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) 提供冠心病 (CHD) 事件风险的预测信息 除了传统心血管疾病 (CVD) 风险因素之外，西班牙裔/拉丁裔的风险因素也较低。 即使考虑了 CVD 危险因素的差异，他们的 CAC 患病率也低于白人。 尽管危险因素和不利因素的发生率较高，但 CVD 死亡率和预期寿命更长 失业状况（“西班牙裔悖论”），证明西班牙裔/拉丁裔特定群体的存在 目前关于 CAC 和 CT 是否存在以及程度的数据很少。 不同西班牙裔/拉丁裔的斑块体积、密度和分布及其与 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 健康研究/拉丁裔研究 (HCHS/SOL) 和其他群体的另一个关键知识差距是是否。 表观遗传机制，即 DNA 甲基化，单独或与遗传因素结合，起着重要的作用。 这些风险或保护因素与西班牙裔/拉丁裔亚临床/临床 CVD 之间的生物学联系。 拟议的研究旨在生成亚临床冠状动脉粥样硬化（CAC 和 CT 衍生的）的关键数据 美国所有主要传统群体的西班牙裔/拉丁裔成年人的牙菌斑体积、密度和分布 （墨西哥、波多黎各、古巴、多米尼加和中/南美洲）并检查与 本研究将包括社会文化因素、生活方式因素、传统 CVD 危险因素和表观基因组模式。 与正在进行的 HCHS/SOL 一起进行，该调查检查了 16,415 名西班牙裔/拉丁裔男性和女性 第 1 次访问（2008-2011 年）时年龄为 18-74 岁，来自 4 个美国社区（加利福尼亚州圣地亚哥、伊利诺伊州芝加哥、纽约州布朗克斯和迈阿密） 佛罗里达州）和第 2 次访问（2014-2017 年）的 11,623 名参与者（81.4% 随访率）。 可用的 HCHS/SOL 数据，并将结合正在进行的评估 CAC 的缺失/存在和特征 HCHS/SOL 访问 3 (2020-2023)，4,109 名年龄 >45 岁的参与者（平均年龄 60.5 岁，最佳时间 CAC 检测窗口）并且没有已知的 CVD 病史。 将使用来自 HCHS/SOL 访问 1 和 2 的存储的一部分参与者的血液 DNA 样本进行 （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，以极具成本效益的方式。 这个异质的、特征鲜明的群体中的这些因素有可能产生新颖且富有洞察力的成果 除了从以前的研究中获得的信息之外，还可以获取流行病学、病因学和机制信息 帮助确定新的预防目标并为制定精准的预防/治疗策略提供信息 可能使所有种族/族裔群体受益。