Open Access Research article

Jugular venous reflux and plasma endothelin-1 are associated with cough syncope: a case control pilot study

Chih-Ping Chung12, Chun-Yu Cheng12, Robert Zivadinov3, Wei-Chih Chen45, Wen-Yung Sheng1, Yu-Chin Lee26, Han-Hwa Hu12, Hung-Yi Hsu10119 and Kuang-Yao Yang678*

Author affiliations

1 Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan

2 School of Medicine, National Yang Ming University, Taipei, Taiwan

3 Buffalo Neuroimaging Analysis Center, and the Department of Neurology, State University of New York at Buffalo, New York, USA

4 Department of Respiratory Therapy, Taipei Veterans General Hospital, Taipei, Taiwan

5 Division of Pulmonary Medicine, Department of Medical Affairs, Taipei Municipal Gan-Dau Hospital, Taipei, Taiwan

6 Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, 112, Taiwan

7 Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan

8 Institute of Clinical Medicine, Infection and Immunity Research Center, School of Medicine, National Yang Ming University, Taipei, Taiwan

9 Department of Neurology, Tungs' Taichung Metro Harbor Hospital, Wuci Township, Taichung County, Taiwan

10 School of Medicine, Chung Shan Medical University, Taichung, Taiwan

11 Department of Neurology, Taichung Veterans General Hospital, Taichung, Taiwan

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Citation and License

BMC Neurology 2013, 13:9  doi:10.1186/1471-2377-13-9

Published: 16 January 2013



Jugular venous reflux (JVR) has been reported to cause cough syncope via retrograde-transmitted venous hypertension and consequently decreased cerebral blood flow (CBF). Unmatched frequencies of JVR and cough syncope led us to postulate that there should be additional factors combined with JVR to exaggerate CBF decrement during cough, leading to syncope. The present pilot study tested the hypothesis that JVR, in addition to an increased level of plasma endothelin-1 (ET-1), a potent vasoconstrictor, is involved in the pathophysiology of cough syncope.


Seventeen patients with cough syncope or pre-syncope (Mean[SD] = 74.63(12.37) years; 15 males) and 51 age/gender-matched controls received color-coded duplex ultrasonography for JVR determination and plasma ET-1 level measurements.


Multivariate logistic analysis showed that the presence of both-side JVR (odds ratio [OR] = 10.77, 95% confident interval [CI] = 2.40-48.35, p = 0.0019) and plasma ET-1 > 3.43 pg/ml (OR = 14.57, 95% CI = 2.95-71.59, p = 0.001) were independently associated with the presence of cough syncope/ pre-syncope respectively. There was less incidence of cough syncope/ pre-syncope in subjects with the absence of both-side JVR and a plasma ET-1 ≦3.43 pg/ml. Presence of both side JVR and plasma ET-1 level of > 3.43 pg/ml, increased risk for cough syncope/pre-syncope (p < 0.001).


JVR and higher plasma levels of ET-1 are associated with cough syncope/ pre-syncope. Although sample size of this study was small, we showed a synergistic effect between JVR and plasma ET-1 levels on the occurrence of cough syncope/pre-syncope. Future studies should confirm our pilot findings.

Cough syncope; Endothelin-1; Jugular venous reflux