Age-related trends of blood pressure levels by apolipoprotein E genotype: the Bambuì cohort study of ageing (1997–2008)

Abstract

The role of apolipoprotein E (apoE) polymorphisms in regulating blood pressure (BP) is still not clear. The aim of this study was to examine longitudinal changes in BP levels by apoE genotypes in a population-based prospective cohort of elderly subjects, and explore interactions with plasma lipids and uric acid. Subjects whose apoE genes had been genotyped at baseline (1408, representing 80.8% of all the elderly residents in Bambuì city, south-eastern Brazil; age range 60-95 years) were included in the analysis. Repeated BP measurements were obtained in four waves. Multi-level random-effects pattern-mixture models were used to evaluate the age-related BP trajectories, accounting for non-ignorable dropouts/deaths and handling heterogeneities as random parameter variations. Subjects with the ɛ4/4 genotype and high levels of low-density lipoprotein cholesterol had higher systolic BP levels at 60 years of age than those with the other genotypes (154.5 vs. 133.2 mm Hg, P=0.020), but this was not the case among the older subjects. Systolic BP increased more rapidly with age in the ɛ2 carriers, leading to significantly higher levels among the oldest. This relationship seemed to be modulated by uric acid levels, as it was present in the subjects with the ɛ2/3 genotype and high uric acid levels, and in those with the ɛ2/4 genotype and low or normal uric acid levels. The differences in systolic BP between the genotypes were age dependent, and the shift between the ɛ4 and ɛ2 alleles suggest that these alleles are involved in the different mechanisms leading to increased BP in middle-aged and elderly subjects.