Aldosterone Synthase Promoter Polymorphism Predicts Outcome in African Americans With Heart Failure
Results From the A-HeFT Trial
Dennis M. McNamara, MD*,*,
S. William Tam, PhD ,
Michael L. Sabolinski, MD,
Page Tobelmann, BS*,
Karen Janosko, MSN*,
Anne L. Taylor, MD ,
Jay N. Cohn, MD,
Arthur M. Feldman, MD, PhD and
Manuel Worcel, MD
* University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
NitroMed Inc., Lexington, Massachusetts
University of Minnesota, Rochester, Minnesota
Thomas Jefferson Medical College, Philadelphia, Pennsylvania
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Figure 1 Genotype frequencies for the aldosterone synthase (CYP11B2) –344 T/C polymorphism in the white heart failure cohort in the GRACE trial and the African American heart failure cohort from GRAHF substudy. The prevalence of the T allele is significantly higher (p < 0.001) in African Americans.
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Figure 2 Event-free survival by CYP11B2 –344 genotype subsets. Freedom from heart failure hospitalization was significantly poorer (p = 0.018) in subjects with the C allele, with the worst outcomes in CC homozygotes, best outcomes in TT subjects, and intermediate in heterozygotes.
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Figure 3 Impact of therapy with isosorbide dinitrate and hydralazine (I/H) on outcomes in heart failure. (A) Effect on composite score in –344 genotype subsets. Treatment associated with marked improvement in the –344TT subset (n = 218, p = 0.01), but minimal effect in subjects with the –344 C allele (CC + TC, n = 136, p = NS). (B) Effect on change in quality-of-life scores from baseline to 6 months in –344 genotype subsets.
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