Initial disease severity, cardiovascular events and all-cause mortality among patients with systemic lupus erythematosus

Abstract

Objective SLE is associated with high risks of cardiovascular disease (CVD) and mortality, and has a wide spectrum of presentations. We investigated whether SLE severity at diagnosis was associated with CVD or mortality risk. Methods Within Medicaid (2000–10), we identified patients 18–65 years of age with incident SLE. Initial SLE severity was classified—mild, moderate, or severe—during the baseline year prior to the start of follow-up (incident index date) using a published algorithm based on SLE-related medications and diagnoses. Patients were followed from the index date to the first CVD event or death, disenrollment, loss to follow-up or end of follow-up period. Cox and Fine–Gray regression models, adjusted for demographics and comorbidities accounting for the competing risk of death (for CVD), estimated CVD and mortality risks by baseline SLE severity. Results Of 15 120 incident SLE patients, 48.7% had mild initial SLE severity, 33.9% moderate and 17.4% severe. Mean (s.d.) follow-up was 3.3 (2.4) years. After multivariable adjustment, CVD subdistribution hazard ratios (HRSD) were higher for initially severe [HRSD 1.64 (95% CI 1.32, 2.04)] and moderate [HRSD 1.19 (95% CI 1.00, 1.41)] SLE vs mild SLE. Mortality HRs were also higher for initially severe [HR 3.11 (95% CI 2.49, 3.89)] and moderate [HR 1.61 (95% CI 1.29, 2.01)] SLE vs mild SLE. Conclusion SLE patients with high initial severity had elevated mortality and CVD events risks compared with those who presented with milder disease. This has implications for clinical care and risk stratification of newly diagnosed SLE patients.

High Comorbidity Burden in Patients with SLE: Data from the Community-Based Lupus Registry of Crete

“…Rather than focusing on isolated diseases, we analyzed for factors associated with physical and mental multimorbidity as well as CCI-defined morbid status. We found that increasing SLE severity, reflected in a BILAG-based classification of manifestations or the number of ACR 1997 classification criteria, correlated with increased odds for physical morbidity, thus corroborating evidence on the effects of high disease activity and medications (e.g., glucocorticoids) on the development of comorbid disorders [ 7 , 34 , 60 , 61 , 88 ]. This finding might be mirrored by the positive correlation between exposure to immunosuppressive and biological agents and physical comorbidities, although drug-intrinsic effects cannot be ruled out.…”

“…Although direct comparisons are hampered due to differences in the study design, assessment and documentation methods, and the definitions used, our findings concord with published data underpinning increased occurrence of metabolic and atherosclerotic factors such as hypertension, dyslipidemia, obesity, diabetes, cardiovascular, and cerebrovascular disease as compared to the general population [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 54 , 55 , 56 , 57 , 58 ]. Cardiovascular burden is also increased in SLE, attributable to the interplay between demographic (e.g., gender, ethnicity), disease duration, traditional risk factors (including smoking), lupus autoimmunity such as type I interferon signaling, and the known deleterious effects of chronic glucocorticoids use [ 7 , 56 , 58 , 59 , 60 , 61 , 62 , 63 ]. In line with this, circumstantial non-randomized evidence suggests that attainment of low disease activity state on a minimal background dose of glucocorticoids is associated with reduced risk for cardiovascular events in SLE [ 64 ].…”

Long-term outcomes in systemic lupus erythematosus: trends over time and major contributors

“…An interplay between the traditional CVD risk factors and disease-related factors such as disease activity and damage, GCs and aPLs has been involved in CVD pathogenesis in SLE [ 34 ]. Despite a growing awareness of CVD risk among patients with SLE, CVD burden remains high [ 20 , 39 , 40 ]. Data from a US population-based study using nationwide data showed increased age-adjusted rates of hospitalizations for myocardial infarction and stroke between 1996 and 2012 in both younger (age 18–49 years) and older (age ≥50 years) women and in men with SLE, while, in contrast, the hospitalization rates for both cardiovascular events were decreased in those without SLE.…”

Anifrolumab, a monoclonal antibody to the type I interferon receptor subunit 1, for the treatment of systemic lupus erythematosus: an overview from clinical trials

“…In another smaller cohort, 5-, 10-, 15-, and 20-year survival rates were 99.3%, 94.6%, 92.0%, and 85.4%, respectively [5]. SLE severity at diagnosis is associated with mortality risk, with a hazard ratio (HR) of 3.11 (95% confidence interval [CI] 2.49, 3.89) for initially severe and 1.61 (95% CI 1.29, 2.01) for moderate SLE compared with mild SLE [6].…”