Background. Systemic lupus erythematosus (SLE) is associated with considerably elevated rates of coronary heart disease (CHD). Understanding the reasons for this is crucial for developing effective CHD prevention and treatment in SLE patients. / Objective. To gain insights into biological mechanisms underlying the accelerated atherosclerosis in SLE, this thesis examines (i) the longitudinal evolution of traditional coronary risk factors and global coronary risk, and (ii) the independent effects of corticosteroid use and lupus disease activity on this evolution. / Methods. First, a systematic comparison between alternative approaches to global coronary risk assessment was performed based on data from the Framingham Heart Study to determine the optimal method of representing the aggregate impact of individual risk factors. Next, data on up to 30 years of follow up of 310 lupus patients of the Montreal General Hospital Lupus Clinic and 26 years of follow-up of 4,367 control subjects from the Framingham Offspring Study were used to investigate, in separate analyses, the independent associations of lupus disease duration with the global coronary risk and each conventional risk factor. Finally, the lupus cohort was used to study the associations of recent corticosteroid use and recent lupus disease activity with a series of CHD risk factors and global CHD risk. Main analyses relied on multivariable linear mixed models for longitudinal data. / Findings. Updated risk factor values improved the predictive ability of the multivariable coronary risk score compared with prediction based on baseline values. Longer lupus disease duration was associated with increased blood glucose levels, systolic blood pressure and total cholesterol. Recent corticosteroid use and recent lupus disease activity were both positively associated with increases in the levels of conventional risk factors and the global risk. / Conclusions. Conventional coronary risk factors play an especially important role in the etiology of CHD in lupus patients. The accelerated atherosclerosis in SLE could be mediated by conventional coronary risk factors, which are affected by both lupus disease activity and corticosteroid therapy.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.85922 |
| Date | January 2005 |
| Creators | Karp, Igor |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Epidemiology and Biostatistics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002261198, proquestno: AAINR21659, Theses scanned by UMI/ProQuest. |
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