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: 10674059
• 负责人: UMA RAO
• 金额: $ 69.59万
• 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/10674059
• 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; Dimensions; Disease; Disease Marker; Early Intervention; Environmental Risk Factor; Ethnic Origin; Ethnic Population; Exhibits; Female; Female Adolescents; Femur; 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; 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; Vascular Endothelium; 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 disparity; 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 difference; racial disparity; racial minority; racial population; response; sex; social disparities; sociocultural determinant; 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 2019年的死亡人数。2015至2018年间，1.269亿美国成年人患有心血管疾病，导致每年的成本 3634亿美元的医疗保健、生产力损失和死亡率。心血管疾病的负担并不是在 种族/民族(R/E)群体：大约60%的非裔美国人(AA)成年人患有心血管疾病，而西班牙裔/西班牙裔的这一比例约为48%。 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 以及社会文化因素，一些R/E群体承受的长期压力负担加剧了这些因素。 慢性应激引起应激反应系统的反复激活，增加了稳态负荷(AL)和 危及健康。高AL可能增加早期血管老化(EVA)的风险：动脉僵硬，亚临床 内皮功能障碍、高血压和左心室重量增加。EVA中的R/E差异通过以下方式出现 青春期，在出现明显的心血管疾病迹象之前，但没有研究同时测量垂直整合的心血管疾病 处于早期发展阶段的标记。慢性应激、急性白血病和心血管疾病之间的联系已被提出，但尚未进行研究 全面的。在一些高危人群(如HL)中，可能预防心血管疾病的因素尚未得到 跨R/E组进行了探索。目前的心血管疾病预防和治疗指南是根据数据制定的 主要发生在男性身上，导致漏诊或延误诊断，治疗效果不佳 结果，特别是在R/E少数民族妇女中。对再障患者心血管风险的发生机制进行了研究。 几乎只发生在男性，尽管男女的心血管疾病患病率都很高。重要的是，心血管疾病中的R/E差异 在女性身上更明显。心血管疾病可以解释AA和NHW男性之间33%的死亡率差异，但45% 为女性准备的。许多心血管疾病危险因素在妇女中的患病率更高(例如肥胖)或影响更大； 例如，慢性应激对R/E少数民族的影响不成比例，是心血管疾病相关的更强预测因子 女性死亡率。我们目前的研究测量了多个领域的心血管疾病风险因素，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、代谢标记物和脂肪因子)对13至17岁的AA、HL和NHW青春期女孩的影响。我们建议 对这一特征良好的队列在4到6年后的成人期(关键时期)进行的随访研究 当身体成熟基本完成，但具有长期影响的生物、心理和社会风险因素时 对于心血管疾病的出现。我们将随着时间的推移确定累积压力和AL负担的大小，包括 垂直整合的EVA指标与最先进的技术，并检验累积的效果 关于EVA的压力、AL和适应性文化应对做法。表征可修饰生物材料的R/E差异 在发育阶段与亚临床脑血管病相关的心理社会风险和保护因素 人类可以对他们的生活施加更多的控制(自主性增加，但成年人的责任很少) 这是一个先发制人的机会，可以预防从健康到疾病的过渡，减少高危人群中的心血管疾病差距。