the EcoRI genotype R-/R- (homozygosity for the absence of EcoRI cutting site) was somewhat lower in the nonagenarians (4.5%) than in the middle-aged and young adults (7.0% and 5.9% respectively) (P < 0.05). The frequency of the EcoRI allele R- was also lowest (14.6%) in the nonagenarians (Table 4). When women were anal- ysed separately, the frequency of R- allele was lower in the nonagenarians (n = 81) than in the middle-aged group (n = 30) (x2 = 6.6, P < 0.01) but not lower than in the young adult group (n = 48) (x2 = 1.5, NS). Also, the frequency for the R- allele was lower in the female nonagenarians than in the control group (n = 78) (x2 = 4.6, P < 0.05). The genotype distribution and the allele frequencies for the X&I polymor- phism did not differ between the nonagenarians and the control groups (Table 5).

The distribution of the apo E phenotype categories (Table 3) was different between the age groups (x2 = 10.4, P c 0.05), so that 33.1%, 37.5% and 19.0% of the young adults, middle-aged adults and nonagenarians, respectively, fell into the E4 category. In contrast, 8.9%, 5.9% and 11.6% of the young and middle-aged adults and nonagenarians, respectively, belonged to the E2 category, the E3 category consisting of 58.1%, 56.6% and 69.5% of the young, middle-aged and nonagenarian groups respectively. There were 6 individuals with the phenotype E 414 out of 124 young adults (4.9%) and also 6 with E 414 out of 136 middle-aged adults (4.4%), but only one E 4/4 out of 95 subjects (l.l”/,) in the nonagenarian group (Table 3). Of the 8 nonagenarian men, 2 had the phenotype E 213, 5 E 313, and one E 413. Again, when only females were included, the distribution of the apo E phenotype categories tended to be dif- ferent between the age groups (x2 = 7.3, NS) so that 34.0%, 37.2% and 19.5% of the female young adults, middle-aged adults and nonagenarians, respectively, fell into the E4 category.

4. Discussion

The major finding of this study was the low prevalence of the ~4 allele of apo E in the group of nonagenarians. This result supports the view that the presence of ~4 allele increases the susceptibility to CHD death and thus prevents the attainment of an extremely old age. This conclusion was also suggested by Davignon et al., who found a low frequency of the ~4 allele in Canadian octogenarias [21]. The present data show that the ~4 allele is a major risk factor for CHD also in a population in which the ~4 prevalence is exceptionally high [4,6]. Accordingly, the prevalence of ~4 allele is high in

The distribution of genotypes and the allele fre- quencies for the EcoRI RFLP polymorphism of apo B in the nonagenarians and in the younger age

previously been associated with an enhanced risk for CHD. This study strongly suggests that the presence of the e4 allele of apo E or the R allele of apo B decreases the probability of an individual reaching an extremely old age, although the reasons for increased mortality other than CHD cannot be excluded.

Finnish subjects with CHD compared with sub- jects without CHD [22,23].

lower and triglycerides were higher than in the younger age groups. This is in accordance with the study of Davignon et al. [21] in octogenarians. It is likely that low HDL cholesterol and high trigly- ceride values do not protect from atherosclerosis and thereby lead to longevity, but nutritional and metabolic changes associated with aging may rather result in low HDL and high triglyceride levels. This kind of lipid profile might be associ- ated with a high prevalence of impaired glucose tolerance frequently observed in aged individuals. The similarity in the Lp(a) levels among the

5. Acknowledgements

The skilful technical and secretarial assistance of MS Saija Kortetjarvi, MS Tuulikki Haataja, MS Marja-Leena Kytlikangas, MS Anna-Riitta Malinen and MS Tuija Ranta is greatly appre- ciated. This research was supported by The Medi- cal Council of the Academy of Finland, the Finnish Foundation for Cardiovascular Research and the Finnish Cultural Foundation.

various age groups of our study suggests that high Lp(a) levels may not be a strong factor associated with longevity in Finland, an observation also made in an 80-year-old Swedish cohort [24]. In- terestingly, a recent survey on the Helsinki Heart Study participants also failed to elucidate high Lp(a) levels as a predictor of CHD [25], but another previous investigation on the Finns reported a positive association between plasma Lp(a) and CHD [26].

6. References

Uemura, K. and Pisa, Z., Recent trends in cardiovascular disease mortality in

industrialized countries, World Health Stat. Q.,

(

)

Pyiirlll, K., Salonen, J.T. and Valkonen, T., Trends in coronary heart disease mortality and morbidity and re- lated factors in Finland, Cardiology,

(

)

Hegele, R.A. and Breslow, J.L., Apolipoprotein genetic variation in the assessment of atherosclerosis susceptibili- ty, Genet. Epidemiol.,

(

)

Utermann, G., Apolipoprotein E polymorphism in health and disease, Am. Heart J.,

(

)

Davignon, J., Gregg, R.E., and Sing, C.F., Apolipopro- tein E polymorphism and atherosclerosis, Arterio- sclerosis,

(

)

Ehnholm, C., Lukka, M., Kuusi, T., Nikkilii, E. and Uter- mann, G., Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations, J. Lipid Res.,

(

)

Myant, N.B., Gallagher, J., Barbir, M., Thompson, G.R., Wile, D. and Humphries, S.E., Restriction fragment length polymorphism on the ap

gene in relation to coronary heart disease, Atherosclerosis,

(

)

Paulweber, B., Friedl, W., Krempler, F., Humphries, S.E. and Sandhofer, F., Association of DNA polymorphism at the apolipoprotein B gene locus with coronary heart disease and serum very low density lipoprotein levels, Arteriosclerosis,

(

)