Cardiovascular Project 3

心血管项目3

• 批准号: 10231032
• 负责人: ARSHED A QUYYUMI
• 金额: $ 32.36万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10231032
• 关键词: Adipose tissue; Arterial Fatty Streak; Atherosclerosis; Blood Vessels; Bone Marrow; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Carotid Artery Diseases; Carotid Artery Plaques; Cell Count; Centers of Research Excellence; Characteristics; Clinical; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Disease Progression; Dyslipidemias; Endothelium; Estrogens; Event; Fatty acid glycerol esters; Future; HIV; HIV Infections; HIV antiretroviral; Homeostasis; Hypertension; Immune; Impairment; Inflammation; Insulin Resistance; Low Prevalence; Magnetic Resonance Imaging; Measures; Mediating; Metabolic syndrome; Myocardial Infarction; Natural regeneration; Outcome; Patients; Play; Premature Menopause; Process; Regenerative capacity; Reproducibility; Risk; Risk Factors; Role; Sex Differences; Smoking; Specialized Center; Stroke; Structure; Surrogate Markers; Technology; Thick; Time; Ultrasonography; Woman; antiretroviral therapy; arterial stiffness; attenuation; brachial artery; calcification; cardiovascular disorder risk; cardiovascular risk factor; carotid intima-media thickness; coronary computed tomography angiography; coronary plaque; defined contribution; density; early onset; endothelial dysfunction; follow-up; high risk; men; mortality; rapid weight gain; regenerative; repaired; stem cells

ABSTRACT: PROJECT 3: CARDIOVASCULAR RISK IN WOMEN WITH HIV Although heightened cardiovascular disease (CVD) risk in HIV is partly attributable to an increased burden of CVD traditional risk factors and to antiretroviral therapy-mediated effects, persistent inflammation and immune dysregulation may also play a role. Women have a greater burden of CVD risk factors, including inflammation, despite having less obstructive coronary artery disease (CAD), but nevertheless have worsening clinical outcomes. Among HIV+ women, CVD risk is further compounded by estrogen deficiency and early menopause. Coronary computed tomographic angiography (CCTA) can not only detect the presence and volume of plaque, but assess high risk plaque (HRP) characteristics. Vascular functional and structural measures including carotid intima-media thickness (CIMT), carotid plaque, and brachial artery endothelial function are predictive of future MI and stroke. In HIV+ subjects, CIMT is thicker and carotid plaque 1.5-fold more prevalent compared to controls. Magnetic resonance imaging (MRI) of the carotid arteries provides a state-of-the-art, accurate and reproducible measure of carotid arterial wall thickness, plaque and its high risk characteristics, and permits reliable measures of disease progression. Circulating bone marrow-derived progenitor cells (PCs) are actively involved in cardiovascular homeostasis and mediate cardiovascular repair and regeneration. We have shown that a reduction in the number and migratory activity of PCs is higher CVD risk and mortality. Moreover, women have lower numbers of circulating PCs compared to men, and levels of PCs correlate with estrogen status. In HIV+ subjects, PC counts are lower providing evidence for reduced regenerative capacity. Our overall objective in this Project is to define the contribution of HIV infection in women to both injurious factors (inflammation, HIV status) and to endogenous reparative/regenerative processes in the setting of estrogen deficiency and their combined impact on the presence and progression of sub-clinical coronary and carotid artery atherosclerosis measured using CCTA and carotid MRI. In Aim 1, we will study the impact of HIV-related changes in regenerative capacity, endothelial function and arterial stiffness on prevalent coronary and carotid arterial disease. In Aim 2, we propose to assess the factors that underlie the progression of carotid arterial disease, measured using serial MRI over a 2-year period. In Aim 3, we will compare the extent of total atherosclerotic plaque volume and its' high risk characteristics, measured using CCTA in women with and without HIV.

摘要：项目3：HIV感染女性的心血管风险 尽管艾滋病毒感染者心血管疾病（CVD）风险的增加部分归因于 CVD的传统危险因素和抗逆转录病毒治疗介导的影响，持续性炎症和免疫 失调也可能起作用。女性有更大的心血管疾病风险因素的负担，包括炎症， 尽管具有较少的阻塞性冠状动脉疾病（CAD），但仍然具有恶化的临床症状， 结果。在HIV阳性女性中，雌激素缺乏和早期妊娠使CVD风险进一步加剧。 绝经 冠状动脉计算机断层血管造影（CCTA）不仅可以检测斑块的存在和体积， 但评估高危斑块（HRP）特征。血管功能和结构测量，包括 颈动脉内膜中层厚度（CIMT）、颈动脉斑块和肱动脉内皮功能是预测 未来的心肌梗死和中风在HIV+受试者中，CIMT更厚，颈动脉斑块的发生率是对照组的1.5倍。 对照颈动脉的磁共振成像（MRI）提供了一种最先进的、准确的、 可重复测量颈动脉壁厚度、斑块及其高危特征，并允许 疾病进展的可靠指标。 循环中骨髓来源的祖细胞（PC）积极参与心血管稳态 并介导心血管修复和再生。我们已经表明，减少数量和 PC的迁移活动是更高的CVD风险和死亡率。此外，妇女的循环次数较少， PC与男性相比，PC水平与雌激素状态相关。在HIV+受试者中，PC计数较低 提供了再生能力降低的证据。 我们在这个项目中的总体目标是确定妇女感染艾滋病毒对伤害性疾病和艾滋病的贡献。 因素（炎症，HIV状态）和内源性修复/再生过程的背景下， 雌激素缺乏及其对亚临床冠状动脉病变的存在和进展的联合影响 使用CCTA和颈动脉MRI测量颈动脉粥样硬化。 在目标1中，我们将研究HIV相关变化对再生能力、内皮功能和 动脉僵硬度与冠心病和颈动脉疾病的关系在目标2中，我们建议评估这些因素 这是颈动脉疾病进展的基础，使用连续MRI在2年内测量。在 目的3、比较动脉粥样硬化斑块总体积的大小及其高危特征， 使用CCTA在感染和未感染艾滋病毒的女性中进行测量。