Rheumatoid Arthritis Increases Nonischemic Heart Failure Risk

Patients with rheumatoid arthritis (RA) have an increased risk of nonischemic heart failure (HF)-associated disease severity, according to a recent study from Swedish researchers published in the Journal of the American College of Cardiology.¹

Ängla Mantel, MD, from the department of medicine Solna and the clinical epidemiology unit at Karolinska Institutet in Stockholm, Sweden, and colleagues evaluated the risk of ischemic and nonischemic HF in 45,982 patients with established RA in a 1:10 ratio with 385,551 comparator participants as well as 12,943 patients with new-onset RA and 113,884 comparator participants. Ischemic and nonischemic classifications were determined by evidence of ischemic heart disease (IHD) through registry linkage. Patients had a median follow-up of 5 years and a median disease duration of 3.4 years (interquartile range 0.3-7.7 years), with 72% of patients in the established RA group and 66% of patients in the new-onset RA group having rheumatoid factor-positive RA.

The researchers found 2.8% of established RA patients (n=41) and 2.5% of comparator participants (n=217) had diagnosed HF prior to follow-up (odds ratio [OR] 1.01; 95% CI, 0.92-1.14), whereas 2.6% (n=332) of new-onset RA patients and 2.0% of their comparator participants (n=2325) developed HF during follow-up (hazard ratio [HR]1.22; 95% CI, 1.09-1.37). During follow-up, 1.2% of new-onset patients (n=152) and 0.9% of comparator participants (n=1025) developed ischemic HF (HR 1.27; 95% CI, 1.07-1.51), while 1.5% of new-onset patients with RA (n=184) and 1.2% of comparator participants (n=1312) developed nonischemic HF during follow-up (HR 1.22; 95% CI, 1.04-1.43).

The researchers found the relative risk of HF increased after RA diagnosis, with nonischemic HF increasing approximately 2-fold (HR 2.06; 95% CI, 1.37-3.20), whereas relative risk of ischemic HF “remained and increased after 10 years with RA,” according to the researchers’ analysis. Patients with RA of any duration had a 2.5% rate of HF (n=1129) and their comparator participants had a rate of 1.4% (n=5193) for HF (HR 1.77; 95% CI, 1.69-1.85), while 1.2% of patients with RA (n=529) developed ischemic HF compared with 0.8% (n=2883) of comparator participants (HR 1.88; 95% CI, 1.71-2.0) and 1.4% of patients with RA (n=596) developed ischemic HF compared with 0.8% (n=2883) of comparator participants (HR 1.71; 95% CI, 1.57-1.87).

Summary and Clinical Applicability

“Patients with RA are at increased risk of both ischemic and nonischemic HF, which does not appear to be readily explained by established risk factors for HF,” Dr Mantel and colleagues wrote in their study. “The risk increase, especially in the absence of IHD, develops rapidly after RA onset and is associated with high inflammatory and disease activity. From a clinical point of view, our findings emphasize the importance of clinical awareness and adequate assessment of HF in patients with RA.”

In a related commentary, Paul Heidenreich, MD, from the VA Palo Alto Health Care System in California, said that the results of this study show “inflammation is part of a direct causal pathway of heart failure.”²

Dr Heidenreich noted that depending on whether inflammation is a direct cause of HF or a marker of disease, a patient should be receiving immune modulating treatment or screened for potentially undiagnosed left ventricular dysfunction, respectively.

“Although effective treatments for heart failure targeting inflammation are at least years away, an immediate clinical implication of the association of rheumatoid arthritis and heart failure is the potential for improved diagnosis of left ventricular dysfunction,” Dr Heidenreich wrote in his analysis.

Study Limitations

• Patients in this study were included only if they had a known diagnosis of IHD, but the hospital data used may have missed some patients with IHD, especially patients who had experienced silent myocardial infarctions or had subclinical IHD
• Because patients with RA are also more likely to have extensive subclinical IHD, the researchers may have overestimated rates of HF in this population

Disclosures

Dr Lund has received grants and speaker’s honoraria from AstraZeneca and Novartis, and has served as a consultant to AstraZeneca, Novartis, Relypsa, and Vifor Pharma. Dr Askling has received research grants from Abbvie, Pfizer, Union Chimique Belge, Roche, Merck, Janssen, and AstraZeneca.

References

1. Mantel Ä, Holmqvist M, Andersson DC, et al. Association between rheumatoid arthritis and risk of ischemic and nonischemic heart failure. J Am Coll Cardiol. 2017;69(10):1275-1285. doi:10.1016/j.jacc.2016.12.033
2. Heidenreich P. Inflammation and heart failure: therapeutic or diagnostic opportunity? J Am Coll Cardiol. 2017;69(10):1286-1287. doi:10.1016/j.jacc.2017.01.013

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