Willeit J, Kiechl S
Department of Neurology, Innsbruck University Clinic, Innsbruck, Austria.
Cerebrovasc Dis. 2000;10 Suppl 5:1-8. doi: 10.1159/000047599.
Endothelial dysfunction and changes in arterial wall morphology including thickening of the tunica intima, excess synthesis of collagenous matrix (fibroblastic intimal thickening) and permanent or dynamic deposition of lipids (fatty streaks) already occur in childhood or adolescence. Definite atherosclerotic plaques in the carotid arteries usually do not manifest themselves before menopause in women or age 40 in men. Obviously, cumulative (long-term) and excessive exposure of the vessel wall to risk factors is required to overcome highly effective defense mechanisms which have not yet been fully investigated. Initiation and early progression of atherosclerosis rely on conventional vascular risk factors such as hyperlipidemia, hypertension, smoking, severe alcohol consumption and chronic infections. Plaque extension is effectively compensated by a focal widening of the vessel, thereby preventing the development of lumen obstruction (vascular remodeling). For stenosis to emerge conventional plaques must convert to complicated plaques characterized by plaque rupture and consecutive atherothrombosis. This process usually starts with small- to medium-sized plaques. Potential determinants of plaque rupture are the composition of the lesion (large lipid-rich core), damage of the fibrous cap (destabilization by chronic inflammation) and hemodynamic stress. According to pathological observations, fissuring of atherosclerotic lesions is a frequent event, while the formation of overlying large thrombi (with progression of stenosis or vessel occlusion) is definitely rare. This conjecture emphasizes the significance of local and systemic thrombus-promoting factors. Actually, the risk profile of advanced atherogenesis in the Bruneck Study was primarily composed of markers of enhanced prothrombotic capacity, attenuated fibrinolysis and clinical conditions known to interfere with coagulation. Almost all subjects with > or =3 procoagulant risk conditions developed carotid stenosis or showed progression of preexisting stenosis during a 5-year period. Increasing insights into the complex biology of arterial atheroma and awareness of the etiologic peculiarities of advanced complicated plaques may serve as a basis for identifying high-risk subjects and for novel vascular prevention strategies with focus on plaque stabilization and antithrombotic/anticoagulant measures.
内皮功能障碍以及动脉壁形态的改变，包括内膜增厚、胶原基质过度合成（纤维母细胞性内膜增厚）和脂质的永久性或动态性沉积（脂纹）在儿童期或青少年期就已出现。女性在绝经前或男性在40岁之前，颈动脉中通常不会出现明确的动脉粥样硬化斑块。显然，血管壁需要长期累积性地过度暴露于危险因素，才能克服尚未得到充分研究的高效防御机制。动脉粥样硬化的起始和早期进展依赖于传统的血管危险因素，如高脂血症、高血压、吸烟、大量饮酒和慢性感染。斑块扩展可通过血管局部增宽得到有效代偿，从而防止管腔阻塞的发生（血管重塑）。要出现狭窄，传统斑块必须转变为以斑块破裂和连续性动脉粥样硬化血栓形成为特征的复杂斑块。这个过程通常从小到中等大小的斑块开始。斑块破裂的潜在决定因素包括病变的组成（富含脂质的大核心）、纤维帽的损伤（因慢性炎症而不稳定）和血流动力学应激。根据病理学观察，动脉粥样硬化病变的破裂很常见，而形成覆盖其上的大血栓（伴有狭窄进展或血管闭塞）则肯定很少见。这一推测强调了局部和全身血栓形成促进因素的重要性。实际上，布伦瑞克研究中晚期动脉粥样硬化的风险特征主要由促血栓形成能力增强、纤溶减弱以及已知会干扰凝血的临床状况的标志物组成。在5年期间，几乎所有具有≥3种促凝风险状况的受试者都出现了颈动脉狭窄或已存在的狭窄病情进展。对动脉粥样瘤复杂生物学的深入了解以及对晚期复杂斑块病因特殊性的认识，可能为识别高危受试者以及制定以斑块稳定和抗血栓/抗凝措施为重点的新型血管预防策略奠定基础。
