Autopsy and observational data suggest that systemic lupus erythematosus (SLE) is associated with premature atherosclerosis and myocardial infarction; however, clinical studies have reported widely varying event rates, and the prevalence of underlying disease (atherosclerosis and myocardial disease) in SLE patient samples and its relation to that in a control population are unknown. The prevailing hypothesis has been that accelerated atherosclerosis is attributable to an increased frequency of conventional risk factors in SLE patients such as hypertension, hyperlipidemia and obesity, all of which may be provoked or potentiated by therapeutic use of corticosteroids. Alternatively, anti-phospholipid antibody (APLA), present in about 20% of the SLE patients, may result in vascular occlusions due to abnormal clotting rather than atherosclerosis; however, data are accumulating that suggest that the inflammatory process per se may be important in the initiation and progression of atherosclerosis. Pilot data for this study indicate that underlying non-invasively- detected atherosclerosis is several-fold more common in patients with SLE in comparison to matched control subjects. Furthermore, left ventricular mass, a marker for and mediator of enhanced cardiovascular morbidity and mortality, is strikingly higher in SLE patients, even after adjustment for differences in body size. Neither of these observations is explained by standard risk factors. Thus, the goals of this project are to: 1) establish the prevalence of atherosclerosis and myocardial disease in an unselected population of SLE patients; 2) compare findings to those in a control population; 3) determine whether the excess prevalence of pre-clinical cardiovascular disease is independent of known cardiovascular risk factors and is additionally related to markers of inflammation and immune system activation; and 4) determine whether atherosclerosis and LV hypertrophy progress more rapidly in SLE patients than in control subjects. Based on preliminary data, the investigators hypothesize that pre-clinical disease will be more common in SLE and will not be fully explained by conventional risk factors for atherosclerosis or thrombosis. They further hypothesize that basic aspects of the inflammatory process (to be partially investigated using soluble markers in the current project) are primarily responsible for non-valvular cardiovascular disease in SLE.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Special Emphasis Panel (ZRG4-ALTX-4 (06))
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Serrate-Sztein, Susana
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Weill Medical College of Cornell University
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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Perna, Michelle; Roman, Mary J; Alpert, Deborah R et al. (2010) Relationship of asymmetric dimethylarginine and homocysteine to vascular aging in systemic lupus erythematosus patients. Arthritis Rheum 62:1718-22
Rudominer, Rebecca L; Roman, Mary J; Devereux, Richard B et al. (2009) Independent association of rheumatoid arthritis with increased left ventricular mass but not with reduced ejection fraction. Arthritis Rheum 60:22-9
Salmon, Jane E; Roman, Mary J (2008) Subclinical atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Am J Med 121:S3-8
Roman, Mary J; Crow, Mary K; Lockshin, Michael D et al. (2007) Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 56:3412-9
Pieretti, Janice; Roman, Mary J; Devereux, Richard B et al. (2007) Systemic lupus erythematosus predicts increased left ventricular mass. Circulation 116:419-26
Farzaneh-Far, Afshin; Roman, Mary J; Lockshin, Michael D et al. (2006) Relationship of antiphospholipid antibodies to cardiovascular manifestations of systemic lupus erythematosus. Arthritis Rheum 54:3918-25
Roman, Mary J; Moeller, Elfi; Davis, Adrienne et al. (2006) Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern Med 144:249-56
Roman, Mary J; Devereux, Richard B; Schwartz, Joseph E et al. (2005) Arterial stiffness in chronic inflammatory diseases. Hypertension 46:194-9
Roman, Mary J; Shanker, Beth-Ann; Davis, Adrienne et al. (2003) Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 349:2399-406
Lockshin, M D; Salmon, J E; Roman, M J (2001) Atherosclerosis and lupus: a work in progress. Arthritis Rheum 44:2215-7

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