Soluble Concentrations of the Interleukin Receptor Family Member ST2 and Beta Blocker Therapy in Chronic Heart Failure

Study Questions:

What is the interplay between the soluble form of ST2 (sST2) and beta-adrenergic blocker (BB) therapy in patients with chronic heart failure (CHF)?

Methods:

A total of 151 subjects with HF due to left ventricular systolic dysfunction were examined in this post-hoc analysis; >96% were taking BBs at enrollment. Medication regimen and sST2 values were obtained over 10 months. Cardiovascular (CV) events were examined as a function of baseline sST2 status (“low” ≤35 vs. “high” >35 ng/ml) and final achieved BB dose (“high” ≥50 vs. “low” <50 mg daily equivalent dose of metoprolol succinate). Univariable and multivariable logistic regression analyses were performed, modeling the association between baseline sST2 values, final achieved BB dose, and the presence of any CV events.

Results:

Patients with low sST2 titrated to high-dose BB had the lowest CV event rate at 0.53 events (p = 0.001), and lowest cumulative hazard (p = 0.003). Those with low sST2/low-dose BB, or high sST2/high-dose BB had intermediate outcomes (0.92 and 1.19 events). Patients with high sST2 treated with low-dose BB had the highest CV event rate (2.08 events) and highest cumulative hazard. Compared to low sST2/high-dose BB, those with high sST2 treated with low-dose BB had an odds ratio (OR) of 6.77 (p < 0.001) for a CV event. Patients with low sST2/low-dose BB or high sST2/high-dose BB had intermediate odds ratios for CV events (p = 0.18 and 0.02). Similar results were found for HF hospitalization and CV death.

Conclusions:

The authors concluded that sST2 measurement identifies CHF patients who may particularly benefit from higher BB doses.

Perspective:

This study suggests that while BB therapy exerted benefit across all strata of risk within categories of low- or high-dose BB therapy, patients were particularly at high risk for CV events if their baseline sST2 values were above 35 ng/ml. Those with the highest risk for subsequent CV events were identified by an elevated baseline sST2 value, but this risk was not entirely realized in those titrated to higher dose BB. This suggests that biomarker concentrations may identify a risk that may be mitigated by specific drug therapy, raising the possibility that higher dose BB therapy may be particularly efficacious in the face of an elevated sST2, and open up the possibility for biomarker-guided HF management.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension

Keywords: Heart Diseases, Biological Markers, Troponin I, Heart Failure, Cardiovascular Diseases, Receptors, Interleukin, Energy Metabolism, Ventricular Dysfunction, Left, Hypertension


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