Apolipoprotein E e4 Allele Interacts with Sex and Cognitive Status to Influence All-Cause and Cause-Specific Mortality in U.S. Older Adults

• Autores: May A. Beydoun, Hind A. Beydoun, Jay S. Kaufman, Yang An, Susan M. Resnick, Richard O'Brien, Luigi Ferrucci, Alan B. Zonderman
• Localización: Journal of the American Geriatrics Society, ISSN 0002-8614, Vol. 61, Nº. 4, 2013, págs. 525-534
• Idioma: inglés
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• Resumen

  • Objectives: To confirm associations of apolipoprotein E (ApoE) ?4 carrier status, sex, and time-dependent cognitive status with mortality risk and to investigate these joint effects of these associations in a cohort of community-dwelling U.S. adults.

    Design: Prospective cohort study.

    Setting: The Baltimore Longitudinal Study of Aging (BLSA).

    Participants: Of 3,047 BLSA participants aged 17 to 98 at first visit (60.1% male), 1,704 with complete ApoE genotype data were included, of whom 1,461 aged 50 and older with one or more visits were eligible.

    Measurements: Time to death from all, cardiovascular, and noncardiovascular causes.

    Results: Probability of survival was lower for ApoE ?4 carriers, particularly those who were older. A Cox proportional hazards model for all-cause mortality yielded a hazard ratio (HR) for ApoE ?4 carrier versus noncarriers of 1.31 (95% confidence interval (CI) = 1.02�1.68). This association was also found for cardiovascular mortality. Time-dependent all-cause dementia (HR = 1.73, 95% CI = 1.33�2.26) and mild cognitive impairment (HR = 1.95, 95% CI = 1.42�2.67) increased all-cause mortality risk, associations that were also detected for noncardiovascular mortality. When individuals were free of cognitive impairment, a dose-response relationship with ?4 alleles was found for all-cause mortality (HR = 1.40, 95% CI = 0.94�2.07 for 1 ?4; HR = 2.61, 95% CI = 1.12�6.07 for 2 ?4). After onset of Alzheimer's disease (AD), carrying only one ?4 allele resulted in an approximately 77% greater all-cause mortality risk than in noncarriers. ApoE ?4 carrier status increased all-cause mortality risk in men and interacted with time-dependent AD to increase the risk of this outcome (relative excess risk due to interaction = 2.15, 95% CI = 1.22�3.07).

    Conclusion: ApoE ?4 carrier status was found to increase all-cause and cardiovascular mortality risks and interacted with sex and time-dependent AD status to affect all-cause mortality.