NEW population-level evidence from the UK Biobank shows that people with rheumatoid arthritis (RA) face a substantially higher risk of multiple cardiovascular diseases, with genetic analyses suggesting that some of these associations may be causal rather than explained by shared risk factors alone.
Cardiovascular disease is a leading cause of morbidity and mortality in RA, but disentangling the effects of inflammation from lifestyle and socioeconomic factors has been challenging. To address this, researchers combined long-term observational data with Mendelian randomisation analyses to examine both associations and potential causality between RA and cardiovascular outcomes.
Large-Scale UK Biobank Analysis
The study included 1,436 participants with RA and nearly 477,000 controls without RA, followed prospectively for an average of 14 years. RA status was identified using linked hospital records, self-reported diagnoses, and medication data, while cardiovascular outcomes were captured through hospital records.
At baseline, people with RA were more likely to live in socioeconomically deprived areas, have lower physical activity levels, and smoke, and they had a higher prevalence of cardiovascular disease. Importantly, analyses were adjusted for these and other demographic and clinical confounders.
Elevated Risk Across Multiple Cardiac Conditions
After full adjustment, RA was associated with significantly higher risks of several incident cardiovascular conditions. The strongest associations were seen for pericardial disease, where risk was more than doubled, as well as heart failure and acute myocardial infarction. Increased risks were also observed across a broader spectrum of cardiovascular outcomes, reinforcing the systemic impact of RA beyond the joints.
To explore whether these associations reflected causality, the investigators conducted Mendelian randomisation analyses using large genetic datasets. These analyses supported causal links between RA and acute myocardial infarction, ischaemic heart disease, and arrhythmias, suggesting that RA-related biological pathways may directly contribute to cardiovascular pathology.
Imaging Findings Offer Reassurance
Among participants who underwent cardiovascular magnetic resonance imaging, the study did not identify significant associations between RA and measures of cardiac structure or function. This finding suggests that while RA increases the risk of developing clinical cardiovascular disease, it may not be associated with detectable subclinical changes on cardiac imaging in this cohort.
Implications for Clinical Care
The findings reinforce the need for proactive cardiovascular risk assessment and management in people with RA. While traditional risk factors remain important, the results indicate that RA itself contributes independently to cardiovascular risk, likely through chronic systemic inflammation and immune-mediated mechanisms.
The authors conclude that heightened awareness, early screening, and aggressive control of both inflammation and cardiovascular risk factors are essential to improving long-term outcomes in RA. By combining observational data with genetic evidence, the study strengthens the case for viewing cardiovascular disease as a core comorbidity in rheumatoid arthritis rather than a secondary concern.
Reference
Salatzki J et al. Rheumatoid arthritis and cardiovascular disease associations in the UK Biobank. BMC Med. 2025;23(1):605.
