Combining longitudinal cohort studies to examine cardiovascular risk factor trajectories across the adult lifespan and their association with disease

结合纵向队列研究来检查成人寿命期间的心血管危险因素轨迹及其与疾病的关联

• 批准号: 10618846
• 负责人: Michael J Daniels
• 金额: $ 57.65万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618846
• 关键词: Adult; Age; Agreement; Behavior; Blood Pressure; Cardiovascular Diseases; Cause of Death; Cessation of life; Characteristics; Cholesterol; Clinical; Cohort Studies; Communities; Data; Data Pooling; Data Set; Development; Diagnostic tests; Disease; Disease Outcome; Education; Elderly; Evaluation; Event; Geographic Locations; Goals; Health; Individual; Intervention; Life; Life Cycle Stages; Life Style; Literature; Longevity; Longitudinal Studies; Longitudinal cohort study; Measurement; Measures; Modeling; Outcome; Participant; Persons; Pharmaceutical Preparations; Physiological; Population; Prevention strategy; Process; Prospective, cohort study; Race; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; Statistical Methods; Time; Training; United States; Validation; Vital Status; Work; adjudication; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; clinical development; clinically relevant; cohort; critical period; emerging adult; flexibility; follow-up; health difference; human old age (65+); innovation; lifetime risk; men; middle age; phenotypic data; preservation; response; sex; treatment strategy; young adult

PROJECT SUMMARY/ABSTRACT The development of clinical cardiovascular disease (CVD) is a process that occurs across the lifespan, beginning early in life and spanning late into life as clinical event rates increase. Much of our understanding of the impact of cardiovascular risk factors comes from studies examining the association between risk factor levels measured at a single point in time, often in middle age, with incident disease over the short- to intermediate-term. However, risk factor levels in young adulthood are significantly associated with the development of CVD later in life and our recent work has demonstrated that not only the levels at specific ages, but also cumulative exposures and long-term trajectories in cardiovascular health are significantly related to the risk for subsequent CVD. Therefore, a life course approach is critical in order to understand how cardiovascular risk factors develop and impact an individual's risk for CVD events later in life. Yet there is no single study that has collected detailed phenotypic data spanning young adulthood through old age on a broadly representative sample of the U.S. population. In response to NOT-HL-19-712: Innovative Data Evaluation and Analysis to Health, we propose to de- velop a statistical framework for combining longitudinal risk factors and clinical outcomes data from multiple cohort studies to create a “synthetic cohort” enabling the study of long-term cardiovascular health starting in early adulthood. The investigative team of this proposal has pooled the data from 20 community-based CVD cohorts through the Lifetime Risk Pooling Project (LRPP), which now has >11 million person-years of follow- up data on repeated measures of CVD risk factors, detailed information about medication use (including blood pressure- and cholesterol-lowering therapy), nearly 100% follow-up for vital status, and detailed CVD event adju- dication. Few cohorts in the LRPP cover the entire adult lifespan; therefore, we propose to view risk factors and outcomes at ages not included in each cohort study as missing data, and to use multiple imputation to fill in these unobserved measurements to facilitate analysis. The overall goal of this project is to identify and measure the characteristics of CVD risk factor trajectories across the adult lifespan that are most amenable to intervention. Measuring these characteristics can help identify critical periods for intervention, more precisely define thresholds for known risk factors, elucidate the role of lifestyle behaviors, explain differences in health among populations, and promote CVD prevention strategies at younger ages. Our specific aims are: 1) Develop and validate a statistical framework for imputing unobserved CVD risk factors and events across the lifespan using data from the LRPP; 2) Inform treatment strategies by identifying clinically relevant features of longitudi- nal risk factor trajectories that are associated with CVD outcomes; 3) Leverage the work from Aims 1 and 2 to facilitate the dissemination and use of the synthetic LRPP data by the research community.

项目概要/摘要 临床心血管疾病（CVD）的发展是一个贯穿一生的过程，从 随着临床事件发生率的增加，从生命早期到生命晚期。我们对影响的大部分了解 心血管危险因素来自研究测量的危险因素水平之间的关联 在某个时间点，通常是在中年，在短期到中期突发疾病。然而， 成年早期的危险因素水平与以后生活中 CVD 的发展显着相关 我们最近的工作表明，不仅特定年龄的水平，而且累积暴露和 心血管健康的长期轨迹与后续心血管疾病的风险显着相关。所以， 为了了解心血管危险因素如何发展和影响，生命全程方法至关重要 个人在晚年发生 CVD 事件的风险。然而，还没有一项研究收集了详细的表型 涵盖具有广泛代表性的美国人口样本的从青年期到老年期的数据。 为了回应 NOT-HL-19-712：健康的创新数据评估和分析，我们建议 de- 开发一个统计框架，将纵向风险因素和来自多个方面的临床结果数据结合起来 队列研究创建一个“综合队列”，使长期心血管健康研究能够从 成年早期。该提案的调查团队汇集了 20 个社区 CVD 的数据 通过终生风险共担项目 (LRPP) 进行队列研究，该项目目前已拥有超过 1100 万人年的跟踪记录 收集有关 CVD 危险因素重复测量的数据、有关药物使用的详细信息（包括血液 降压和降胆固醇治疗）、近 100% 的生命状态随访以及详细的 CVD 事件调整 指示。 LRPP 中很少有队列涵盖整个成人寿命；因此，我们建议查看风险因素并 未包含在每个队列研究中的年龄结果作为缺失数据，并使用多重插补来填补这些 未观察到的测量，以方便分析。该项目的总体目标是识别和衡量 整个成人生命周期中最适合的 CVD 危险因素轨迹特征 干涉。测量这些特征可以帮助更准确地确定干预的关键时期 定义已知风险因素的阈值，阐明生活方式行为的作用，解释健康差异 人群，并促进年轻化的 CVD 预防策略。我们的具体目标是： 1) 开发 并验证统计框架，用于估算整个生命周期中未观察到的 CVD 风险因素和事件 使用来自 LRPP 的数据； 2）通过识别纵向的临床相关特征来告知治疗策略 与 CVD 结果相关的最终危险因素轨迹； 3) 利用目标 1 和 2 的工作 促进研究界传播和使用合成 LRPP 数据。