Antihypertensive medications and risk for incident dementia and Alzheimer's disease: a meta-analysis of individual participant data from prospective cohort studies,The Lancet Neurology

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Antihypertensive medications and risk for incident dementia and Alzheimer's disease: a meta-analysis of individual participant data from prospective cohort studies
The Lancet Neurology ( IF 46.5 ) Pub Date : 2020-01-01 , DOI: 10.1016/s1474-4422(19)30393-x
Jie Ding ₁ , Kendra L Davis-Plourde ₂ , Sanaz Sedaghat ₃ , Phillip J Tully ₄ , Wanmei Wang ₅ , Caroline Phillips ₁ , Matthew P Pase ₆ , Jayandra J Himali ₂ , B Gwen Windham ₅ , Michael Griswold ₅ , Rebecca Gottesman ₇ , Thomas H Mosley ₅ , Lon White ₈ , Vilmundur Guðnason ₉ , Stéphanie Debette ₄ , Alexa S Beiser ₂ , Sudha Seshadri ₁₀ , M Arfan Ikram ₁₁ , Osorio Meirelles ₁ , Christophe Tzourio ₄ , Lenore J Launer ₁

Affiliation

Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; The Framingham Heart Study, Framingham, MA, USA.
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Université Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux, Bordeaux, France.
University of Mississippi Medical Center, The MIND Center, Jackson, MS, USA.
The Framingham Heart Study, Framingham, MA, USA; Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia; Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, VIC, Australia.
Johns Hopkins Medical Institutes, Baltimore, MD, USA.
Pacific Health Research and Education Institute, Honolulu, HI, USA.
Icelandic Heart Association, Kopavogur, Iceland; University of Iceland, Reykjavik, Iceland.
The Framingham Heart Study, Framingham, MA, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.

BACKGROUND Dementia is a major health concern for which prevention and treatment strategies remain elusive. Lowering high blood pressure with specific antihypertensive medications (AHMs) could reduce the burden of disease. We investigated whether specific AHM classes reduced the risk for dementia. METHODS We did a meta-analysis of individual participant data from eligible observational studies published between Jan 1, 1980, and Jan 1, 2019. Cohorts were eligible for inclusion if they prospectively recruited community-dwelling adults; included more than 2000 participants; collected data for dementia events over at least 5 years; had measured blood pressure and verified use of AHMs; included in-person exams, supplemented with additional data, to capture dementia events; and had followed up cases for mortality. We assessed the association of incident dementia and clinical Alzheimer's disease with use of five AHM classes, within strata of baseline high (systolic blood pressure [SBP] ≥140 mm Hg or diastolic blood pressure [DBP] ≥90 mm Hg) and normal (SBP <140 mm Hg and DBP <90 mm Hg) blood pressure. We used a propensity score to control for confounding factors related to the probability of receiving AHM. Study-specific effect estimates were pooled using random-effects meta-analyses. RESULTS Six prospective community-based studies (n=31 090 well phenotyped dementia-free adults older than 55 years) with median follow-ups across cohorts of 7-22 years were eligible for analysis. There were 3728 incident cases of dementia and 1741 incident Alzheimer's disease diagnoses. In the high blood pressure stratum (n=15 537), those using any AHM had a reduced risk for developing dementia (hazard ratio [HR] 0·88, 95% CI 0·79-0·98; p=0·019) and Alzheimer's disease (HR 0·84, 0·73-0·97; p=0·021) compared with those not using AHM. We did not find any significant differences between one drug class versus all others on risk of dementia. In the normal blood pressure stratum (n=15 553), there was no association between AHM use and incident dementia or Alzheimer's disease. INTERPRETATION Over a long period of observation, no evidence was found that a specific AHM drug class was more effective than others in lowering risk of dementia. Among people with hypertensive levels of blood pressure, use of any AHM with efficacy to lower blood pressure might reduce the risk for dementia. These findings suggest future clinical guidelines for hypertension management should also consider the beneficial effect of AHM on the risk for dementia. FUNDING The Alzheimer's Drug Discovery Foundation and the National Institute on Aging Intramural Research Program.

中文翻译：

抗高血压药物与痴呆和阿尔茨海默氏病的风险：前瞻性队列研究中个体参与者数据的荟萃分析

背景痴呆症是一个主要的健康问题，其预防和治疗策略仍然难以捉摸。使用特定的抗高血压药物（AHM）降低高血压可以减轻疾病负担。我们调查了特定的 AHM 类别是否可以降低患痴呆症的风险。方法我们对 1980 年 1 月 1 日至 2019 年 1 月 1 日期间发表的符合条件的观察性研究中的个体参与者数据进行了荟萃分析。包括超过2000名参与者；收集至少 5 年的痴呆事件数据；测量了血压并验证了 AHM 的使用；包括现场检查，辅以额外数据，以捕获痴呆症事件；并对死亡病例进行了随访。我们使用五个 AHM 类别，在基线高（收缩压 [SBP] ≥140 mm Hg 或舒张压 [DBP] ≥90 mm Hg）和正常（SBP）层内评估了痴呆事件与临床阿尔茨海默氏病的关联。 <140 mm Hg 和 DBP <90 mm Hg) 血压。我们使用倾向评分来控制与接收 AHM 的概率相关的混杂因素。使用随机效应荟萃分析汇总研究特定效应估计。结果六项基于社区的前瞻性研究（n = 31 090 名 55 岁以上表型良好的无痴呆成年人）的中位随访时间为 7-22 年，符合分析资格。共有 3728 例痴呆症病例和 1741 例阿尔茨海默病诊断病例。在高血压人群 (n=15 537) 中，使用任何 AHM 的患者患痴呆症的风险降低（风险比 [HR] 0·88，95% CI 0·79-0·98；p=0·019 ）和阿尔茨海默病（HR 0·84、0·73-0·97；p=0·021）与不使用 AHM 的患者相比。我们没有发现某一类药物与所有其他药物类别在痴呆风险方面存在任何显着差异。在正常血压层（n=15 553）中，AHM 的使用与痴呆或阿尔茨海默病的发生之间没有关联。解释经过长期观察，没有发现任何证据表明特定 AHM 药物类别在降低痴呆风险方面比其他药物更有效。对于高血压患者，使用任何有效降低血压的 AHM 都可能降低患痴呆症的风险。这些发现表明，未来高血压管理的临床指南还应考虑 AHM 对痴呆风险的有益影响。资助阿尔茨海默病药物发现基金会和国家老龄化研究所校内研究计划。

更新日期：2020-01-01

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