Biomarkers May Predict Hospitalization Among Persons With Heart Failure, AFib

Elevated levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), both inflammatory biomarkers, may be able to accurately predict hospitalization risk among patients with heart failure and comorbid atrial fibrillation (AFib), reports a study in the Journal of the American Heart Association.

“Heart failure and AFib are closely linked, and both conditions often occur concurrently, predisposing affected patients to poor outcomes,” the investigators wrote. “In addition, established therapies providing a survival benefit in most patients with heart failure, may be less effective in patients with heart failure and concomitant AFib. Thus, there is an unmet clinical need to identify potentially modifiable risk factors for heart failure hospitalization in patients with AF.”

For this prospective cohort study, the investigators enrolled 3784 patients who all had at least 1 baseline measure of hs-CRP or IL-6. This was a combined data set of patients from the BEAT-AF and Swiss-AF studies conducted in Switzerland between January 2010 and August 2017. Multivariable Cox proportional hazard models were incorporated to find any individual associations with the biomarkers and total inflammation score with hospitalization from heart failure.

The median (interquartile range [IQR]) overall plasma level for hs-CRP was 1.64 (0.81-3.69) mg/L, and the level for IL-6 was 3.42 (2.14-5.60) pg/mL. An overall incidence of 3.04 hospitalizations for heart failure per 100 person-years was seen, as was a consistently higher total of hospitalizations with increasing inflammation scores.

“We calculated an inflammation score ranging from 0 to 4 (1 point for each biomarker between the 50th and 75th percentile, 2 points for each biomarker above the 75th percentile),” the authors noted.

Hospitalizations for heart failure rose an astonishing 446%, from 1.34 to 7.31 per 100 person-years, across inflammation score categories.

Multivariable adjustment resulted in a probable link between hs-CRP and IL-6 and higher risk of heart failure–related hospitalization:

• Per increase in 1 SD, there was a 22% greater risk associated with hs-CRP (adjusted HR [aHR], 1.22; 95% CI, 1.11-1.34 for log-transformed hs-CRP).
• Per increase in 1 SD, there was a 48% greater risk associated with IL-6 (aHR, 1.48; 95% CI, 1.35-1.62 for log-transformed IL-6).

And when comparing risks associated with the lowest inflammation score and the highest score, there was a 143% greater risk of hospitalization linked to the highest score (aHR, 2.43; 95% CI, 1.80-3.30; P <.001).

The median (IQR) age of the patients was 72 (66-78) years, 68.8% had arterial hypertension, 24% had a history of heart failure, 26.6% had coronary artery disease (CAD), and 23% had permanent AFib. In this last group at baseline, 51.8% were in sinus rhythm and 43.6%, AFib or atrial flutter. The mean (SD) overall CHA₂DS₂-VASc score at baseline was 3.2 (1.7).

The follow-up period was a median (IQR) of 4 (2.9-5.1) years, during which 11.8% of the study patients had at least 1 heart failure–related hospitalization.

In addition, the authors noted, “both hs-CRP and IL-6 were significantly associated with all-cause mortality, cardiovascular death, and the composite of ischemic stroke, myocardial infarction, or cardiovascular death after multivariable adjustment (all P <.001).”

Of especial note was that absent a history of heart failure or CAD, a strong association was still seen between the 2 biomarkers and heart failure hospitalization (P <.05), while no such associations were seen for either when sex, AFib type, and history of stroke or heart attack were accounted for.

However, further study is needed into the link between these inflammatory biomarkers and hospitalization risk, because uncertainty remains about the potential for treatments that target inflammation pathways to improve patient outcomes. “There has been ongoing controversy aroundthe inflammatory hypothesis in cardiovascular disease,” the authors concluded.

Reference

Benz AP, Aeschbacher S, Krisai P, et al; BEAT-AF, Swiss-AF Investigators. Biomarkers of inflammation and risk of hospitalization for heart failure in patients with atrial fibrillation. J Am Heart Assoc. Published online April 10, 2021. doi:10.1161/JAHA.120.019168