Author + information
- Brian B. Løgstrup, MD, PhD∗ (, )
- Torkell Ellingsen, MD, PhD,
- Alma B. Pedersen, MD, PhD, DMSc,
- Anders Kjærsgaard, Biostatistician, PhD,
- Hans Erik Bøtker, MD, PhD, DMSc and
- Michael Maeng, MD, PhD, DMSc
- ↵∗Department of Cardiology, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, Skejby, Aarhus N, 8200, Denmark
Ischemic heart disease (IHD) and heart failure (HF) may be extra-articular manifestations of rheumatoid arthritis (RA) (1). The observed increased risk of HF among patients with RA may not be explained solely by IHD (2). Nonischemic HF is associated with RA severity, suggesting that RA-related factors, the autoimmune processes, drive the risk of this HF phenotype. The aim of this population-based, cohort comparison study, based on all patients diagnosed with RA in Denmark over a 21-year period, was to determine the prevalence of HF and IHD before and the incidence after the established RA diagnosis. Moreover, we compared patients with RA versus age- and sex-matched persons from the general population without RA.
Our study was conducted by using prospectively collected data from population-based health registries. The Danish National Patient Register contains data on all inpatient hospitalizations in Denmark since 1977 and on all outpatient and emergency department visits to hospital specialist clinics since 1995. Using this register, we identified all patients with a first-time primary or secondary diagnosis of RA in Denmark since 1995 until July 2016. Each patient with RA was matched on age and sex at the date of the RA diagnosis (index date) with 5 persons from the general population without a RA diagnosis in the entire study period. HF and IHD were defined as any new inpatient discharge diagnosis of HF or IHD after the RA index date. Information on comorbid conditions for both cohorts was sampled by using the Charlson comorbidity index.
Crude and adjusted proportional subdistribution hazards ratios (sHRs) with 95% confidence intervals (CIs) accounting for competing risk of death were calculated to assess the risk of HF and IHD by comparing patients with RA and the comparison cohort without RA in a pre-defined 0 to 10-year time period after the index date. The adjusted models included age and sex by design, and Charlson comorbidity index as an additional factor.
We identified 52,830 patients with RA and 264,355 matched members of the comparison cohort followed up for a mean duration of 6.1 and 6.5 years, respectively. Of the patients with RA, the mean age was 59.9 years, and 69.3% were female; in the comparison cohort index data (i.e., date of RA diagnosis), mean age was 59.9 years and 69.3% were female.
We identified 745 patients (1.4%) with HF before the diagnosis of RA and 2,074 patients (0.8%) with HF in the comparison cohort (p = 0.15). A total of 266 patients (0.5%) had IHD before the diagnosis of RA compared with 1,026 patients (0.4%) in the comparison cohort (p = 0.82).
After removing the patients with previous HF (n = 745) and their control subjects (n = 3,662), as well as control subjects with previous HF (n = 2,074), the Kaplan-Meier estimates of cumulative incidence of HF during 10 years’ follow-up were 6.3% (95% CI: 6.1% to 6.6%) in patients with RA and 4.1% (95% CI: 4.0% to 4.1%) in the comparison cohort, corresponding to an adjusted sHR of 1.49 (95% CI: 1.43 to 1.56) (Figure 1A).
After removing patients with RA and previous IHD (n = 266) and their control subjects (n = 1,324), as well as control subjects with previous IHD (n = 1,026), the Kaplan-Meier estimates of cumulative incidence of IHD during follow-up was 5.3% (95% CI: 5.1% to 5.5%) in patients with RA and 3.9% (95% CI: 3.8% to 3.9%) in the comparison cohort, corresponding to an adjusted sHR of 1.34 (95% CI: 1.28 to 1.40) (Figure 1B).
When restricting analyses to patients without previous heart disease (excluding previous HF and IHD; RA group = 51,819; comparison group = 256,653), 2,047 patients with RA were diagnosed with IHD during the 10-year follow-up. Of these, 291 patients (14.2%) were also diagnosed with HF subsequent to IHD. In the comparison cohort, 7,193 (2.8%) were diagnosed with IHD during the 10-year follow-up with only 850 (0.3%) having a HF diagnosis subsequent to IHD. The risk of HF thus seems to be much higher among patients with RA and IHD than in their counterparts from the comparison cohort.
Among 49,812 patients with RA without previous heart disease and without IHD during the 10-year follow-up, 1,895 patients (3.8%) were diagnosed with HF during the same follow-up period. In the comparison cohort, 5,797 patients (2.3%) were diagnosed with HF during the same follow-up period; that is, the increased risk of HF in the RA cohort versus the comparison was much smaller in patients with RA without IHD.
In conclusion, RA patients have a similar prevalence of HF and IHD before the RA diagnosis as a matched comparison cohort, but patients with RA are at increased risk of HF and IHD up to 10 years after a diagnosis of RA.
Please note: The study was supported by the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
- Gabriel S.E.
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