Association of blood pressure variability with orthostatic intolerance symptoms

RESEARCH ARTICLE Association of blood pressure variability with orthostatic intolerance symptoms Jun-Sang Sunwoo1, Tae-Won Yang2, Do-Yong Kim3,4, Jung-Ah Lim5, Tae-Joon Kim3,4, Jung-Ick Byun6, Jangsup Moon3,4, Soon-Tae Lee3,4, Keun-Hwa Jung3,4, Kyung-Il Park7, KiYoung Jung3,4, Manho Kim3,4,8, Sang Kun Lee3,4*, Kon Chu3,4* a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Neurology, Soonchunhyang University College of Medicine, Seoul, South Korea, 2 Department of Neurology, Gyeongsang National University Changwon Hospital, Changwon, South Korea, 3 Department of Neurology, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea, 4 Program in Neuroscience, Seoul National University College of Medicine, Seoul, South Korea, 5 Department of Neurology, National Center for Mental Health, An affiliate of the Ministry for Health & Welfare, Seoul, South Korea, 6 Department of Neurology, Kyung Hee University Hospital at Gangdong, Seoul, South Korea, 7 Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea, 8 Protein Metabolism Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea * (SKL); (KC) Abstract OPEN ACCESS Citation: Sunwoo J-S, Yang T-W, Kim D-Y, Lim JA, Kim T-J, Byun J-I, et al. (2017) Association of blood pressure variability with orthostatic intolerance symptoms. PLoS ONE 12(6): e0179132. https://doi.org/10.1371/journal. pone.0179132 Editor: Tatsuo Shimosawa, The University of Tokyo, JAPAN Received: March 21, 2017 Accepted: May 24, 2017 Published: June 7, 2017 Copyright: © 2017 Sunwoo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Data contains information that could be used to identify study participants, and is available upon request from the corresponding author. The short-term blood pressure variability (BPV) reflects autonomic regulatory mechanisms. However, the influence of BPV in orthostatic intolerance (OI) is unknown. Herein, we assessed BPV profiles in patients with OI and determined their association with orthostatic symptoms. In this cross-sectional study, we prospectively enrolled 126 patients presenting with OI at the Seoul National University Hospital from December 2014 to August 2016. Among them, those with other neurological diseases (n = 8) and insufficient BP measurements (n = 15) were excluded. The degree of OI symptoms were measured using the selfadministered orthostatic intolerance questionnaire (OIQ). All patients underwent ambulatory BP monitoring and we calculated the standard deviation and coefficient of variation as a measure of BPV. The mean age was 48.6 years and the average of the total OIQ score was 11.6. The severe OI group had higher BPV values than the mild group, although mean BP profiles did not differ significantly. Correlation analysis demonstrated that the orthostatic symptoms were positively correlated with diastolic BPV for the total and awake periods. Multiple linear regression analysis revealed that diastolic BPV (B = 0.46, p = 0.031) and current smoking (B = 4.687, p = 0.018) were independent factors for higher OI symptom scores after adjusting for covariates. The results of the current study demonstrated that a positive correlation exists between BPV and OI symptoms. Further studies are required to confirm the present findings and understand the neural mechanisms contributing to the excessive BPV in patients with OI. Funding: This study was supported by the fund from Daiichi Sankyo Korea (06-2014-3970) and SK Plasma (06-2016-4080). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. PLOS ONE | https://doi.org/10.1371/journal.pone.0179132 June 7, 2017 1 / 13 Blood pressure variability and orthostatic intolerance Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: K.C. received research grants from Daiichi Sankyo Korea and SK plasma. The other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Introduction Orthostatic intolerance (OI) refers to symptoms and signs caused by an upright posture, which can be relieved by lying down [1]. Common presentations include dizziness, lightheadedness, blurred vision, headache, and fainting. OI can also manifest as various nonspecific symptoms, such as concentration difficulties, anxiety, chest discomfort, and tremulousness [2]. OI is a common condition in the adult population; prior studies reported the prevalence of orthostatic hypotension (OH) ranging between 14% and 30.3% and orthostatic dizziness ranging between 4.8% and 19.7% [3–5]. OI is a syndrome consisting of different clinical variants, such as OH, postural orthostatic tachycardia syndrome (POTS), and vasovagal syncope [6]. Accumulating evidence has shown that disruption of autonomic hemodynamic regulation contributes to the mechanisms of these OI subtypes with abnormal orthostatic responses [1, 7–9]. However, a considerable number of patients with OI show normal orthostatic vital sign response in clinical practice. This subgroup remains undiagnosed based on the current classification system. Furthermore, little is known about the pathophysiology and treatment of OI without excessive hypotension or tachycardia. Blood pressure (BP) continuously fluctuates and its variability indicates the complex interaction between multiple cardiovascular mechanisms, which are mediated by central autonomic regulation, sympathetic vascular modulation, baroreflex, and humoral influences [10, 11]. Although there are several types of blood pressure variability (BPV), the short-term BPV with a time range between minutes and hours represents the effects of autonomic and vasomotor modulation [12]. It can be measured noninvasively by ambulatory BP monitoring. Of note, BPV gained attention because of the findings that it acts as an independent risk factor for cardiovascular diseases [13, 14]. Accumulating evidence has shown that increased BPV is associated with target organ damage, including left ventricular hypertrophy and carotid atherosclerosis [15, 16]. Furthermore, BPV is considered to reflect central and reflex autonomic regulation [12]. Although OI was reported to involve abnormal autonomic responses [17], there has been little information regarding the influence of BPV in OI. Therefore, in this study, we evaluated short-term BPV profiles in patients presenting with OI by using ambulatory BP monitoring and determined the association between the degree of BPV and OI symptoms. Materials and methods Subjects We prospectively enro (...truncated)