Survival Analysis for the Association between Anti-hypertensive Medication and Time to Dementia with Competing Risk

Abstract

Background: High blood pressure (HBP) is a common risk factor for dementia in elder population. Anti-hypertensive medications have been reported to associate with lower incidence rate of dementia in elder African Americans. The Apolipoprotein E (ApoE) epsilon 4 allele has been shown to be associated with both increased dementia and hypertension risk. However, previous studies had not examined the association between anti-hypertensive medications by ApoE status accounting for the competing risk from death. Methods: This is a prospective observational cohort study in 1236 community-dwelling hypertensive African Americans aged 65 years and older without dementia at baseline, with follow-up cognitive assessment and clinical evaluation for dementia diagnosis. Dementia-free mortality was considered as the competing risk. Of these, 707 participants were genotyped for ApoE status. Anti-hypertensive medication use was obtained from prescription records in the electronic medical records of the Indiana Network for Patient Care (INPC). Cox proportional cause-specific hazard (CSH) regression models were applied to assess the association between anti-hypertensive medication use and CSHs for dementia and death in ApoE epsilon 4 carriers and non-carriers separately. Key results: In ApoE epsilon 4 carriers, participants using anti-hypertensive medications had lower CSH of dementia compared to those not on anti-hypertensive medications before adjusting for blood pressure (BP) (hazard ratio (HR), 0.365; 95% CI, 0.170 – 0.785; p = 0.0099). The HR was no longer significant once BP control was adjusted (HR, 0.784; 95% CI, 0.197 – 3.123; p = 0.7303). Anti-hypertensive medications were not associated with dementia rate in non-carriers. In ApoE epsilon 4 non-carriers, participants on anti-hypertensive treatment showed significantly lower CSH of death compared to those not on mediations adjusting for covariates and BP control (HR, 0.237; 95% CI, 0.149 – 0.375; p < 0.0001). There was no significant association between anti-hypertensive medication use and death in ApoE epsilon 4 carriers. Conclusions: Anti-hypertensive medication was associated with lower dementia rate in ApoE epsilon 4 carriers and that rate was primarily mediated through BP control. In non-carriers, anti-hypertensive medication was significantly associated with lower mortality rate and this association appears to be independent of BP control.