Evaluation of HIV-associated Cardiac Dysfunction in Women

 描述（由申请人提供）：联合抗逆转录病毒疗法（cART）的出现导致艾滋病毒感染者的艾滋病相关死亡率显著下降。虽然这已经伴随着与晚期HIV相关的严重扩张型心肌病的减少，但在cART时代对HIV感染队列的超声心动图研究已经强调了轻度LV收缩功能障碍，特别是舒张功能障碍的患病率明显增加。鉴于这些队列的年轻年龄，以及艾滋病毒感染者的年龄增长，这些回声结果预示着该人群中HF的潜在激增。此外，新的心脏磁共振（CMR）技术显示，间质纤维化和心肌内甘油三酯（TG）含量增加的心血管和代谢危险因素的设置，并与受损的LV功能。众所周知，这些风险因素与HIV及其治疗相关，最近对HIV感染患者进行的中等规模CMR研究表明，心肌纤维化和TG含量增加，沿着心肌力学降低。与大多数可用的超声心动图研究一样，这些CMR研究并不关注女性，并且由于纳入健康志愿者作为对照以及缺乏对HIV相关因素或治疗的详细纵向评估而受到限制。与此同时，斑点追踪回波心肌变形评估的发展，现在允许更准确地评估亚临床心功能不全，使用广泛适用的非侵入性技术。我们建议利用最大和最长的艾滋病毒感染者和匹配良好的未感染妇女的前瞻性队列，妇女的跨部门艾滋病毒研究，建立在我们以前的回声研究布朗克斯和布鲁克林的参与者，并执行重复回声约12年后。这将允许第一个长期的纵向评估左心室功能障碍的艾滋病毒感染和未感染的妇女，并在这样的个人心肌变形的大小评价。这将通过CMR评估间质纤维化和心肌TG含量以及梗死来补充。使用HIV特异性暴露和ART的重复测量，以及增加的心脏应激、炎症和脂质失调的生物标志物，这一提议将提供关于HIV感染和相关因素在亚临床心肌功能障碍和疾病中的作用的重要新知识。在此过程中，拟议的项目将确定策略和未来的研究，以避免在cART时代威胁HIV感染人群的有症状HF的潜在增加。

 DESCRIPTION (provided by applicant): The advent of combination antiretroviral therapy (cART) has led to marked decreases in AIDS- related mortality in people with HIV infection. Although this has been accompanied by reduction of severe dilated cardiomyopathy associated with late-stage HIV, echocardiographic studies of HIV-infected cohorts in the cART era have highlighted pronounced increases in the prevalence of milder forms of LV systolic dysfunction and, particularly, diastolic dysfunction. Given the young age of such cohorts, and the advancing age of people living with HIV, these echo findings herald a potential upsurge of HF in this population. Moreover, novel cardiac magnetic resonance (CMR) techniques have shown interstitial fibrosis and intramyocardial triglyceride (TG) content to be increased in the setting f cardiovascular and metabolic risk factors, and to correlate with impaired LV function. Such risk factors are well-known to be associated with HIV and its treatment, and modest-sized CMR studies of HIV-infected patients have recently demonstrated increased myocardial fibrosis and TG content, along with depressed myocardial mechanics. Like the majority of available echo studies, these CMR studies did not focus on women, and are limited both by inclusion of healthy volunteers as controls, and by lack of detailed longitudinal assessment of HIV-related factors or treatment. Meanwhile, the development of speckle-tracking echo assessment of myocardial deformation now permits more accurate evaluation of subclinical cardiac dysfunction using a widely applicable non-invasive technique. We propose to leverage the largest and longest prospective cohort of HIV-infected and well-matched uninfected women, the Women's Interagency HIV Study, to build on our previous echo study among Bronx and Brooklyn participants, and perform repeat echoes approximately 12 years later. This will allow the first long-term longitudinal assessment of LV dysfunction in HIV-infected and uninfected women, and a well-sized evaluation of myocardial deformation in such individuals. This will be complemented by CMR assessment of interstitial fibrosis and myocardial TG content, as well as infarct. Using repeated measures of HIV-specific exposures and ART, and added biomarkers of cardiac stress, inflammation and lipid dysregulation, this proposal stands to provide important new knowledge concerning the role of HIV infection and related factors in subclinical myocardial dysfunction and disease. In so doing, the proposed project will identify strategies and future research to avert the potential rise in symptomatic HF that threatens the HIV-infected population in the cART era.