在有和没有 HIV 的人群中，循环生物标志物与左心房大小和心肌细胞外体积分数相关。
Circulating biomarker correlates of left atrial size and myocardial extracellular volume fraction among persons living with and without HIV.
机构信息
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
出版信息
BMC Cardiovasc Disord. 2022 Sep 3;22(1):393. doi: 10.1186/s12872-022-02835-y.
BACKGROUND
Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH).
METHODS
Participants from three cohorts of PLWH and PLWOH underwent cardiovascular magnetic resonance imaging for measurement of LAVI and ECV. Levels of circulating proteins (IL-6, sCD14, galectin-3, NT-proBNP, GDF-15, TIMP-2, MMP-2, and hsTnI) were measured using immunoassays. Associations were assessed using logistic and linear regression, adjusting for demographics, substance use, and clinical characteristics.
RESULTS
Among 381 participants with and without HIV, median age (IQR) was 55.1 (51.2, 58.4) years, 28% were female, 69% were Black, and 46% were current smokers. Sixty-two percent were PLWH (n = 235), of whom 88% were receiving cART and 72% were virally suppressed. PLWH had higher levels of sCD14 (p = < 0.001), GDF-15 (p = < 0.001), and NT-proBNP (p = 0.03) compared to PLWOH, while levels of other biomarkers did not differ by HIV serostatus, including IL-6 (p = 0.84). Among PLWH, higher sCD14, GDF-15, and NT-proBNP were also associated with lower CD4 + cell count, and higher NT-proBNP was associated with detectable HIV viral load. NT-proBNP was associated with elevated LAVI (OR: 1.79 [95% CI: 1.31, 2.44]; p < 0.001) with no evidence of effect measure modification by HIV serostatus. Other associations between HIV-associated biomarkers and LAVI or ECV were small or imprecise.
CONCLUSIONS
Our findings suggest that elevated levels of sCD14, GDF-15, and NT-proBNP among PLWH compared to PLWOH observed in the current cART era may only minimally reflect HIV-associated elevations in LAVI and ECV. Future studies of excess risk of myocardial disease among contemporary cohorts of PLWH should investigate mechanisms other than those connoted by the studied biomarkers.
背景
尽管现在有联合抗逆转录病毒疗法（cART），但人类免疫缺陷病毒（HIV）感染与心肌疾病风险增加有关。然而，导致这种风险增加的因素仍未得到很好的描述。我们旨在评估左心房容积指数（LAVI）和心肌细胞外容积（ECV）分数升高与炎症、纤维化和肌细胞拉伸的循环生物标志物水平之间的横断面关系，这些生物标志物在 HIV 感染者（PLWH）和非 HIV 感染者（PLWOH）中均有报道。
方法
来自三个 PLWH 和 PLWOH 队列的参与者接受心血管磁共振成像检查，以测量 LAVI 和 ECV。使用免疫测定法测量循环蛋白（IL-6、sCD14、半乳糖凝集素-3、NT-proBNP、GDF-15、TIMP-2、MMP-2 和 hsTnI）的水平。使用逻辑回归和线性回归进行关联评估，调整了人口统计学、物质使用和临床特征。
结果
在 381 名有和没有 HIV 的参与者中，中位年龄（IQR）为 55.1（51.2，58.4）岁，28%为女性，69%为黑人，46%为当前吸烟者。62%为 PLWH（n=235），其中 88%正在接受 cART，72%病毒得到抑制。PLWH 的 sCD14（p<0.001）、GDF-15（p<0.001）和 NT-proBNP（p=0.03）水平均高于 PLWOH，而其他生物标志物的水平则没有因 HIV 血清状态而不同，包括 IL-6（p=0.84）。在 PLWH 中，较高的 sCD14、GDF-15 和 NT-proBNP 也与较低的 CD4+细胞计数相关，而较高的 NT-proBNP 与可检测到的 HIV 病毒载量相关。NT-proBNP 与升高的 LAVI 相关（OR：1.79[95%CI：1.31，2.44]；p<0.001），且无证据表明 HIV 血清状态存在效应修正。HIV 相关生物标志物与 LAVI 或 ECV 之间的其他关联较小或不精确。
结论
我们的研究结果表明，与当前 cART 时代 PLWOH 相比，PLWH 中 sCD14、GDF-15 和 NT-proBNP 水平升高可能仅能轻微反映 HIV 引起的 LAVI 和 ECV 升高。对当代 PLWH 队列心肌疾病风险增加的进一步研究应调查这些生物标志物所暗示的以外的机制。
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