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)

Premenopausal women have a significant reduction in coronary artery disease compared to age-matched males. Little is known about the mechanism underlying this cardioprotective effect of estrogen. Contradictory evidence has been published and our lack of basic understanding of hormone interactions and bioavailability of different estrogens prevents definitive interpretation of these data. We demonstrate gender-specific effects in the proliferation of coronary artery vascular smooth muscle cells obtained from a sexually mature animal model. Vascular smooth muscle cells are an integral component of the atherosclerotic plaque, and inhibition of cell proliferation by estrogen may be one mechanism by which estrogen exerts its cardioprotective effect. Various types of estrogen may also have different mechanistic actions on the vascular system. No differences are demonstrated in overall estradiol binding in vascular smooth muscle cells obtained from male or female animals: however, differences in c-jun, c-fos and TIEG gene expression were gender related. Inhibition of vascular smooth muscle cell proliferation may have important implications in the prevention of atherosclerotic disease and these studies may provide evidence for the cardioprotective effect of estrogen.
Lupus 1999
PMID:Gender-related differences in vascular smooth muscle cell proliferation: implications for prevention of atherosclerosis. 1045 21

SLE is a multifaceted disease; over the past 20 years, as survival has improved dramatically, new challenges have emerged. It is now clear from the results of studies at several centers that SLE is associated with at least a fivefold increased risk of CAD, which is accelerated at its onset and seems to abolish a female premenopausal protection against CAD. Several groups have also found by various techniques that subclinical disease occurs at a frequency of about 35% to 40%. The pathogenesis of atherosclerosis in this context seems to be a complex interaction of factors associated with the disease, its therapy, and traditional risk factors. Indeed, experimental models suggest a synergy of these different dimensions in plaque formation. Hypercholesterolemia has been identified as predictive of both future CAD events and sub-clinical disease. This is mainly the case in those patients in whom hypercholesterolemia is a sustained phenomenon. In addition, SLE itself seems to be a strong risk factor for CAD over and above the effects of the known traditional CAD risk factors. There is a lot that is still unknown about the pathogenesis of CAD in SLE. Current knowledge is sufficient to justify the belief that an aggressive approach to management of traditional CAD risk factors in patients with SLE is likely to have a major impact on morbidity and mortality in this population. For this to happen, patients must be educated about this issue and be encouraged to play an active role in lifestyle modifications. In addition, clinicians who care for patients with SLE need to assume a primary role in screening and coordinating the management of CAD risk factors in these high-risk patients.
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PMID:Premature atherosclerosis in systemic lupus erythematosus. 1076 12

Observational cohort studies in SLE have led to the description of accelerated atherosclerosis as an important cause of mortality and morbidity in this disease. The clinical observation of coronary artery disease occurring in premenopausal females with SLE gave rise to the concept of the bimodal mortality pattern. This pattern was confirmed in autopsy and epidemiological studies. These studies identified hypercholesterolemia and particularly its persistence in the first three years of disease, hypertension, and lupus itself as important risk factors for the development of accelerated atherosclerosis in these patients. It also became evident that corticosteroid therapy plays an important role in the elevation of plasma lipids while antimalarials resulted in a reduction of plasma cholesterol, LDL, and VLDL, especially in steroid-induced hyperlipidemia. Studies of clinical outcomes for atherosclerotic disease (angina, myocardial infarction) have shown a prevalence of 6-12% in a number of SLE cohorts. However, more sensitive investigations including myocardial perfusion imaging and carotid ultrasound have demonstrated a prevalence of atherosclerotic disease in 40% of patients studied. Further studies of SLE disease process, including immunological factors, may more clearly define the pathogenesis of accelerated atherosclerosis in patients with SLE, and may help elucidate mechanisms of atherosclerosis in the general population.
Lupus 2000
PMID:Accelerated atheroma in lupus--background. 1080 81

Coronary artery disease (CAD) is a major cause of morbidity and mortality in SLE, including the Hopkins Lupus Cohort. Currently, 9% of the cohort have had clinical evidence (angina or myocardial infarction) of CAD. In our initial prospective study we found that duration of prednisone, hypertension, hyperlipidemia and obesity were risk factors for later CAD. We can now extend that list to include age, male sex, elevated homocysteine, renal insufficiency and antiphospholipid antibodies. Many of the risk factors are amenable to intervention, but the timing of intervention, and the effectiveness of intervention, must be determined.
Lupus 2000
PMID:Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort. 1080 83

The circulating levels of angiotensin I-converting enzyme (ACE) are linked with a 287-base pair insertion/deletion (I/D) polymorphism at intron 16 of the ACE gene. Thus, the homozygous deletion (D/D genotype) could cause chronic vasoconstriction, arterial hypertension and, possibly, coronary artery disease. Also, the increase in plasminogen activator inhibitor-1 level and impaired fibrinolysis were related with the D/D genotype. The D allele has been recently associated with venous thrombosis among African-American men as well as among patients that underwent elective total hip replacement. We assess the risk of venous thromboembolism (VTE) linked with each genotype of the I/D ACE gene polymorphism in a Caucasian population by means of a case-control study. We genotyped the ACE gene in a series of 148 patients aged 45.0 +/- 16.0 years (range, 11-80 years), objectively diagnosed in our centre of deep-vein thrombosis or pulmonary embolism, and in 240 thrombosis-free subjects (25-75 years) from the same geographic area. The observed difference in D allele frequencies between patients (0.56) and controls (0.62) was nonsignificant overall; however, statistical significance (P = 0.05) was found by considering the recessive hypothesis (D/D versus I/ D + I/I) [odds ratio (OR) = 0.64, 95% confidence interval (CI95) = 0.42-0.99]. The OR was 0.88 (CI95 = 0.51-1.53; P = 0.65) for the dominant hypothesis (D/D + I/D versus I/I genotypes). The relative risk for the D allele was close to 1 for the dominant hypothesis, both considering gender and recurrent tendency; however, it was protective in men regarding the recessive hypothesis (OR = 0.53, CI95 = 0.29-0.97, P = 0.04). The I/D ACE allele distribution was similar among the 46 thrombophilic patients (antithrombin, protein C or protein S deficiencies, factor V R506Q, factor II G20210A or lupus anticoagulant). In conclusion, among (Spanish) Caucasians, this study does not support the hypothesis that the deletion allele (D) of the ACE gene could be a significant risk factor for VTE, being protective in men.
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PMID:Risk of venous thromboembolism associated with the insertion/deletion polymorphism in the angiotensin-converting enzyme gene. 1093 9

Our purpose was to examine prospectively the relationship between systemic hypertension and vascular events in patients with SLE. SLE patients followed in the University of Toronto Lupus Clinic presenting between 1980 and 1988 and within one year of their diagnosis of SLE were identified. Standard definitions were used for hypertension and for all vascular events (MI, angina, CVA, PVD). The presence of traditional CAD risk factors, along with disease- and therapy-related risk factors for the development of vascular disease, were compared in the hypertensive and normotensive group. A multivariate logistic regression was performed to determine the best predictor of a vascular event. One hundred and fifty patients were identified in our inception cohort [75 hypertensive (50%) and 75 (50%) normotensive]. Seventeen hypertensive patients (22.7%) had at least one vascular event as compared to six (8.0%) normotensive patients (p = 0.022). The vascular events included 7 with CAD, 5 with CVA, and 5 with PVD in the hypertensive group while in the normotensive group 3 patients developed CAD, 2 CVA and 1 PVD. Fifteen deaths were recorded in the hypertensive group as compared to eight deaths in the non-hypertensive groups (P = 0.09). The groups were comparable with respect to associated risk factors, except for higher frequency of hypercholesterolemia (P = 0.003), azotemia (P = 0.001) and corticosteroid use (P = 0.038) in the hypertension group. In a multivariate analysis the best predictor of a vascular event was hypercholesterolemia (OR 6.9, 95% CI 2.4-24.8, P < 0.001). We conclude that systemic hypertension is associated with an increased frequency of vascular events in SLE. This is best explained by its association with hypercholesterolemia.
Lupus 2000
PMID:Vascular events in hypertensive patients with systemic lupus erythematosus. 1143 83

Primary antiphospholipid syndrome is associated with an increased risk of vascular thrombosis. The authors describe a young patient without any risk factor for coronary artery disease who was admitted to the hospital because of a transient cerebral ischemic attack. Standard EKG showed signs of a previous silent inferior wall myocardial infarction, confirmed by echocardiography, technetium-99 scintigraphy, and left ventricular angiography. Coronary arteries appeared normal at angiography. Blood tests showed the presence of antiphospholipid antibodies and lupus anticoagulant. Since there is evidence that these antibodies are associated with an increased risk of microvascular thrombosis, the authors conclude that this silent myocardial infarction could be caused by a cardiac microvascular disease accompanying the antiphospholipid syndrome.
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PMID:Myocardial infarction with normal coronary arteries in a patient with primary antiphospholipid syndrome--case report and literature review. 1171 32

Large increases in mortality related to premature atherosclerosis with coronary artery disease and stroke have been reported in patients with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APLS), or rheumatoid arthritis (RA). Studies found relative risks of 5 for myocardial infarction, 6 to 10 for stroke in SLE patients, and 3.6 for cardiovascular deaths in RA patients. The main risk factors for atherosclerosis included not only the classic factors identified in epidemiological studies such as the Framingham study (advanced age, high cholesterol levels, hypertension, diabetes mellitus, and obesity), but also prolonged glucocorticoid therapy, long duration of SLE, postmenopausal status, and heart failure. SLE per se is an independent risk factor. The current pathogenic hypothesis for atherosclerosis involves an inflammatory response (erythrocyte sedimentation rate, C-reactive protein, and fibrin), autoantibodies, immune complexes (containing antibodies to phospholipids, to oxidized LDLs, and to endothelial cells), cytokine-producing activated T cells, and bacterial or viral infections responsible for an immune response against heat shock proteins (endogenous HSP60 and its equivalent, bacterial HSP65). Early risk factor intervention and effective control of inflammation should be incorporated into the management of connective tissue disease with the goal of protecting patients against atherosclerosis.
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PMID:Atherosclerosis and connective tissue diseases. 1295 20

Stroke has enormous clinical, social, and economic implications, and demands a significant effort from both basic and clinical science in the search for successful therapies. Atherosclerosis, the pathologic process underlying most coronary artery disease and the majority of ischemic stroke in humans, is an inflammatory process. Complex interactions occur between the classic risk factors for atherosclerosis and its clinical consequences. These interactions appear to involve inflammatory mechanisms both in the periphery and in the CNS. Central nervous system inflammation is important in the pathophysiologic processes occurring after the onset of cerebral ischemia in ischemic stroke, subarachnoid hemorrhage, and head injury. In addition, inflammation in the CNS or in the periphery may be a risk factor for the initial development of cerebral ischemia. Peripheral infection and inflammatory processes are likely to be important in this respect. Thus, it appears that inflammation may be important both before, in predisposing to a stroke, and afterwards, where it is important in the mechanisms of cerebral injury and repair. Inflammation is mediated by both molecular components, including cytokines, and cellular components, such as leukocytes and microglia, many of which possess pro- and/or antiinflammatory properties, with harmful or beneficial effects. Classic acute-phase reactants and body temperature are also modified in stroke, and may be useful in the prediction of events, outcome, and as therapeutic targets. New imaging techniques are important clinically because they facilitate dynamic evaluation of tissue damage in relation to outcome. Inflammatory conditions such as giant cell arteritis and systemic lupus erythematosus predispose to stroke, as do a range of acute and chronic infections, principally respiratory. Diverse mechanisms have been proposed to account for inflammation and infection-associated stroke, ranging from classic risk factors to disturbances of the immune and coagulation systems. Considerable opportunities therefore exist for the development of novel therapies. It seems likely that drugs currently used in the treatment of stroke, such as aspirin, statins, and modulators of the renin-angiotensin-aldosterone system, act at least partly via antiinflammatory mechanisms. Newer approaches have included antimicrobial and antileukocyte strategies. One of the most promising avenues may be the use of cytokine antagonism, for example, interleukin-1 receptor antagonist.
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PMID:Inflammation and infection in clinical stroke. 1246 86

A 21-year-old woman with a history of systemic lupus erythematosus (SLE) presented to the emergency room with a chief complaint of substernal chest pain and palpitations. She had undergone a four-vessel coronary artery bypass graft operation with separate saphenous vein grafts to the left anterior descending (LAD), obtuse marginal (OM) 1 and 2, and distal right coronary arteries (RCA) 8 months prior to admission. The patient underwent angiography of the coronary vessels, which showed severe diffuse disease with a long, 90% narrowing of the vein graft to the LAD and closed vein grafts to OM1 and OM2. The RCA graft showed mild diffuse disease. An intervention was done in which the LAD was stented twice with subsequent TIMI 3 flow. Advances in medical therapy and a better understanding of the disease have contributed to a dramatic improvement in the long-term survival of patients with SLE. However, despite the overall long-term improvement, coronary artery disease remains a major cause of morbidity and mortality with an incidence of approximately nine-fold greater than would be expected for this population.
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PMID:Premature coronary artery disease in systemic lupus erythematosus with extensive reocclusion following coronary artery bypass surgery. 1261 93


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