Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aortic valve calcification is associated with atherosclerosis in the general population. We investigated the prevalence of and associates of aortic valve calcification in systemic lupus erythematosus (SLE). One-hundred and ninety-nine SLE patients enrolled in a clinical trial had aortic valve calcification assessed by helical CT. The patients had a mean age of 44.3 +/- 11.4 years and were 92% female, 61% Caucasian, 34% African-American, 2% Asian and 2% Hispanic. Aortic valve calcification was present in 1.5%, whereas coronary calcium was found in 43% and carotid plaque in 17%. Among cardiovascular risk factors, hs-CRP (P = 0.0592), fibrinogen (P = 0.0507), and lipoprotein(a) (P = 0.0250), were associated with aortic valve calcification. Prednisone use (P = 0.049) and use of methotrexate (P = 0.0174) were also associated with aortic valve calcification. Aortic valve calcification was associated with antiphospholipid antibody positivity (0.0287) (lupus anticoagulant, by dilute Russell viper venom time). It was not associated with coronary calcium or carotid plaque. Aortic valve calcification, although rare in SLE, was associated with some novel cardiovascular risk factors and with a marker of hypercoagulability (lupus anticoagulant). In contrast to the general population, aortic valve calcification in SLE is not associated with subclinical measures of atherosclerosis, such as coronary calcium or carotid plaque.
Lupus 2006
PMID:Aortic valve calcification in systemic lupus erythematosus. 1721 93

Systemic lupus erythematosus (SLE) patients suffer from excess cardiac deaths due to accelerated atherosclerosis. Endothelial dysfunction is a marker of early atherosclerosis. We tested the hypothesis that SLE patients have impaired endothelial function and assessed the relationship between endothelial function and clinical outcome over the subsequent five years. Thirty-six female SLE patients were compared with 22 healthy age and sex matched controls. Endothelial dependent vasodilatation (EDD) was assessed at the brachial artery in response to shear stress. Endothelium-independent dilatation induced by glyceryl trinitrate was also measured. Patients were followed for up to five years and the development of damage in the cardiovascular and other systems recorded. SLE patients showed significantly impaired endothelial function (median EDD 5.6%, IQR 3.1-7.2%) compared with healthy controls (median EDD 8.0%, IQR 6.3-9.3%; P = 0.001). Endothelium independent dilatation did not differ between the two groups. Endothelial function was significantly worse in postmenopausal compared with premenopausal women (median EDD 6.6%, IQR 3.9-7.8% versus 3.1%, IQR 2.6-5.1%; P = 0.016). Total cholesterol was inversely correlated with endothelial function in SLE patients (Spearman correlation r = -0.422, P = 0.025). There was no relationship between endothelial function and the development of damage in any organ system, including the cardiovascular system during patient follow-up. Patients with SLE have impaired endothelial Lupus (2007) 16, 84-88.
Lupus 2007
PMID:Impaired endothelial function in systemic lupus erythematosus. 1740 63

The main goal of therapy for lupus nephritis is to achieve remission, as this has a major impact on patient and renal survival. Furthermore, early treatment success has been shown to improve long-term prognosis. This has traditionally been achieved with intravenous cyclophosphamide, but recent data show that mycophenolate mofetil is equally effective and causes fewer adverse effects. Research is ongoing to find new treatment targets. Possible future therapies include monoclonal antibodies against CD20 (rituximab), CD22 (epratuzumab) and CD40, and therapies targeted at cytokine secretion, immunoglobulin secretion, B-cell maturation and T-cell proliferation and differentiation. Rituximab has shown promise in patients with active proliferative lupus nephritis, which suggests that B-cell depletion may be successful. Anti-double-stranded DNA antibodies correlate with flares of lupus nephritis and may represent another therapeutic target. Therapy with LIP 394, which crosslinks anti-double-stranded DNA antibodies in solution or on the B-cell surface, has been shown to reduce flares. Cardiovascular disease is a major cause of mortality in systemic lupus erythematosus, and this must also be addressed if long-term outcomes are to be improved. Many patients with systemic lupus erythematosus have subclinical atherosclerosis quite early in the disease course, and the risk of coronary artery disease at any level of traditional cardiovascular risk factors is higher than in the general population. Specific lupus-associated risk factors include the inflammatory process itself and anticardiolipin antibodies. Possible strategies to reduce the risk include reduction of disease activity to improve endothelial function and reduction of steroid dose whenever possible. Therapy with aspirin or statins may be another possibility. Thus treatment of lupus nephritis is evolving from standardised therapy to individualised therapy based on analysis of organ involvement, risk factors and cytokine, antibody or cell profiles.
Lupus 2007
PMID:Exploring new territory: the move towards individualised treatment. 1743 12

Deficiency of mannan-binding lectin (MBL) has been reported to impact susceptibility to severe infections and atherosclerosis in systemic lupus erythematosus (SLE). In this study, MBL gene polymorphisms were analysed in 143 SLE patients and the frequency of severe infections and organ damage according to SLICC/ACR Damage Index regarding cerebrovascular accidents, angina pectoris, coronary by-pass surgery, myocardial infarction and peripheral arterial disease leading to significant tissue loss, were recorded during a mean follow-up time of 15 years from diagnosis. In a multiple logistic regression model, smoking (P = 0.001), hypertension (P = 0.030), alcohol intake (P = 0.027) and higher triglyceride concentration (P = 0.026) were associated with cerebrovascular, cardiovascular and peripheral arterial organ damage (CPAD), while the association with MBL deficiency did not reach significance (P = 0.098). Alcohol intake (>15 g/month) was inversely correlated with CPAD (OR = 0.29, 95%CI 0.096-0.87). MBL deficiency was not significantly more common in SLE patients with severe infections in a multivariate analysis (P > 0.3). In conclusion, classical risk factors such as smoking, hypertension, low alcohol intake and elevated triglyceride concentration were relatively more important for development of CPAD than MBL deficiency in SLE. Furthermore, MBL deficiency did not contribute to development of major infections in SLE.
Lupus 2007
PMID:Genetically determined mannan-binding lectin deficiency is of minor importance in determining susceptibility to severe infections and vascular organ damage in systemic lupus erythematosus. 1743 30

Antiphospholipid and anti-oxidized LDL (anti-oxLDL) antibodies are associated with thrombosis and atherosclerosis. Rheumatoid arthritis (RA) is characterized by excess atherosclerosis and cardiovascular diseases. Our aim was to determine whether antiphospholipid and anti-oxLDL antibodies are associated with early atherosclerotic changes in RA. The levels of IgG and IgM anticardiolipin, IgG and IgM anti-beta-2-glycoprotein-I and anti-oxLDL autoantibodies have been evaluated in 82 patients having RA. Carotid artery intima-media thickness (IMT) was measured in the carotid arteries in the common carotid, bifurcation and internal carotid arteries. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 7 with medium-to-high levels considered being clinically relevant. These patients had significantly elevated mean carotid and carotid bifurcation IMT compared with RA patients without elevated anticardiolipin. No such association was found regarding other autoantibodies tested. Anticardiolipin antibodies are prevalent in RA and are associated with early atherosclerotic changes, supporting a rational for measuring them in RA, and upon detection treat the patients in order to decrease chances of atherosclerosis progression and thrombosis.
Lupus 2007
PMID:Thickened carotid artery intima-media in rheumatoid arthritis is associated with elevated anticardiolipin antibodies. 1743 32

The present study aims to report a-20-year old girl with systemic lupus erythematosus (SLE) who developed myocardial infarction (MI) and also aims to review acute myocardial infarction (AMI) in young SLE cases (< or =35 years) reported in the literature. We conducted a comprehensive review of the English literature from 1975 to 2006 to analyse data on MI in SLE patients who had developed AMI either at 35 or earlier. In 32 English articles, we identified 49 SLE patients, plus our case, with AMI. They consist of 41 female and nine male patients, their mean age being 24 +/- 6.4 years (range of 5-35). Disease duration varied between 0 and 13 years. The lag time between the onset of the SLE manifestations and development of AMI was 7.7 +/- 5.4 year (range of 1 month to 20.5 years). We divided the patients into three subgroups according to their coronary involvement type (Group I: normal coronary artery or coronary thrombosis (n = 16); Group II: coronary aneurysm/arteritis (n = 12); Group III: coronary atherosclerosis (n = 22)). The lag time between the onset of the SLE manifestations and development of MI in the subgroups showed variations: Group I < Group II < Group III. Both prevalence of renal involvement and steroid therapy were higher in patients with coronary atherosclerosis than were in Group I. There were one or more risk factors for atherosclerosis in 39 SLE patients. AMI in young SLE patients may be seen, albeit rare. We suggest that clinicians should have a low threshold for cardiac evaluation in patients with SLE. Also, traditional risk factors could be managed through preventive measures.
Lupus 2007
PMID:Myocardial infarction in young patients (< or =35 years of age) with systemic lupus erythematosus: a case report and clinical analysis of the literature. 1743 37

Individuals with systemic lupus erythematosus (SLE) have a striking increase in premature atherosclerosis of unclear etiology. Accelerated endothelial cell apoptosis occurs in SLE and correlates with endothelial dysfunction. Endothelial progenitor cells (EPCs) and myelomonocytic circulating angiogenic cells (CACs) are crucial in blood vessel repair after vascular damage, and decreased levels or abnormal function of EPCs/CACs are established atherosclerosis risk factors. We investigated if vascular repair is impaired in SLE. We report that SLE patients display abnormal phenotype and function of EPCs/CACs. These abnormalities are characterized by significant decreases in the number of circulating EPCs (310 +/- 50 EPCs/mL of blood in SLE versus 639 +/- 102 in controls) and significant impairments in the capacity of EPCs/CACs to differentiate into mature ECs and synthesize adequate levels of the proangiogenic molecules vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF). These abnormalities are triggered by interferon-alpha (IFN-alpha), which induces EPC and CAC apoptosis and skews myeloid cells toward nonangiogenic phenotypes. Lupus EPCs/CACs have increased IFN-alpha expression and their supernatants promote higher induction of IFN-inducible genes. Importantly, neutralization of IFN pathways restores a normal EPC/CAC phenotype in lupus. SLE is characterized by an imbalance between endothelial cell damage and repair triggered by type I IFNs, which might promote accelerated atherosclerosis.
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PMID:Interferon-alpha promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis. 1763 46

Primary antiphospholipid syndrome (APS) is characterized by venous or arterial thrombotic events and/or recurrent abortions, fetal death, preeclasmpsia, eclampsia in the presence of anticardiolipin antibodies or lupus anticoagulant, in the absence of accompanying diseases. Antiphospholipid antibodies can activate endothelial cells, and were recently implicated in atherosclerosis. To assess potential endothelial impairment and early signs of atherosclerosis, flow-mediated (endothelium-dependent) and nitrate-mediated (endothelium independent) vasodilation, as well as von Willebrand factor antigen level and carotid artery intima-media thickness (IMT) were measured in patients with primary antiphospholipid syndrome and in healthy controls. Flow-mediated vasodilation in patients with primary APS was significantly lower than that of controls (3.43 +/- 2.86% versus 7.96 +/- 3.57%; P < 0.0001). We also found significantly higher von Willebrand antigen levels in patients with primary APS than in the control group (157.91 +/- 52.45% versus 125.87 +/- 32.8%; P = 0.012). Moreover, carotid artery IMT was significantly larger in the primary APS group compared to controls (0.714 +/- 0.2 mm versus 0.58 +/- 0.085 mm; P = 0.0037). Our results reflect ongoing endothelial damage and accelerated atherosclerosis in patients with primary APS, and suggest that vasoprotective therapy may be beneficial in the treatment of these patients.
Lupus 2007
PMID:Impaired endothelial function and increased carotid intima-media thickness in association with elevated von Willebrand antigen level in primary antiphospholipid syndrome. 1767 Aug 48

The objective of this report is to focus on the problems of patients with childhood onset systemic lupus erythematosus (SLE) at the age of transition to an adult care Unit. SLE is a multisystem disease characterised by diffuse internal organ involvement and by the presence of antinuclear and anti DNA antibodies. Central nervous system and renal damage are the main complications especially in children. Transition in health-care is a multifaceted, active process that attends to the medical, psychosocial and educational-vocational needs of adolescents when they move from child to adult-oriented lifestyles and systems. Lack of institutional support and difficulty in communicating and in identifying adult specialists are the major concerns in a transition care Unit. Psychosocial matters can make this change dramatic and hard for young people and their families. Patients with juvenile-onset SLE require specialised and multidisciplinary care when entering a transition clinic; physicians need to focus on preventing long-term complications of SLE, including atherosclerosis, obesity, osteoporosis and their treatment. We report on our experience in a cohort of patients with juvenile SLE cared for at our transition clinic over last six years.
Lupus 2007
PMID:Systemic lupus erythematosus in the young: the importance of a transition clinic. 1771 97

Systemic lupus erythematosus (SLE) is an independent risk factor for atherosclerosis, placing children and adolescents with SLE at great risk for developing cardiovascular sequelae, including myocardial infarction, in adulthood. Dyslipidemia and other traditional cardiac risk factors occur frequently in pediatric SLE and are often under-recognized and under-treated. Two dyslipidemia patterns are evident in pediatric SLE. Active disease is characterized by elevated triglycerides (TG) and low high density lipoprotein (HDL). With SLE treatment HDL and TG often normalize, while total cholesterol and low density lipoprotein (LDL) rise. The complex pathophysiology of dyslipidemia in SLE involves cytokines, autoantibodies, disease activity, medications, diet, and physical activity level, as well as other factors. Routine screening for dyslipidemia with fasting lipid profiles is indicated for children and adolescents with SLE. If lipoprotein levels are abnormal, first line therapy involves diet and exercise interventions for a minimum of six months. For persistent dyslipidemia, several pharmacologic therapies are available. Hydroxychloroquine, a common treatment for SLE, can improve lipid profiles and should be considered for all patients with SLE. Statins and bile acid sequestrants are typically added first for dyslipidemia, while niacin and fibrates are reserved for refractory disease and optimally prescribed in a multidisciplinary lipid clinic. Future research is needed to further illuminate the mechanisms of dyslipidemia in pediatric SLE with well designed clinical trials to determine the safest and most effective interventions to correct lipid profiles and prevent atherosclerosis.
Lupus 2007
PMID:Management of dyslipidemia in children and adolescents with systemic lupus erythematosus. 1771 98


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