ORIGINAL ARTICLE Heart rate and heart rate variability in resistant versus controlled hypertension and in true versus white-coat resistance A de la Sierra 1 , DA Calhoun 2 , E Vinyoles 3 , JR Banegas 4 , JJ de la Cruz 4 , M Gorostidi 5 , J Segura 6 and LM Ruilope 6 Sympathetic nervous system has an important role in resistant hypertension. Heart rate (HR) is a marker of sympathetic activity, but its association with resistant hypertension has not been assessed. We aimed to evaluate differences in HR values and variability between resistant and controlled patients and between true and white-coat resistant hypertensives (RHs). We compared office and ambulatory HR, nocturnal dip and s.d. in 14 627 RHs versus 11 951 controlled patients (on p3 drugs) and in 8730 true (24 h blood pressure (BP)X130 and/or 80 mm Hg) versus 4825 white-coat (24-h BPo130/80 mm Hg) RHs. After adjusting for age, gender, body mass index, diabetes status and beta blocker use, HR values and variability were significantly elevated in resistant versus controlled patients and in true versus white-coat RHs. In logistic regression models, after adjustment for confounders, office HR (odds ratio for each increase in tertile: 1.337; 95% confidence interval: 1.287–1.388; Po0.001), nocturnal dip (0.958; 0.918–0.999; P ¼ 0.035) and night time s.d. (1.115; 1.057–1.177; P ¼ 0.013) were all significantly associated with the presence of resistant hypertension. Moreover, night time HR (1.160; 1.065–1.265; Po0.001), nocturnal dip (0.876; 0.830–0.925; Po0.001) and 24-h s.d. (1.148; 1.092–1.207; Po0.001) were all significantly associated with true resistant hypertension. In conclusion, both increased HR and variability are associated with resistant hypertension and with true resistance. These suggest the involvement of the sympathetic nervous system in the development of resistance to antihypertensive treatment. Journal of Human Hypertension advance online publication, 9 January 2014; doi:10.1038/jhh.2013.135 Keywords: Resistant hypertension; ambulatory blood pressure monitoring; white-coat hypertension; heart rate; heart rate variability INTRODUCTION An increased sympathetic nervous system activity has been postulated as one of the main factors in hypertension develop- ment and maintenance. 1 However, measuring sympathetic activity in humans is difficult and requires complex techniques, such as noradrenaline spillover or muscle sympathetic nerve traffic. 2 Resting heart rate (HR) is an indirect indicator of sympathetic tone, 3,4 but possibly the only one which can be easily measured in the entire hypertensive population. Resting tachycardia has been related with increased mortality and morbidity in both general 5 and hypertensive populations. 6 Resistant hypertension is characterised by uncontrolled blood pressure (BP) values with the concomitant use of at least three antihypertensive drugs, one of them a diuretic. Its prevalence is estimated between 10% and 15%. 7,8 With the use of ambulatory BP monitoring (ABPM), more than one-third of resistant hyper- tensives (RHs) show normal values of 24-h BP and are classified as having white-coat resistant hypertension. 7 Recent studies show that sympathetic overactivity may have a key role in resistant hypertension as procedures which reduce sympathetic drive, such as renal sympathetic denervation 9 and baroreflex stimulation, 10 are able to importantly reduce BP in RH patients. Moreover, a modest reduction in resting HR has also been observed after these procedures. 11,12 The association between HR and resistant hypertension has not been previously addressed in large groups of patients. Only Acelajado et al. 13 reported that among RH patients those considered refractory (unable to get BP control despite maximum therapeutic effort) had an increased office HR in comparison with those who finally achieved BP control. The aim of the present study was to examine the association between HR (measured both at the office and during 24 h ABPM) and RH, by comparing patients diagnosed of RH versus those controlled on p3 drugs and by comparing true versus white-coat RH. PATIENTS AND METHODS Study design The Spanish ABPM Registry was developed to promote the use of ABPM in clinical practice. The ABPM Registry is based on the distribution of 41000 ambulatory BP monitors (Spacelabs 90207; Spacelabs Inc., Redmond, WA, USA) for routine use by physicians from primary care centres and specialised units across Spain. Details of physicians’ recruitment and characteristics of the registry have been previously reported. 7,14–16 Specifically, patients with atrial fibrillation or other supraventricular tachyarrhythmias were excluded. The current analysis was carried out in a database containing 114 901 valid patients. Among them, 88 859 were under antihyper- tensive treatment and had enough information regarding office HR measurement, ABPM of good quality and clinical information with special attention given to antihypertensive treatment (number and types of drugs used). 1 Department of Internal Medicine, Hospital Mutua Terrassa, University of Barcelona, Terrassa, Spain; 2 Division of cardiovascular disease, University of Alabama, Birmingham, AL, USA; 3 CAP la Mina, University of Barcelona, San Adrian del Besos, Spain; 4 Department of Preventive Medicine and Public Health, Autonomous University, Madrid, Spain; 5 Department of Nephrology, Hospital Universitario Central de Asturias, Oviedo, Spain and 6 Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain. Correspondence: Professor A de la Sierra, Department of Internal Medicine, Hospital Mutua Terrassa, University of Barcelona, Plaza Dr. Robert, 5, Terrassa 08221, Spain. E-mail: asierra@ub.edu or adelasierra@mutuaterrassa.cat Received 23 September 2013; revised 7 November 2013; accepted 22 November 2013 Journal of Human Hypertension (2014), 1–5 & 2014 Macmillan Publishers Limited All rights reserved 0950-9240/14 www.nature.com/jhh