Soluble concentrations of the interleukin receptor family member ST2 and β-blocker therapy in chronic heart failure

Circ Heart Fail. 2013 Nov;6(6):1206-13. doi: 10.1161/CIRCHEARTFAILURE.113.000457. Epub 2013 Oct 10.

Abstract

Background: Concentrations of soluble (s)ST2 predict prognosis in heart failure. We recently found changing doses of β-blocker (BB) may affect sST2 concentrations. It remains unclear whether sST2 concentrations identify benefit of BB therapy, however.

Methods and results: A total of 151 subjects with heart failure attributable to left ventricular systolic dysfunction were examined in this post hoc analysis; >96% were taking BB at enrollment. Medication regimen and sST2 values were obtained during 10 months. Cardiovascular events were examined as a function of baseline sST2 status (low ≤35 versus high >35 ng/mL) and final achieved BB dose (high ≥50 versus low <50 mg daily equivalent dose of metoprolol succinate). Patients with low sST2 titrated to high-dose BB had the lowest cardiovascular 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 cardiovascular event rate (2.08 events) and the highest cumulative hazard. Compared with low sST2/high-dose BB, those with high sST2 treated with low-dose BB had an odds ratio of 6.77 (P<0.001) for a cardiovascular event. Patients with low sST2/low-dose BB or high sST2/high-dose BB had intermediate odds ratios for cardiovascular events (P=0.18 and 0.02). Similar results were found for heart failure hospitalization and cardiovascular death.

Conclusions: Although BB therapy exerted dose-related benefits across all study participants, sST2 measurement identifies patients with chronic heart failure who may particularly benefit from higher BB doses.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00351390.

Keywords: biological markers; heart failure; prognosis; β-adrenergic blockers.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Aged
  • Biomarkers / blood
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Heart Failure / blood*
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Receptors, Cell Surface / blood*
  • Receptors, Interleukin-1 / blood
  • Stroke Volume / drug effects
  • Stroke Volume / physiology*

Substances

  • Adrenergic beta-Antagonists
  • Biomarkers
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Receptors, Cell Surface
  • Receptors, Interleukin-1

Associated data

  • ClinicalTrials.gov/NCT00351390