Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction.
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 < or =1, 20% for those with 2 to 4, and 13% for those with > or =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.
Moss
Arthur J
AJ
Cardiology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. heartajm@heart.rochester.edu
Ryan
Daniel
D
Oakes
David
D
Goldstein
Robert E
RE
Greenberg
Henry
H
Bodenheimer
Monty M
MM
Brown
Mary W
MW
Case
Robert B
RB
Dwyer
Edward M
EM
Eberly
Shirley W
SW
Francis
Charles W
CW
Gillespie
John A
JA
Krone
Ronald J
RJ
Lichstein
Edgar
E
MacCluer
Jean W
JW
Marcus
Frank I
FI
McCarthy
Jeanette
J
Sparks
Charles E
CE
Zareba
Wojciech
W
D000368:Aged; D000789:Angina, Unstable / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D011336:Probability; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis