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

摘要 冠状动脉钙（CAC）可为冠心病（CHD）事件的风险提供预测信息 超过了传统的心血管疾病（CVD）风险因素。西班牙裔/拉丁裔的比例较低 CAC的患病率高于白人，即使考虑到CVD危险因素的差异。他们也有较低的 尽管危险因素和不良反应发生率较高， 社会经济条件（“西班牙裔议会”），借贷信任西班牙裔/拉丁裔特定的存在， CVD保护机制目前关于CAC和CT的存在/不存在和程度的数据很少- 在不同的西班牙裔/拉丁裔中推导出的斑块体积、密度和分布，以及它们与 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/拉丁美洲人研究（HCHS/SOL）和其他队列。另一个关键的知识差距是， 表观遗传机制，即，DNA甲基化，单独或与遗传因素结合，作为一个重要的 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。的 拟议的研究旨在产生亚临床冠状动脉粥样硬化的关键数据（CAC和CT衍生 牙菌斑体积、密度和分布），来自美国所有主要遗产群体的西班牙裔/拉丁裔成年人 （墨西哥人，波多黎各人，古巴人，多米尼加人和中美洲/南美洲人），并检查与 社会文化因素、生活方式因素、传统CVD风险因素和表观基因组模式。本研究将 进行辅助正在进行的HCHS/SOL，其中检查了16，415名西班牙裔/拉丁裔男性和女性年龄 访视1（2008-2011年）时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， FL）和11，623例受试者（81.4%随访率）。拟议的研究将利用 现有的HCHS/SOL数据，并将评估CAC的存在/缺失和特征， HCHS/SOL访视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。表观遗传生物标志物的纵向检查 将使用HCHS/SOL访视1和2中储存的血液DNA样本对一部分受试者进行 (50接受扫描的参与者%，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，以高成本效益的方式实现这一目标。审查 这些因素在这个异质性，特征鲜明的队列，有可能产生新的和有见地的 流行病学，病因学和机制信息超出了以前的研究，可以 帮助确定新的预防目标，并为制定精确的预防/治疗战略提供信息， 它可以使所有种族/民族受益。

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.