Clinical and Genetic Modifiers of Long-Term Survival in Heart Failure

Citations of this article
Mendeley users who have this article in their library.


Objectives: This study sought to identify genetic modifiers of β-blocker response and long-term survival in heart failure (HF). Background: Differences in β-blocker treatment effect between Caucasians and African Americans with HF have been reported. Methods: This was a prospective cohort study of 2,460 patients (711 African American, 1,749 Caucasian) enrolled between 1999 and 2007; 2,039 patients (81.7%) were treated with a β-blocker. Each was genotyped for β1-adrenergic receptor (ADRB1) Arg389>Gly and G-protein receptor kinase 5 (GRK5) Gln41>Leu polymorphisms, which are more prevalent among African Americans than Caucasians. The primary end point was survival time from HF onset. Results: There were 765 deaths during follow-up (median 46 months). β-blocker treatment increased survival in Caucasians (log-rank p = 0.00038) but not African Americans (log-rank p = 0.327). Among patients not taking β-blockers, ADRB1 Gly389 was associated with decreased survival in Caucasians (hazard ratio [HR]: 1.98, 95% confidence interval [CI]: 1.1 to 3.7, p = 0.03) whereas GRK5 Leu41 was associated with improved survival in African Americans (HR: 0.325, CI: 0.133 to 0.796, p = 0.01). African Americans with ADRB1 Gly389Gly GRK5 Gln41Gln derived a similar survival benefit from β-blocker therapy (HR: 0.385, 95% CI: 0.182 to 0.813, p = 0.012) as Caucasians with the same genotype (HR: 0.529, 95% CI: 0.326 to 0.858, p = 0.0098). Conclusions: These data show that differences caused by β-adrenergic receptor signaling pathway gene polymorphisms, rather than race, are the major factors contributing to apparent differences in the β-blocker treatment effect between Caucasians and African Americans; proper evaluation of treatment response should account for genetic variance. © 2009 American College of Cardiology Foundation.




Cresci, S., Kelly, R. J., Cappola, T. P., Diwan, A., Dries, D., Kardia, S. L. R., & Dorn, G. W. (2009). Clinical and Genetic Modifiers of Long-Term Survival in Heart Failure. Journal of the American College of Cardiology, 54(5), 432–444.

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free