Statin restores cardiac autonomic response to acute hypoxia in hypercholesterolaemia Maria S. Brasileiro-Santos *,†‡ , Jos e A. S. Barreto-Filho *,§ , Raul D. Santos * , Ana P. M. Chacra * , Carine Teles Sangaleti *,¶ , Gisele Alvez *,† , Otavio Coelho Bezerra ** , Luiz Aparecido Bortoloto * , Maria C. Irigoyen *,† and Fernanda M. Consolim-Colombo *,§ * Instituto do Corac ß~ ao (InCor), Universidade de S~ ao Paulo, S~ ao Paulo, Brazil, † Universidade Federal de S~ ao Paulo (UNIFESP), S~ ao Paulo, Brazil, ‡ Universidade Federal da Para  ıba, Jo~ ao Pessoa, Brazil, § Universidade Federal de Sergipe, Aracaju, Brazil, ¶ Universidade Estadual do Centro-Oeste do Paran a, Guarapuava, Brazil, ** Universidade Nove de Julho (UNINOVE), S~ ao Paulo, Brazil ABSTRACT Background Hypercholesterolaemia may alter cardiovascular autonomic function. We investigated the auto- nomic cardiovascular regulation during normoxia and hypoxia in familial isolated HC patients with or without statin treatment. Materials and methods Low (LF-RR) and high (HF-RR) components of spectral analysis of RR interval and systolic arterial pressure (LF-SAP) were obtained during 5 min of normoxia and isocapnic hypoxia (10% O 2 ) in 10 normotensive familial HC patients without medication, in seven HC patients after a 12-week treatment period with 40 mg of simvastatin (HC + SVT) and in eight matched normal volunteers (CO). Results The HC patients had significant impairment of cardiac autonomic modulation parameters compared with CO at normoxia, which was maintained or even accentuated during hypoxia; these parameters included lower total variance of RR, increased normalized LF-RR, decreased normalized HF-RR, increased LF-RR/HF-RR ratio, higher LF-SAP component and reduced a index. However, the HC + SVT group had a significant improvement in all parameters: the LF-RR and LF-SAP decreased (indicating a decrease in cardiac and vascular sympathetic activity), the HF-RR increased (indicating an increase in parasympathetic activity) and the sponta- neous baroreflex sensitivity improved. These changes were detected at normoxia and were maintained during hypoxia. Conclusions Our data are the first to show that isolated HC is characterized by an increase in cardiac and vasomotor sympathetic drive, a decrease in cardiac vagal modulation and baroreflex impairment during norm- oxia and hypoxia. In addition, our data suggest that statin treatment has a potential role in restoring the phys- iological cardiovascular autonomic control at baseline and during cardiovascular challenge. Keywords Autonomic nervous system, blood pressure, hypercholesterolaemia, hypoxia, simvastatin. Eur J Clin Invest 2013; 43 (12): 1291–1298 Introduction Hypercholesterolaemia is a major risk factor for cardiovas- cular diseases, and familial isolated hypercholesterola- emia represents the most severe form within the spectrum of dyslipidaemias [1]. The most addressed mechanism that links hypercholesterolaemia, the development of atherosclerosis and premature coronary heart disease, is endothelial dysfunction [2,3]. Recently, attention has been focused on the relationship between cardiac autonomic modulation and cardiovascular diseases [4]. Decreased baroreflex sensitivity and sympathovagal dysfunction, characterized by sympathetic activation and parasympathetic withdrawal, have been found in patients with established heart diseases and several related risk factors [5,6]. These markers of autonomic dysfunction are independently associated with adverse prognostic outcomes, including sudden cardiac death [7–9]. We have previously demonstrated that isolated hypercho- lesterolaemic patients present blunted forearm vasorelaxation and dysregulation of the overall cardiovascular response dur- ing an acute episode of systemic hypoxia [10]. These findings European Journal of Clinical Investigation Vol 43 1291 DOI: 10.1111/eci.12177 ORIGINAL ARTICLE