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

摘要 冠状动脉钙化(CAC)为冠心病(CHD)事件的风险提供预测信息 超过从传统的心血管疾病(CVD)危险因素获得的。西班牙裔/拉美裔美国人的比例较低 CAC的患病率高于白人，即使在考虑了心血管疾病危险因素的差异后也是如此。他们也有更低的 心血管疾病死亡率和预期寿命延长，尽管危险因素和不良反应发生率较高 社会经济条件(西班牙裔悖论)，证明了拉美裔/拉美裔人的存在 CVD的保护机制。目前关于CAC和CT的存在/不存在及其程度的数据很少。 不同拉美裔/拉丁裔人群中衍生斑块的体积、密度和分布及其与 西班牙裔社区与心血管疾病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。另一个关键的知识差距是 表观遗传机制，即DNA甲基化，单独或与遗传因素一起起着重要的作用 这种风险或保护因素与拉美裔/拉丁裔亚临床/临床心血管疾病之间的生物学联系。这个 拟议的研究旨在生成关于亚临床冠状动脉粥样硬化(CAC和CT)的关键数据 斑块体积、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、多米尼加人和中南美洲人)，并检查与 社会文化因素、生活方式因素、传统心血管疾病风险因素和表观基因组模式。这项研究将是 对正在进行的HCHS/SOL进行了辅助调查，检查了16,415名西班牙裔/拉丁裔男女 18-74年访问1(2008-2011年)，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， 在访问2(2014-2017年)时，有11,623名参与者(随访率为81.4%)。拟议的研究将利用 可用的HCHS/SOL数据，并将评估CAC缺席/存在和功能，与正在进行的 HCHS/SOL访问3次(2020-2023年)，4,109名参与者，年龄和>45岁(平均年龄60.5岁，最佳时间 用于CAC检测的窗口)并且没有已知的CVD病史。表观遗传生物标志物的纵向检验 将使用来自HCHS/SOL访问1和2的存储的血液DNA样本对部分参与者进行 (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问题 以极具成本效益的方式利用已建立的HCHS/SOL基础设施。审查 这些因素在这个异质的、特征良好的队列中，具有产生新奇和有洞察力的潜力 流行病学、病因学和机械性信息超越了以前的研究，这些研究可以 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 可能使所有种族/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.