title: Neurogenic hyperadrenergic orthostatic hypotension: a newly recognized variant of orthostatic hypotension in older adults with elevated norepinephrine (noradrenaline).
abstract: 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.
authors.affiliation: *Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Mar
authors.affiliation: *Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
authors.forename: Cyndya A
authors.initials: CA
authors.lastname: Shibao
authors.affiliation: *Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Garland
authors.affiliation: *Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
authors.forename: Bonnie K
authors.initials: BK
authors.lastname: Black
authors.affiliation: *Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
authors.affiliation: *Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.affiliation: *Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
authors.forename: Sachin Y
authors.initials: SY
authors.lastname: Paranjape
authors.affiliation: *Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.affiliation: *Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2102, U.S.A.
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
mesh_terms: D000368:Aged; D001341:Autonomic Nervous System / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D005260:Female; D006339:Heart Rate; D006801:Humans; D007024:Hypotension, Orthostatic / Q000097:blood* / Q000145:classification / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D011187:Posture; D012189:Retrospective Studies; D013714:Tennessee; D015854:Up-Regulation; D014636:Valsalva Maneuver
chemical_list: D015415:Biomarkers; D009638:Norepinephrine