ACE and Atherosclerosis: pieces of the puzzle

There is increasing evidence that atherosclerosis is not only involved in cardiovascular diseases (CVD) but also other diseases of the elderly such as Alzheimer’s disease (AD). Since CVD are highly fatal and usually occur earlier than Alzheimer’s disease, the co-morbidity by CVD might hamper studies on the association between atherosclerosis risk factors and AD. Here we used the inverse probability of censoring weighted analyses method to test this hypothesis, in a study on the relationship between the insertion/deletion polymorphism of the angiotensin converting enzyme gene (ACE I/D) and risk of AD. We used data from the Rotterdam Study, a prospective population based study. We .rst performed a Cox proportional hazards model including all available cardiovascular risk factors to calculate the probability of death from CVD and thereby the probability of being free from fatal CVD events. These probabilities were then used to weight the subjects who were uncensored by fatal disease by the inverse of their survival probability. In a weighted analysis we estimated the association between the ACE I/D polymorphism and AD. Among 2431 men that were free from Alzheimer’s disease at baseline, 51 persons were diagnosed for AD and 196 individual had fatal cardiovascular events without occurrence of AD during the follow up. Among 3281 women, these numbers were 89 and 159, respectively. Survival analyses showed that the association between the I allele and AD was mainly present in women (p values for trend was 0.09). In the weighted analyses the hazard ratios did not materially change in any of the gender groups. Our results indicate that the association between the I allele of the ACE gene and Alzheimer’s disease is not due to the co-morbidity effect of CVD.

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