The study has some limitations. The older population studied did not include those who may have physical limitations and thus were not able to attend the study center. The medical history relied on participants' reports of doctors' diagnoses. No electrocardiograms or physical examinations were carried out 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.

However, 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 many nutritional factors associated with cardiovascular disease in detail.

The lower frequency of the D/D genotype relative to I/I & I/D in this population is compatible with previous observations of lower frequency of D/D among Asians (17.9%) compared with Blacks (37.9%) and Whites (32.5%). The genotype frequencies did not vary significantly with age, which is a finding similar to that of a large Danish study of all ages and among Japanese but contrary to other studies among Europeans and Colombians and the finding of higher frequencies of the D allele among centenarians. However, this study only included participants age 65 years and older, and changes in the genotype frequencies with age may occur in younger populations.Frequency changes with age may not be detected within this narrow age range. The study did not include centenarians, and the population represented fitter individuals who were able to survive. In conclusion, the ACE polymorphism may be considered deleterious to longevity in a Chinese elderly population, with the D/D genotype being associated with 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 renin-angiotensin system may possibly have a role in reducing cardiovascular disease incidence. The lower mean ABI values in women have not been observed in other populations, although it is known that there is a lower prevalence of cardiovascular disease in women after menopause. This finding may reflect a survivor effect in men or a true association. 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 atherosclerotic process and consequently the onset of cardiovascular diseases. Possible explanations for the lack of association in men may be that other environmental factors are at play.

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