Association Between Inflammatory Arthritis, Genetic Risk, and the Long-Term Risk of Degenerative Aortic Stenosis: A Prospective Cohort Study

Abstract

Background: Inflammatory arthritis is recognized to increase cardiovascular disease risk, but its association with degenerative aortic stenosis is not well understood.

Methods: This prospective cohort study used participants from the UK Biobank, focusing on 4 major types of inflammatory arthritis, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and gout. The primary outcome was the incidence of degenerative aortic stenosis. The primary analysis used Cox proportional hazards models to evaluate the association between inflammatory arthritis and the long-term risk of degenerative aortic stenosis, as well as to explore potential effect modifiers. Genetic risk was evaluated using polygenic risk scores and self-reported family history of cardiovascular diseases.

Results: The study included 497 567 participants, with 271 129 women (54.5%) and 468 015 White individuals (94.1%). The median age was 58 years. Over a median follow-up of 12.58 years, 4571 cases (0.9%) of degenerative aortic stenosis were identified. Compared with the control group, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and gout were associated with increased risks of degenerative aortic stenosis by 54% (hazard ratio [HR], 1.54 [95% CI, 1.28-1.85]), 72% (HR, 1.72 [95% CI, 1.19-2.50]), 176% (HR, 2.76 [95% CI, 1.43-5.32]), and 36% (HR, 1.36 [95% CI, 1.20-1.54]), respectively. These associations were independent of genetic risk (P for interaction>0.05). Additionally, we identified significant interactions between sex (P for interaction=0.036), age (P for interaction<0.001), and socioeconomic status (P for interaction=0.014) with rheumatoid arthritis, ankylosing spondylitis, and gout on the incidence of degenerative aortic stenosis, respectively.

Conclusions: Inflammatory arthritis is significantly associated with an increased long-term risk of degenerative aortic stenosis, underscoring the need for enhanced risk assessment for degenerative aortic stenosis in these populations.

Keywords: UK Biobank; aortic stenosis; degenerative; genetic risk; inflammatory arthritis; prospective cohort study.

Figure 1. Cumulative hazard of degenerative aortic stenosis among participants with or without rheumatoid arthritis (A), ankylosing spondylitis (B), psoriatic arthritis (C), and gout (D).

Group comparisons were conducted using log‐rank test.

Figure 2. Associations between rheumatoid arthritis (A), ankylosing spondylitis (B), psoriatic arthritis (C), and gout (D), with degenerative aortic stenosis in individuals with different genetic predispositions for degenerative aortic stenosis.

HR indicates hazard ratio.

Figure 3. Associations between rheumatoid arthritis (A), ankylosing spondylitis (B), psoriatic arthritis (C), and gout (D), with degenerative aortic stenosis in individuals with or without a family history of cardiovascular disease.

Results are presented as HR with 95% CI using a Cox proportional hazards model, adjusted for age, sex, ethnicity, Townsend deprivation index, education levels, body mass index, C‐reactive protein, estimated glomerular filtration rate, smoking and drinking status, physical activity, sleep and diet patterns, hypertension, diabetes, hyperlipemia. CVD indicates cardiovascular disease; and HR, hazard ratio.