Biomarkers of inflammation predict HF hospitalization and adverse outcomes in AF
Biomarkers of Inflammation and Risk of Hospitalization for Heart Failure in Patients With Atrial Fibrillation
Introduction and methods
HF and AF conditions often occur concomitantly, which predisposes patients to poor outcomes [1,2]. The event rates for HF hospitalization in patients with AF have remained high and unchanged over the last 2 decades [3,4]. In fact, HF accounts for a substantial amount of deaths in adequately coagulated AF patients . In addition, established therapies for patients with HF, such as beta-blockers, may be less effective in patients with AF and HF . So identifying potentially modifiable risk factors for HF hospitalization in patients with AF to improve clinical outcomes in these patients is necessary.
Biomarkers of inflammation have been associated with atherothrombotic events in multiple patient populations and with HF hospitalization in patients with a prior MI [8-12]. Whether poor outcomes in patients with AF, in whom pathophysiologic patterns are mostly unrelated to atherosclerosis and ischemia, can be predicted by these biomarkers has not been investigated.
This prospective study used a combined data set of patients with established AF who were included in the BEAT-AF and Swiss-AF multicenter cohort studies between January 2010 and August 2017. AF patients with any acute illness or hospitalization for all-causes were enrolled at least 4 weeks after the acute episode or after hospital discharge. The prespecified primary outcome was hospitalization for HF, defined as an unplanned hospital visit with at least one overnight stay due to signs of HF. The secondary prespecified outcomes were all-cause mortality, CV death, a composite endpoint of ischemic stroke, MI, or CV death, and a composite endpoint of ischemic stroke or systemic embolism. Baseline plasma levels of hs-CRP and IL-6 were assessed (median hs-CRP: 1.64 mg/L [IQR: 0.81-3.69 mg/dL]) and median IL-6: 3.42 pg/mL [IQR: 2.14-5.60 pg/mL). Patients (n=3784) were stratified according to an inflammation score ranging from 0 to 4 (1 point for each biomarker between the 50th and 75th percentile and 2 points for each biomarker above the 75th percentile). Median (IQR) follow-up was 4 years (2.9-5.1 years).
- There were 447 patients (11.8%) with at least one hospitalization for HF, which corresponded to an overall incidence rate of 3.04 per 100 person-years. The incidence rate across inflammation score categories increased from 1.34 (score 0) to 7.31 (score 4) per 100-person-years.
- 1 SD increase in IL-6 or hs-CRP was significantly associated with increased hospitalization due to HF (aHR 1.48, 95% CI: 1.35-1.62, P<0.001 for log-transformed IL-6 and aHR 1.22 95% CI: 1.11-1.34, P<0.001 for log-transformed hsCRP).
- There was a non-linear relationship for log-transformed IL-6 levels and HF hospitalization, suggesting less steep increases in risk at higher IL-6 levels (β=-0.086, SE=0.031, P=0.006).
- Increase in inflammation score per 1-point was associated with higher risk of HF hospitalization after multivariable adjustment (score of 4 vs. score of 0: aHR: 2.43, 95%CI: 1.80-3.30, P for trend<0.001).
- After multivariable adjustment, IL-6 and hs-CRP were significantly associated with the secondary outcomes all-cause mortality, CV death, and the composite endpoint ischemic stroke, MI, or CV death (all P<0.001). Only hs-CRP was associated with the composite endpoint ischemic stroke or systemic embolism (P=0.04).
- Also, inflammation score was associated with all-cause mortality, CV death, and the composite outcome ischemic stroke, MI, or CV death (all P for trends<0.001) and ischemic stroke or systemic embolism (P for trend=0.03).
- Hs-CRP and IL-6 were both stronger associated with HF hospitalization in patients without a history of HF (both biomarkers P interactions=0.04) or coronary artery disease (both biomarker P interactions=0.001).
This combined cohort study showed that elevated levels of IL-6 and hs-CRP were associated with increased HF hospitalization and other adverse outcomes in patients with AF. The risk for HF hospitalization increased with increasing inflammation scores for IL-6 and hs-CRP.
The authors further stated that RCTs need to determine whether treatment targeted at inflammation improve clinical outcomes in patients with AF.