Inflammation Associated with Heart Failure in Rheumatoid Arthritis

Heart failure is a major cause of morbidity and mortality in Rheumatoid Arthritis (RA), but data for the subtypes of heart failure, with preserved ejection fraction versus reduced ejection fraction, have been sparse.

The two subtypes of heart failure are thought to differ in pathophysiology. The subtype with reduced ejection fraction is believed to result from ischemic factors, whereas with preserved ejection fraction, the primary driver is considered to be inflammation, reflected by the presence of inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α.

Rheumatologists at the Brigham and Women’s Hospital (Boston, MA, USA) and their colleagues explored the association with heart failure in RA that could be specific to the subtype with preserved ejection fraction. Heart failure with reduced ejection fraction was defined as an ejection fraction of 40% or less, while preserved ejection fraction was 50% or higher. Those whose ejection fraction was 40%-50% were classified as mid-range and were not considered a specific subtype. Elevated inflammation at the time of RA diagnosis was defined as an erythrocyte sedimentation rate (ESR) of 20-30 mm/h, and/or a C-reactive protein (CRP) of 8-10 mg/L. The analysis included 9,087 RA patients, whose median follow-up was 10.7 years. Three-quarters were women, mean age was 56, and 55% were seropositive.

The scientists reported that the median ESR at baseline was 24.7 mm/h, and median CRP was 5.9 mg/L. Patients whose inflammatory markers were elevated typically were older, female, seropositive, and taking corticosteroids. They also more often had cardiovascular comorbidities such as hypertension, coronary artery disease, and diabetes. During 10 years of follow-up, heart failure was diagnosed in 749 patients, for an incidence rate of 11 per 1,000 person-years. The heart failure developed within five years of RA diagnosis in 379 patients. Ejection fraction was reduced in 127 and preserved in 561; the remainder of patients had mid-range ejection fraction.

In a secondary analysis that considered tertiles of inflammation, higher levels of inflammation were significantly associated with any heart failure at years 5 and 10, and also for the subtype with preserved ejection fraction; however, no association was seen among patients with reduced ejection fraction. Other factors that influenced heart failure risk included lower risks with seropositivity and the use of methotrexate, and higher risk with coronary artery disease, particularly among patients with reduced ejection fraction. That observation supports the concept that ischemia, rather than inflammation, is central to the pathogenesis of the reduced ejection fraction subtype of heart failure. After adjustment for demographics, traditional risk factors for heart failure, and RA disease factors, the hazard ratio for heart failure at 10 years was 1.46 (95% CI 1.13-1.90) among patients with elevated levels of inflammatory markers.

The authors concluded that a sizeable number of patients developed heart failure by five years suggested that evaluations for risk factors for heart failure in RA may need to begin earlier than the usual 10 years Moreover, although this study was conducted in RA patients, the findings also may inform the effect of chronic inflammation on heart failure risk in the general population without RA. The study was published on October 9, 2021 in the journal Arthritis Care & Research.

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