Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1277-1282 |
| Number of pages | 6 |
| Journal | Journal of the American College of Cardiology |
| Volume | 48 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 19 2006 |
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Aldosterone Synthase Promoter Polymorphism Predicts Outcome in African Americans With Heart Failure. Results From the A-HeFT Trial. / McNamara, Dennis M.; Tam, S. William; Sabolinski, Michael L.; Tobelmann, Page; Janosko, Karen; Taylor, Anne L.; Cohn, Jay N.; Feldman, Arthur M.; Worcel, Manuel.
In: Journal of the American College of Cardiology, Vol. 48, No. 6, 19.09.2006, p. 1277-1282.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aldosterone Synthase Promoter Polymorphism Predicts Outcome in African Americans With Heart Failure. Results From the A-HeFT Trial
AU - McNamara, Dennis M.
AU - Tam, S. William
AU - Sabolinski, Michael L.
AU - Tobelmann, Page
AU - Janosko, Karen
AU - Taylor, Anne L.
AU - Cohn, Jay N.
AU - Feldman, Arthur M.
AU - Worcel, Manuel
PY - 2006/9/19
Y1 - 2006/9/19
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jacc.2006.07.030
DO - 10.1016/j.jacc.2006.07.030
M3 - Article
C2 - 16979018
AN - SCOPUS:33748428075
VL - 48
SP - 1277
EP - 1282
JO - Journal of the American College of Cardiology.
JF - Journal of the American College of Cardiology.
SN - 0735-1097
IS - 6
ER -