Clinical Impact Ratings

In patients with new-onset rheumatoid arthritis (RA), what is the risk for ischemic and nonischemic heart failure (HF)?


Inception cohort followed for a median of approximately 5 years.




 12 943 patients ≥ 18 years of age (mean age 58 y, 69% women) with new-onset RA (< 12 mo of symptoms) were identified from the Swedish Rheumatology Quality Register. The control group comprised 113 884 people from the general population who were matched on birth year, sex, and area of residency. Exclusion criteria were heart failure before start of follow-up.

Prognostic factors

New-onset RA, sex, age, and area of residency.


First-ever diagnosis of HF during inpatient or specialized outpatient care, categorized as ischemic HF (previous history of ischemic heart disease or diagnostic code for ischemic HF) or nonischemic HF (data obtained by linkage with National Patient Registry).

Main results

 The main results are in the Table. 332 (2.6%) patients with new-onset RA developed HF during follow-up.


Adults in Sweden with new-onset rheumatoid arthritis had increased risk for ischemic and nonischemic heart failure over 5 years of follow-up.

Risk for heart failure in Swedish adults with new-onset rheumatoid arthritis (RA)*

Outcomes Subgroup Event rate/1000 person-y At a median 5 y
Rheumatoid arthritis Control† Hazard ratio (95% CI)‡
HF All 4.1 3.2 1.2 (1.1 to 1.4)
Ischemic HF All 1.9 1.4 1.3 (1.1 to 1.5)
Nonischemic HF All 2.5 2.0 1.2 (1.0 to 1.4)
HF RF positive 4.0 3.2 1.4 (1.2 to 1.6)§
Ischemic HF RF positive 1.9 1.4 1.5 (1.2 to 1.8)§
Nonischemic HF RF positive 2.4 2.0 1.3 (1.1 to 1.6)§
HF RF negative 4.2 3.2 1.0 (0.83 to 1.2)§
Ischemic HF RF negative 1.8 1.4 0.97 (0.73 to 1.3)§
Nonischemic HF RF negative 2.6 2.0 1.0 (0.79 to 1.3)§

*HF = heart failure; RF = rheumatoid factor; other abbreviations defined in Glossary.

†113 884 people from the general population were matched on birth year, sex, and area of residency.

‡Adjusted for sex, age, and area of residency.

§Compared with the entire control group.

Source of funding: No external funding.
For correspondence: Dr. A. Mantel, Karolinska Institutet, Stockholm, Sweden. E-mail


Cardiovascular disease is a major extraarticular comorbidity and a leading cause of premature mortality in RA (1). Traditional risk factors are prevalent and mediate ischemic events and HF, but nonischemic, RA-associated inflammatory mechanisms may have an independent role in the pathogenesis of HF (2).
Mantel and colleagues used an impressive large-scale contemporary cohort study to confirm an increased risk for both ischemic and nonischemic HF (hazard ratio 1.33 to 1.45, narrow CI) in RF-positive patients recently diagnosed with RA. This is a new observation, which suggests inflammation-induced myocardial damage, possibly mediated by cytokines, such as tumor necrosis factor-α (TNF) (2).
At RA onset, risk for HF was not increased, and notably, incident nonischemic HF peaked in the first year of RA (hazard ratio 2.06) in correlation with markers of disease severity. In contrast, ischemic HF risk took > 10 years to evolve. Although 2.6% of patients in the cohort had HF, incidence is probably higher in patients with more severe disease and when asymptomatic HF (detected by screening echocardiography or B-type natriuretic peptide) is included.
The findings of Mantel and colleagues highlight that HF prevention is an additional compelling reason to diagnose and treat RA as early as possible, monitoring markers to ensure optimal disease suppression. In addition, strict attention to identifying and aggressively treating traditional ischemic risk factors seems essential; this may include use of corticosteroids as adjunctive therapy while trying to avoid high cumulative doses that may worsen atherosclerosis (3).
Biologic treatments, primarily TNF inhibitors, should be avoided in patients with previous HF; however, together with methotrexate, they are effective for treatment of patients with more severe new-onset RA where TNF may contribute to the cause of HF (2). Future studies may confirm a reduction in HF with the use of TNF inhibitors, in addition to the reduced risk for cardiovascular events.