(Circulation. 1999;100:608-613.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Age-Dependent Association of Apolipoprotein E Genotype With Coronary and Aortic Atherosclerosis in Middle-Aged Men
An Autopsy Study
From the Medical School, University of Tampere, and Tampere University Hospital (E.I., T.L., P.J.K.); the Department of Human Molecular Genetics, National Public Health Institute, Helsinki (M.P.); the Department of Clinical Chemistry, Tampere University Hospital, and the Laboratory of Atherosclerosis Genetics, Tampere (E.I., T.L., T.K.); the Tampere School of Public Health, University of Tampere, and Tampere University Hospital (P.L.); and the Department of Forensic Medicine, University of Helsinki (V.S., J.P., A.P., K.H.L., A.M., K.K.L.), Finland.
Correspondence to Erkki Ilveskoski, MD, Medical School, University of Tampere, PO Box 607, FIN-33101, Tampere, Finland. E-mail ei46478{at}uta.fi
Background—Apolipoprotein E
(apoE) polymorphism is one of the genetic determinants of serum
cholesterol values. The apoE 
4 allele has been
associated with advanced coronary heart disease (CHD) diagnosed
by angiography, but the role of the apoE genotype in
atherosclerosis has not been confirmed at vessel-wall
level, nor is any age-dependent effect of the apoE genotype on
the development of CHD known.
Methods and Results—The right and left anterior descending
coronary arteries (RCA and LAD) and the aorta from 700 male
autopsy cases (Helsinki Sudden Death Study) in 1981-1982 and 1991-1992
(average age 53 years, range 33 to 70 years) were stained for fat, and
all areas covered with fatty streaks, fibrotic plaques, and complicated
lesions were measured. In the RCA and LAD, the apoE genotype
was significantly associated with the area of total atherosclerotic
lesions in men <53 years old but not with that in older men
(P=0.0085 and P=0.041, respectively, for
age-by-genotype interaction). Men <53 years old with the
4/3 genotype showed 61% larger total atherosclerotic lesion
area in the RCA (P=0.0027) and 26% larger area in the
LAD (P=0.12) than did men with the 3/3. The apoE
4/3 was also associated with atherosclerotic lesions in the
abdominal (P=0.014) and thoracic (P=0.12)
aorta, but this effect, unlike that of the coronary arteries,
was not age-related.
Conclusions—In men, the apoE 4 allele is a significant
genetic risk factor for coronary
atherosclerosis in early middle age. This suggests that
at older age, other known risk factors of CHD play a more important
role in the atherosclerotic process than apoE polymorphisms.
Key Words: apolipoproteins • atherosclerosis • coronary disease
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