Steroid use and cardiovascular risk (CV risk)

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

• glucocorticoids (steroids) are widely used to reduce disease activity and inflammation in patients with a range of immune-mediated inflammatory diseases, such as rheumatoid arthritis, polymyalgia rheumatica, giant cell arteritis, and inflammatory bowel disease
  • however, prolonged glucocorticoid treatment often causes adverse events, including cardiovascular diseases (CVDs) (1,2,3)
    • in SLE, both recent use of corticosteroids and recent lupus activity are independently associated with higher values of several well-recognized CHD risk factors (1)
    • treatment with high-dose glucocorticoids seemed to be associated with increased risk for cardiovascular disease (2)
• widely recognised that high-dose steroids may increase the risk of cardiovascular disease (CVD; heart disease, stroke, or other vascular diseases), but it is debated whether this increase also applies to lower steroid doses

Study summary:

• Pujades-Rodriguez et al conducted a population-based cohort analysis of medical records from 389 primary care practices contributing data to the United Kingdom Clinical Practice Research Datalink (CPRD), linked to hospital admissions and deaths in 1998-2017
  • estimated time-variant daily and cumulative glucocorticoid prednisolone-equivalent dose-related risks and hazard ratios (HRs) of first all-cause and type-specific cardiovascular diseases (CVDs)
  • were 87,794 patients with giant cell arteritis and/or polymyalgia rheumatica (25,581), inflammatory bowel disease (27,739), rheumatoid arthritis (25,324), systemic lupus erythematosus (3,951), and/or vasculitis (5,199), and no prior CVD
  • mean age was 56 years and 34.1% were men
  • median follow-up time was 5.0 years, and the proportions of person–years spent at each level of glucocorticoid daily exposure were 80% for non-use, 6.0% for <5 mg, 11.2% for 5.0-14.9 mg, 1.6% for 15.0-24.9 mg, and 1.2% for >=25.0 mg.

Study results:

• in 87,794 adults with immune-mediated inflammatory diseases and no prior CVD (5-year median follow-up), studied the risk of 6 common CVDs associated with the steroid dose prescribed, quantified either as current or as cumulative dose
• found strong dose-dependent risks of all CVDs, including myocardial infarction, heart failure, atrial fibrillation, and cerebrovascular disease, in patients diagnosed with the 6 inflammatory diseases studied
• one-year cumulative risks of all-cause CVD increased from 1.4% in periods of non-use to 8.9% for a daily prednisolone-equivalent dose of >=25.0 mg
  • five-year cumulative risks increased from 7.1% to 28.0%, respectively
  • compared to periods of non-glucocorticoid use, those with <5.0 mg daily prednisolone-equivalent dose had increased all-cause CVD risk (HR = 1.74; 95% confidence interval [CI] 1.64-1.84; range 1.52 for polymyalgia rheumatica and/or giant cell arteritis to 2.82 for systemic lupus erythematosus)
  • increased dose-dependent risk ratios were found regardless of disease activity level and for all type-specific CVDs
  • HRs for type-specific CVDs and <5.0-mg daily dose use were: 1.69 (95% CI 1.54-1.85) for atrial fibrillation, 1.75 (95% CI 1.56-1.97) for heart failure, 1.76 (95% CI 1.51-2.05) for acute myocardial infarction, 1.78 (95% CI 1.53-2.07) for peripheral arterial disease, 1.32 (95% CI 1.15-1.50) for cerebrovascular disease, and 1.93 (95% CI 1.47-2.53) for abdominal aortic aneurysm.
• after 1 year, the overall absolute risk of CVD doubled for individuals using less than 5 mg prednisolone per day and was 6 times higher for users of 25 mg or greater
• many individuals had known modifiable cardiovascular risk factors, including current smoking (24%), obesity (25%), or hypertension (25%).

Study authors concluded:

• it was previously believed that less than 5 mg of prednisolone was safe long term, but even at this "low dose" patients with immune-mediated inflammatory diseases have a doubling of their underlying risk of CVD

Reference:

• Karp I, Abrahamowicz M, Fortin PR, Pilote L, Neville C, Pineau CA, et al. Recent corticosteroid use and recent disease activity: independent determinants of coronary heart disease risk factors in systemic lupus erythematosus? Arthritis Rheum. 2008;59(2):169-75.
• Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med. 2004;141(10):764-70.
• Pujades-Rodriguez M, Morgan AW, Cubbon RM, Wu J. Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: A population-based cohort study. PLoS Med. 2020 Dec 3;17(12):e1003432.