TY - JOUR
T1 - Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction
AU - Moss, Arthur J.
AU - Ryan, Daniel
AU - Oakes, David
AU - Goldstein, Robert E.
AU - Greenberg, Henry
AU - Bodenheimer, Monty M.
AU - Brown, Mary W.
AU - Case, Robert B.
AU - Dwyer, Edward M.
AU - Eberly, Shirley W.
AU - Francis, Charles W.
AU - Gillespie, John A.
AU - Krone, Ronald J.
AU - Lichstein, Edgar
AU - MacCluer, Jean W.
AU - Marcus, Frank I.
AU - McCarthy, Jeanette
AU - Sparks, Charles E.
AU - Zareba, Wojciech
N1 - Funding Information:
This study was supported by Research Grant HL048259 from the National Institutes of Health, Bethesda, Maryland, and by a contract from Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts.
PY - 2005/7/15
Y1 - 2005/7/15
N2 - The association of a group of prespecified atherosclerotic risk genotypes with recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) was investigated in a cohort of 1,008 patients after infarction during an average follow-up of 28 months. We used a carrier-ship approach with time-dependent survivorship analysis to evaluate the average risk of each carried genotype. Contrary to expectation, the hazard ratio for recurrent coronary events per carried versus noncarried genotype was 0.89 (95% confidence interval 0.80 to 0.99, p = 0.03) after adjustment for relevant genetic, clinical, and environmental covariates. This hazard ratio, derived from the 7 prespecified genotypes, indicated an average 11% reduction in the risk of recurrent coronary events per carried versus noncarried genotype. At 1 year after hospital discharge, the cumulative probability of recurrent coronary events was 26% in those who carried ≤1, 20% for those with 2 to 4, and 13% for those with ≥5 of these genotypes (p = 0.02). This unexpected risk reversal is a likely consequence of changes in the mix of risk factors in pre- and postinfarction populations. In conclusion, this under appreciated, population-based, risk-reversal phenomenon may explain the inconsistent associations of genetic risk factors with outcome events in previous reports involving coronary populations with different risk attributes.
AB - The association of a group of prespecified atherosclerotic risk genotypes with recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) was investigated in a cohort of 1,008 patients after infarction during an average follow-up of 28 months. We used a carrier-ship approach with time-dependent survivorship analysis to evaluate the average risk of each carried genotype. Contrary to expectation, the hazard ratio for recurrent coronary events per carried versus noncarried genotype was 0.89 (95% confidence interval 0.80 to 0.99, p = 0.03) after adjustment for relevant genetic, clinical, and environmental covariates. This hazard ratio, derived from the 7 prespecified genotypes, indicated an average 11% reduction in the risk of recurrent coronary events per carried versus noncarried genotype. At 1 year after hospital discharge, the cumulative probability of recurrent coronary events was 26% in those who carried ≤1, 20% for those with 2 to 4, and 13% for those with ≥5 of these genotypes (p = 0.02). This unexpected risk reversal is a likely consequence of changes in the mix of risk factors in pre- and postinfarction populations. In conclusion, this under appreciated, population-based, risk-reversal phenomenon may explain the inconsistent associations of genetic risk factors with outcome events in previous reports involving coronary populations with different risk attributes.
UR - https://www.scopus.com/pages/publications/22144468092
U2 - 10.1016/j.amjcard.2005.03.039
DO - 10.1016/j.amjcard.2005.03.039
M3 - Article
C2 - 16018837
AN - SCOPUS:22144468092
SN - 0002-9149
VL - 96
SP - 177
EP - 182
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 2
ER -