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强化与标准血压控制与脑小血管病生物标志物区域性变化的关联:SPRINT MIND 随机临床试验的事后二次分析。

Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers: Post Hoc Secondary Analysis of the SPRINT MIND Randomized Clinical Trial.

机构信息

Neuroimage Analytics Laboratory and the Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio.

Department of Neurology, University of Florida, Gainesville.

出版信息

JAMA Netw Open. 2023 Mar 1;6(3):e231055. doi: 10.1001/jamanetworkopen.2023.1055.

Abstract

IMPORTANCE

Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers.

OBJECTIVE

To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF).

DESIGN, SETTING, AND PARTICIPANTS: The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022.

INTERVENTIONS

At baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment.

MAIN OUTCOMES AND MEASURES

The main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest).

RESULTS

At baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]).

CONCLUSIONS AND RELEVANCE

This study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT01206062.

摘要

重要性

对于严格的血压(BP)控制与小血管疾病标志物的微观结构变化之间的关联,人们知之甚少。

目的

研究强化与标准 BP 控制与小血管疾病生物标志物(如白质病变[WML]、分数各向异性[FA]、平均弥散度[MD]和脑血流[CBF])的区域性关联。

设计、地点和参与者:收缩期血压干预试验(SPRINT)是一项多中心随机临床试验,比较了强化收缩压(SBP)控制(SBP 目标<120mmHg)与标准控制(SBP 目标<140mmHg)在 50 岁或以上有高血压且无糖尿病或中风史的患者中的疗效。研究于 2010 年 11 月 8 日开始随机分组,于 2016 年 7 月 1 日停止,随访时间约为 4 年。共有 670 名和 458 名参与者分别在基线和随访时完成了脑部磁共振成像,他们构成了本事后分析的队列。本事后分析的统计分析于 2020 年 8 月至 2022 年 10 月进行。

干预

在基线时,355 名参与者接受强化 SBP 治疗,315 名参与者接受标准 SBP 治疗。

主要结局和测量

主要结局是 WML、FA、MD(在白质感兴趣区)和 CBF(在灰质感兴趣区)的区域性变化。

结果

在基线时,355 名参与者(平均[标准差]年龄,67.7[8.0]岁;200 名男性[56.3%])接受强化 BP 治疗,315 名参与者(平均[标准差]年龄,67.0[8.4]岁;199 名男性[63.2%])接受标准 BP 治疗。与标准治疗相比,强化治疗与 WML 体积的平均增加较小(644.5mm3 与 1258.1mm3)。这种较小的平均增加主要发生在左侧前冠状辐射的深部白质区域(强化治疗,30.3mm3[95%置信区间,16.0-44.5mm3];标准治疗,80.5mm3[95%置信区间,53.8-107.2mm3])、左侧 tapetum(强化治疗,11.8mm3[95%置信区间,4.4-19.2mm3];标准治疗,27.2mm3[95%置信区间,19.4-35.0mm3])、左侧额顶枕束(强化治疗,3.2mm3[95%置信区间,0.7-5.8mm3];标准治疗,9.4mm3[95%置信区间,5.5-13.4mm3])、左侧后冠状辐射(强化治疗,26.0mm3[95%置信区间,12.9-39.1mm3];标准治疗,52.3mm3[95%置信区间,34.8-69.8mm3])、左侧胼胝体压部(强化治疗,45.4mm3[95%置信区间,25.1-65.7mm3];标准治疗,83.0mm3[95%置信区间,58.7-107.2mm3])、左侧丘脑后辐射(强化治疗,53.0mm3[95%置信区间,29.8-76.2mm3];标准治疗,106.9mm3[95%置信区间,73.4-140.3mm3])和右侧丘脑后辐射(强化治疗,49.5mm3[95%置信区间,24.3-74.7mm3];标准治疗,102.6mm3[95%置信区间,71.0-134.2mm3])。

结论和相关性

本研究表明,与标准治疗相比,强化 BP 治疗与 WML 增加较慢、扩散张量成像改善以及几个代表脆弱区域的脑区的 FA 和 CBF 变化相关,这些区域可能受益于更严格的 BP 控制。

试验注册

ClinicalTrials.gov 标识符:NCT01206062。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c75/9978954/3d180d3493cc/jamanetwopen-e231055-g001.jpg

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