Department of Health and Human Physiology, University of Iowa, Iowa City, Iowa.
Department of Internal Medicine, University of Iowa, Iowa City, Iowa.
Physiology (Bethesda). 2022 May 1;37(3):154-173. doi: 10.1152/physiol.00035.2021. Epub 2021 Nov 15.
Aortic stiffness increases with advancing age, more than doubling during the human life span, and is a robust predictor of cardiovascular disease (CVD) clinical events independent of traditional risk factors. The aorta increases in diameter and length to accommodate growing body size and cardiac output in youth, but in middle and older age the aorta continues to remodel to a larger diameter, thinning the pool of permanent elastin fibers, increasing intramural wall stress and resulting in the transfer of load bearing onto stiffer collagen fibers. Whereas aortic stiffening in early middle age may be a compensatory mechanism to normalize intramural wall stress and therefore theoretically "good" early in the life span, the negative clinical consequences of accelerated aortic stiffening beyond middle age far outweigh any earlier physiological benefit. Indeed, aortic stiffness and the loss of the "windkessel effect" with advancing age result in elevated pulsatile pressure and flow in downstream microvasculature that is associated with subclinical damage to high-flow, low-resistance organs such as brain, kidney, retina, and heart. The mechanisms of aortic stiffness include alterations in extracellular matrix proteins (collagen deposition, elastin fragmentation), increased arterial tone (oxidative stress and inflammation-related reduced vasodilators and augmented vasoconstrictors; enhanced sympathetic activity), arterial calcification, vascular smooth muscle cell stiffness, and extracellular matrix glycosaminoglycans. Given the rapidly aging population of the United States, aortic stiffening will likely contribute to substantial CVD burden over the next 2-3 decades unless new therapeutic targets and interventions are identified to prevent the potential avalanche of clinical sequelae related to age-related aortic stiffness.
主动脉僵硬度随年龄增长而增加，在人类寿命期间增加超过两倍，并且是心血管疾病 (CVD) 临床事件的有力预测因子，独立于传统危险因素。主动脉随着身体大小和心输出量的增长而增加直径和长度，以适应青年时期的生长，但在中年和老年时期，主动脉继续向更大的直径重塑，减少永久性弹性纤维的储备，增加壁内应力，导致承载负荷转移到更硬的胶原纤维上。虽然中年早期的主动脉僵硬可能是一种代偿机制，以正常化壁内应力，因此从理论上讲在生命早期是“好”的，但中年以后主动脉僵硬加速的负面临床后果远远超过任何早期的生理益处。事实上，主动脉僵硬和随年龄增长而丧失“缓冲器效应”导致下游微血管中的脉动压力和流量升高，与大脑、肾脏、视网膜和心脏等高流量、低阻力器官的亚临床损伤相关。主动脉僵硬的机制包括细胞外基质蛋白的改变（胶原蛋白沉积、弹性蛋白碎片化）、动脉张力增加（氧化应激和炎症相关的血管舒张剂减少和血管收缩剂增加；增强的交感神经活动）、动脉钙化、血管平滑肌细胞僵硬和细胞外基质糖胺聚糖。鉴于美国人口老龄化迅速，除非确定新的治疗靶点和干预措施来预防与年龄相关的主动脉僵硬相关的潜在临床后果雪崩，否则主动脉僵硬在未来 2-3 十年内可能会对心血管疾病负担产生重大影响。
