Modeling Aortic Valve Calcification and Risk of Aortic Valve Events In Asymptomatic Individuals from the Multi-Ethnic Study of Atherosclerosis

通过多种族动脉粥样硬化研究对无症状个体的主动脉瓣钙化和主动脉瓣事件风险进行建模

• 批准号: 10226914
• 负责人: Seamus Paul Whelton
• 金额: $ 12.72万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10226914
• 关键词: Affect; Agatston Score; Age; Algorithms; Aortic Valve Stenosis; Area; Biological Markers; Calcium; Cardiac; Clinical; Clinical stratification; Code; Data; Detection; Development; Disease; Early treatment; Echocardiography; Elderly; Elements; Ethnic Origin; Event; Future; Guidelines; Heart Valve Diseases; Heterogeneity; Individual; Inflammation; Inflammatory; Intervention; Life Expectancy; Link; Lipoprotein (a); Literature; Low-Density Lipoproteins; Measurement; Measures; Methods; Modeling; Morbidity - disease rate; Multi-Ethnic Study of Atherosclerosis; National Heart, Lung, and Blood Institute; Outcome; Participant; Patients; Persons; Pharmacology; Phenotype; Population; Positioning Attribute; Prevalence; Procedures; Process; Race; Research; Risk; Risk Factors; Sample Size; Scanning; Simvastatin; Subgroup; Time; United States; United States National Institutes of Health; Visit; X-Ray Computed Tomography; adjudicate; aortic valve; aortic valve disorder; aortic valve replacement; calcification; clinical risk; clinically significant; cohort; coronary artery calcium; coronary calcium scoring; design; ezetimibe; high risk; imaging modality; innovation; lifetime risk; middle age; mortality; novel; novel strategies; novel therapeutics; personalized risk prediction; risk stratification; screening guidelines; sex; surveillance imaging; working group

Calcific aortic valve disease (CAVD) is slowly progressive and begins in midlife. Calcification of the aortic valve leaflets is the core underlying process leading to severe aortic stenosis with both inflammation and Lp(a) serving as key underlying pathophysiologic contributors. Severe aortic stenosis is the most common heart valve disorder in the US. It predominantly affects older individuals and with an increasing life expectancy in the United States, the proportion of individuals ≥75 years old is expected to be 12% by the year 2050. Accordingly, the number of individuals requiring aortic valve replacement (AVR) is expected to nearly double between 2025 and 2015 to 1.4 million individuals. The only approved treatment available is AVR, although a recent subgroup analysis from the SEAS trial demonstrated a reduced rate of AVR for patients with a LDL >155 mg/dL and mild aortic stenosis who were treated with simvastatin and ezetimibe. There is no accepted risk stratification method for the long-term prediction of which patients are most likely to require AVR. Therefore, it is imperative to develop novel strategies to identify patients with early AVC who have the highest lifetime risk for developing severe aortic stenosis, as these patients are most likely to benefit from new treatment therapies/strategies. The 2011 NIH Working Group on Calcific Aortic Valve Disease highlighted crucial areas for future research including 1) developing imaging modalities to identify early AVC prior to detection by echocardiography, 2) determining whether the measurement of early AVC may identify patients most likely to benefit from earlier pharmacologic interventions, and 3) determining whether there are interactions between risk factors for aortic stenosis. Non-contrast cardiac computed tomography (CT) is the ideal imaging modality for measuring early CAVD, because it provides a precise, absolute, and direct measurement of aortic leaflet damage from the very earliest stage. However, the long-term relationship between AVC and clinical aortic stenosis events is unknown, as prior studies investigating CT visualized AVC have had small sample sizes, used a cross-sectional design, or focused on determining the optimal timing for AVR. By leveraging the AVC measurements from coronary artery calcium scans performed at MESA Visit 1 we will create an adjudicated severe aortic stenosis outcome, making MESA the only NHLBI cohort with the ability to comprehensively describe the long-term relationship between AVC and clinical aortic stenosis events. Accordingly, these results will have a direct impact on 1) long-term personalized risk stratification, 2) identification of high-risk patients most likely to benefit from new or earlier therapies/strategies, and 3) reducing future aortic valve morbidity and mortality.

钙化性主动脉瓣疾病（CAVD）是一种缓慢进展的疾病，始于中年。钙化 主动脉瓣叶是导致严重主动脉瓣狭窄的核心基础过程， 炎症和Lp（a）作为关键的潜在病理生理贡献者。重度主动脉 狭窄是美国最常见的心脏瓣膜疾病。它主要影响老年人 随着美国人预期寿命的增加，≥75岁的人所占比例 预计到2050年将达到12%。因此，需要主动脉瓣的人数 预计2025年至2015年期间，替代（AVR）人口将增加近一倍，达到140万人。 唯一批准的治疗方法是AVR，尽管最近的亚组分析显示， SEAS试验表明，LDL >155 mg/dL和轻度主动脉瓣狭窄患者的AVR发生率降低 狭窄患者接受辛伐他汀和依折麦布治疗。没有公认的风险分层 用于长期预测哪些患者最有可能需要AVR的方法。因此有 迫切需要开发新的策略来识别早期AVC患者， 发生严重主动脉瓣狭窄的终生风险，因为这些患者最有可能受益于 新的治疗方法/策略。 2011年NIH钙化性主动脉瓣疾病工作组强调了 未来的研究包括：1）开发成像模式，以在检测之前识别早期AVC， 超声心动图，2）确定早期AVC的测量是否可以识别患者最 可能受益于早期的药物干预，以及3）确定是否有 主动脉瓣狭窄风险因素之间的相互作用。非造影心脏计算机断层扫描（CT） 是测量早期CAVD的理想成像方式，因为它提供了精确、绝对和 从最早期直接测量主动脉瓣叶损伤。但长期 AVC与临床主动脉瓣狭窄事件之间的关系未知，因为既往研究 研究CT可视化AVC的样本量较小，使用横截面设计，或 专注于确定AVR的最佳时机。 通过利用在梅萨进行的冠状动脉钙扫描的AVC测量值 访视1时，我们将创建裁定的重度主动脉瓣狭窄结局，使梅萨成为唯一的NHLBI 有能力全面描述AVC与 临床主动脉瓣狭窄事件。因此，这些结果将对1）长期 个性化的风险分层，2）识别最有可能从新的或 早期治疗/策略，和3）降低未来主动脉瓣发病率和死亡率。

项目成果

Prevalence of Aortic Valve Calcium and the Long-Term Risk of Incident Severe Aortic Stenosis.

主动脉瓣钙化的患病率和严重主动脉瓣狭窄事件的长期风险。

• DOI: 10.1016/j.jcmg.2023.02.018
• 发表时间: 2024
• 期刊: JACC. Cardiovascular imaging
• 作者: Whelton,SeamusP;Jha,Kunal;Dardari,Zeina;Razavi,AlexanderC;Boakye,Ellen;Dzaye,Omar;Verghese,Dhiran;Shah,Sanjiv;Budoff,MatthewJ;Matsushita,Kunihiro;Carr,JJeffery;Vasan,RamachandranS;Blumenthal,RogerS;Anchouche,Khalil;Thanas
• 通讯作者: Thanas

Risk Markers for Limited Coronary Artery Calcium in Persons With Significant Aortic Valve Calcium (From the Multi-ethnic Study of Atherosclerosis).

• DOI: 10.1016/j.amjcard.2021.06.035
• 发表时间: 2021-10-01
• 期刊: The American journal of cardiology
• 作者: Razavi AC;Cardoso R;Dzaye O;Budoff M;Thanassoulis G;Post WS;Shah S;Berman DS;Nasir K;Blaha MJ;Whelton SP
• 通讯作者: Whelton SP