Atherosclerosis 213 (2010) 212–217 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis LDL apheresis improves deranged cardiovagal modulation in hypercholesterolemic patients Manja Reimann a,b,∗ , Ulrich Julius c , Kristin Haink a , Birgit Lippold c , Sergey Tselmin c , Stefan R. Bornstein c , Heinz Reichmann a , Heinz Rüdiger a,b , Tjalf Ziemssen a,b a Autonomic and Neuroendocrinological Laboratory, Department of Neurology, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany b Research Group Neuro-Metabolism, Department of Neurology and Internal Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany c LDL-Apheresis Center, Department of Internal Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany article info Article history: Received 29 January 2010 Received in revised form 26 May 2010 Accepted 16 July 2010 Available online 22 July 2010 Keywords: Baroreflex sensitivity Trigonometric regressive spectral analysis Autonomic nervous system LDL apheresis abstract Objective: Hypotensive episodes are relatively frequent adverse effects during LDL apheresis. To evaluate the impact of LDL apheresis on autonomic cardiovascular control we investigated hypercholesterolemic patients before and after a single LDL apheresis in comparison to an age-matched control group. Methods: We continuously recorded systemic arterial blood pressure, electrocardiogram and respiration in 21 hypercholesterolemic patients (57 ± 15 years) on regular LDL apheresis treatment and 22 healthy control subjects (56 ± 4 years) during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head-up tilt). Baroreflex sensitivity and frequency spectra of R–R intervals and systolic blood pressure were evaluated by trigonometric regressive spectral analysis. Results: Hypercholesterolemic patients had reduced resting baroreflex sensitivity and high-frequency power of heart rate variability compared to controls. Consequently, there was a sympathetic predom- inance of heart rate modulation reflected by increased ratio of low-to-high frequency power of R–R intervals. Cardiovascular stimulation failed to adequately activate baroreflex mechanisms before LDL apheresis. After LDL apheresis, the parasympathetic response to cardiovascular stimulation improved and sympathetic outflow to peripheral vasculature was reduced. Baroreflex sensitivity remained low. Conclusion: Hypercholesterolemic patients on regular LDL apheresis treatment have significant auto- nomic dysfunction. A single LDL apheresis does not evoke sympathetic overactivation but improved deranged cardiovagal heart rate modulation in hypercholesterolemia. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Low-density lipoprotein (LDL) apheresis is implicated as adjunct therapy in homozygous cases of familial hypercholesterolemia and in patients with severe hypercholesterolemia who are insuf- ficiently responsive to dietary and pharmacological interventions [1]. Beyond considerable LDL reduction, soluble peptides and pro- teins modulating inflammation, thrombosis and hemostasis are also removed to some degree by LDL apheresis [2]. Consequently, multiple benefits of LDL apheresis have been reported including improvements of blood rheology, vascular reactivity as well as reduction of thrombosis and inflammation [3–6]. These changes ∗ Corresponding author at: Autonomic and Neuroendocrinological Laboratory, Department of Neurology, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetscherstr. 74, 01307 Dresden, Germany. Tel.: +49 351 458 3862; fax: +49 351 458 5873. E-mail address: manjareimann@uniklinikum-dresden.de (M. Reimann). in the cardiovascular environment may account for the observed regression of atherosclerosis, reduction of cardiovascular events and improvements of central, peripheral and cerebral perfusion in LDL apheresis patients [7–9]. Although LDL apheresis is tolerated well, safety and efficacy studies suggested hypotension as most frequent adverse effect [10]. Cardiovascular instability has also been reported in patients undergoing hemodialysis [11–13]. Sympathetic overactivation and associated harmful hypertensive periods have been recognized as another serious problem of hemodialysis [14]. Whether this is true for LDL apheresis cannot be answered yet. Since cardiovascular stress typically results in sympathetic acti- vation it may be speculated that LDL apheresis which resembles a cardiovascular stressor may likewise stimulate the sympathetic nervous system. To investigate this hypothesis we performed extensive autonomic testing including spectral and baroreflex sen- sitivity (BRS) analysis in hypercholesterolemic patients before and after a single LDL apheresis and compared these results to those obtained in healthy controls. 0021-9150/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2010.07.019