Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, Canada.
Department of Medicine, Faculty of Medicine, Université Laval, Québec, Québec, Canada.
JAMA Cardiol. 2024 Sep 1;9(9):835-842. doi: 10.1001/jamacardio.2024.1882.
IMPORTANCE: There are currently no pharmacological treatments available to slow hemodynamic progression of aortic stenosis. Plasma lipoprotein(a) concentrations predict incident aortic stenosis but its association with hemodynamic progression is controversial. OBJECTIVE: To determine the association between plasma lipoprotein(a) concentrations and hemodynamic progression in patients with aortic stenosis. DESIGN, SETTINGS AND PARTICIPANTS: The study included patients with aortic stenosis from 5 longitudinal clinical studies conducted from March 2001 to March 2023 in Canada and the UK. Of 757 total patients, data on plasma lipoprotein(a) concentrations and rates of hemodynamic progression assessed by echocardiography were available for 710, who were included in this analysis. Data were analyzed from March 2023 to April 2024. EXPOSURE: Cohort-specific plasma lipoprotein(a) concentration tertiles. MAIN OUTCOMES AND MEASURES: Hemodynamic aortic stenosis progression on echocardiography as assessed by annualized change in peak aortic jet velocity, mean transvalvular gradient, and aortic valve area. RESULTS: Among the included patients, 497 (70%) were male and 213 (30%) were female. The mean (SD) age was 65.2 (13.1) years. Patients in the top lipoprotein(a) tertile demonstrated 41% (estimate, 1.41; 95% CI, 1.13-1.75) faster progression of peak aortic jet velocity and 57% (estimate, 1.57; 95% CI, 1.18-2.10) faster progression of mean transvalvular gradient than patients in the bottom tertile. There was no evidence of heterogeneity across the individual cohorts. Progression of aortic valve area was comparable between groups (estimate, 1.23; 95% CI, 0.71-2.12). Similar results were observed when plasma lipoprotein(a) concentrations were treated as a continuous variable. CONCLUSIONS AND RELEVANCE: In this study, higher plasma lipoprotein(a) concentrations were associated with faster rates of hemodynamic progression in patients with aortic stenosis. Lowering plasma lipoprotein(a) concentrations warrants further investigation in the prevention and treatment of aortic stenosis.
重要性：目前尚无可用的药物治疗方法来减缓主动脉瓣狭窄的血液动力学进展。血浆脂蛋白（a）浓度可预测主动脉瓣狭窄的发生，但它与血液动力学进展的关系存在争议。 目的：确定主动脉瓣狭窄患者血浆脂蛋白（a）浓度与血液动力学进展之间的关系。 设计、地点和参与者：这项研究纳入了来自 2001 年 3 月至 2023 年 3 月期间在加拿大和英国进行的 5 项纵向临床研究中的主动脉瓣狭窄患者。在总共 757 名患者中，有 710 名患者提供了血浆脂蛋白（a）浓度和超声心动图评估的血液动力学进展率的数据，他们被纳入了本分析。数据于 2023 年 3 月至 2024 年 4 月进行分析。 暴露：队列特异性血浆脂蛋白（a）浓度三分位组。 主要结果和测量：超声心动图评估的血液动力学主动脉瓣狭窄进展情况，表现为峰值主动脉射流速度、平均跨瓣梯度和主动脉瓣口面积的年变化率。 结果：在纳入的患者中，497 名（70%）为男性，213 名（30%）为女性。平均（SD）年龄为 65.2（13.1）岁。脂蛋白（a）三分位组中患者的峰值主动脉射流速度进展速度比脂蛋白（a）三分位组快 41%（估计值，1.41；95%CI，1.13-1.75），平均跨瓣梯度进展速度快 57%（估计值，1.57；95%CI，1.18-2.10）。各队列之间没有异质性的证据。各组之间的主动脉瓣口面积进展情况相当（估计值，1.23；95%CI，0.71-2.12）。当将血浆脂蛋白（a）浓度视为连续变量时，也观察到了类似的结果。 结论和相关性：在这项研究中，较高的血浆脂蛋白（a）浓度与主动脉瓣狭窄患者的血液动力学进展速度较快相关。降低血浆脂蛋白（a）浓度在主动脉瓣狭窄的预防和治疗中值得进一步研究。
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