Heart Rate Variability in Systemic Hypertension Heikki V. Huikuri, MD, Antti Ylitalo, MD, Sirkku M. PikkujGms6, MD, Markku J. Iktiheimo, MD, K.E. Juhani Airaksinen, MD, Asko 0. Rantala, MD, Mauno Lilia, MD, and Y. Antero Kestniemi, MD low heart rate (HR) variability is a risk factor for cardiac mortality in various patient populations, but it has not been well established whether patients with long-stand- ing hypertension have abnormalities in the autonomic modulation of HR. Time and frequency domain mea- sures of HR variability were compared in randomly se- lected, age-matched populations of 188 normotensive and 168 hypertensive males (mean age 50 ? 6 years for both). The standard deviation of the RR intervals was lower in the hypertensive subjects than in the normoten- sive ones (52 -+ 19 vs 59 t 20 mss; p <O.O 1 ), and the very low and low-frequency spectral components of HR variability analyzed as absolute units were reduced in the hypertensive patients relative to the normotensive controls (p <O.OOl for both). Hypertensive subjects also had blunted changes of the normalized low- and high- frequency components in response to an upright (sitting) posture (NS) as compared with normotensive subjects (p <O.OOl for both). Multiple regression analysis showed the standard deviation of the RR intervals to be predicted most strongly by systolic blood pressure, both in the pa- tients with hypertension (p - 0.20, p = 0.01) and in the normotensive subjects (p - 0.28, p = 0.0002). After adjustment for the baseline differences in blood pressure and body mass index, none of the absolute measures of the HR variability or the responses of the normalized units of HR variability to a change in the body posture differed between the hypertensive subjects and normo- tensive controls. These data show that long-standing hy- pertension results in reduced overall HR variability and blunted autonomic responses to a change in body pos- ture. Altered autonomic modulation of HR in hyperten- sion is mainly due to elevated blood pressure and obe- sity in males with long-standing hypertension as compared with normotensive subjects. (Am J Cardiol 1996;77: 1073-l 077) xperimental and clinical studies have shown that cardiovascular autonomic regulation plays an im- portant role in cardiac mortality in various patient populations, I-5 but no large-scale population-based attempt has been made to evaluate the heart rate (HR) variability in subjects with systemic hyperten- sion. The purposes of the present study were to com- pare the measures of HR variability in randomly se- lected populations of middle-aged hypertensive and age-matched normotensive men and to assess the re- lations of HR variability to lifestyle, demographic variables, systolic and diastolic blood pressures, an- tihypertensive medication, and echocardiographic data. METHODS Study population: Three hundred normotensive and 300 hypertensive white men aged 40 to 60 years were invited for the studies. The hypertensive sub- jects were randomly selected from the register for the reimbursement of antihypertensive medication maintained by the Social Insurance Institute ( 15 pa- tients from each age class), and the age-matched From the Division of Cardiology and Atherosclerosis Research Group, Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland. This work was supported by grants from the Finnish Foundation for Cardiovascular Research, and the Medical Council of the Academy of Finland, Helsinki, Finland. Manuscript received October 3, 1995; revised manuscript received and ac- cepted December 18, 1995. Address for reprints: Heikki V. Huikuri, MD, Drvision of Cardiol- ogy, Department of Medicine, University of Oulu, Kajaanintie 50, 90220 Oulu, Finland. 01996 by Excerpta Medico, Inc All rights reserved. normotensive subjects were from the register cov- ering all inhabitants of the Oulu district. Hyperten- sive patients had received antihypertensive medica- tion for more than 5 years. The set of tests was completed by 259 normotensive and 261 hyperten- sive subjects (87%). Patients with symptoms, med- ication, or electrocardiographic evidence of coronary artery disease (35 normotensive and 64 hypertensive subjects), atria1 fibrillation, or technically inade- quate Holter recordings because of technical artifacts or frequent ectopic beats were excluded from the analyses. Based on these exclusion criteria, the final analyses included data from 188 normotensive and 168 hypertensive men. The subjects filled in a standardized health ques- tionnaire for past medical history, cardiac symptoms, medication, smoking habits, alcohol consumption, and physical activity, and they all underwent a clin- ical examination. Blood pressure was measured and a conventional 12-lead electrocardiogram was re- corded. Modifications of the questionnaires of Rose et al’ were used to obtain past medical history and smoking data. Four leisure-time physical activity groups were formed using a method described by Grimby.’ An automatic oscillometric recorder (Dinamap; Criticon Ltd.) was used for all the blood pressure measurements. The subject was seated for at least 5 minutes, after which blood pressure was measured 3 times at l-minute intervals from the right arm. The mean of 3 measurements was used in the analysis. Demographic variables, lifestyle data, and blood pressures of the normotensive and hypertensive sub- 0002.9 149/96/S 15.00 1073 PII 50002-9149(96)00135-X