Racial/Ethnic Influences on Early Vascular Aging and Cardiac Strain: Role of Cumulative Stress, Inflammatory and Metabolic Burden

种族/民族对早期血管老化和心脏劳损的影响：累积压力、炎症和代谢负担的作用

• 批准号: 10503004
• 负责人: UMA RAO
• 金额: $ 70.04万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10503004
• 关键词: 17 year old; Accounting; Adolescence; Adolescent; Adolescent obesity; Adrenal Glands; Adult; Affect; African American; African American population; Aging; American; Anthropometry; Arteries; Black Populations; Blood Pressure; Blood Vessels; Blood flow; Cardiac; Cardiovascular Diseases; Caucasians; Cause of Death; Cessation of life; Chronic stress; Coping Skills; Data; Development; Diagnosis; Diastole; Diet; Disease; Disease Marker; Early Intervention; Endothelium; Ethnic group; Exhibits; Female; Female Adolescents; Follow-Up Studies; Genetic; Health; Health Transition; Healthcare; Heart Diseases; Heating; High Prevalence; Hispanic; Hispanic Americans; Human; Hypertension; Hypothalamic structure; Inflammation; Inflammatory; Interruption; Lasers; Latinx; Lead; Left Ventricular Mass; Link; Measures; Mediating; Metabolic; Metabolic Marker; Metabolic syndrome; Methods; Mexican Americans; Minority Groups; Minority Women; Morbidity - disease rate; Myocardial; Not Hispanic or Latino; Obesity; Outcome; Peripheral; Persons; Phase; Physiologic pulse; Physiological; Pituitary Gland; Play; Populations at Risk; Prevalence; Prevention Guidelines; Productivity; Race; Research; Risk; Risk Factors; Role; Shapes; Skin; Social support; Stress; Stress and Coping; Structure; System; Systole; Techniques; Testing; Time; United States; Variant; Woman; adipokines; allostatic load; arterial stiffness; biological adaptation to stress; biopsychosocial; blood pressure elevation; burden of illness; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; cohort; coping; cost; critical period; disease disparity; disorder risk; emerging adulthood; endothelial dysfunction; ethnic difference; ethnic minority; flexibility; follow-up; heart rate variability; high risk population; hypothalamic-pituitary-adrenal axis; indexing; inflammatory marker; men; mortality; mortality risk; preempt; prevent; protective factors; racial and ethnic; racial and ethnic disparities; response; sex; social culture; social inequality; stressor; therapy development; treatment guidelines; volunteer; young adult; young woman

Cardiovascular disease (CVD) is the leading global cause of death, accounting for approximately 18.6 million deaths in 2019. Between 2015 and 2018, 126.9 million American adults had CVD, resulting in an annual cost of $363.4 billion in healthcare, lost productivity and mortality. The CVD burden is not distributed equally among racial/ethnic (R/E) groups: ~60% of African American (AA) adults have CVD compared to ~48% of Hispanic/ Latinx (HL) and Non-Hispanic Whites (NHW). R/E disparities in CVD are likely due to an interplay of genetic and sociocultural factors, which are exacerbated by the chronic stress burden that some R/E groups endure. Chronic stress elicits repeated activation of the stress response systems, increasing allostatic load (AL) and compromising health. High AL may increase risk for early vascular aging (EVA): arterial stiffness, subclinical endothelial dysfunction, hypertension and increased left ventricular mass. R/E disparities in EVA emerge by adolescence, before overt signs of CVD, but no studies simultaneously measured vertically integrated CVD markers early in development. Links between chronic stress, AL and CVD have been proposed but not studied comprehensively. Factors that may protect against CVD in some high-risk groups (e.g., HL) have not been explored across R/E groups. Current CVD prevention and treatment guidelines were developed from data obtained primarily in men, contributing to missed or delayed diagnoses, non-optimal treatment and poor outcomes, especially in R/E minority women. Research on the mechanisms of CVD risk in AA was conducted almost exclusively in men despite high CVD prevalence in both sexes. Importantly, R/E disparities in CVD are more marked in women. CVDs explain 33% of the mortality variation between AA and NHW men but 45% for women. Many CVD risk factors have a higher prevalence (e.g., obesity) or a greater impact in women; for example, chronic stress, which disproportionately affects R/E minorities, is a stronger predictor of CVD-related mortality in women. Our current study measures multidomain CVD risk factors including cumulative stress, hypothalamic-pituitary-adrenal activity, inflammatory markers and obesity indices (anthropometry, adiposity, diet, metabolic markers, and adipokines) in 13 to 17-year-old AA, HL and NHW adolescent girls. We propose a follow-up study of this well-characterized cohort 4 to 6 years later in emerging adulthood, a critical period when physical maturity is largely complete but biopsychosocial risk factors that have longterm implications for CVD emerge. We will determine the magnitude of cumulative stress and AL burden over time, incorporate vertically integrated markers of EVA with state-of-the-art techniques, and examine the effects of cumulative stress, AL and adaptive cultural coping practices on EVA. Characterizing R/E differences in modifiable bio- psychosocial risk and protective factors associated with subclinical CVD during a developmental phase when humans can exert more control over their lives (with increased autonomy but few adult responsibilities) offers an opportunity to preempt the transition from health to disease and reduce CVD disparities in at-risk groups.

心血管疾病（CVD）是全球主要的死亡原因，约占1860万人 2019年死亡。在2015年至2018年期间，1.269亿美国成年人患有CVD，导致每年的成本 3634亿美元的医疗保健，生产力和死亡率的损失。心血管疾病的负担并不是平均分布在 种族/民族（R/E）组：约60%的非洲裔美国人（AA）成年人患有CVD，而西班牙裔/ 拉丁裔（HL）和非西班牙裔白人（NHW）。心血管疾病的R/E差异可能是由于遗传因素的相互作用， 和社会文化因素，这是加剧了慢性压力负担，一些R/E组忍受。 慢性应激诱发应激反应系统的反复激活，增加非稳态负荷（AL）， 损害健康。高AL可能增加早期血管老化（伊娃）的风险：动脉僵硬，亚临床 内皮功能障碍、高血压和左心室质量增加。伊娃中的R/E差异出现在 青春期，在明显的CVD迹象之前，但没有研究同时测量垂直整合的CVD 早期发育的标志物。慢性压力、急性白血病和心血管疾病之间的联系已经被提出，但尚未研究 全面地在一些高危人群中可能预防CVD的因素（例如，HL）没有被 在R/E组中进行了探索。目前的心血管疾病预防和治疗指南是根据数据制定的 主要在男性中获得，导致漏诊或延迟诊断，非最佳治疗和不良反应。 结果，特别是在R/E少数民族妇女。对AA患者心血管危险机制进行了研究 尽管男女的心血管疾病患病率都很高，但几乎完全是男性。重要的是，CVD中的R/E差异 在女性中更为明显。心血管疾病解释AA和NHW男性之间死亡率差异的33%，但45% 包女许多CVD风险因素的患病率较高（例如，肥胖）或对女性的影响更大; 例如，慢性压力，这不成比例地影响R/E少数民族，是一个更强的预测心血管疾病相关的 妇女死亡率。我们目前的研究测量了多领域CVD风险因素，包括累积压力， 下丘脑-垂体-肾上腺活性、炎症标志物和肥胖指数（人体测量，肥胖， 饮食、代谢标志物和脂肪因子）。我们提出 一项对这一特征鲜明的队列的随访研究在4到6年后的成年初显期， 当身体成熟基本完成，但生物心理社会风险因素有长期影响时， CVD出现。我们将确定随着时间的推移累积应力和AL负担的大小， 垂直整合标记的伊娃与国家的最先进的技术，并检查累积的影响， 压力、主动适应能力和适应性文化应对方式对伊娃影响。在可修改的生物技术中表征R/E差异 在发育阶段与亚临床CVD相关的心理社会风险和保护因素， 人类可以对自己的生活施加更多的控制（增加自主权，但很少承担成年人的责任） 这是一个机会，可以抢先从健康过渡到疾病，并减少高危人群中心血管疾病的差异。