OBJECTIVES: We sought to evaluate the effect of the aldosterone synthase promoter polymorphism on heart failure outcomes for subjects in the African American Heart Failure Trial (A-HeFT). BACKGROUND: Genetic heterogeneity modulates clinical outcomes in subjects with heart failure (HF); however, little data exist in African American populations. A common polymorphism exists in the promoter region of the aldosterone synthase gene (CYP11B2) at position -344 (T/C). The -344C allele, associated with higher aldosterone synthase activity, has been linked to hypertension; however, its impact on outcomes in HF is unknown. METHODS: A total of 354 subjects from A-HeFT participated in the GRAHF (Genetic Risk Assessment of Heart Failure in African Americans) substudy and were genotyped for the aldosterone synthase polymorphism. Patients were followed prospectively, and event-free survival (freedom from death and HF hospitalization) compared by CYP11B2 genotype. RESULTS: Of the cohort, 218 patients were TT, 114 CT, and 22 patients were CC. Baseline etiology, blood pressure, and functional class were not significantly different among the 3 cohorts. The C allele was associated with significantly poorer HF hospitalization-free survival with the best survival among TT subjects, intermediate for heterozygotes, and the poorest for CC homozygotes (p = 0.018), and a higher rate of death (% death TT/TC/CC = 1.8/3.5/18.2, p = 0.001). The TT genotype, more prevalent in blacks, was associated with greater impact of fixed combination of isosorbide dinitrate and hydralazine on the primary composite end point (p = 0.01). CONCLUSIONS: The aldosterone synthase promoter -344C allele linked to higher aldosterone levels is associated with poorer event-free survival in blacks with HF. The role of aldosterone receptor antagonists in diminishing this apparent genetic risk remains to be explored.
OBJECTIVES: We sought to evaluate the effect of the aldosterone synthase promoter polymorphism on heart failure outcomes for subjects in the African American Heart Failure Trial (A-HeFT). BACKGROUND: Genetic heterogeneity modulates clinical outcomes in subjects with heart failure (HF); however, little data exist in African American populations. A common polymorphism exists in the promoter region of the aldosterone synthase gene (CYP11B2) at position -344 (T/C). The -344C allele, associated with higher aldosterone synthase activity, has been linked to hypertension; however, its impact on outcomes in HF is unknown. METHODS: A total of 354 subjects from A-HeFT participated in the GRAHF (Genetic Risk Assessment of Heart Failure in African Americans) substudy and were genotyped for the aldosterone synthase polymorphism. Patients were followed prospectively, and event-free survival (freedom from death and HF hospitalization) compared by CYP11B2 genotype. RESULTS: Of the cohort, 218 patients were TT, 114 CT, and 22 patients were CC. Baseline etiology, blood pressure, and functional class were not significantly different among the 3 cohorts. The C allele was associated with significantly poorer HF hospitalization-free survival with the best survival among TT subjects, intermediate for heterozygotes, and the poorest for CC homozygotes (p = 0.018), and a higher rate of death (% death TT/TC/CC = 1.8/3.5/18.2, p = 0.001). The TT genotype, more prevalent in blacks, was associated with greater impact of fixed combination of isosorbide dinitrate and hydralazine on the primary composite end point (p = 0.01). CONCLUSIONS: The aldosterone synthase promoter -344C allele linked to higher aldosterone levels is associated with poorer event-free survival in blacks with HF. The role of aldosterone receptor antagonists in diminishing this apparent genetic risk remains to be explored.
Authors: Richard Sheppard; Eileen Hsich; Julie Damp; Uri Elkayam; Angela Kealey; Gautam Ramani; Mark Zucker; Jeffrey D Alexis; Benjamin D Horne; Karen Hanley-Yanez; Jessica Pisarcik; Indrani Halder; James D Fett; Dennis M McNamara Journal: Circ Heart Fail Date: 2016-03 Impact factor: 8.790
Authors: Robert J Mentz; Vera Bittner; Phillip J Schulte; Jerome L Fleg; Ileana L Piña; Steven J Keteyian; Gordon Moe; Anil Nigam; Ann M Swank; Anekwe E Onwuanyi; Meredith Fitz-Gerald; Andrew Kao; Stephen J Ellis; William E Kraus; David J Whellan; Christopher M O'Connor Journal: Am Heart J Date: 2013-07-12 Impact factor: 4.749