclinical involvement. It is important to consider what factors may underlie this excess risk. We have found that certain 'classic' risk factors, i.e. hypertension and diabetes mellitus, are more prevalent in SLE and that persistent hypercholesterolaemia independently predicts patients who will develop CHD. These risk factors alone do not completely explain the excess risk observed, and after adjusting for classic risk factors SLE remains independently associated with both clinical and subclinical outcomes. Certain other metabolic changes also occur more frequently in SLE, namely premature menopause, renal impairment, high triglycerides and higher plasma homocysteine. In addition, insulin resistance is more pronounced in patients with SLE, and approximately 18% have the metabolic syndrome. It is also increasingly accepted that atherosclerosis is a chronic inflammatory condition, and in SLE systemic complement activation as well as immune complex formation can result in changes that promote the development of atheroma. Similarly, autoantibody production, especially antibodies directed against lipoprotein subtypes and those in the antiphospholipid (APLA) family, are gaining increasing attention. The role of the latter are particularly controversial as different subtypes have been shown to both promote and protect against atherogenesis. In a study looking at carotid plaque in SLE, we found that APLA was independently associated with the presence of plaque; this study also found that patients with plaque had higher white cell counts, suggesting ongoing chronic inflammation. We have also noted a negative correlation between activation of transforming growth factor beta-1 and carotid intima-medial thickness. This cytokine, which is known to be a potent anti-inflammatory molecule, has also been shown to be protective against atherogenesis. With regard to therapy, steroids may be a true double-edged sword, with low doses exerting a beneficial anti-inflammatory role whereas higher doses may be detrimental through exacerbation of metabolic risk factors. In contrast, we have found that antimalarials have a beneficial effect on lipids especially when co-prescribed with steroids, and this, along with anti-inflammatory and proposed antiplatelet effects, may confer protection against CHD in lupus. The risk of premature CHD in SLE is therefore mediated by a number of factors that involve not only classic risk factors but also a range of factors associated with SLE itself. Preventative strategies will therefore need to address all potential risk factors of relevance. A more through understanding of the interplay between autoimmunity and atherogenesis should be possible by the study of SLE, and this may not only benefit lupus patients but also may have implications for our understanding of atherosclerosis in general.
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PMID:'Not only...but also': factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus. 1623 77

Systemic lupus erythematosus (SLE) is increasingly recognized as a risk factor for the development of premature atherosclerosis. The inflammatory process in both of these diseases is controlled by a variety of cell types of the innate and adaptive immune systems. Recent studies from several groups, including ours, have revealed a critical role of a unique subset of lymphocytes, termed invariant natural killer T (iNKT) cells, in the development of lupus-like autoimmunity and atherosclerosis in animal models. iNKT cells appear to play complex and divergent roles in the development of SLE and atherosclerosis. Our findings suggest that alterations in iNKT cell functions during the development of SLE may be related to the increased risk of SLE patients to develop atherosclerosis and coronary heart disease. We found that iNKT cell activation with the sponge-derived glycolipid alpha- galactosylceramide generally protects against the development of lupus-like autoimmunity in mice, whereas it exacerbates atherosclerosis. Therefore, while our studies have identified iNKT cells as potential therapeutic targets for SLE, further studies are necessary to design drugs that will avoid the underlying harmful effects of iNKT cell activation on the development of atherosclerosis.
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PMID:The role of invariant natural killer T cells in lupus and atherogenesis. 1672 Aug 98


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