Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Center for Biomedical Semantics and Data Intelligence, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Department of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, FL 32224, USA.
EBioMedicine. 2024 Nov;109:105378. doi: 10.1016/j.ebiom.2024.105378. Epub 2024 Oct 3.
Findings regarding the protective effect of Angiotensin II receptor blockers (ARBs) against Alzheimer's disease and related dementias (AD/ADRD) and cognitive decline have been inconclusive.
Individuals with hypertension who do not have any prior ADRD diagnosis were included in this retrospective cohort study from Optum's de-identified Clinformatics® Data Mart. We identified antihypertensive medication (AHM) drug classes and subclassified ARBs by blood-brain barrier (BBB) permeability. We compared baseline characteristics and used the Kaplan-Meier (KM) survival curve and adjusted Cox proportional hazards (PH) model for survival analyses.
From 6,390,826 individuals with hypertension, there were 1,839,176 ARB users, 3,366,841 non-ARB AHM users, and 1,184,809 AHM non-users. The unadjusted KM curve showed that ARB users had lower cumulative hazard than other AHM users or AHM non-users (P < 0.0001). In Cox PH analysis, ARB users showed a 20% lower adjusted hazard of developing ADRD compared to angiotensin-converting enzyme inhibitor (ACEI) users and a 29% and 18% reduced hazard when compared to non-ARB/ACEI AHM users and AHM non-users (all P < 0.0001). Consumption of BBB-crossing ARBs was linked to a lower hazard of ADRD development than non-BBB-crossing ARBs, undetermined ARBs, and non-consumption of AHMs by 11%, 25%, and 31% (all P < 0.0001).
This study suggests that ARBs are superior to ACEIs, non-ARB/ACEI AHMs, or non-use of AHMs in reducing the hazard of ADRD among patients with hypertension. Also, BBB-permeability in ARBs was associated with lower ADRD incidence. There is no cure for AD, ADRD, or vascular dementia; hence, these findings are significant in preventing those disorders in an inexpensive, convenient, and safe way. Limitations in claims data should be considered when interpreting our findings.
This research was supported by the National Institute on Aging grants (R01AG084236, R01AG083039, RF1AG072799, R56AG074604).
血管紧张素 II 受体阻滞剂 (ARB) 对阿尔茨海默病和相关痴呆症 (AD/ADRD) 及认知能力下降的保护作用的研究结果尚无定论。
本回顾性队列研究纳入了来自 Optum 去识别 Clinformatics® Data Mart 的高血压患者，这些患者无任何 AD/ADRD 诊断。我们确定了降压药物 (AHM) 药物类别，并根据血脑屏障 (BBB) 通透性对 ARB 进行了亚分类。我们比较了基线特征，并使用 Kaplan-Meier (KM) 生存曲线和调整后的 Cox 比例风险 (PH) 模型进行生存分析。
在 6390826 例高血压患者中，有 1839176 例 ARB 使用者、3366841 例非 ARB AHM 使用者和 1184809 例 AHM 非使用者。未经调整的 KM 曲线显示，ARB 使用者的累积风险低于其他 AHM 使用者或 AHM 非使用者 (P<0.0001)。在 Cox PH 分析中，与血管紧张素转换酶抑制剂 (ACEI) 使用者相比，ARB 使用者发生 AD/ADRD 的调整后风险降低了 20%，与非 ARB/ACEI AHM 使用者和 AHM 非使用者相比，风险分别降低了 29%和 18% (均 P<0.0001)。与非 BBB 穿透性 ARB、未确定的 ARB 和不使用 AHM 相比，穿透 BBB 的 ARB 的使用与 AD/ADRD 发展风险降低 11%、25%和 31%相关 (均 P<0.0001)。
本研究表明，与 ACEI、非 ARB/ACEI AHM 或不使用 AHM 相比，ARB 可降低高血压患者发生 AD/ADRD 的风险。此外，ARB 的 BBB 通透性与较低的 AD/ADRD 发生率相关。AD、AD/ADRD 或血管性痴呆目前尚无治愈方法；因此，以一种廉价、方便且安全的方式发现这些疾病并进行预防，这一发现具有重要意义。在解释我们的研究结果时，应考虑到索赔数据的局限性。
这项研究得到了美国国立卫生研究院拨款的支持（R01AG084236、R01AG083039、RF1AG072799、R56AG074604）。
