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Natriuretic peptide system gene variants are associated with ventricular dysfunction after coronary artery bypass grafting.

ABSTRACT:

Background

Ventricular dysfunction (VnD) after primary coronary artery bypass grafting is associated with increased hospital stay and mortality. Natriuretic peptides have compensatory vasodilatory, natriuretic, and paracrine influences on myocardial failure and ischemia. The authors hypothesized that natriuretic peptide system gene variants independently predict risk of VnD after primary coronary artery bypass grafting.

Methods

A total of 1,164 patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass at two institutions were prospectively enrolled. After prospectively defined exclusions, 697 patients of European descent (76 with VnD) were analyzed. VnD was defined as need for at least 2 new inotropes and/or new mechanical ventricular support after coronary artery bypass grafting. A total of 139 haplotype-tagging single nucleotide polymorphisms (SNPs) within 7 genes (NPPA, NPPB, NPPC, NPR1, NPR2, NPR3, CORIN) were genotyped. SNPs univariately associated with VnD were entered into logistic regression models adjusting for clinical covariates predictive of VnD. To control for multiple comparisons, permutation analyses were conducted for all SNP associations.

Results

After adjusting for clinical covariates and multiple comparisons within each gene, seven NPPA/NPPB SNPs (rs632793, rs6668352, rs549596, rs198388, rs198389, rs6676300, rs1009592) were associated with decreased risk of postoperative VnD (additive model; odds ratios 0.44-0.55; P = 0.010- 0.036) and four NPR3 SNPs (rs700923, rs16890196, rs765199, rs700926) were associated with increased risk of postoperative VnD (recessive model; odds ratios 3.89-4.28; P = 0.007-0.034).

Conclusions

Genetic variation within the NPPA/NPPB and NPR3 genes is associated with risk of VnD after primary coronary artery bypass grafting. Knowledge of such genotypic predictors may result in better understanding of the molecular mechanisms underlying postoperative VnD.

SUBMITTER: Fox AA

PROVIDER: S-EPMC2735337 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Elevated B-type natriuretic peptide is associated with increased morbidity and mortality in ambulatory patients with congestive heart failure or acute coronary syndromes. Its utility in predicting adverse cardiac surgical outcomes is less certain. We hypothesized that preoperative plasma B-type natriuretic peptide would independently predict in-hospital postoperative ventricular dysfunction, hospital stay, and up to 5-year mortality after primary coronary artery bypass grafting.This is a prospective, longitudinal study of 1023 patients at two institutions undergoing primary coronary artery bypass grafting with cardiopulmonary bypass. Ventricular dysfunction was defined as requirement for at least two inotropes or new intra-aortic balloon pump or ventricular assist device support after coronary artery bypass grafting. Multivariable analyses assessed independent roles of preoperative B-type natriuretic peptide in predicting postoperative ventricular dysfunction, hospital stay, and 5-year all-cause mortality.Preoperative plasma B-type natriuretic peptide concentration predicted ventricular dysfunction, hospital stay, and mortality in univariate and multivariable analyses. Logistic regression demonstrated preoperative B-type natriuretic peptide to independently predict ventricular dysfunction (odds ratio 1.92, 95% confidence interval 1.12-3.29, P = .018), after adjustment for preoperative left ventricular ejection fraction, congestive heart failure severity, and other clinical predictors. Multivariable Cox proportional hazards models showed preoperative B-type natriuretic peptide to independently predict hospital stay (hazard ratio 1.42, 95% confidence interval 1.18-1.72, P = .0002) and mortality (hazard ratio 1.89, 95% confidence interval 1.08-3.33, P = .026).Preoperative plasma B-type natriuretic peptide independently predicted in-hospital ventricular dysfunction, hospital stay, and up to 5-year all-cause mortality after primary coronary artery bypass grafting.