Factors Associated with the Risk of Major Adverse Cardiovascular Events in Patients with Ankylosing Spondylitis: A Nationwide, Population-Based Case—Control Study

Abstract

Background: Potential risk factors for major adverse cardiovascular events (MACE) in patients with ankylosing spondylitis (AS) requiring medical therapy should be investigated. Methods: We identified newly diagnosed AS patients without previous MACE from 2004 to 2012 using the National Health Insurance Research Database, matched MACE cases with non-MACE controls at a 1:4 ratio for age, gender, AS duration, and index date, and included 947 AS patients with MACE and 3896 matched controls for final analyses. By using conditional logistic regression analyses, we examined the associations of MACE with low income, urbanisation, comorbidities, common extra-articular manifestations (EAM), and medications, including nonsteroidal anti-inflammatory drugs (NSAID) of three categories (traditional NSAIDs, selective cyclooxygenase-2 inhibitors (COX-2i), and preferential COX-2is) with their annual cumulative defined daily dose (cDDD) within a year before MACE development. Results: MACE development was associated with the use of selective COX-2is (especially with annual cDDD > 132) and corticosteroids, residence in rural regions, and well-known associated comorbidities, but not with the use of traditional NSAIDs, preferential COX-2i, biologics, methotrexate, sulfasalazine, and common EAMs. Conclusions: The risk factors of MACE in newly diagnosed AS patients include residence in rural regions, well-known associated comorbidities, and the use of corticosteroids and selective COX-2is. A major limitation was the lack of information on individual lifestyle patterns and disease activity.

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“…Similar rates were reported by the other studies [ 32 , 33 , 35 , 36 ]. Interestingly, the prevalence rates in López-Medina’s and Kao's studies were relatively lower than the previously documented rates [ 1 , 6 ]. In the ASAS–COMOSPA study, the patients from the Mediterranean area had lower CVD rates (1.8% and 1.3% for ischemic heart disease and stroke) than those in Northern European countries (6.2% and 2.5% for ischemic heart disease and stroke), indicating potential regional disparities [ 1 ].…”

“…In the ASAS–COMOSPA study, the patients from the Mediterranean area had lower CVD rates (1.8% and 1.3% for ischemic heart disease and stroke) than those in Northern European countries (6.2% and 2.5% for ischemic heart disease and stroke), indicating potential regional disparities [ 1 ]. Kao et al [ 6 ] highlighted a 2.9% CVD prevalence in newly diagnosed AS patients, suggesting a potential link between increased prevalence and older age or prolonged disease duration [ 6 ]. In the current study, the overall prevalence rate for CVD in patients with SpA was 3.0%.…”

“…The association between traditional CV risk factors and SpA has been investigated for decades [ 5 , 6 ]. It is generally believed that SpA patients present with an atherogenic metabolic profile, with chronic systemic inflammation potentially exacerbating both past and future CV events.…”

“…Notably, indicators of systemic inflammation such as uveitis or elevated CRP levels have been linked to increased CVD in ankylosing spondylitis patients [ 8 , 37 , 38 ]. In that way, these patients might see atherosclerotic events more frequently [ 6 ]. However, conflicting outcomes in some studies [ 39 – 41 ] underscore methodological differences and patient characteristics, contributing to varied results.…”

“…Disease activity has been proposed as a potential risk factor for major adverse CV events (MACEs) in SpA patients, with higher disease activity potentially linked to an increased number of traditional CV risk factors [ 2 , 6 ]. While our study did not specifically analyze the correlation between the number of CV risk factors and disease characteristics, no significant association was found between disease activity based on BASDAI and ASDAS–CRP groups and CVD development.…”