目的:先前的随机对照试验和纵向研究表明,在晚年持续使用抗高血压药物可降低全因痴呆的风险,但对阿尔茨海默痴呆(AD)和非AD风险的具体影响尚不清楚.这项研究调查了以前使用高血压或抗高血压药物是否会改变晚年的AD或非AD风险,以及在不同的队列研究中降低风险的理想血压(BP)。
方法:该个体参与者数据荟萃分析包括来自先前存在的联盟的基于社区的衰老纵向研究。主要结果是发生AD和非AD的风险。主要暴露为高血压病史/使用降压药物和基线收缩压/舒张压。使用混合效应Cox比例风险模型来评估风险,并应用自然样条来建模BP与痴呆结果之间的关系。主要模型控制年龄,年龄2,性别,教育,小鼠组,和研究队列。补充分析包括一个完全调整的模型,一项针对随访时间>5年的分析,以及检查年龄调节作用的模型,性别,和小鼠组。
结果:分析中有来自14个国家的31,250名参与者(41%为男性),平均基线年龄为72岁(SD7.5,范围60-110)。未经治疗的高血压参与者与“健康对照”和接受治疗的高血压患者相比,AD的风险增加了36%(风险比[HR]1.36,95%CI1.01-1.83,p=0.0406)和42%(HR1.42,95%CI1.08-1.87,p=0.0135),分别。与“健康对照”相比,接受治疗的高血压患者(HR1.29,95%CI1.03-1.60,p=0.0267)和未经治疗的高血压患者(HR1.69,95%CI1.19-2.40,p=0.0032)的非AD风险更高,但治疗组与未治疗组之间没有差异。基线舒张压血压与非AD风险有显著的U型关系(p=0.0227),在一项分析中仅限于5年随访者,但基线BP与AD或非AD风险之间没有显著关系.
结论:使用抗高血压药与降低AD风险相关,但与晚年非AD风险无关。这表明,在整个生命后期治疗高血压仍然是缓解AD风险的关键。单一的血压测量与AD风险无关,但DBP可能与晚年较长时期的非AD风险呈U型关系.
OBJECTIVE: Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies.
METHODS: This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age2, sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group.
RESULTS: There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with \"healthy controls\" and those with treated hypertension, respectively. Compared with \"healthy controls\" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship (p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk.
CONCLUSIONS: Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.