Departments of Cardiology and Internal Medicine, Royal Perth Hospital.
School of Medicine, The University of Western Australia, Perth, Western Australia, Australia.
Curr Opin Clin Nutr Metab Care. 2024 Jan 1;27(1):77-86. doi: 10.1097/MCO.0000000000000976. Epub 2023 Aug 28.
Calcific aortic valve disease (CAVD), the most common cause of aortic stenosis (AS), is characterized by slowly progressive fibrocalcific remodelling of the valve cusps. Once symptomatic, severe AS is associated with poor survival unless surgical or transcatheter valve replacement is performed. Unfortunately, no pharmacological interventions have been demonstrated to alter the natural history of CAVD. Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle, has been implicated in the pathophysiology of CAVD.
The mechanisms by which Lp(a) results in CAVD are not well understood. However, the oxidized phospholipids carried by Lp(a) are considered a crucial mediator of the disease process. An increasing number of studies demonstrate a causal association between plasma Lp(a) levels and frequency of AS and need for aortic valve replacement, which is independent of inflammation, as measured by plasma C-reactive protein levels. However, not all studies show an association between Lp(a) and increased progression of calcification in individuals with established CAVD.
Epidemiologic, genetic, and Mendelian randomization studies have collectively suggested that Lp(a) is a causal risk factor for CAVD. Whether Lp(a)-lowering can prevent initiation or slow progression of CAVD remains to be demonstrated.
钙化性主动脉瓣疾病（CAVD）是主动脉瓣狭窄（AS）最常见的原因，其特征是瓣膜瓣叶进行性缓慢的纤维钙化重塑。一旦出现症状，严重的 AS 患者预后不良，除非进行手术或经导管瓣膜置换。不幸的是，目前尚无药物干预措施被证实可以改变 CAVD 的自然病程。脂蛋白（a）[Lp(a)]是一种类似于低密度脂蛋白的颗粒，与 CAVD 的病理生理学有关。
目前尚不清楚 Lp(a) 导致 CAVD 的机制。然而，Lp(a) 携带的氧化磷脂被认为是疾病过程的关键介质。越来越多的研究表明，血浆 Lp(a)水平与 AS 的发生频率和主动脉瓣置换的需求之间存在因果关系，这与炎症无关，炎症可以通过血浆 C 反应蛋白水平来衡量。然而，并非所有研究都表明 Lp(a)与已确诊的 CAVD 患者钙化进展之间存在关联。
流行病学、遗传学和孟德尔随机化研究共同表明，Lp(a) 是 CAVD 的一个因果风险因素。降低 Lp(a) 是否可以预防 CAVD 的发生或减缓其进展仍有待证实。
