Technical University of Munich, School of Medicine, Department of Prevention, Rehabilitation and Sports Medicine, Germany.
Preventive Cardiology, Ludwig-Maximilians University, Munich, Germany.
Eur J Prev Cardiol. 2020 Mar;27(4):394-406. doi: 10.1177/2047487319869400. Epub 2019 Aug 13.
Despite major efforts to reduce atherosclerotic cardiovascular disease (ASCVD) burden with conventional risk factor control, significant residual risk remains. Recent evidence on non-traditional determinants of cardiometabolic health has advanced our understanding of lifestyle-disease interactions. Chronic exposure to environmental stressors like poor diet quality, sedentarism, ambient air pollution and noise, sleep deprivation and psychosocial stress affect numerous traditional and non-traditional intermediary pathways related to ASCVD. These include body composition, cardiorespiratory fitness, muscle strength and functionality and the intestinal microbiome, which are increasingly recognized as major determinants of cardiovascular health. Evidence points to partially overlapping mechanisms, including effects on inflammatory and nutrient sensing pathways, endocrine signalling, autonomic function and autophagy. Of particular relevance is the potential of low-risk lifestyle factors to impact on plaque vulnerability through altered adipose tissue and skeletal muscle phenotype and secretome. Collectively, low-risk lifestyle factors cause a set of phenotypic adaptations shifting tissue cross-talk from a proinflammatory milieu conducive for high-risk atherosclerosis to an anti-atherogenic milieu. The ketone body ß-hydroxybutyrate, through inhibition of the NLRP-3 inflammasome, is likely to be an intermediary for many of these observed benefits. Adhering to low-risk lifestyle factors adds to the prognostic value of optimal risk factor management, and benefit occurs even when the impact on conventional risk markers is discouragingly minimal or not present. The aims of this review are (a) to discuss novel lifestyle risk factors and their underlying biochemical principles and (b) to provide new perspectives on potentially more feasible recommendations to improve long-term adherence to low-risk lifestyle factors.
尽管通过常规危险因素控制来降低动脉粥样硬化性心血管疾病（ASCVD）负担已取得重大进展，但仍存在显著的残余风险。关于代谢健康的非传统决定因素的新证据，加深了我们对生活方式与疾病相互作用的理解。慢性暴露于不良饮食质量、久坐不动、环境空气污染和噪音、睡眠剥夺和心理社会压力等环境应激源，会影响到许多与 ASCVD 相关的传统和非传统中间途径。这些途径包括身体成分、心肺健康、肌肉力量和功能以及肠道微生物群，这些因素越来越被认为是心血管健康的主要决定因素。有证据表明存在部分重叠的机制，包括对炎症和营养感应途径、内分泌信号、自主功能和自噬的影响。特别值得关注的是，低风险生活方式因素可能通过改变脂肪组织和骨骼肌表型和分泌组来影响斑块脆弱性。总之，低风险生活方式因素会引起一系列表型适应，使组织间通讯从有利于高危动脉粥样硬化的促炎环境转变为抗动脉粥样硬化的环境。酮体β-羟丁酸通过抑制 NLRP-3 炎性小体，可能是这些观察到的益处的中间介质。坚持低风险生活方式因素增加了最佳危险因素管理的预后价值，即使对传统风险标志物的影响令人沮丧地最小化或不存在，也能带来获益。本综述的目的是：（a）讨论新的生活方式危险因素及其潜在的生化原理；（b）为改善对低风险生活方式因素的长期坚持提供新的观点。
