Open AccessEffect of the Asp 298 Variant of Endothelial Nitric Oxide Synthase on Survival for Patients With Congestive Heart Failure
Author(s) -
Dennis M. McNamara,
Richard Holubkov,
Lisa A. Postava,
Rama Ramani,
Karen Janosko,
Michael A. Mathier,
Guy A. MacGowan,
Srinivas Murali,
Arthur M. Feldman,
Barry London
Publication year - 2003
Publication title -
circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.795
H-Index - 607
eISSN - 1524-4539
pISSN - 0009-7322
DOI - 10.1161/01.cir.0000060540.93836.aa
Subject(s) - medicine , heart failure , ejection fraction , cardiology , cardiomyopathy , heart transplantation , nitric oxide synthase , population , endothelial dysfunction , nitric oxide , clinical endpoint , randomized controlled trial , environmental health
Background— Significant variation exists within the endothelial nitric oxide synthase (NOS3) gene that may influence cardiovascular risk. The Asp298 variant of NOS3 has a shorter half-life in endothelial cells. Given the importance of nitric oxide in the heart failure syndrome, we evaluated the effect of this variant on event-free survival in a population with systolic dysfunction.Methods and Results— Four hundred sixty-nine patients (72% male, 49% ischemic; mean age, 56±12 years) with systolic dysfunction (left ventricular ejection fraction ≤0.45) were enrolled in a study of Genetic Risk Assessment of Cardiac Events (GRACE). The polymorphism in exon 7 of NOS3, a G-T transition at position 894 that results in a Glu to Asp amino acid substitution for codon 298, was genotyped and subjects were followed prospectively to the end point of death or heart transplantation. Event-free survival was compared on the basis of the presence (group 1, n=266) or absence (group 2, n=203) of the Asp298 variant. Event-free survival was significantly poorer in patients with the Asp298 variant (percent event-free survival group 1 at 1/2/3 years=78/65/54; group 2=82/72/64,P =0.03). In subset analysis, the adverse impact of the Asp298 variant was primarily in patients with nonischemic cardiomyopathy (group 1=82/73/63; group 2=87/79/71,P =0.03) and was not apparent among patients with ischemic heart disease (group 1=75/59/47; group 2=74/62/54,P =0.71).Conclusions— For patients with heart failure caused by systolic function, the Asp298 variant of NOS3 is associated with poorer event-free survival, particularly in patients with nonischemic cardiomyopathy.