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，约有1,860万 2019年的死亡。2015年至2018年之间，1.2690亿美国成年人患有CVD，导致每年成本 医疗保健的3634亿美元，生产力和死亡率失去。 CVD负担在 种族/种族（R/E）群体：约60％的非裔美国人（AA）成年人患有CVD，而西班牙裔则约有48％ 拉丁裔（HL）和非西班牙裔白人（NHW）。 CVD中的R/E差异可能是由于遗传的相互作用 和社会文化因素，这些因素因某些R/E组所承受的慢性压力负担而加剧。 慢性应力引起应力反应系统的重复激活，增加了同性载荷（AL）和 损害健康。高Al可能会增加早期血管衰老（EVA）的风险：动脉僵硬，亚临床 内皮功能障碍，高血压和左心室肿块增加。 EVA中的R/E差异出现 青春期，在CVD的明显迹象之前，但没有同时测量垂直整合的CVD的研究 在开发初期的标记。已经提出了慢性应激，AL和CVD之间的联系，但未研究 全面。在某些高风险组（例如HL）中可能预防CVD的因素尚未是 跨R/E组探索。当前的CVD预防和治疗指南是根据数据制定的 主要是在男性中获得的，导致错过或延迟的诊断，非最佳治疗和差 结果，尤其是在R/E少数族裔女性中。研究了AA中CVD风险机制的研究 尽管两性的CVD患病率很高，但几乎完全在男性中。重要的是，CVD中的R/E差异 女性更明显。 CVD解释了AA和NHW男性之间的死亡率差异的33％，但45％ 对女性来说。许多CVD危险因素的患病率更高（例如肥胖症）或对女性的影响更大；为了 例如，慢性压力不成比例地影响R/E少数群体，是CVD相关的更强的预测指标 女性死亡率。我们当前的研究测量了多域CVD风险因素，包括累积应力， 下丘脑 - 垂体 - 肾上腺活性，炎症标记和肥胖指数（人体测量法，肥胖， 13至17岁的AA，HL和NHW青春期女孩的饮食，代谢标记和脂肪因子）。我们建议 在成年后4到6年对这一特征良好的队列的后续研究，一个关键时期 当物理成熟度基本完整，但具有长期影响的生物心理社会风险因素 对于CVD出现。我们将随着时间的推移确定累积应力和负担的大小 EVA的垂直整合标记与最先进的技术，并检查累积的影响 压力，AL和对EVA的适应性文化应对实践。表征R/E可修改生物的差异 发育阶段的心理社会风险和与亚临床CVD相关的保护因素 人类可以对自己的生活产生更多的控制（具有自主权的增加，但很少有成人职责） 有机会抢占从健康过渡到疾病的过渡，并减少高危人群中的CVD差异。