Coronary Artery Calcium and its Association with Protective/Risk Factors and Epigenetic Patterns in Diverse US Hispanic/Latino Adults

美国不同西班牙裔/拉丁裔成年人的冠状动脉钙及其与保护/危险因素和表观遗传模式的关系

• 批准号: 10654571
• 负责人: MATTHEW J BUDOFF
• 金额: $ 218.6万
• 依托单位: UNIVERSITY OF ILLINOIS 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: 2021-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10654571
• 关键词: Accounting; Acculturation; Adult; Agatston Score; Age; American; American Heart Association; Ancillary Study; Archives; Atherosclerosis; Biological; Biological Markers; Blood; Calcium; Cardiac; Cardiology; Cardiovascular Diseases; Characteristics; Chicago; Cholesterol; Clinical; Communities; Coronary; Coronary Arteriosclerosis; Coronary heart disease; Cuban; DNA; DNA Methylation; Data; Decision Making; Detection; Development; Diabetes Mellitus; Diet; Dominican; Economic Conditions; Epidemiology; Epigenetic Process; Ethnic Population; Etiology; Event; Exposure to; Family; Genetic; Genomics; Guidelines; Health; Hispanic; Hispanic Community Health Study/Study of Latinos; Hispanic Populations; Hypertension; Infrastructure; Knowledge; Language; Latino; Latino Population; Life Expectancy; Life Style; Link; Longitudinal Studies; Low Prevalence; Maps; Measures; Mediation; Mendelian randomization; Methylation; Mexican; National Heart, Lung, and Blood Institute; National origin; Not Hispanic or Latino; Obesity; Participant; Pattern; Physical activity; Population; Population Heterogeneity; Population Study; Prevalence; Prevention; Prevention strategy; Preventive; Process; Prospective Studies; Puerto Rican; Quantitative Trait Loci; Random Allocation; Recording of previous events; Resources; Risk; Risk Factors; Role; Sampling; Scanning; Social support; South American; Time; Trans-Omics for Precision Medicine; Variant; Visit; Woman; cardiovascular disorder prevention; cardiovascular disorder risk; cigarette smoking; cohesion; cohort; college; coronary artery calcium; coronary event; cost effective; critical period; density; early detection biomarkers; epigenetic marker; epigenomic profiling; epigenomics; ethnic identity; follow-up; genome sequencing; high dimensionality; hypercholesterolemia; individualized prevention; lifestyle factors; men; methylation biomarker; mortality; novel; prospective; protective factors; racial population; residence; social culture; sociocultural determinant; socioeconomic adversity; socioeconomics; specific biomarkers; tool; treatment strategy; whole genome

ABSTRACT Coronary artery calcium (CAC) provides predictive information for risk of coronary heart disease (CHD) events beyond that gained from traditional cardiovascular disease (CVD) risk factors. Hispanics/Latinos have lower prevalence of CAC than whites, even after accounting for differences in CVD risk factors. They also have lower rates of CVD mortality and longer life expectancies despite higher rates of risk factors and adverse socioeconomic conditions (the ‘Hispanic Paradox’), lending credence to the existence of Hispanic/Latino-specific CVD protective mechanisms. Little data currently exist on the presence/absence and extent of CAC and CT- derived plaque volume, density, and distribution in diverse Hispanics/Latinos, and their associations with sociocultural characteristics and lifestyle factors that have been associated with CVD in the Hispanic Community Health Study/ Study of Latinos (HCHS/SOL) and other cohorts. Another critical knowledge gap is whether epigenetic mechanisms, i.e., DNA methylation, alone or in conjunction with genetic factors, act as an important biological link between such risk or protective factors and subclinical/clinical CVD in Hispanics/Latinos. The proposed study aims to generate critical data on subclinical coronary atherosclerosis (CAC and CT-derived plaque volume, density, and distribution) for Hispanic/Latino adults from all major heritage groups in the US (Mexican, Puerto Rican, Cuban, Dominican, and Central/South American) and examine relationships with sociocultural factors, lifestyle factors, traditional CVD risk factors, and epigenomic patterns. This study will be conducted ancillary to the ongoing HCHS/SOL, which examined 16,415 Hispanic/Latino men and women ages 18-74 years at Visit 1 (2008-2011) from 4 US communities (San Diego, CA; Chicago, IL; Bronx, NY; and Miami, FL) and 11,623 participants (81.4% follow-up rate) at Visit 2 (2014-2017). The proposed study will capitalize on available HCHS/SOL data and will assess CAC absence/presence and features in conjunction with ongoing HCHS/SOL Visit 3 (2020-2023) in 4,109 participants ages >45 years (mean age 60.5 years, an optimal time window for CAC detection) and free of known history of CVD. Longitudinal examination of epigenetic biomarkers will be conducted using stored blood DNA samples from HCHS/SOL Visits 1 and 2 for a subset of participants (50% of participants who undergo scanning, n=2,054). The proposed study will address critical knowledge gaps in a highly cost-effective manner by capitalizing on the established HCHS/SOL infrastructure. Examination of these factors in this heterogeneous, well-characterized cohort, has the potential to generate novel and insightful epidemiological, etiologic, and mechanistic information beyond that gained from previous studies, which can help to identify novel preventive targets and inform development of precision prevention/treatment strategies that may benefit all racial/ethnic groups.

抽象的 冠状动脉钙（CAC）提供了冠心病（CHD）事件风险的预测信息 除了从传统的心血管疾病（CVD）危险因素中获得的收益之外。西班牙裔/拉丁美洲人的情况较低 即使考虑到CVD风险因素的差异，CAC的患病率也比白人患病率。他们也较低 CVD死亡率和更长的预期寿命任务较高的危险因素和逆境率更高 社会经济条件（“西班牙裔悖论”），借助西班牙裔/拉丁裔特定的存在 CVD保护机制。目前很少有关于CAC和CT-的存在/不存在和程度的数据 衍生的斑块数量，密度和分布在潜水西班牙裔/拉丁美洲人的分布及其与他们的关联 西班牙裔社区中与CVD相关的社会文化特征和生活方式因素 Latinos（HCHS/ SOL）和其他队列的健康研究/研究。另一个关键的知识差距是是否 表观遗传机制，即单独或与遗传因素结合的DNA甲基化，起作用 这种风险或受保护因素与西班牙裔/拉丁美洲人的亚临床/临床CVD之间的生物学联系。这 拟议的研究旨在生成有关亚临床冠状动脉粥样硬化的关键数据（CAC和CT衍生 来自美国所有主要遗产组的西班牙裔/拉丁裔成年人的牌匾数量，密度和分布） （墨西哥，波多黎各，古巴，多米尼加和中美洲/南美洲）以及与 社会文化因素，生活方式因素，传统的CVD风险因素和表观基因组模式。这项研究将是 进行了正在进行的HCHS/SOL的辅助，该HCHS/SOL检查了16,415个西班牙裔/拉丁裔男女 来自美国4个社区（加利福尼亚州圣地亚哥；伊利诺伊州芝加哥市；纽约州布朗克斯；和迈阿密，迈阿密，18-74年（2008-2011）访问1（2008-2011）。 fl）和11,623名参与者（2014-2017）的参与者（81.4％的随访率）。拟议的研究将大写 可用的HCHS/SOL数据，并将评估CAC的吸收/存在和特征与持续 HCHS/SOL访问3（2020-2023）4,109名参与者> 45岁（平均年龄60.5岁，最佳时间 CAC检测的窗口），没有CVD的已知历史。表观遗传生物标志物的纵向检查 将使用来自HCHS/SOL访问1和2的储存的血液DNA样品进行一部分参与者 （接受扫描的参与者中有50％，n = 2,054）。拟议的研究将解决关键的知识差距 通过利用已建立的HCHS/SOL基础设施来利用高昂的成本效益。检查 这些因素中的这些因素在这种异质，良好的队列中具有产生新颖和有见地的潜力 流行病学，病因和机械信息超出了先前的研究，这可以 帮助识别新颖的预防目标，并告知开发预防/治疗策略 可能受益于所有种族/族裔。