Dose-dependent oral glucocorticoid cardiovascular risk in people with immune-mediated inflammatory diseases

Background Evidence for the association between glucocorticoid dose and cardiovascular risk is weak for moderate and low doses. To quantify glucocorticoid dose-dependent cardiovascular risk in people with six immune-mediated inflammatory diseases.

Methods and Findings Population-based cohort analysis of medical records from 389 primary care practices contributing data to the UK Clinical Practice Research Datalink, linked to hospital admissions and deaths in 1998-2017. There were 87,794 patients with giant cell arteritis and/or polymyalgia rheumatica (n=25,581), inflammatory bowel disease (n=27,739), rheumatoid arthritis (n=25,324), systemic lupus erythematosus (n=3951), and/or vasculitis (n=5199); and no prior cardiovascular disease (CVD). Mean age was 56 years and 34.1% were men. Median follow-up time was 5.0 years. Time-variant daily and cumulative glucocorticoid prednisolone-equivalent dose-related risks and hazard ratios of first all-cause and type-specific CVD.

We found 13,426 (15.3%) people with incident CVD, including 6,013 atrial fibrillation, 7,727 heart failure and 2,809 acute myocardial infarction events. At 1 and 5 years, the cumulative risks of all-cause CVD increased from 1.5% in periods of non-use to 9.1% for a daily prednisolone-equivalent dose of ≥25.0mg, and from 7.6% to 29.9%, respectively. We found strong dose-dependent estimates for all immune-mediated diseases (hazard ratio [HR] for <5.0mg daily dose vs. non-use=1.74, 95%CI 1.64-1.84; range 1.52 for polymyalgia rheumatica and/or giant cell arteritis to 2.82 for systemic lupus erythematosus), all cardiovascular outcomes, regardless of disease activity level. The highest estimates were for heart failure and acute myocardial infarction.

Conclusions We estimated glucocorticoid dose-dependent cardiovascular risk in six immune-mediated diseases. Results highlight the importance of prompt and regular monitoring of cardiovascular risk and use of primary prevention treatment at all glucocorticoid doses.