Background: Ankylosing spondylitis (AS) is a chronic, systemic inflammatory disease with major pharmacological treatment with long-term nonsteroidal anti-inflammatory drugs (NSAIDs). Patients with AS are notably at risk for comorbidities involving the cardiovascular system [1]. Development of a predictive chart score or algorithm for risk of major adverse cardiovascular events (MACE) in patients with incident AS requiring pharmacologic therapy based on identified risk factors is a clinical necessity for a better holistic management. The related epidemiologic studies are still lacking currently.

Objectives: To investigate factors associated with major adverse cardiovascular events (MACE) in patients with incident ankylosing spondylitis (AS) requiring medical therapy.

Methods: We conducted a population-based case-control study using the Taiwanese National Health Insurance Research Database, and 42,595 newly-diagnosed AS patients requiring medical therapy without previous MACE (the composite outcome of myocardial infarction, ischemic stroke, or patients who underwent coronary artery bypass graft or percutaneous coronary intervention) from 2004 to 2012 was identified. Totally 1,151 patients (2.7%) developed MACE during the follow-up period. We matched MACE cases with non-MACE controls at a 1:4 ratio for age, gender and AS follow-up duration and included 947 AS patients with MACE and 3896 matched controls for final analyses. Using conditional logistic regression analyses, we examined the associations of MACE with low income (≤ 21000 new Taiwan dollars per month), urbanisation, extra-articular manifestations (uveitis, psoriasis and inflammatory bowel disease), comorbidities and use of medications within a year before MACE development. We also examined the influence of NSAIDs of three categories (traditional NSAIDs, selective cyclooxygenase-2 inhibitors [COX-2i] and preferential COX-2i) with their annual cumulative defined daily dose (cDDD) on MACE risk with a Bonferroni correction of the cut-off of probability value for statistical significance. The risk was shown as adjusted odds ratio (aOR) with 95% confidence intervals (CIs).

Results: MACE development was associated with selective COX-2i use especially with annual cDDD > 132 (aOR, 1.61; 95% CI, 1.12-2.32, p = 0.011), corticosteroid use with a dose–response relationship (prednisolone equivalent dose < 5 mg/day: aOR, 1.25; 95% CI, 1.02-1.54, p = 0.028; ≥ 5 mg/day: aOR, 4.75; 95% CI, 3.51-6.43, p < 0.001), residence in rural region (aOR, 1.32; 95% CI, 1.03-1.69, p = 0.028), hypertension (aOR, 3.12; 95% CI, 2.57-3.80, p < 0.001), diabetes mellitus (aOR, 1.69; 95% CI, 1.37-2.07, p < 0.001), hyperlipidaemia (aOR, 5.00; 95% CI, 4.14-6.03, p < 0.001), chronic kidney disease (aOR, 1.98; 95% CI, 1.35-2.90, p = 0.001), heart failure (aOR, 4.04; 95% CI, 2.74-5.94, p < 0.001) and valvular heart disease (aOR, 2.06; 95% CI, 1.33-3.20, p = 0.001), but not with use of traditional NSAIDs, preferential COX-2i, biologics, methotrexate, sulfasalazine, uveitis, psoriasis or inflammatory bowel disease.

Conclusion: The risk factors of MACE in AS patients include use of selective COX-2i, corticosteroids, residence in rural region and other well-known associated comorbidities. The major limitation of this study was a lack of information on individual smoking status. The findings might aid in the development of a predictive chart score or algorithm for MACE risk in patients with AS.

REFERENCES:

[1]Zhao SS, Robertson S, Reich T, et al. Prevalence and impact of comorbidities in axial spondyloarthritis: systematic review and meta-analysis. Rheumatology (Oxford ) 2020;59(Suppl4):iv47-iv57. doi: 10.1093/rheumatology/keaa246 [published Online First: 2020/10/15]

Acknowledgements: The authors would like to thank the Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan, ROC for statistical support.

Disclosure of Interests: None declared