Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: results of the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials

Cardiology. 2015;130(2):69-81. doi: 10.1159/000368221. Epub 2015 Jan 13.

Abstract

Objectives and background: We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials.

Methods: Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass grafting (CABG). Those assigned to STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction.

Results: In patients assigned to STICH Hypothesis 2 (n = 714), no genetic variant met the prespecified Bonferroni-adjusted threshold for statistical significance (p < 0.002); however, several variants met nominal prognostic significance: variants in the β2-adrenergic receptor gene (β2-AR Gln27Glu) and in the A1-adenosine receptor gene (A1-717 T/G) were associated with an increased risk of a subject dying or being hospitalized for a cardiac problem (p = 0.027 and 0.031, respectively). These relationships remained nominally significant even after multivariable adjustment for prognostic clinical variables. However, none of the 23 genetic variants influenced all-cause mortality or the combination of death or cardiovascular hospitalization in the STICH Hypothesis 1 population (n = 532) by either univariate or multivariable analysis.

Conclusion: We were unable to identify the predictive genotypes in optimally treated patients in these two ischemic heart failure populations.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Cohort Studies
  • Coronary Artery Bypass / methods
  • Coronary Artery Disease / genetics*
  • Female
  • Genetic Markers
  • Genotype*
  • Heart Failure / genetics*
  • Heart Failure / mortality
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Receptor, Adenosine A1 / genetics*
  • Receptors, Adrenergic, beta-2 / genetics*
  • Risk Factors
  • Treatment Outcome
  • Ventricular Dysfunction, Left / genetics*

Substances

  • Genetic Markers
  • Receptor, Adenosine A1
  • Receptors, Adrenergic, beta-2