Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
JACC Cardiovasc Imaging. 2015 Jan;8(1):26-33. doi: 10.1016/j.jcmg.2014.09.016. Epub 2014 Nov 1.
OBJECTIVES: The purpose of this prospective study was to examine the relationship between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and the progression rate of aortic stenosis (AS). BACKGROUND: We recently reported that Lp-PLA2 is highly expressed in stenotic aortic valves where it may contribute to the mineralization of valvular interstitial cells. METHODS: Patients with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study. AS progression rate was assessed by annualized increase in peak aortic jet velocity (Vpeak), mean gradient (MG), and aortic valve area index (AVAi). Circulating Lp-PLA2 activity was measured and dichotomized based on the median value. RESULTS: Of 183 patients included in this subanalysis of the PROGRESSA study, 70% were men and the mean age was 66 ± 13 years. Over the 2.5 ± 1.4 years of follow up, the AS progression rate tended to be higher in patients with high versus low Lp-PLA2 activity (annualized Vpeak = 0.17 ± 0.23 m/s vs. 0.12 ± 0.18 m/s; p = 0.14). There was a significant interaction (p < 0.05) between baseline AS severity and Lp-PLA2 activity with respect to impact on AS progression rate. In patients with mild AS (i.e., Vpeak <3 m/s; n = 123), increased Lp-PLA2 activity was associated with a significantly faster AS progression rate (Vpeak 0.16 ± 0.18 m/s vs. 0.09 ± 0.14 m/s; p = 0.01) but not in patients with moderate or severe AS (p = 0.99). After adjustment for other risk factors, increased Lp-PLA2 activity remained independently associated with faster AS progression rate (p = 0.005) in the former subset. CONCLUSIONS: There was no significant association between plasma Lp-PLA2 activity or mass and stenosis progression in the whole cohort. However, increased Lp-PLA2 activity was associated with a faster stenosis progression rate in the subset of patients with mild AS. These findings provide an impetus for the elaboration of a randomized trial targeting Lp-PLA2 activity in patients with early stages of calcific aortic valve disease.
目的：本前瞻性研究旨在探讨血浆脂蛋白相关磷脂酶 A2（Lp-PLA2）活性与主动脉瓣狭窄（AS）进展速度之间的关系。
背景：我们最近报道，Lp-PLA2 在狭窄的主动脉瓣中高度表达，可能有助于细胞间质的矿化。
方法：在 PROGRESSA（代谢决定因素对主动脉瓣狭窄进展的影响）研究中，前瞻性招募了 AS 患者。通过每年主动脉瓣射流峰值速度（Vpeak）、平均梯度（MG）和主动脉瓣面积指数（AVAi）的增加来评估 AS 进展速度。测量循环 Lp-PLA2 活性并根据中位数进行二分法。
结果：在 PROGRESSA 研究的这项亚分析中，183 例患者中有 70%为男性，平均年龄为 66±13 岁。在 2.5±1.4 年的随访中，高 Lp-PLA2 活性组患者的 AS 进展速度似乎高于低 Lp-PLA2 活性组（年增长率为 0.17±0.23m/s 比 0.12±0.18m/s；p=0.14）。在基线 AS 严重程度和 Lp-PLA2 活性对 AS 进展速度的影响方面，存在显著的交互作用（p<0.05）。在轻度 AS 患者（即 Vpeak<3m/s；n=123）中，增加 Lp-PLA2 活性与 AS 进展速度显著加快相关（Vpeak 为 0.16±0.18m/s 比 0.09±0.14m/s；p=0.01），但在中度或重度 AS 患者中无此关联（p=0.99）。在调整其他危险因素后，在前一组患者中，增加 Lp-PLA2 活性仍与 AS 进展速度加快独立相关（p=0.005）。
结论：在整个队列中，血浆 Lp-PLA2 活性或质量与狭窄进展之间无显著相关性。然而，在轻度 AS 患者亚组中，增加的 Lp-PLA2 活性与更快的狭窄进展速度相关。这些发现为在早期钙化性主动脉瓣疾病患者中靶向 Lp-PLA2 活性的随机试验提供了动力。
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