Heart Rate Variability Characteristics in Sedentary Postmenopausal Women Following Six Months of Exercise Training: The DREW Study Conrad P. Earnest1*, Carl J. Lavie2, Steven N. Blair3,4, Timothy S. Church1 1 Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, United States of America, 2 Department of Cardiology, Ochsner Health System, New Orleans, Louisiana, United States of America, 3 Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, United States of America, 4 The University of North Texas, Denton, Texas, United States of America Abstract Background: Decreased heart rate variability (HRV) is associated with a higher risk of mortality. Overall, postmenopausal women have lower levels of HRV than premenopausal women, which may be additionally complicated by lifestyle related behaviors such as physical inactivity and obesity. Though cardiorespiratory exercise training increases HRV, little is known regarding the exercise dose necessary to promote this improvement. Methodology/Principal Findings: Our primary aim was to measure HRV in post-menopausal women following 6-months of exercise training. We examined supine resting HRV in 373 post-menopausal women (45–75 y) after 6-months of randomly assigned and double-blinded administered exercise training exercise training at 50%, 100% and 150% of the NIH Consensus Development Panel’s recommended minimal physical activity level. This corresponded to 4, 8, or 12 kcal/kg per week (KKW) of energy expenditure. At baseline, we observed no significant differences in HRV or hormone replacement use between treatment groups. However, we did observe that Caucasian women and those taking antidepressant medications had lower levels of baseline HRV. After 6-months of exercise intervention, we observed a dose dependent increase in all parasympathetically derived time and frequency domain measurements across exercise groups after adjustment for age, ethnicity, antidepressants, and baseline rMSSD (all, P,0.001). For example, the parasympathetic index rMSSD was greater than control (23.1961.0) for the 4-KKW (25.9860.8; P = 0.14), 8-KKW (27.6661.0; P,0.05), and 12-KKW (27.4060.0; P,0.05) groups at follow-up. Conclusions/Significance: Moderate intensity exercise training exercise is sufficient to improve HRV in previously sedentary postmenopausal women in a dose-dependent manner, as 4-KKW is insufficient to improve parasympathetic indices of HRV, while 12-KKW conferred no greater improvement than 8-KKW. Trial Registration: Clinicaltrials.gov NCT 00011193 Citation: Earnest CP, Lavie CJ, Blair SN, Church TS (2008) Heart Rate Variability Characteristics in Sedentary Postmenopausal Women Following Six Months of Exercise Training: The DREW Study. PLoS ONE 3(6): e2288. doi:10.1371/journal.pone.0002288 Editor: Jose AL Calbet, University of Las Palmas de Gran Canaria, Spain Received March 4, 2008; Accepted April 16, 2008; Published June 4, 2008 Copyright: 2008 Earnest 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. Funding: The DREW study as financially supported by in part by American Heart Association Texas Affiliate award 02651404; the National Institutes of Health grant HL-66262 and an exercise equipment donation from Life Fitness (Schiller Park, IL). Competing Interests: The authors have declared that no competing interests exist. * E-mail: conrad.earnest@pbrc.edu Introduction Menopause represents a key transition period in a woman’s health. A fundamental etiology associated with menopause is the intricate link between estrogen metabolism and the autonomic nervous system. Autonomic nervous system balance can be assessed non-invasively via the use of heart rate variability (HRV). While a thorough review of HRV can be obtained elsewhere,[1] HRV is clinically useful because reduced HRV is associated with an increased risk of CV disease, type II diabetes and insulin resistance and has been shown to be reduced in postmenopausal women as compared with premenopausal women [2,3,4,5]. Equally, the assessment of HRV in postmenopause is important because cardiovascular (CV) disease typically occurs later in women than in men; yet, the fact remains that CV disease is one of the two leading causes of death in women [6,7]. A lifestyle behavior that has a significant affect on the metabolic processes surrounding CV disease is cardiorespiratory exercise training. Current recommendations from the National Institutes of Health (NIH) Consensus Development Panel recommend that women attain a minimal level of moderate intensity activity such as walking briskly for 30 minutes [8]. In a recent report, we observed significant improvements in peak aerobic power for varying doses of exercise in postmenopausal women obtaining ,50%, 100%, and 150% of the NIH recommendation [9]. Cross- sectional reports, as well as reports in cardiac rehabilitation,[10] suggest that regular exercise training improves HRV; however, exercise training studies elaborating on the dose necessary to affect beneficial HRV changes are not clear [11,12,13,14]. Limited exercise training studies conducted on postmenopausal women PLoS ONE | www.plosone.org 1 June 2008 | Volume 3 | Issue 6 | e2288