The effect of raloxifene on cardiac autonomic regulation in osteoporotic women

Objective There are suggestive data that raloxifene may have favorable effects on the arterial systems in postmenopausal women and thereby lowering the incidence of future adverse cardiovascular events. Reduction of heart rate variability appears to be a marker for identifying subjects with an increased risk for cardiac mortality, particularly in patients after myocardial infarction and in elderly people. Although there are conflicting data with regard to the effects of estrogen and progesterone on heart rate variability in postmenopausal women, the impact of raloxifene treatment on heart rate variability is fully unknown. Study design Forty-three osteoporotic postmenopausal women were recruited in a prospective, randomized, and placebo-controlled 6-month study. Of these women, 23 received raloxifene hydrocloride, 60 mg once daily, whereas 20 women received alendronate, 10 mg daily. Time and frequency domains of heart rate variability were measured at baseline and at 3 months and 6 months of the treatment. Results Time domain indices of heart rate variability, mean RR, and SD of all beat-to-beat intervals remained identical within the groups at the end of treatment. The square root of the mean of the sum of squares of successive RR intervals, a sensitive index of parasympathetic activity, tended to increase with raloxifene. Frequency domain indices of heart rate variability were as follows: low-frequency power of heart rate variability tended to stay the same, compared with the baseline values in both treatment regimens. High-frequency power of heart rate variability increased significantly in the raloxifene group (P = .039) at 3 months, and this significance persisted at the end of the treatment. A nonsignificant decrease was observed in the alendronate group. Accordingly, the low-frequency power/high-frequency power ratio, an index of sympathovagal balance, decreased significantly by the raloxifene treatment (P = .028) at 3 months and persisted at 6 months. There was no significant change in low-frequency power/high-frequency power ratio of patients taking alendronate. Conclusion Raloxifene seems to have a positive effect on cardiac autonomic regulation in postmenopausal osteoporotic women. This observation could at least partially explain the reduced cardiovascular events in the subset of women with increased cardiovascular risk in the Multiple Outcomes of Raloxifene Evaluation trial. However, the results of ongoing studies should be awaited to have a conclusion of its effects on the cardiovascular system.