No statistically significant differences among genotypes. Differences were tested with multivariate linear regression for continuous data with the DD genotype as reference, controlling for age of the participants. Twins from intact pairs were analyzed as clusters of two in the multivariate models. aParticipants in 1999 follow-up were approximately 2 years younger at baseline than twins who only participated in 1997 survey (p »<( 0.001). bMean composite measure of walking, running, and cycling distance I+s standard deviation. cBeats per minute

TABLE 3. Mini Mental State Examination (MMSE) scores and ACE genotype

Females Males ACE genotype II DI DD II DI DD Median MMSE score 1997 (quartiles) 26.0 (23.0, 28.0) 27.0 (24.0, 28.0) 27.0 (25.0, 29.0) 27.0 (23.0, 29.0) 27.0 (24.0, 29.0) 27.0 (25.0, 28.0) Number with test score (cid:7)24 (percent) 25 (25.3) 42 (18.4) 21 (17.9) 18 (27.3) 22 (19.8) 10 (18.9) Median MMSE score 1999 (quartiles)a 26.0 (23.0, 28.0) 27.0 (24.0, 28.0) 26.5 (24.0, 29.0) 28.0 (25.0, 29.0) 27.0 (24.0, 28.5) 27.0 (24.0, 29.0) Number with test score (cid:7)24 (percent) 19 (26.4) 34 (19.5) 15 (16.7) 8 (15.4) 18 (20.2) 7 (17.1) Mean relative MMSE score differences 1997 to 1999 (SD) 0.02 (0.1) 0.01 (0.1) 0.0 (0.1) (cid:8)0.01 (0.1) 0.02 (0.1) 0.04 (0.1)

No statistically significant differences among genotypes. Differences were tested with Logistic regression for categorical data and with multivariate linear regression for continuous data with the DD genotype as reference, controlling for age of the participants. Twins from intact pairs were analyzed as clusters of two in the multivariate models. aParticipants in 1999 follow-up were approximately 2 years younger at baseline than their non-participating counter-parts (p  < 0.001).

in 1999 follow-up were approximately 2 years younger at baseline than their non-participating counter-parts (p 0.001).

130 participants died. The participants with the II genotype peee*= |  had marginally poorer survival, p 0.02 (Fig. 2). Control- ling for sex, age at baseline, self-rated health and MMSE score in a Cox regression analysis indicated that the II geno- type may be an independent risk factor for death, the hazard rates (HR) (95 percent confidence intervals) for the II com- pared with the ID and DD genotype being 1.6 (1.1–2.5), and 1.3 (0.8–2.1) respectively. The survival was not signifi-

both sexes in the 1997 survey. The proportion not partici- pating in cognitive testing did not vary by genotype (results not shown).

Survival

The mean follow-up time (SD) was 39.5 (10.3) months and none were lost to follow-up. During the follow-up period

ersons at risk1DoT[Proportional survival171344169163331155156316147144298135 Months142118

FIGURE 2. Survival curves of 684 ACE genotyped twins from the Longitudinal Study of Aging Danish Twins - the 1997 and 1999

cantly different in DD and DI persons (Fig. 2). Using the D as the dominant allele resulted in hazard rates of 1.5 (1.0– 2.2) for II compared with DI/DD persons.

body anaerobic response (31) after physical training in II persons exceeding that of the D allele persons. The associa- tion studies have determined ACE genotype prevalence in élite athletes compared with controls. Some have found in- creased prevalence of the II genotype in mountaineers who ascended beyond 7,000 m without supplementary oxygen (3) or in Olympic competitors (5, 6), whereas others found no difference in ACE genotype prevalence (32). All the in- tervention studies have as expected found comparable physical performance at baseline between different ACE genotypes since the range of physical abilities is narrow in young persons especially when using selected groups e.g. military recruits for the intervention. In old age, however, the variation of physical abilities is large, therefore differ- ences in a cross-sectional study should occur if the ACE genotype was important for physical performance in this age group. Furthermore, ACE genotype was not associated with rate of change in self-reported physical abilities. The cause of the discrepancy between this and the previous studies is unknown. A possible explanation could be the highly selected populations used in the previous studies of ACE genotype and physical performance.

Subgroup Analyses

Seventy-nine intact DZ twin pairs were discordant for ACE genotype. Physical and cognitive abilities as well as survival did not differ significantly between the individuals in these pairs (results not shown). Although statistics were not sig- nificant here, the proportion of self-reported diseases dif- fered by genotype (Table 1). We therefore repeated the analyses restricted to those not suffering from any of the mentioned diseases but the results were virtually unaltered by this (results not shown).

DISCUSSION

In this study, we have focused on the possible association of the ACE genotypes with physical and cognitive perfor- mance and survival among the elderly. The study design provided both cross-sectional and longitudinal data. In our study, the ACE genotype was not associated with self-reported or measured physical performance or cognitive function. Having the D allele, however, improved chances of survival even after controlling for the effect of sex, age, cognitive function, and self-rated health. None of the analyses re- vealed any stepwise trends of the examined phenotypes with regard to ACE genotype.