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) 是全球最主要的死亡原因，约占 1860 万人的死亡原因 2019 年死亡人数。2015 年至 2018 年间，1.269 亿美国成年人患有 CVD，导致每年花费 医疗保健、生产力损失和死亡率高达 3,634 亿美元。 CVD 负担并未平均分配 种族/族裔 (R/E) 群体：大约 60% 的非洲裔美国人 (AA) 成年人患有 CVD，而大约 48% 的西班牙裔/ 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造成的 和社会文化因素，一些 R/E 群体承受的长期压力负担加剧了这些因素。 慢性压力会引起应激反应系统的反复激活，增加稳态负荷（AL）和 损害健康。高 AL 可能会增加早期血管老化 (EVA) 的风险：动脉硬化、亚临床 内皮功能障碍、高血压和左心室质量增加。 EVA 中的 R/E 差异表现为 青春期，出现明显的 CVD 症状之前，但没有研究同时测量垂直整合的 CVD 开发早期的标记。慢性压力、AL 和 CVD 之间的联系已被提出，但尚未研究 全面地。可能预防某些高危人群（例如 HL）发生 CVD 的因素尚未得到研究 跨 R/E 小组进行探索。目前的CVD预防和治疗指南是根据数据制定的 主要发生在男性中，导致漏诊或延迟诊断、非最佳治疗和效果不佳 结果，特别是在 R/E 少数族裔女性中。 AA CVD风险机制研究 尽管心血管疾病在两性中的患病率都很高，但几乎全部发生在男性中。重要的是，CVD 中的 R/E 差异 在女性中更为明显。 CVD 解释了 AA 和 NHW 男性死亡率差异的 33%，但也解释了 45% 对女性来说。许多 CVD 危险因素对女性的患病率较高（例如肥胖）或影响更大；为了 例如，慢性压力对 R/E 少数族裔影响尤为严重，但它是 CVD 相关疾病的更强预测因素 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-肾上腺活动、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）在 13 至 17 岁的 AA、HL 和 NHW 青春期女孩中。我们建议 4 至 6 年后，在成年初期（这是一个关键时期）对这个特征明确的队列进行了一项后续研究 当身体基本成熟但生物心理社会风险因素具有长期影响时 CVD出现。我们将确定随着时间的推移累积压力和 AL 负担的大小，包括 采用最先进的技术垂直整合 EVA 标记，并检查累积的影响 EVA 的压力、AL 和适应性文化应对实践。表征可修饰生物的 R/E 差异 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，但很少承担成人责任） 这是一个预防从健康向疾病转变并减少高危人群心血管疾病差异的机会。