title: Importance of cumulative exposure to elevated cholesterol and blood pressure in development of atherosclerotic coronary artery disease in systemic lupus erythematosus: a prospective proof-of-concept cohort study.
abstract: BACKGROUND
  Previous studies have shown that traditional risk factors such as hypercholesterolemia and hypertension account for only a small proportion of the dramatically increased risk of atherosclerotic coronary artery disease (CAD) in systemic lupus erythematosus (SLE). However, in these studies, exposure to risk factors was measured only at baseline. In this study, our objective was to compare measures of cumulative exposure with remote and recent values for each of total cholesterol (TC), systolic (SBP), and diastolic (DBP) blood pressure in terms of ability to quantify risk of atherosclerotic CAD in patients with SLE.
  
  
  METHODS
  Patients in the Toronto lupus cohort had TC and BP measured at each clinic visit and were followed up prospectively for the occurrence of CAD. For each patient, arithmetic mean, time-adjusted mean (AM) and area-under-the-curve (AUC) were calculated for serial TC, SBP, and DBP measurements. Proportional hazards regression models were used to compare these summary measures with recent and first-available ("remote") measurements in terms of ability to quantify risk of CAD events, defined as myocardial infarction, angina, or sudden cardiac death.
  
  
  RESULTS
  The 991 patients had a mean ± SD of 19 ± 19 TC measurements per patient. Over a follow-up of 6.7 ± 6.4 years, 86 CAD events occurred; although remote TC was not significantly predictive of CAD, mean and AM TC were more strongly predictive (hazard ratio (HR) 2.07; P = 0.003) than recent TC (HR 1.86, P = 0.001). AUC TC was not predictive of CAD. A similar pattern was seen for DBP and SBP. Older age, male sex, higher baseline and recent disease activity score, and corticosteroid use also increased CAD risk, whereas antimalarials were protective.
  
  
  CONCLUSIONS
  In contrast to the population-based Framingham model, first-available TC and BP are not predictive of CAD among patients with SLE, in whom measures reflecting cumulative exposure over time are better able to quantify CAD risk. This is an important consideration in future studies of dynamic risk factors for CAD in a chronic relapsing-remitting disease such as SLE. Our findings also underpin the importance of adequate control of SLE disease activity while minimizing corticosteroid use, and highlight the cardioprotective effect of antimalarials.
authors.affiliation: University of Toronto Lupus Clinic and the Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
authors.forename: Mandana
authors.initials: M
authors.lastname: Nikpour
authors.forename: Murray B
authors.initials: MB
authors.lastname: Urowitz
authors.forename: Dominique
authors.initials: D
authors.lastname: Ibanez
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Harvey
authors.forename: Dafna D
authors.initials: DD
authors.lastname: Gladman
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D002784:Cholesterol / Q000097:blood*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000453:epidemiology*; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000453:epidemiology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D015854:Up-Regulation / Q000502:physiology; D055815:Young Adult
chemical_list: D002784:Cholesterol