NEWS & PERSPECTIVE
Rheumatoid arthritis is associated with an increased risk of heart failure
The burden of heart failure (HF) is increasing worldwide.1 Cardiovascular disease (CVD) risk scores have identified rheumatoid arthritis (RA) patients to be at higher risk of developing HF.2 Studies have shown a 50% higher risk of CVD-associated death among RA patients and a similar increased risk of both ischemic heart diseases and cerebrovascular diseases.3 Recent evidence indicated that there was elevated C‐reactive protein (CRP) in the blood of CVD and RA patients. Lately, a retrospective study aimed at determining the relationship between inflammatory conditions and HF risk has established an association between higher CRP and increased HF risk in patients with RA. Furthermore, the data highlighted the potential of adopting therapies targeted to lower inflammation, such as methotrexate treatment, as a strategy to reduce the risk of both inflammatory disorders and cardiovascular disease.4
Inflammation has been implicated as one of the mechanisms to cause HF, particularly HF with preserved ejection fraction (HFpEF). Patients with HFpEF exhibit heterogeneous syndromes with numerous underlying causes and pathophysiological abnormalities. As such, there is a current unmet need towards the diagnosis and treatment of HFpEF patients. Thus, a more comprehensive understanding between the immunological mechanism related to left ventricular remodeling and progression of HF is needed to facilitate the development of new treatments.1
Conversely, over the past few years, a higher risk of CVD-associated death has been observed in patients which chronic inflammatory disease, namely RA. A recent meta-analysis illustrated that patients with RA were at a 50% higher risk of developing CVD such as ischemic heart diseases and cerebrovascular diseases. Besides, there was an increased level of an inflammatory marker CRP in the blood of RA patients. Similarly, elevated levels of CRP are a vital indicator of mortality outcomes in HF patients.4
To get the fuller picture, Dr. Michael Ahlers, Vanderbilt University School of Medicine, Nashville, and colleagues aimed to determine the link between inflammatory conditions and HF risk by employing a human model consisting of RA patients. Dr. Ahlers shared, "RA is a prototypic chronic inflammatory disorder that has been associated with an increased risk for HF independent of traditional cardiovascular risk factors, including coronary artery disease. Therefore, patients with RA may represent a human model for studying how chronic inflammation contributes to HF, and possibly HFpEF."
The study consisted of 2 key areas. The first was a retrospective analysis of the Vanderbilt University Medical Center (VUMC) electronic health record comparing patients with RA (n=9,889) and their corresponding control without the autoimmune disease (n=9,889), matched for age, sex and race. Exclusion criteria included patients with pre-existing HF or preliminary RA diagnosis. International Classification of Diseases, Ninth Revision (ICD-9), codes and medications determined the incident of HF. For the second area of investigations, experiments using proteomics and cardiac magnetic resonance imaging were used on the second group of enrolled patients (n=115) with and without RA, to determine the relationship between expressed inflammation markers with cardiac structure and function.4
The retrospective analysis revealed a 21% greater risk of HF (95% CI: 3%-42%) in patients with RA obtained from over 177,566 person-years of follow-up, regardless of traditional cardiovascular risks such as diabetes, hypertension, dyslipidemia, smoking, and family history of premature heart disease. Moreover, there was a link between RA patients with higher CRP levels and a significantly greater risk of HF (p<0.001). The study also found elevated levels of artemin in patients with RA in contrast to patients in the control group (p=0.009). Consequently, RA patients with higher levels of artemin also had poor ventricular end-systolic elastance (p=0.044) and ventricular-vascular coupling ratio (p=0.031).4
Interestingly, patients treated with the anti-inflammatory drug methotrexate were associated with a substantial lower HF risk by 25% (p=0.021). Also, there was a decrease of HFpEF risk in patients treated with methotrexate. However, risk of HFpEF for patients treated with antimalaria medications such as hydroxychloroquine was increased.4
In summary, the study established a correlation between RA and greater risk of HF. Higher levels of CRP in RA patients were found to be contributing the higher HF risk. Therefore, adopting the anti‐inflammatory therapies has the potential to lower HF risk, specifically for patients with HFpEF.
- Dutka M et al. Various aspects of inflammation in heart failure. Heart Fail Rev. 2020; 25: 537-548.
- Vazquez R et al. The MUSIC Risk score: a simple method for predicting mortality in ambulatory patients with chronic heart failure. Eur Heart J. 2009; 30:1088-96.
- Avina-Zubieta A et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008; 15;59(12):1690–1697.
- Ahlers M et al. Heart Failure Risk Associated with rheumatoid arthritis-related chronic inflammation. J Am Heart Assoc. 2020;9(10).
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