Variability over time and correlates of cholesterol and blood pressure in systemic lupus erythematosus: a longitudinal cohort study

Mandana Nikpour 0 2 Dafna D Gladman 0 Dominique Ibanez 0 Paula J Harvey 1 Murray B Urowitz 0 0 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 1 Division of Cardiology and Clinical Pharmacology, Toronto Western Hospital , 399 Bathurst Street, Toronto, ON, M5T 2S8 , Canada 2 University of Melbourne Department of Medicine, St. Vincent's Hospital , 41 Victoria Parade, Fitzroy, Melbourne, Victoria, 3065 , Australia Introduction: Total cholesterol (TC) and blood pressure (BP) are likely to take a dynamic course over time in patients with systemic lupus erythematosus (SLE). This would have important implications in terms of using single-point-intime measurements of these variables to assess coronary artery disease (CAD) risk. The objective of this study was to describe and quantify variability over time of TC and BP among patients with SLE and to determine their correlates. Methods: Patients in the Toronto lupus cohort who had two or more serial measurements of TC and systolic and diastolic BP (SBP and DBP) were included in the analysis. Variability over time was described in terms of the proportion of patients whose TC and BP profile fluctuated between normal and elevated (TC > 5.2 mmol/L; SBP 140 mm Hg or DBP 90 mm Hg), and also in terms of within- and between-patient variance quantified by using analysis of variance modeling. Generalized estimating equations (GEEs) were used to determine independent correlates of each of TC, SBP, and DBP, treated as continuous outcome variables. Results: In total, 1,260 patients, comprising 26,267 measurements of each of TC, SBP, and DBP, were included. Mean SD number of measurements per patient was 20.8 20. Mean SD time interval between measurements was 5.4 9.7 months. Mean SD time interval from the start to the end of the study was 9.3 8.5 years. Over time, 64.7% of patients varied between having normal and elevated cholesterol levels, whereas the status of 46.4% of patients varied between normotensive and hypertensive. By using analysis of variance (ANOVA), the within-patient percentage of total variance for each of TC, SBP, and DBP was 48.2%, 51.2%, and 63.9%, respectively. By using GEE, independent correlates of TC and BP included age, disease activity, and corticosteroids; antimalarial use was negatively correlated with TC (all P values < 0.0001). Conclusions: TC and BP vary markedly over time in patients with SLE. This variability is due not only to lipid-lowering and antihypertensive medications, but also to disease- and treatment-related factors such as disease activity, corticosteroids, and antimalarials. The dynamic nature of TC and BP in SLE makes a compelling case for deriving summary measures that better capture cumulative exposure to these risk factors. - Introduction Systemic lupus erythematosus (SLE) is strongly associated with premature atherosclerotic CAD [1,2]. Indeed, young women aged 35 to 44 years are > 50 times more likely to have myocardial infarction than are their agematched peers [3]. One in 10 patients with SLE is diagnosed with clinical CAD, making this complication one of the leading causes of morbidity and mortality in SLE [4,5]. Whilst traditional cardiovascular risk factors only partly account for the increased risk of CAD in SLE, many of these risk factors are potentially treatable [6]. Hypercholesterolemia and hypertension are two traditional cardiac risk factors that have been shown to be independently predictive of coronary events in patients with SLE when measured at the first available visit ('baseline') or defined as 'abnormal ever' during follow-up [3,4,7]. However, to date, the magnitude of risk associated with these risk factors may not have been accurately estimated by using approaches that fail to take into account the possible variability of these risk factors over time. Evidence suggests that in the first 3 years of disease, one third of patients with SLE have 'variable hypercholesterolemia', with cholesterol levels that fluctuate between 'normal' and 'abnormal', which, in this case, is defined as total serum cholesterol > 5.2 mmol/L [8]. Similarly, in the general population, systolic and diastolic blood pressure have been shown to vary over time, a phenomenon that likely also affects SLE patients in whom both disease manifestations and treatments may affect blood pressure [9-11]. To date, the variability over time of TC, SBP, and DBP over the course of disease in patients with SLE has not been rigorously evaluated. The objective of this study was to describe and quantify variability over time of TC, SBP, and DBP and to determine their correlates in patients with SLE. We used > 26,000 measurements of each of TC, SBP, and DBP taken in > 1,200 SLE patients, in > 9 years of follow-up. In assessment of variability over time, we defined each of TC, SBP, and DBP dichotomously and as continuous variables. Generalized estimating equations (GEEs) were used to determine independent correlates of TC, SBP, and DBP over time. Among the University of Toronto lupus cohort, patients who had two or more serial measurements of TC, SBP, and DBP were included in the analysis. Patients attending the University of Toronto lupus clinic are followed up at 2- to 6-month intervals, and clinical and laboratory data obtained at each visit are stored in a dedicated database. All patients fulfill four or more of the ACR classification criteria for SLE, or have three criteria and a typical lesion of SLE on renal or skin biopsy [12,13]. Collection and storage of data are approved by the research ethics board of the University Health Network, and patients give informed consent on entry into the clinic. In addition to TC, SBP, and DBP, data on patients' demographic profiles (including age, sex, menopausal status, and race), disease duration, disease activity, medications, intercurrent infections, smoking, and diabetes were routinely collected according to a set protocol. The data were stored and tracked in the lupus database at each clinic visit for the period from entry into the clinic up to the most recent visit as of August 2008. Each measurement of TC, SBP, and DBP was therefore tied to a clinic visit. We used only visits wherein all of three of TC, SBP, and DBP had been measured and recorded. Definitions of variables Age and disease duration at the time of each visit were reported in years. Disease duration was calculated from the date of physician diagnosis of SLE to the date of each visit. Disease activity at each visit was reported by using the SLE Disease Activity Index 2000 (SLEDAI-2K), wherein scores range from 0 to 105, with higher scores indicating more-active disease [14]. Corticosteroid, antimalarial, and immunosuppressive use at each visit were reported categorically, irrespective of dose. Antimalarials included chloroquine and hydroxychloroquine. Immunosuppressives (...truncated)