An increased incident rate (IR) of comorbidities including cardiovascular disease (CVD) development, stroke, end-stage renal disease (ESRD), cancer, osteoporosis, and infection was found in patients with systemic lupus erythematosus (SLE) in a large retrospective cohort study in the general UK population. 

Specific comorbidity IRs appeared to vary according to gender, with men having higher IR of CVD, stroke, and malignancy as compared to women while women had higher IR of osteoporosis and infection. These findings were recently published in Arthritis Care & Research. 



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Age also appears to influence specific comorbidity risk, with patients who were younger having the greatest relative risk of developing disease comorbidity. These findings should prompt clinicians to tailor risk factor mitigation counseling, including smoking cessation and minimization of corticosteroid use to optimize primary prevention. 

To identify the IR of CVD, stroke, ESRD, malignancy, and infection in a large SLE population in the UK,  Frances Rees, BMBS, MRCP, from the University of Nottingham and Nottingham University Hospitals NHS Trust, UK, and colleagues analyzed data from the UK Clinical Practice Research Datalink (CPRD) from the years 1999–2012.

The CPRD database is  a large longitudinal collection of data, in which clinical information is entered by individual practice suing Read codes.  This data is then deidentified of patient private data prior to availability to researchers.

High Yield Clinical Pearls

  • An increased incidence rate of CVD, stroke, ESRD, cancer, osteoporosis, and infection was found in patients with SLE
  • Gender differences in specific morbidity were identified

SLE cases were defined by having 1 of 14 Read codes specifying SLE and meeting eligibility criteria within the specified study period year. Controls without SLE were matched in a 1:4 ratio to patients with SLE by age (within 5 years), sex, and practice.

Researchers then utilized the Charlson Index score, a previously validated and weighted comorbidity score covering the following diagnostic categories: myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatologic disease, peptic ulcer disease, liver disease, diabetes mellitus (DM), chronic complications associated with DM, renal diseases, cancer, metastatic solid tumor, and human immunodeficiency virus infection.  According to the scoring method, each category is given a score of 1 through 6 to account for the risk of mortality. 

Chi-square test statistical analysis was used to compare the differences between SLE cases and matched controls in baseline Charlson Index scores and potential confounders.  IRs for each comorbidity associated with a case was calculated by  dividing the number of SLE cases who developed a specific comorbidity by the number of person-years Incidence rate ratios (IRRs) for CVD, stroke, ESRD, malignancy, osteoporosis and infection per 1000 person-years as compared to controls were calculated utilizing Poisson regression analyses. 

Researchers analyzed 7732 cases of SLE along with 28 079 matched controls and found that unadjusted IRR for CVD was 1.98 (95% confidence interval [95% CI] 1.69–2.31), for stroke 1.81 (95% CI 1.49–2.19), for ESRD 7.81 (95% CI 4.68–13.05) , for malignancy 1.28 (95% CI 1.17–1.40), for osteoporosis 2.53 (95% CI 2.27–2.82), and for infection 1.49 (95% CI 1.40–1.58) for infection.  

After adjusting for age, sex, and other confounding variables, researchers found that increased rates of comorbities remained significantly higher in cases with SLE compared to those without.  Gender differences in risk were found, including the fact that men with SLE had higher rates of CVD, stroke, and cancer while women with SLE had higher rates of comorbid osteoporosis and infection.  In terns of age, those patients who were youngest has the greatest increased degree of relative risk as compared to matched controls. 

Summary and Clinical Applicability

Patients with SLE have an increased IR of comorbidity, and are more likely than those without SLE to develop CVD, stroke, ESRD, cancer, osteoporosis, and infection.

Limitations and Disclosures

The results of this study was limited by the retrospective analysis of data that was dependent on the accurate entry and coding of patient data into the general practitioner databases, in addition to missing data for potentially confounding variables such as body mass index. 

This research was funded by Lupus UK.

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Reference

Rees F, Doherty M, Grainge M, Lanyon P, Davenport G, Zhang W. Burden of Comorbidity in Systemic Lupus Erythematosus in the UK, 1999-2012. Arthritis Care Res (Hoboken). 2016;68(6):819-27.