不明原因晕厥发作中的新型心血管生物标志物：SYSTEMA 队列研究。

Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort.

机构信息

Department of Clinical Sciences, Lund University, Clinical Research Center, Malmö, Sweden.

出版信息

J Intern Med. 2013 Apr;273(4):359-67. doi: 10.1111/joim.12043.

DOI:10.1111/joim.12043

PMID:23510366

Abstract

OBJECTIVES

The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.

DESIGN AND SETTING

An observational study was conducted including 255 patients (mean age 60 years, range 15-93; 45% men) with unexplained syncopal attacks. Subjects underwent an expanded head-up tilt test including carotid sinus massage, and nitroglycerin provocation if indicated. Using logistic regression, we explored the associations between specific diagnoses of syncope and resting levels of circulating biomarkers: C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1 precursor fragment (CT-proET-1), midregional fragments of pro-atrial natriuretic peptide (MR-proANP) and pro-adrenomedullin (MR-proADM).

RESULTS

A total of 142 (56%) patients were diagnosed with vasovagal syncope (VVS), 85 (33%) with orthostatic hypotension (OH) and 47 (18%) with carotid sinus hypersensitivity (CSH); in addition, 74 (29%) patients had more than one diagnosis. Thirty-five patients (14%) demonstrated a cardioinhibitory reflex. The probability of VVS was highest in the first quartile of MR-proANP [Q1 vs. Q4: odds ratio (OR) 5.57, 95% confidence interval (CI) 1.86-16.74; P < 0.001] and CT-proET-1 (OR 7.17, 95% CI 2.43-21.13; P < 0.001). By contrast, the probability of OH was highest in the fourth quartile of CT-proET-1 (Q4 vs. Q1: OR 8.66, 95% CI 2.49-30.17; P < 0.001). Furthermore, CSH was most frequently observed in the first quartile of MR-proANP (Q1 vs. Q4: OR 6.57, 95% CI 1.62-26.62; P = 0.008) among those over 60 years of age, whereas the cardioinhibitory reflex was strongly associated with low CT-proET-1 levels (Q1 vs. Q4: OR 69.7, 95% CI 6.97-696.6; P < 0.001). Moreover, in patients with VVS, a high concentration of CT-proET-1 was predictive of OH (OR per 1 SD 2.4, 95% CI 1.15-5.02; P = 0.02), whereas low CT-proET-1 suggested involvement of the cardioinhibitory reflex (OR per 1SD 0.42, 95% CI 0.25-0.70; P = 0.001).

CONCLUSIONS

The levels of MR-proANP and CT-proET-1 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks.

摘要

目的

本研究旨在探讨常见非心源性晕厥患者新型心血管生物标志物的静息水平。

设计和设置

本观察性研究纳入了 255 名（平均年龄 60 岁，范围 15-93 岁；45%为男性）不明原因晕厥发作的患者。所有患者均接受了扩展的头倾斜试验，包括颈动脉窦按摩，如果需要还进行了硝酸甘油激发试验。我们采用逻辑回归方法，探讨了特定晕厥诊断与循环生物标志物静息水平之间的关系：C 端脯氨酸血管加压素（CT-proAVP）、C 端内皮素-1 前体片段（CT-proET-1）、前利尿钠肽中区域片段（MR-proANP）和前肾上腺髓质素（MR-proADM）。

结果

共有 142 名（56%）患者被诊断为血管迷走性晕厥（VVS）、85 名（33%）为体位性低血压（OH）和 47 名（18%）为颈动脉窦过敏（CSH）；此外，74 名（29%）患者有不止一种诊断。35 名（14%）患者表现为心脏抑制反射。MR-proANP 第 1 四分位（Q1 与 Q4：比值比 [OR] 5.57，95%置信区间 [CI] 1.86-16.74；P < 0.001）和 CT-proET-1（OR 7.17，95% CI 2.43-21.13；P < 0.001）中 VVS 的可能性最高。相比之下，CT-proET-1 的第 4 四分位（Q4 与 Q1：OR 8.66，95% CI 2.49-30.17；P < 0.001）中 OH 的可能性最高。此外，CSH 最常发生在 60 岁以上患者的 MR-proANP 第 1 四分位（Q1 与 Q4：OR 6.57，95% CI 1.62-26.62；P = 0.008）中，而心脏抑制反射与低 CT-proET-1 水平密切相关（Q1 与 Q4：OR 69.7，95% CI 6.97-696.6；P < 0.001）。此外，在 VVS 患者中，CT-proET-1 浓度升高预示着 OH（OR 每 1SD 2.4，95% CI 1.15-5.02；P = 0.02），而 CT-proET-1 降低提示心脏抑制反射的参与（OR 每 1SD 0.42，95% CI 0.25-0.70；P = 0.001）。