Coronary Microvascular Dysfunction in HIV: A Review.
Coronary Microvascular Dysfunction in HIV: A Review.
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HIV 患者的冠状动脉微血管功能障碍：综述。
DOI：
10.1161/jaha.119.014018
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发表时间：
2020
影响因子：
5.4
通讯作者：
Shah,SanjivJ
中科院分区：
文献类型：
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作者：
Rethy,Leah;Feinstein,MatthewJ;Sinha,Arjun;Achenbach,Chad;Shah,SanjivJ
在美国，超过100万人感染艾滋病毒，50%的人年龄超过50岁。1有效的联合抗逆转录病毒疗法（ART）大大降低了艾滋病毒感染者（PLWH）的发病率和死亡率。然而，随着艾滋病相关死亡率的下降，心血管疾病（CVD）和非艾滋病相关恶性肿瘤导致的死亡率却在上升。3，4这种死亡率模式的变化可部分归因于以下事实：艾滋病毒携带者在有效的抗逆转录病毒疗法下的寿命更长，因此现在面临与年龄有关的疾病的风险，但艾滋病毒携带者死于这些疾病的比率更高，而且比一般人口更年轻。1，5，6流行病学研究表明，与未感染艾滋病毒的人相比，接受ART的PLWH心力衰竭（HF）、7-10冠状动脉疾病（CAD）、11，12肺动脉高压、13心源性猝死、14，15和中风8的发生率更高，即使控制了传统的心血管危险因素。PLWH在ART也被证明有亚临床CVD的发生率较高。包括心肌纤维化和脂肪变性，16-18以及收缩和舒张功能受损19，20。由于这些原因，临床心血管专家很可能会遇到PLWH谁是风险或谁有明显的心血管疾病，艾滋病毒相关的心血管疾病准备成为一个主要的公共卫生问题，在未来几十年。在ART时代，CVD研究主要集中在PLWH中CAD的机制和预防上，部分原因是ART治疗（特别是较老的含蛋白酶的方案）可以直接快速导致异常脂质谱的发展，这种异常脂质谱被与HIV相关的慢性炎症放大。21-25尽管炎症和动脉粥样硬化之间的联系已经得到了很好的建立，26慢性炎症越来越多地被理解为其他类型CVD（包括HF）的关键介质，并且可能是PLWH中CVD风险增加的主要介质。27，27-31冠状动脉微血管功能障碍（CMD）是心血管危险因素、慢性炎症、内皮活化和临床CVD发展之间的重要病理生理联系。17，32，33 CMD也是一种风险标志物，可用于风险分层和研究特定干预措施对冠状动脉微血管功能的影响。鉴于PLWH中亚临床和临床CVD的发生率升高，沿着缺乏可用于特异性靶向治疗HIV的CVD风险增加的循证疗法，我们认为研究特定机制（如CMD）至关重要，这可能为PLWH中CVD的潜在机制提供见解。此外，PLWH中的CMD也可能提供一个独特的模型，以更好地了解无HIV人群中免疫激活，炎症和CVD之间的关系。在这篇综述中，我们描述了（1）炎症和内皮功能障碍之间的关系，以及外周内皮功能的评估方法;（2）CMD的病理生理学及其对PLWH CVD的可能贡献;（3）以前研究PLWH CMD的优势和局限性;以及（4）未满足的需求和未来的PLWH CMD研究方向。
In the United States,> 1 million people are living with HIV, and% 50% are> 50 years old. 1 Potent combination antiretroviral therapy (ART) has significantly reduced the morbidity and mortality of people living with HIV (PLWH). 1, 2 However, as AIDS-related mortality has declined, death due to cardiovascular disease (CVD) and non–AIDS-associated malignancies has increased. 3, 4 This changing pattern of mortality can be partly attributed to the fact that PLWH are living longer on effective ART and thus are now at risk for age-related diseases, but PLWH are dying from these diseases at higher rates and at younger ages than the general population. 1, 5, 6 Epidemiologic research has demonstrated higher rates of heart failure (HF), 7–10 coronary artery disease (CAD), 11, 12 pulmonary hypertension, 13 sudden cardiac death, 14, 15 and stroke8 in PLWH on ART compared with those without HIV, even when controlling for traditional cardiovascular risk factors. PLWH on ART have also been shown to have higher rates of subclinical CVD. including myocardial fibrosis and steatosis, 16–18 as well as impaired systolic and diastolic function19, 20 compared with controls without HIV. For these reasons, clinical cardiovascular specialists are likely to encounter PLWH who are at risk for or who have overt CVD, and HIV-related CVD is poised to become a major public health problem in the coming decades. In the ART era, CVD research has focused largely on mechanisms and prevention of CAD in PLWH, motivated in part by the fact that treatment with ART (particularly older, protease inhibitor–containing regimens) can directly and quickly lead to the development of an abnormal lipid profile that is amplified by the chronic inflammation associated with HIV. 21–25 Although the link between inflammation and atherosclerosis is well established, 26 chronic inflammation is increasingly being understood as a key mediator of other types of CVD, including HF, and may be a prominent mediator of the increased risk of CVD in PLWH. 27, 27–31 Coronary microvascular dysfunction (CMD) is an important pathophysiologic link between cardiovascular risk factors, chronic inflammation, endothelial activation, and the development of clinical CVD. 17, 32, 33 CMD is also a risk marker and can be used to risk stratify and to study the effects of particular interventions on coronary microvascular function. Given the elevated rates of both subclinical and clinical CVD among PLWH, along with the lack of evidence-based therapeutics that can be used to specifically target the increased risk of CVD in treated HIV, we believe it is critical to investigate specific mechanisms, such as CMD, that might provide insight into the mechanisms underlying CVD in PLWH. In addition, CMD in PLWH may also provide a unique model to better understand the relationship among immune activation, inflammation, and CVD in people without HIV. In this review, we describe (1) the relationship between inflammation and endothelial dysfunction, as well as methods for the assessment of peripheral endothelial function;(2) the pathophysiology of CMD and its possible contribution to CVD in PLWH;(3) strengths and limitations of prior studies that have examined CMD in PLWH; and (4) unmet needs and future directions for the study of CMD in PLWH.