Hypertension is a risk factor for cognitive decline and dementia, as well as the most common condition observed in primary care in older adults. Over 70% of adults aged 65 years or older in the United States have blood pressure levels necessitating treatment. Promisingly, previous work has suggested that treating hypertension can stave off not only cognitive decline but also the development of neuropathology. However, which blood pressure drugs may be the most beneficial remains to be fully elucidated. Drugs targeting the renin-angiotensin system, namely, angiotensin II receptor blockers and ACE (angiotensin-converting-enzyme) inhibitors, have been highlighted as possibly conferring the greatest benefit. This may be because the renin-angiotensin system in the brain is implicated in functions critical to cognition, including neuronal differentiation and nerve regeneration. We examined the effect of a particular pharmacokinetic property of angiotensin II receptor blockers and ACE-inhibitors—namely, whether or not they cross the blood-brain barrier (BBB). We hypothesized that BBB-crossing drugs may positively impact cognition through increased neuronal effects. We harmonized data from cognitively normal participants from 14 aging cohorts across 6 countries (Australia, Canada, Germany, Ireland, Japan, United States), for a total of 12 849 individuals. We compared individuals who took BBB-crossing drugs to those who had taken non-BBB-penetrant drugs. Meta-analyses showed that individuals taking BBB-crossing drugs exhibited better memory recall over up to 3 years of follow-up, relative to those taking nonpenetrant medications. This finding has implications for hypertensive individuals who remain symptom-free but who may experience future cognitive benefit from simply changing their antihypertensive regimen.

Chronic sleep debt is highly prevalent and the current American College of Cardiology/American Heart Association guidelines for primary prevention of cardiovascular disease recognize sleep deficiency as a cardiovascular risk factor. Compelling epidemiological data link insufficient sleep to the risk of hypertension and suggest that women and younger individuals are particularly vulnerable. Nonetheless, experimental human studies in support of this observational evidence are lacking. We conducted a randomized, controlled, crossover, 16-day inpatient study showing that young, healthy individuals undergoing a sleep restriction protocol exhibited an increase in 24-hour and sleep blood pressure compared with the control sleep condition. Blood pressure effects were especially prominent and sustained in women, in whom systolic blood pressure increased up to 11 mm Hg. Endothelial dysfunction and norepinephrine increases accompanied blood pressure changes, suggesting activation of several cardiovascular disease mechanisms in response to sleep curtailment. Importantly, such adverse effects only partially reversed upon resumption of normal sleep. Thus, we provide experimental evidence that insufficient sleep poses a significant health hazard because it raises blood pressure and is likely a precursor of hypertension and cardiovascular disease. Our findings further substantiate epidemiological data of sex-dependent vulnerability to sleep loss and may implicate insufficient sleep in the recent observations of divergent blood pressure trajectories in men and women, with women exhibiting more rapid progression toward hypertension from a relatively young age.

Increased aortic pulse wave velocity, a measure of cardiovascular disease (CVD) risk, can be detected in childhood, with some individuals following a steeper trajectory of risk. Mechanistic processes underlying CVD risk may operate before birth in some cases and are not determined solely by inherited fixed genetic factors. Interaction between the fetal genome and the developmental environment of the fetus, transduced by the mother and influenced by her diet, body composition, and behavior can result in epigenetic changes to the child’s genome. By measuring genome-wide genetic and epigenetic marks in umbilical cord blood at birth we derived a set of 14 mechanistically plausible DNA methylation sites which, together with other covariates, explained 45.4% of the variance in late childhood pulse wave velocity. This observation provides proof of principle for development of predictive tools of future CVD risk, more predictive than genetic risks alone, to identify children who would particularly benefit from measures to promote healthy behaviors including diet and physical activity. Because a child’s later CVD risk trajectory could start in utero, our observations that maternal weight gain and nutrition during pregnancy influence the epigenetic biomarkers of cardiovascular risk identified in cord blood offers a new avenue for preventive interventions. Since these factors operate from early gestation, greater emphasis needs to be placed on promoting healthy nutrition, body weight, and lifestyle in the preconception period in women and their partners. Unlike deterministic genetic risks, these findings offer an optimistic message about reducing CVD risk in current and future generations.

高血压是认知能力下降和痴呆的危险因素，也是老年人初级保健中最常见的疾病。在美国 65 岁或以上的成年人中，超过 70% 的血压水平需要治疗。令人鼓舞的是，以前的工作表明，治疗高血压不仅可以防止认知能力下降，还可以防止神经病理学的发展。然而，哪些降压药可能是最有益的仍有待充分阐明。靶向肾素-血管紧张素系统的药物，即血管紧张素 II 受体阻滞剂和 ACE（血管紧张素转换酶）抑制剂，已被强调为可能带来最大益处。这可能是因为大脑中的肾素-血管紧张素系统与对认知至关重要的功能有关，包括神经元分化和神经再生。我们检查了血管紧张素 II 受体阻滞剂和 ACE 抑制剂的特定药代动力学特性的影响，即它们是否穿过血脑屏障 (BBB)。我们假设 BBB 交叉药物可能通过增加神经元效应对认知产生积极影响。我们统一了来自 6 个国家（澳大利亚、加拿大、德国、爱尔兰、日本、美国）的 14 个老龄队列的认知正常参与者的数据，共计 12849 人。我们将服用 BBB 交叉药物的个体与服用非 BBB 渗透药物的个体进行了比较。荟萃分析表明，与服用非渗透性药物的人相比，服用 BBB 穿越药物的人在长达 3 年的随访中表现出更好的记忆力。

慢性睡眠债务非常普遍，目前美国心脏病学会/美国心脏协会心血管疾病一级预防指南将睡眠不足​​视为心血管危险因素。令人信服的流行病学数据将睡眠不足​​与高血压风险联系起来，并表明女性和年轻人尤其容易受到伤害。尽管如此，缺乏支持这种观察证据的实验性人体研究。我们进行了一项随机、对照、交叉、为期 16 天的住院研究，结果表明，与对照睡眠条件相比，接受睡眠限制方案的年轻健康个体的 24 小时血压和睡眠血压升高。血压影响在女性中尤为突出和持续，其中收缩压升高至 11 毫米汞柱。内皮功能障碍和去甲肾上腺素升高伴随着血压变化，表明睡眠减少会激活几种心血管疾病机制。重要的是，这种不利影响在恢复正常睡眠后仅部分逆转。因此，我们提供了实验证据，证明睡眠不足会对健康构成重大危害，因为它会升高血压，并且可能是高血压和心血管疾病的先兆。我们的研究结果进一步证实了性别依赖的睡眠不足易感性的流行病学数据，并且在最近对男性和女性不同血压轨迹的观察中可能暗示睡眠不足，女性从相对年轻的时候就表现出更快的高血压进展。

主动脉脉搏波速度增加，这是衡量心血管疾病 (CVD) 风险的一种指标，可以在儿童时期检测到，有些人的风险轨迹更陡峭。在某些情况下，潜在 CVD 风险的机制过程可能在出生前就开始运作，并不仅仅由遗传的固定遗传因素决定。胎儿基因组与胎儿发育环境之间的相互作用、由母亲转导并受其饮食、身体成分和行为的影响，可导致儿童基因组的表观遗传变化。通过测量出生时脐带血中的全基因组遗传和表观遗传标记，我们得出了一组 14 个机械上合理的 DNA 甲基化位点，这些位点与其他协变量一起解释了儿童晚期脉搏波速度变化的 45.4%。这一观察结果为开发未来 CVD 风险的预测工具提供了原理证明，比单独的遗传风险更具预测性，以确定哪些儿童会特别受益于促进健康行为的措施，包括饮食和身体活动。因为孩子以后的 CVD 风险轨迹可以在子宫内开始，我们观察到母亲怀孕期间体重增加和营养会影响脐带血中确定的心血管风险表观遗传生物标志物，这为预防干预提供了新途径。由于这些因素从妊娠早期开始起作用，因此需要更加重视促进女性及其伴侣在孕前阶段的健康营养、体重和生活方式。与确定性遗传风险不同，