血压降低与痴呆症预防：一项个体患者数据的荟萃分析。

Blood pressure lowering and prevention of dementia: an individual patient data meta-analysis.

作者信息

Peters Ruth, Xu Ying, Fitzgerald Oisin, Aung Htein Linn, Beckett Nigel, Bulpitt Christopher, Chalmers John, Forette Francoise, Gong Jessica, Harris Katie, Humburg Peter, Matthews Fiona E, Staessen Jan A, Thijs Lutgarde, Tzourio Christophe, Warwick Jane, Woodward Mark, Anderson Craig S

机构信息

Neuroscience Research Australia, Barker Street, Randwick, Sydney, New South Wales 2031, Australia.

Faculty of Science, University of New South Wales, High Street Kensington, Sydney, New South Wales 2052, Australia.

出版信息

Eur Heart J. 2022 Dec 21;43(48):4980-4990. doi: 10.1093/eurheartj/ehac584.

DOI:10.1093/eurheartj/ehac584

PMID:36282295

Abstract

AIMS

Observational studies indicate U-shaped associations of blood pressure (BP) and incident dementia in older age, but randomized controlled trials of BP-lowering treatment show mixed results on this outcome in hypertensive patients. A pooled individual participant data analysis of five seminal randomized double-blind placebo-controlled trials was undertaken to better define the effects of BP-lowering treatment for the prevention of dementia.

METHODS AND RESULTS

Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, and presence of prior stroke. Mediation analysis was used to quantify the contribution of trial medication and changes in systolic and diastolic BP on risk of dementia. The total sample included 28 008 individuals recruited from 20 countries. After a median follow-up of 4.3 years, there were 861 cases of incident dementia. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval: 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4 mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age or sex. Mediation analysis confirmed the greater fall in BP in the actively treated group was associated with a greater reduction in dementia risk.

CONCLUSION

The first single-stage individual patient data meta-analysis from randomized double-blind placebo-controlled clinical trials provides evidence to support benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential for additional BP lowering in those with already well-controlled hypertension and of antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia.

CLASSIFICATION OF EVIDENCE

Class I evidence in favour of antihypertensive treatment reducing risk of incident dementia compared with placebo.

摘要

目的

观察性研究表明，老年人群中血压（BP）与新发痴呆呈U型关联，但降压治疗的随机对照试验在高血压患者的这一结局上显示出混合结果。进行了一项对五项开创性随机双盲安慰剂对照试验的个体参与者数据汇总分析，以更好地确定降压治疗对预防痴呆的效果。

方法与结果

采用多水平逻辑回归评估对新发痴呆的治疗效果。对包括年龄、基线收缩压、性别和既往中风史在内的关键人群特征进行效应修饰评估。采用中介分析量化试验药物以及收缩压和舒张压变化对痴呆风险的贡献。总样本包括从20个国家招募的28008名个体。中位随访4.3年后，有861例新发痴呆病例。多水平逻辑回归报告，平均血压降低10/4 mmHg时，支持降压治疗降低新发痴呆风险的调整优势比为0.87（95%置信区间：0.75，0.99）。考虑死亡作为竞争风险的进一步多项回归得出了类似结果。年龄或性别未产生效应修饰。中介分析证实，积极治疗组中更大的血压下降与痴呆风险的更大降低相关。