Patients with neurogenic orthostatic hypotension (OH) typically have impaired sympathetic nervous system tone and therefore low levels of upright plasma norepinephrine (NE) (noradrenaline). We report a subset of patients who clinically have typical neurogenic OH but who paradoxically have elevated upright levels of plasma NE. We retrospectively studied 83 OH patients evaluated at the Vanderbilt Autonomic Dysfunction Center between August 2007 and May 2013. Based on standing NE, patients were dichotomized into a hyperadrenergic OH group [hyperOH: upright NE ≥ 3.55 nmol/l (600 pg/ml), n=19] or a non-hyperadrenergic OH group [nOH: upright NE < 3.55 nmol/l (600 pg/ml), n=64]. Medical history and data from autonomic testing, including the Valsalva manoeuvre (VM), were analysed. HyperOH patients had profound orthostatic falls in blood pressure (BP), but less severe than in nOH [change in SBP (systolic blood pressure): −53±31 mmHg compared with −68±33 mmHg, P=0.050; change in DBP (diastolic blood pressure): −18±23 mmHg compared with −30±17 mmHg, P=0.01]. The expected compensatory increase in standing heart rate (HR) was similarly blunted in both hyperOH and nOH groups [84±15 beats per minute (bpm) compared with 82±14 bpm; P=0.6]. HyperOH patients had less severe sympathetic failure as evidenced by smaller falls in DBP during phase 2 of VM and a shorter VM phase 4 BP recovery time (16.5±8.9 s compared with 31.6±16.6 s; P<0.001) than nOH patients. Neurogenic hyperOH patients have severe neurogenic OH, but have less severe adrenergic dysfunction than nOH patients. Further work is required to understand whether hyperOH patients will progress to nOH or whether this represents a different disorder.
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April 24 2015
Neurogenic hyperadrenergic orthostatic hypotension: a newly recognized variant of orthostatic hypotension in older adults with elevated norepinephrine (noradrenaline)
Philip L. Mar;
Philip L. Mar
*Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
†Division of Cardiovascular Medicine, Department of Medicine, University of Louisville, Louisville, KY 40270-9941, U.S.A.
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Cyndya A. Shibao;
Cyndya A. Shibao
*Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
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Emily M. Garland;
Emily M. Garland
*Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
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Bonnie K. Black;
Bonnie K. Black
*Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
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Italo Biaggioni;
Italo Biaggioni
*Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
‡Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
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André Diedrich;
André Diedrich
*Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
§Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
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Sachin Y. Paranjape;
Sachin Y. Paranjape
*Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
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David Robertson;
David Robertson
*Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
‡Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
║Department of Neurology, Vanderbilt University, Nashville, TN 37212-2102, U.S.A.
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Satish R. Raj
*Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
‡Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
¶Department of Cardiac Science, Libin Cardiovascular Institute, University of Calgary, Calgary, AB T2N 2T9, Canada
Correspondence: Dr Satish R. Raj (email [email protected]).
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Publisher: Portland Press Ltd
Received:
November 21 2014
Revision Received:
February 16 2015
Accepted:
February 23 2015
Accepted Manuscript online:
February 23 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 129 (2): 107–116.
Article history
Received:
November 21 2014
Revision Received:
February 16 2015
Accepted:
February 23 2015
Accepted Manuscript online:
February 23 2015
Citation
Philip L. Mar, Cyndya A. Shibao, Emily M. Garland, Bonnie K. Black, Italo Biaggioni, André Diedrich, Sachin Y. Paranjape, David Robertson, Satish R. Raj; Neurogenic hyperadrenergic orthostatic hypotension: a newly recognized variant of orthostatic hypotension in older adults with elevated norepinephrine (noradrenaline). Clin Sci (Lond) 1 July 2015; 129 (2): 107–116. doi: https://doi.org/10.1042/CS20140766
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