without the protective effect of higher endogenous oestrogen levels are more susceptible to the effect of increase ACE

In women, D/D was more common among those developing hypertension or myocardial infarction (Table 3). However, with respect to mortality, more men with the D/D genotype had died by the 5th year follow up compared with the I/I or I/D group (Table 4). No significant difference was observed for

Although the frequencies of the ACE genotypes did not change with age, another method to examine whether the ACE polymorphism may be considered ‘deleterious’ (17) instead of ‘longevity enabling’ (18) is to examine the association with mortality prospectively. From the findings of association of D/D genotype with the atherosclerotic process in women, one may expect that women with the D/D genotype would also have a higher mortality. Unexpectedly, the association was found only in men. The finding suggests that the association may be mediated by mechanisms other than atherosclerosis. However, the duration of follow-up was not very long, and a

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There are limitations in this study. The older population studied did not include those who may have physical limitations and thus were not able to attend the study centre. The medical history relied on participants’ report of doctor’s diagnoses. We did not do electrocardiagrams on the participants nor carry out any physical examination other than height, weight and blood pressure measurements. The low number of participants with the D/D genotype and the relatively short duration of follow-up are also limitations. Nevertheless, the study has several strengths and contributes to existing inconsistent literature regarding ACE polymorphism, longevity, atherosclerosis and cardiovascular diseases. The large number of men and women, the prospective design, the availability of ABI measurement, and the adjustment for many confounding environmental factors address some of the underlying reasons for inconsistencies in previous studies. In particular, we were able to document the many nutritional factors that have been associated with cardiovascular diseases in a detailed,

The lower frequency of the D/D genotype relative to I/I & I/D in this population is compatible with previous observation of lower frequency of D/D among Asians (17.9%) compared with Blacks (37.9%) and Whites (32.5%) (27). The genotype frequencies did not vary significantly with age, a finding similar to that of a large Danish study of all ages (12) and among Japanese (27), but contrary to other studies among Europeans and Colombians (11, 18, 28) and the finding of higher frequencies of the D allele among centenarians (20, 21). However, this study only included participants age 65 years and older, and changes in frequency with age may not be detected within this relatively narrow age range. It did not include extremely old individuals (centenarians). Furthermore, the population represented fitter individuals who were able to

In conclusion in a Chinese elderly population, ACE polymorphism may be considered ‘deleterious’ to longevity, the D/D genotype being associated mortality, the atherosclerotic process, hypertension and myocardial infarction. However there are gender differences and mortality may not be mediated by the atherosclerotic process alone. A longer period of follow-up may yield further information. In the meantime, therapeutic blockade of the rennin-angiotensin system may possibly have a role in reducing incidence of cardiovascular

The lower mean ABI values in women have not observed in other populations, although it is known that lower prevalence of cardiovascular disease in women is not seen after the menopause. It is possible that finding may reflect a survivor effect in men, or a true

The association between D/D genotype and greater progression of atherosclerosis and incidence of hypertension and myocardial infarction in a large number of women only confirms some previous observations that this association may be stronger among Asians, that there is a gender difference, and that there may be differences between ethnic groups. The fact that this was a prospective study consisting of large numbers of men and women strengthens the validity of this observation, and supports the hypothesis that increased ACE activity (associated with the D/D genotype) accelerates the atherosclerosclerotic process and consequently the onset of cardiovascular diseases. Possible explanations for the lack of association in men may be that other environmental factors



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