血管紧张素 II 刺激型抗高血压药物的使用与痴呆风险的关联：PreDIVA 试验的事后分析。
Association of Angiotensin II-Stimulating Antihypertensive Use and Dementia Risk: Post Hoc Analysis of the PreDIVA Trial.
机构信息
From the Departments of Neurology (J.W.v.D., W.A.v.G., E.R.) and General Practice (E.P.M.v.C.), Amsterdam UMC, University of Amsterdam; Department of Neurology (J.W.v.D., E.R.), Donders Institute for Brain, Behaviour and Cognition, Radboud University Medical Centre, Nijmegen, the Netherlands; Schools of Pharmacy (Z.A.M., S.L.G., D.B.) and Medicine (P.K.C.), University of Washington; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.
出版信息
Neurology. 2021 Jan 5;96(1):e67-e80. doi: 10.1212/WNL.0000000000010996. Epub 2020 Nov 5.
OBJECTIVE
To assess whether angiotensin II-stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin I receptor blockers) convey a lower risk of incident dementia compared to angiotensin II-inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, β-blockers, and nondihydropyridine calcium channel blockers), in accordance with the "angiotensin hypothesis."
METHODS
We performed Cox regression analyses of incident dementia (or mortality as competing risk) during 6-8 years of follow-up in a population sample of 1,909 community-dwelling individuals (54% women) without dementia, aged 70-78 (mean 74.5 ± 2.5) years.
RESULTS
After a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin II-stimulating, 8.2% (59/721) in angiotensin II-inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin II-stimulating antihypertensive users had a 45% lower incident dementia rate (hazard ratio [HR], 0.55; 95% CI, 0.34-0.89) without excess mortality (HR, 0.86; 95% CI, 0.64-1.16), and individuals using both types had a nonsignificant 20% lower dementia rate (HR, 0.80; 95% CI,0.53-1.20) without excess mortality (HR, 0.97; 95% CI, 0.76-1.24), compared to angiotensin II-inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease.
CONCLUSIONS
Users of angiotensin II-stimulating antihypertensives had lower dementia rates compared to angiotensin II-inhibiting antihypertensive users, supporting the angiotensin hypothesis. Confounding by indication must be examined further, although subanalyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment.
目的
根据“血管紧张素假说”，评估血管紧张素Ⅱ刺激型降压药（噻嗪类、二氢吡啶类钙通道阻滞剂和血管紧张素Ⅰ受体阻滞剂）与血管紧张素Ⅱ抑制型降压药（血管紧张素转换酶抑制剂、β受体阻滞剂和非二氢吡啶类钙通道阻滞剂）相比，是否能降低痴呆的发病风险。
方法
我们对 1909 名无痴呆的社区居住者（54%为女性）进行了 Cox 回归分析，这些参与者在 6-8 年的随访期间发生了痴呆（或作为竞争风险的死亡率），年龄为 70-78 岁（平均 74.5±2.5 岁）。
结果
中位随访 6.7 年后，1870 名（98%）参与者可获得痴呆状态，1904 名（>99%）参与者可获得死亡率。血管紧张素Ⅱ刺激型组痴呆发病率为 5.6%（27/480），血管紧张素Ⅱ抑制型组为 8.2%（59/721），两种降压药均使用组为 6.9%（46/669）。在调整了包括血压和病史在内的痴呆风险因素后，血管紧张素Ⅱ刺激型降压药使用者的痴呆发病风险降低了 45%（危险比 [HR]，0.55；95%置信区间，0.34-0.89），且无过度死亡率（HR，0.86；95%置信区间，0.64-1.16），两种降压药均使用的患者痴呆发病风险降低了 20%（HR，0.80；95%置信区间，0.53-1.20），且无过度死亡率（HR，0.97；95%置信区间，0.76-1.24），与血管紧张素Ⅱ抑制型降压药使用者相比。基于糖尿病和中风史的亚组分析结果一致，但可能仅适用于无心血管疾病史的个体。
结论
与血管紧张素Ⅱ抑制型降压药使用者相比，使用血管紧张素Ⅱ刺激型降压药的患者痴呆发病率较低，支持血管紧张素假说。需要进一步检查指示性偏倚，但亚组分析表明这并未影响结果。如果得到证实，预防痴呆可能成为接受降压治疗的老年个体的一个强有力的适应证。
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