Hypertensive Disorders of Pregnancy: Pathways to Future Cardiovascular Disease

妊娠期高血压疾病：未来心血管疾病的途径

• 批准号: 10201985
• 负责人: Odayme Quesada
• 金额: $ 16.02万
• 依托单位: THE CHRIST HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-04 至 2025-08-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10201985
• 关键词: Adult; Affect; Age; Award; Biochemical; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cicatrix; Clinical; Clinical Investigator; Communities; Coronary; Coronary Arteriosclerosis; Data; Development; Diagnostic; Disease; Disease Outcome; Disease Progression; Endothelium; Epidemiology; Etiology; Event; Exhibits; Functional disorder; Future; Goals; Heart Abnormalities; Heart Diseases; Heart failure; Heterogeneity; Hispanic Community Health Study/Study of Latinos; Impaired fasting glycaemia; Inflammation; Inflammatory; Investigation; Knowledge; Magnetic Resonance; Measures; Mediating; Metabolic; Metabolic syndrome; Microvascular Dysfunction; Mission; Modeling; Outcome; Oxidative Stress; Participant; Pathway interactions; Phenotype; Physiological; Population; Population Sciences; Pre-Eclampsia; Pregnancy; Pregnancy Interval; Program Development; Recording of previous events; Reporting; Research; Risk; Risk Factors; Sex Differences; Site; Stress; Structure; Testing; Time; United States National Institutes of Health; Visit; Woman; Women' s Health; aged; base; cardiometabolism; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; cardiovascular imaging; cardiovascular risk factor; career development; case control; cohort; coronary fibrosis; design; experience; heart imaging; high risk; indexing; inflammatory marker; men; mortality; normotensive; perfusion imaging; pregnancy disorder; pregnancy hypertension; prospective; recruit; sex; skill acquisition; skills training; trait

PROJECT ABSTRACT/SUMMARY There are clear sex differences between women and men in the presentation, etiology, and outcomes of cardiovascular disease (CVD). Among the most prominent sex-specific risk factors for women are those related to pregnancy, including hypertensive disorders of pregnancy such as gestational hypertension and preeclampsia. In fact, preeclampsia increases risk of coronary artery disease by 2-fold, heart failure (HF) by 4- fold, and CV mortality by up to 8-fold in affected compared to unaffected women. Despite this substantial risk burden, surprisingly little is known regarding the mechanisms that drive the development of pregnancy-related hypertensive disorders or the subsequent CVD outcomes in these vulnerable women. Emerging but limited data suggest that some, but not all, women with the presence of pre-conception clinical metabolic traits are predisposed to hypertensive disorders of pregnancy. There is also heterogeneity in the extent to which some, but not all, women with a history of preeclampsia have abnormalities in cardiovascular structure or function. We hypothesize that: (i) the stress of pregnancy augments pre-existing metabolic and inflammatory derangements in certain women, making them more susceptible to hypertensive disorders of pregnancy; (ii) in this setting, the hypertensive disorder of pregnancy triggers a cascade of inflammation and oxidative stress that persists and results in additional endothelial damage and coronary microvascular dysfunction (CMD), a previously unrecognized driver of CVD risk; and, (iii) women affected by a hypertensive disorder of pregnancy, especially in the setting of pre-existing metabolic and inflammatory risk and CMD, are more likely to experience accelerated subclinical cardiac disease and progression to clinical CVD. To test our hypotheses and clarify the mechanisms by which certain women are made vulnerable to hypertensive disorders of pregnancy and subsequent CVD, we will comprehensively interrogate clinical, biochemical, and physiological determinants across the spectrum of pregnancy-related CVD risk in both a community cohort enriched with metabolic traits and a clinical cohort that is deeply phenotyped using advanced non-invasive CV diagnostics. This K-23 award will support my goal of becoming a translational clinical investigator in women’s cardiovascular health with expertise in epidemiology, population science, advanced cardiac imaging and hypertensive disorders of pregnancy. The proposed project aligns with the National Institute of Health’s (NIH) mission and highlights the need for “investigations of the many factors underlying the health of women (https://orwh.od.nih.gov).”

项目摘要/摘要 在演讲，病因和结果中，男女之间存在明显的性别差异 心血管疾病（CVD）。女性最杰出的性别危险因素之一是相关的 怀孕，包括怀孕的高血压疾病，例如妊娠高血压和 子痫前期。实际上，先兆子痫增加了2倍心力衰竭（HF）的冠状动脉疾病风险4- 与未受影响的女性相比，受影响的折叠和简历死亡率最高为8倍。尽管有很大的风险 负担，令人惊讶 这些脆弱女性的高血压疾病或随后的CVD结果。新兴但数据有限 表明某些但不是全部，具有概念前临床代谢特征的女性是 易于怀孕的高血压疾病。在某些程度上也存在异质性 但并非全部，具有先兆子痫史的女性在心血管结构或功能方面具有异常。我们 假设：（i）怀孕的压力增加了现有的代谢和炎症演变 在某些妇女中，使她们更容易患怀孕的高血压疾病； （ii）在这种情况下， 怀孕的高血压疾病会触发一系列的感染和氧化应激，并持续存在 导致额外的内皮损伤和冠状动脉微血管功能障碍（CMD），以前 CVD风险的驱动因素无法识别； （iii）受到高血压疾病的妇女，尤其是 在现有的代谢和炎症风险和CMD的情况下，更有可能经历加速 亚临床心脏病和临床CVD的进展。测试我们的假设并阐明机制 通过某些妇女容易受到怀孕和随后的CVD高血压疾病的影响，我们 将全面询问整个范围的临床，生化和物理决定者 在富含代谢特征和临床队列的社区队列中，与怀孕有关的CVD风险 使用先进的非侵入性简历诊断进行了深层表型。 该K-23奖将支持我成为女性心血管的翻译临床研究者的目标 健康方面的专业知识在流行病学，人群科学，高级心脏成像和高血压疾病中 怀孕。拟议的项目与国家卫生研究院（NIH）的任务保持一致，并突出显示 需要“调查妇女健康的许多因素（https://orwh.od.nih.gov）。”