Department of Public Health Sciences, University of California Davis School of Medicine, Davis.
Department of Neurology, University of California Davis School of Medicine, Sacramento.
JAMA Netw Open. 2023 Apr 3;6(4):e236431. doi: 10.1001/jamanetworkopen.2023.6431.
The association between hypertension developed before midlife and late-life brain health is understudied and, because of the cardioprotective benefits of estrogen before menopause, may differ by sex.
To assess the association of early adulthood hypertension and blood pressure (BP) change with late-life neuroimaging biomarkers and examine potential sex differences.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Study of Healthy Aging in African Americans (STAR) and Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, which were harmonized longitudinal cohorts of racially and ethnically diverse adults aged 50 years and older from the San Francisco Bay area and Sacramento Valley in California. The STAR was conducted from November 6, 2017, to November 5, 2021, and the KHANDLE study was conducted from April 27, 2017, to June 15, 2021. The current study included 427 participants from the KHANDLE and STAR studies who received health assessments between June 1, 1964, and March 31, 1985. Regional brain volumes and white matter (WM) integrity were measured via magnetic resonance imaging between June 1, 2017, and March 1, 2022.
Hypertension status (normotension, transition to hypertension, and hypertension) and BP change (last measure minus first measure) were assessed at 2 multiphasic health checkups (MHCs; 1964-1985) in early adulthood (ages 30-40 years).
Regional brain volumes and WM integrity were measured using 3T magnetic resonance imaging and z standardized. General linear models adjusted for potential confounders (demographic characteristics and study [KHANDLE or STAR]) were used to assess the association of hypertension and BP change with neuroimaging biomarkers. Sex interactions were tested.
Among 427 participants, median (SD) ages were 28.9 (7.3) years at the first MHC, 40.3 (9.4) years at the last MHC, and 74.8 (8.0) years at neuroimaging. A total of 263 participants (61.6%) were female and 231 (54.1%) were Black. Overall, 191 participants (44.7%) had normotension, 68 (15.9%) transitioned to hypertension, and 168 (39.3%) had hypertension. Compared with participants who had normotension, those who had hypertension and those who transitioned to hypertension had smaller cerebral volumes (hypertension: β = -0.26 [95% CI, -0.41 to -0.10]; transition to hypertension: β = -0.23 [95% CI, -0.44 to -0.23]), with similar differences in cerebral gray matter volume (hypertension: β = -0.32 [95% CI, -0.52 to -0.13]; transition to hypertension: β = -0.30 [95% CI, -0.56 to -0.05]), frontal cortex volume (hypertension: β = -0.43 [95% CI, -0.63 to -0.23]; transition to hypertension: β = -0.27 [95% CI, -0.53 to 0]), and parietal cortex volume (hypertension: β = -0.22 [95% CI, -0.42 to -0.02]; transition to hypertension: β = -0.29 [95% CI, -0.56 to -0.02]). Participants with hypertension also had smaller hippocampal volume (β = -0.22; 95% CI, -0.42 to -0.02), greater ventricular volumes (lateral ventricle: β = 0.44 [95% CI, 0.25-0.63]; third ventricle: β = 0.20 [95% CI, 0.01-0.39]), larger free water volume (β = 0.35; 95% CI, 0.18-0.52), and lower fractional anisotropy (β = -0.26; 95% CI, -0.45 to -0.08) than those who had normotension. Holding hypertension status constant, a 5-mm Hg increase in systolic BP was associated with smaller temporal cortex volume (β = -0.03; 95% CI, -0.06 to -0.01), while a 5-mm Hg increase in diastolic BP was associated with smaller parietal cortex volume (β = -0.06; 95% CI, -0.10 to -0.02). The negative association of hypertension and BP change with regional brain volumes appeared stronger in men than women for some regions.
In this cohort study, early adulthood hypertension and BP change were associated with late-life volumetric and WM differences implicated in neurodegeneration and dementia. Sex differences were observed for some brain regions whereby hypertension and increasing BP appeared more detrimental for men. These findings suggest that prevention and treatment of hypertension in early adulthood is important for late-life brain health, particularly among men.
中年前和老年期高血压与大脑健康之间的关联尚未得到充分研究，由于雌激素对绝经前心脏有保护作用，这种关联可能因性别而异。
评估成年早期高血压和血压变化与晚年神经影像学生物标志物的关系，并检查潜在的性别差异。
设计、地点和参与者：本队列研究使用了来自非裔美国人健康老龄化研究（STAR）和凯撒健康老龄化和多样化生活经验研究（KHANDLE）的综合纵向队列的数据，这些数据来自加利福尼亚州旧金山湾区和萨克拉门托谷地区年龄在 50 岁及以上的不同种族和族裔的成年人。STAR 于 2017 年 11 月 6 日至 2021 年 11 月 5 日进行，KHANDLE 于 2017 年 4 月 27 日至 2021 年 6 月 15 日进行。本研究包括来自 KHANDLE 和 STAR 研究的 427 名参与者，他们在 1964 年 6 月 1 日至 1985 年 3 月 31 日期间接受了健康评估。通过磁共振成像在 2017 年 6 月 1 日至 2022 年 3 月 1 日之间测量了区域性脑容量和白质（WM）完整性。
在两次多相健康检查（MHC；1964-1985 年）中评估了成年早期（30-40 岁）的高血压状况（正常血压、过渡到高血压和高血压）和血压变化（最后一次测量值减去第一次测量值）。
使用 3T 磁共振成像和 z 标准化测量区域性脑容量和 WM 完整性。使用调整了潜在混杂因素（人口统计学特征和研究[KHANDLE 或 STAR]）的一般线性模型评估高血压和血压变化与神经影像学生物标志物的关系。测试了性别间的相互作用。
在 427 名参与者中，第一次 MHC 的中位（SD）年龄为 28.9（7.3）岁，最后一次 MHC 的中位（SD）年龄为 40.3（9.4）岁，神经影像学检查的中位（SD）年龄为 74.8（8.0）岁。共有 263 名参与者（61.6%）为女性，231 名（54.1%）为黑人。总体而言，191 名参与者（44.7%）血压正常，68 名（15.9%）血压过渡到高血压，168 名（39.3%）血压持续高血压。与血压正常的参与者相比，高血压和血压过渡到高血压的参与者大脑体积较小（高血压：β=-0.26[95%CI，-0.41 至-0.10]；过渡到高血压：β=-0.23[95%CI，-0.44 至-0.23]），大脑灰质体积差异相似（高血压：β=-0.32[95%CI，-0.52 至-0.13]；过渡到高血压：β=-0.30[95%CI，-0.56 至-0.05]），额叶皮质体积（高血压：β=-0.43[95%CI，-0.63 至-0.23]；过渡到高血压：β=-0.27[95%CI，-0.53 至-0.02]）和顶叶皮质体积（高血压：β=-0.22[95%CI，-0.42 至-0.02]；过渡到高血压：β=-0.29[95%CI，-0.56 至-0.02]）。高血压患者的海马体体积也较小（β=-0.22；95%CI，-0.42 至-0.02），侧脑室体积较大（β=0.44[95%CI，0.25-0.63]），第三脑室体积较大（β=0.20[95%CI，0.01-0.39]），自由水体积较大（β=0.35[95%CI，0.18-0.52]），各向异性分数较低（β=-0.26[95%CI，-0.45 至-0.08]）。与血压正常的参与者相比，收缩压增加 5mmHg 与颞叶皮质体积减少相关（β=-0.03[95%CI，-0.06 至-0.01]），而舒张压增加 5mmHg 与顶叶皮质体积减少相关（β=-0.06[95%CI，-0.10 至-0.02]）。在一些区域，成年早期高血压和血压变化与与神经退行性变和痴呆有关的区域脑容量和 WM 差异之间的关联在男性中似乎比女性更强。
在这项队列研究中，成年早期的高血压和血压变化与晚年体积和 WM 差异有关，这些差异与神经退行性变和痴呆有关。一些脑区的性别差异观察到，高血压和血压升高对男性的影响更为不利。这些发现表明，预防和治疗成年早期的高血压对晚年大脑健康很重要，尤其是对男性。
