Exercise & HRV After Menopause Table 4. Heart Rate Variability Outcome Measures at Follow-Up. Heart Rate (b/min) Time Domain (ms) rMSSD*, { SDNN*, { Frequency Domain (ms2) HFLn*, { LFLn*, { VLF*, { LF:HF Ratio TotalLn*, { Control (n = 87) 64.8 (5.0) 23.19 (9.3) 32.93 (10.1) 5.20 (0.9) 5.21 (0.9) 4.64 (0.9) 1.60 (2.0) 6.28 (0.9) 4 KKW (n = 125) 63.9 (4.0) 25.98 (8.9) 34.96 (10.1) 5.40 (1.1) 5.46 (1.1){ 4.94 (1.1){ 1.55 (2.2) 6.49 (1.1){ 8 KKW (n = 77) 63.0 (4.0) 27.66 (8.8){ 37.84 (8.8){ 5.56 (1.0){ 5.63 (1.0){ 5.03 (1.0){ 1.64 (2.0) 6.61 (1.0){ 12 KKW (n = 84) 63.2 (6.0) 27.40 (9.2){ 36.20 (10.1){ 5.49 (0.9){ 5.53 (0.9){ 4.88 (0.9){ 1.41 (1.8) 6.55 (0.9){ Data are mean (SD). Analyses adjusted for age, ethnicity, and antidepressant medication use. Statistical notations: (*) significant overall main effect (P,0.0001); ({) significant group effect (P,0.006); ({) significantly different from control (P,0.05). Abbreviations: SDNN, standard deviation of RR intervals; rMSSD, Root mean square successive difference of RR intervals; HF, log high frequency spectral power (0.15– 0.40 Hz); LF, log low frequency spectral power (0.04–0.15 Hz); VLF, log very low frequency spectral power (0.0033–0.04 Hz); PT, log total spectral power frequency. doi:10.1371/journal.pone.0002288.t004 current trial, parasympathetic tone significant increased following 6-months of exercise training at 8-KKW and 12-KKW. The two most relevant points to be garnered from our findings are (1) that a significant change in HRV does accompany longer periods of exercise training consistent with the NIH recommendation and (2) a greater level of energy expenditure may not be necessary to achieve greater improvements in HRV. In essence, our findings suggest a ‘‘threshold effect’’ regarding aerobic exercise training and improvements in HRV. Nonetheless, we caution readers not to misinterpret that 4-KKW is ineffective for improving HRV as several indices of HRV were increased at the 4-KKW. Unfortunately, the interpretation of these results is more difficult to explain regarding the parasympathetic influence associated with HRV. SDNN and LF power are thought to represent mixed sympathetic and parasympathetic signaling and the physiologic characteristics surrounding VLF are still a matter of debate [1]. It has also been suggested that VLF is a ‘‘dubious’’ measurement when using short-term recordings #5 minutes [1]. With respect to the actual energy expenditure associated with exercising at 4- KKW, changes in HRV may take a longer period to fully realize. A final point to consider is whether an improvement in HRV is actually protective. Specifically, does an improvement in HRV carry with it the inherent assumption that the modification of HRV translates directly into CV protection [1]? The paradox of this question exists whereby it is largely accepted that exercise training decreases CV mortality and regular exercise training is capable of modifying autonomic balance [39,40,41,42]. We believe that improvements in HRV via exercise training are likely to reduce the risk of mortality for several reasons. In animal studies, dogs documented with a high mortality risk due to the previous occurrence of ventricular fibrillation during acute myocardial ischemia were randomly assigned to 6 weeks of either daily exercise training or cage rest. After exercise training, indices of HRV increased by 74% and all animals were better able to survive an experimental ischemic challenge after the exercise training period [43]. In humans, exercise training also accelerates the recovery sympathovagal interaction and improves patient prognosis in post-MI patients [44,45]. Though each of the aforementioned studies has been reported in animal and humans with CV disease, perhaps the most compelling argument for protection is the observation that CV disease mortality is associated with a constellation of risk factors [46,47]. Thus, even if modulating HRV through exercise training does not directly affect mortality, per se, the practice of CV exercise influences multiple risk factors associated with CV disease due to its broad influence and on both the ANS and CV system. A primary strength of the DREW study is that it used a well- controlled dosage of exercise, with a high level of adherence. Moreover, the exercise dose used in our study is easily obtainable in sedentary women. The DREW study has limitations because its sample is limited to sedentary postmen- opausal women. We do not know if the results will apply to other women or men. An interesting finding from our study is that women exercising at a higher caloric expenditure (12- KKW) did not experience greater improvements in HRV than women exercising at 8-KKW. Finally, our findings should not dissuade women from exercise training at a lower dose of they are not able to achieve the minimum level of exercise training necessary to improve HRV. Given the global effects of aerobic exercise training, HRV represents only one measure of CV risk, which may ultimately show improvement accompanying longer periods of exposure. Supporting Information Checklist S1 CONSORT Checklist Found at: doi:10.1371/journal.pone.0002288.s001 (0.23 PDF) MB Acknowledgments We wish to extend our gratitude to the staff of the DREW project for their diligent work and extraordinary performance. Author Contributions Conceived and designed the experiments: SB CE. Performed the experiments: CE TC. Analyzed the data: CE TC. Wrote the paper: SB CE TC CL. PLoS ONE | www.plosone.org 6 June 2008 | Volume 3 | Issue 6 | e2288