Henein Michael Y, Vancheri Sergio, Longo Giovanni, Vancheri Federico
Institute of Public Health and Clinical Medicine, Umea University, 90187 Umea, Sweden.
Brunel University, Middlesex, London UB8 3PH, UK.
J Clin Med. 2022 Jul 28;11(15):4405. doi: 10.3390/jcm11154405.
Endothelial dysfunction is one of the earliest manifestations of atherosclerosis, contributing to its development and progression. Mental stress induces endothelial dysfunction through increased activity of the sympathetic nervous system, release of corticotropin-releasing hormone from the hypothalamus, inhibition of nitric oxide (NO) synthesis by cortisol, and increased levels of pro-inflammatory cytokines. Mental-stress-induced increased output of the sympathetic nervous system and concomitant withdrawal of the parasympathetic inflammatory reflex results in systemic inflammation and activation of a neural-hematopoietic-arterial axis. This includes the brainstem and subcortical regions network, bone marrow activation, release of leukocytes into the circulation and their migration to the arterial wall and atherosclerotic plaques. Low-grade, sterile inflammation is involved in all steps of atherogenesis, from coronary plaque formation to destabilisation and rupture. Increased sympathetic tone may cause arterial smooth-muscle-cell proliferation, resulting in vascular hypertrophy, thus contributing to the development of hypertension. Emotional events also cause instability of cardiac repolarisation due to brain lateralised imbalance of cardiac autonomic nervous stimulation, which may lead to asymmetric repolarisation and arrhythmia. Acute emotional stress can also provoke severe catecholamine release, leading to direct myocyte injury due to calcium overload, known as myocytolysis, coronary microvascular vasoconstriction, and an increase in left ventricular afterload. These changes can trigger a heart failure syndrome mimicking acute myocardial infarction, characterised by transient left ventricular dysfunction and apical ballooning, known as stress (Takotsubo) cardiomyopathy. Women are more prone than men to develop mental-stress-induced myocardial ischemia (MSIMI), probably reflecting gender differences in brain activation patterns during mental stress. Although guidelines on CV prevention recognise psychosocial factors as risk modifiers to improve risk prediction and decision making, the evidence that their assessment and treatment will prevent CAD needs further evaluation.
内皮功能障碍是动脉粥样硬化最早的表现之一，促进其发生和发展。精神压力通过交感神经系统活性增加、下丘脑促肾上腺皮质激素释放激素的释放、皮质醇对一氧化氮（NO）合成的抑制以及促炎细胞因子水平的升高来诱导内皮功能障碍。精神压力诱导的交感神经系统输出增加以及副交感神经炎症反射的伴随性撤离导致全身炎症和神经-造血-动脉轴的激活。这包括脑干和皮质下区域网络、骨髓激活、白细胞释放到循环中并迁移到动脉壁和动脉粥样硬化斑块。低度、无菌性炎症参与动脉粥样硬化发生的所有步骤，从冠状动脉斑块形成到不稳定和破裂。交感神经张力增加可能导致动脉平滑肌细胞增殖，导致血管肥大，从而促进高血压的发展。情绪事件还会由于心脏自主神经刺激的脑侧化失衡导致心脏复极不稳定，这可能导致不对称复极和心律失常。急性情绪应激还可引发严重的儿茶酚胺释放，导致因钙超载引起的直接心肌细胞损伤，即心肌溶解、冠状动脉微血管收缩以及左心室后负荷增加。这些变化可引发类似急性心肌梗死的心力衰竭综合征，其特征为短暂性左心室功能障碍和心尖气球样变，即应激（Takotsubo）心肌病。女性比男性更容易发生精神压力诱导的心肌缺血（MSIMI），这可能反映了精神压力期间大脑激活模式的性别差异。尽管心血管预防指南将社会心理因素视为改善风险预测和决策的风险修饰因素，但评估和治疗这些因素能否预防冠心病的证据仍需进一步评估。
