Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam, the Netherlands; Department of Neurology, Donders Institute for Brain, Behaviour and Cognition, Radboud University Medical Center, Nijmegen, the Netherlands.
Amsterdam UMC, University of Amsterdam, Department of General Practise, Amsterdam, the Netherlands.
J Am Med Dir Assoc. 2019 Sep;20(9):1091-1097.e3. doi: 10.1016/j.jamda.2018.12.006. Epub 2019 Feb 6.
To evaluate whether discontinuation of antihypertensive medication in community-dwelling older people is associated with a reduction in memory complaints and/or incident dementia.
Prospective observational cohort study within the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial.
Community-dwelling participants (aged 70-78 years at baseline) who underwent 2-yearly assessments during 6-8 years of follow-up.
Cox regression analyses of the relation between discontinuation of antihypertensive medication during the study and change in subjective memory complaints, incident dementia, and mortality.
Dementia occurred more often in participants discontinuing antihypertensive treatment (13.4% vs 6.2%, P = .02); mortality was similar (16.5% vs 13.9%, P = .52). Discontinuation of antihypertensive medication was associated with a double dementia hazard [hazard ratio (HR) (95% confidence interval) = 2.15 (1.15-4.03)], which somewhat attenuated after adjustment for sex, blood pressure, number of antihypertensives and other medications [HR = 1.92 (1.01-3.65)], and additionally for stroke, cardiovascular disease, diabetes, smoking, memory complaints, and MMSE score [HR = 1.79 (0.93-3.44)]. Antihypertensive discontinuation was associated with an approximately 50% higher hazard of dementia and/or mortality combined [HR = 1.58 (1.04-2.40); model 2: HR = 1.64 (1.07-2.51); model 3: HR = 1.49 (0.96-2.30)]. Antihypertensive discontinuation was not associated with change in memory complaints [odds ratio (95% confidence interval) = 0.96 (0.55-1.67)]. Subgroup and sensitivity analyses addressing possible sources of bias and confounding gave similar results.
CONCLUSIONS/IMPLICATIONS: Our results suggest that antihypertensive withdrawal in community-dwelling older people does not preserve cognition and may in fact increase dementia risk. This is not due to reduced mortality as competing risk. Additional analyses suggest results are unlikely to be explainable by confounding, reverse causality, or observational biases. Studies with person-specific reasons for antihypertensive discontinuation may be able to exclude reverse causality completely. Given the beneficial effects of antihypertensive medication on cardiovascular risk, observational data may be the best currently obtainable on the pressing issue of when withdrawal of antihypertensives in older people is acceptable and what consequences need to be weighed.
评估社区居住的老年人停止使用降压药物是否与记忆力减退和/或痴呆的发生率降低有关。
预防血管性痴呆强化护理（preDIVA）试验的前瞻性观察队列研究。
参加者为 70-78 岁基线时的社区居住者，在 6-8 年的随访期间每两年进行一次评估。
采用 Cox 回归分析研究期间停止使用降压药物与主观记忆减退、新发痴呆和死亡率变化之间的关系。
停止使用降压药物的参与者发生痴呆的频率更高（13.4% vs 6.2%，P=0.02）；死亡率相似（16.5% vs 13.9%，P=0.52）。停止使用降压药物与痴呆的风险增加两倍相关[风险比（HR）（95%置信区间）=2.15（1.15-4.03）]，经性别、血压、降压药物和其他药物数量以及中风、心血管疾病、糖尿病、吸烟、记忆力减退和 MMSE 评分调整后，风险比有所减弱[HR=1.92（1.01-3.65）]，此外还调整了痴呆和/或死亡率的合并风险[HR=1.79（0.93-3.44）]。停止使用降压药物与痴呆和/或死亡率的合并风险增加约 50%相关[HR=1.58（1.04-2.40）；模型 2：HR=1.64（1.07-2.51）；模型 3：HR=1.49（0.96-2.30）]。停止使用降压药物与记忆减退的变化无关[比值比（95%置信区间）=0.96（0.55-1.67）]。针对潜在偏倚和混杂因素的亚组和敏感性分析得出了类似的结果。
结论/意义：我们的结果表明，社区居住的老年人停止使用降压药物并不能保持认知功能，实际上可能会增加痴呆的风险。这不是由于作为竞争风险的死亡率降低所致。进一步的分析表明，结果不太可能因混杂、反向因果关系或观察性偏倚而解释。针对降压药物停药具体原因的研究可能能够完全排除反向因果关系。鉴于降压药物对心血管风险的有益影响，观察性数据可能是目前关于老年人何时停止使用降压药物可以接受以及需要权衡哪些后果的最紧迫问题的最佳数据。
