Rheumatoid Arthritis Boosts Risk for Some Types of Heart Failure Save

Rates of heart failure with preserved ejection fraction (HFpEF) were doubled in patients with rheumatoid arthritis (RA) relative to other people of the same age and sex, researchers found.

On the other hand, risk for heart failure with reduced ejection fraction (HFrEF) wasn't significantly higher in the RA patients, according to Katherine Liao, MD, MPH, of Brigham and Women's Hospital in Boston, and colleagues.

With 1,445 RA patients and 4,335 matched controls and adjusting for standard cardiovascular risk factors, the hazard ratio for HFpEF was 1.99 in RA patients (95% CI 1.43-2.77), while the corresponding estimate for HFrEF was 1.45 (95% CI 0.81-2.60), the researchers reported in Arthritis Care & Research.

While an increased risk for HF overall had been well documented previously, few studies had examined whether it differed according to HF subtype. In the earlier work, the group explained, "HF was generally studied as a single entity and the differential risk of HF subtypes were limited due to the need for large RA cohorts with detailed clinical documentation of phenotypic data (i.e., echocardiograms, cardiology notes)."

But recent evidence around HFpEF -- which is marked by increased ventricular stiffness, reducing fill volume, rather than weakening outflow, as in HFrEF -- has implicated inflammation as a causative factor. Since RA is a systemic inflammatory disease, it made sense to suspect that it might preferentially boost HFpEF.

Liao and colleagues drew on data from the Mass General Brigham (MGB) Biobank, which has enrolled some 115,000 patients from the Harvard-affiliated Massachusetts General Hospital and Brigham and Women's Hospital. RA cases were identified from diagnostic codes and key words and terms elsewhere in patients' records, and the first recorded date for an RA diagnostic code became the index date for each case, if followed by another such code within 6 months. Each case was then matched with three non-RA patients by age, sex, and year of entry into the records system; the index date for controls was a clinical encounter close to that of the corresponding case. Participants already with HF at the index date were excluded.

Mean patient age at the index date was about 51 and 79% were women. Roughly 85% were white. Only 11% of the RA cases were using tumor necrosis factor inhibitors and 3% were on other advanced therapies, while from one-third to one-half were on steroids, methotrexate, or other conventional anti-rheumatic drugs.

HFpEF was defined as HF with ejection fraction ≥50%, while ejection fraction ≤40% was HFrEF; values in between were considered HF with moderately reduced ejection fraction. This latter group wasn't included in the analysis of HF subtypes, but it was counted in results for overall HF.

Among the 1,445 RA cases, 92 developed some type of HF during a median of 10.3 years of follow-up, as compared with 157 of the 4,335 controls (HR 1.79, 95% CI 1.38-2.32, after adjustment for cardiovascular risk factors). HFpEF was the dominant subtype in both RA patients and controls, accounting for 65% of HF cases in the former group and 59% in the latter.

Besides RA, other variables also appearing to raise rates of HFpEF were those commonly identified as risk factors: age, overweight/obesity, diabetes, hypertension, atrial fibrillation, and existing coronary artery disease. On the other hand, although chronic kidney disease also appears on lists of HFpEF risk factors, it wasn't one in the current data, with hazard ratios around 1.20 in RA patients and controls alike that did not approach statistical significance.

"RA can be considered a human model for inflammation, and findings from this study support the notion that chronic inflammation increases risk for HFpEF," Liao and colleagues concluded. "Since inflammation is modifiable with anti-inflammatory medications, further studies are needed to determine whether anti-inflammatory therapies have the potential to reduce risk of HFpEF in RA and other individuals with chronic inflammation."

Limitations to the study included its reliance on the MGB Biobank, whose participants may not be reflective of the general population (either for RA patients or overall). Also, the researchers noted, the study didn't account for post-baseline variables like drug treatments started during follow-up, nor did it consider RA disease activity.

If patients went outside the MGB system for cardiac care, HF diagnoses and subtyping would not be included in the Biobank records. Liao and colleagues acknowledged, too, that diagnostic codes aren't always reliable.