Exercise & HRV After Menopause Control (n = 87) 4 KKW (n = 125) 8 KKW (n = 77) 12 KKW (n = 84) 57.5 (6.3) 57.5 (5.8) 58.2 (6.4) 57.4 (6.4) 56.7 (6.3) 86.4 (12.4) 32.3 (3.9) 103.4 (11.8) 1.34 (0.3) 142.1 (12.3) 80.7 (7.9) 117.3 (25.9) 56.9 (14.2) 68 24 8 23 16 18 16 49 55 39 6 83.3 (11.4) 31.4 (3.6) 100.2 (10.8) 1.29 (0.2) 138.4 (13.2) 80.4 (9.1) 116.9 (27.6) 58.1 (14.4) 65 29 6 26 10 18 18 45 62 33 5 85.2 (6.4) 32.1 (3.9) 102.5 (11.9) 1.29 (0.2) 139.8 (13.7) 80.9 (8.6) 118.0 (25.4) 57.3 (15.8) 62 30 8 34 18 18 14 45 61 35 4 83.8 (11.6) 31.4 (3.6) 99.2 (11.7) 1.33 (0.2) 138.6 (12.9) 81.8 (8.5) 121.9 (26.3) 57.2 (13.0) 72 26 2 31 20 21 11 46 54 38 8 Table 1. Baseline Characteristics. Demographics Age, mean (SD) y Ethnicity (%) Caucasian African American Hispanic or Other Anthropometry Weight (kg) BMI (kg/m2) Waist circumference (cm) Blood pressure (mmHg) Cardiovascular VO2max (L/min) Systolic Diastolic Hematology* LDL-C (mg/dL) HDL-C (mg/dL) Medication history (%) Antihypertensive Thyroid Antidepressant Hyperlipidemic Hormone Replacement Therapy Smoking (%) Never Past Current Total Cohort (N = 373) 84.5 (12.0) 31.8 (3.7) 101.2 (11.5) 1.31 (0.2) 139.6 (13.0) 80.9 (8.6) 118.4 (26.4) 57.5 (14.3) 67 27 6 22 22 19 22 46 59 36 6 Abbreviations: LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; HRT, hormone replacement therapy. *To convert LDL-C and HDL-C to mmol/L multiply by 0.0259. doi:10.1371/journal.pone.0002288.t001 Resting Heart Rate and HRV Analyses We present the HR, time, and frequency domain analyses in Table 4. All values represent the adjusted least squared means covaried for baseline value, age, antidepressant use, and ethnicity. Our primary GLM analyses for resting HR showed a statistically significant time effect for resting HR (P,0.0001), but not for treatment group effect (P = 0.10) after 6 months of exercise training. Thus, we found no specific exercise training effect despite a trend for a reduction in resting HR. For our time domain HRV measurements, we observed a significant main statistical effect for rMSSD and SDNN (all, P,0.0001) and for treatment group (all, P,0.006). Post hoc comparisons revealed that rMSSD for the 8- KKW and 12-KKW exercise training conditions were greater than the control after 6 months (P,0.05). However, our post-hoc assessment only showed a significant statistical difference in SDNN for the 8-KKW treatment versus control (P,0.05). For the frequency domain analysis, we observed a significant main statistical effect for the HFLn, LFLn, VLF, and PT components (all, P,0.001) and for treatment group (all, P,0.002). Post hoc assessment revealed that the HF index of HRV denoting parasympathetic tone was significantly greater versus the control group for the 8-KKW and 12-kcal KKW treatment conditions (both, P,0.05). Post hoc comparisons for LF, VLF, and PT showed each HRV index to be greater than the control group for the 4-KKW, 8-KKW, and 12-KKW treatment conditions (all, P,0.05). No statistical effects were noted for the LF:HF ratio. Discussion The primary finding from our study is that moderate intensity exercise training improves HRV characteristics in previously sedentary, overweight or obese postmenopausal women. To our knowledge, this is the largest clinically controlled exercise training trial examining this question and the only study examining the dose response of exercise training and HRV. Of particular interest is that these effects appear to be dose-related regarding parasympathetic tone (i.e., rMSSD and HF) as only women exercising at or above the NIH recommendation exhibited a positive change in these HRV characteristics. The same pattern was present for SDNN; however, SDNN represents mixed sympathetic and parasympathetic signaling which makes the PLoS ONE | www.plosone.org 4 June 2008 | Volume 3 | Issue 6 | e2288