This systematic review and meta-analysis of ten randomized controlled trials evaluating the effect of music interventions in the treatment of hypertension found a decrease in pooled mean SBP and DBP after application of music interventions, however this decrease did not reach statistical significance. In the subgroup of three studies with a standard medical therapy or resting control group, random-effects analysis revealed a trend towards a blood pressure decrease in both the intervention and the control groups, while fixed-effect analysis showed a significant decrease in both groups [18–20].
Unfortunately, a valid comparison between the music intervention- and control group did not prove possible, and a cause-effect relationship between music interventions and hypertension remains to be determined.
Research has shown that relatively small decreases, as low as 5 mmHg reduction in systolic blood pressure, would result in 7 % reduction in all-cause mortality, 9 % reduction in coronary heart disease related mortality and 14 % reduction in stroke-related mortality [1, 27]. These numbers illustrate the substantial benefit of even small decreases in blood pressure, and if indeed in future studies music interventions prove to be effective, it would provide a valuable low cost therapeutic measure.
The mechanism by which music modulates blood pressure remains unclear. Studies on device-guided breathing hypothesize that reduction in blood pressure is achieved by modulating autonomous cardiovascular regulation by slowing down the breathing frequency [2, 21–25]. As a result, baroreflex sensitivity is lowered, parasympathetic tonus increases and sympathetic tonus decreases, resulting in a decrease in blood pressure. Music listening might elicit the same relaxation response, resulting in a decrease in blood pressure. Another possible mechanism of action is that music interventions lead to increased brain dopamine levels via a calmodulin-dependent system. This increase in dopamine levels inhibits sympathetic activity via dopamine-2 receptors which in turn reduces blood pressure [28].
Furthermore, music may direct one’s attention to a more pleasant emotional state, thereby triggering feelings associated with physical and mental relaxation [29]. It might also give rise to positive emotions which are connected with the activation of the limbic system, thereby releasing endorphins affecting physiological systems [30]. Moreover, a recent review on magnitude of blood pressure reduction in the placebo arms of hypertension trials found a significant pooled blood pressure reduction of 6 mmHg after placebo intervention [31]. This non-trivial placebo effect should be taken into account when offering these patients any treatment.
The random-effects subgroup analysis of the three trials with comparable control groups showed a trend towards a decrease in blood pressure in both the intervention- and control groups [18–20]. Although a random-effects model may be most appropriate in this case in light of the substantial heterogeneity among these studies, the small number of studies makes quantitative estimation of the between-study variance in this subgroup very unreliable. We therefore chose to apply a fixed-effect model to this subgroup as well, which revealed a significant decrease in blood pressure in both intervention- and control groups. However, this fixed-effect analysis does not take the considerable heterogeneity that we observed into account. Thus, in the case of this subgroup, the inherent limitations of both methods renders these analyses inconclusive and the results should be interpreted with caution.
The observed blood pressure decrease in the control groups of this subgroup analysis may be explained in part by the fact that in two of these studies the patients were prescribed a resting period as control, possibly eliciting autonomic responses similar to those described above [18, 20]. When visually assessing the mean reduction in SBP and DBP in each of these studies, the magnitude of this reduction appeared to be greater in the experimental groups, however a formal comparison of pooled mean reduction of blood pressure between the music and control group was not possible due to missing measures of dispersion concerning this reduction. As a result, a cause-effect relationship could not be established and the only conclusion to be drawn from our meta-analysis, is that we observed a significant decrease in blood pressure in hypertensive patients who underwent music interventions, but also in control patients. These observations could simply be the result of regression toward the mean.
Prevalence of co-morbidities, such as respiratory disease or diabetes mellitus, varied from 26 to 100 % in the three studies that reported it [18, 20, 23]. Data on association of co-morbidities and response to music interventions were not available from these studies. The presence of comorbidities, but also etiology of hypertension, treatment resistance and possible seasonal effects could potentially influence the effect of an intervention [31, 32]. These aspects should be taken into account when evaluating the effect of the intervention.
Anxiety, depression and quality of life
Zanini et al. was the only study that found an association between music interventions and quality of life, which might be explained by the use of music therapy in their study in contrast to recorded music interventions in the other studies [19]. Although recorded music interventions were found to be as effective as music therapy in reducing periprocedural pain and anxiety in children undergoing medical procedures [33], it is likely that the effect of music interventions in other settings may indeed be influenced by the method of administration. In some disease states, for instance in psychological or psychiatric disorders or rehabilitation, the involvement of a credentialed music therapy professional may provide better results than listening to music without a music therapist. Furthermore, the difference in effectiveness of music therapy compared with recorded music interventions may depend not only on the disease state, but also on which outcome is studied. Improvement of quality of life might be an outcome where dedicated involvement of a therapist providing personalized care may yield greater improvement than solely listening to music. Pain relief on the other hand, may be more strongly regulated by mechanisms triggered by both music therapy and recorded music interventions, such as redirecting someone’s attention or activation of the limbic system and the subsequent release of endorphins. Pain relief, in contrast to improvement of quality of life, may therefore be less dependent on involvement of a music therapist. Furthermore, the variation in results concerning quality of life among the included studies might also be explained by the shorter duration of some studies and the difference in study populations.
As for anxiety, Bekiroglu et al. found no significant effects of music interventions [18]. As they suggest, this may be explained by the lack of high anxiety levels at baseline in their patient population, as most likely may be the case in the hypertensive patient population at large. Music interventions might be more effective in decreasing anxiety when patients face a more challenging condition causing extensive anxiety, such as patients suffering from myocardial infarction or facing surgery [6, 10, 34, 35].
Music intervention variability
A major complicating factor in our analysis of music interventions was the large variation in the type of music administered and the frequency and duration of interventions in the included studies (Table 1). Although the majority of interventions included classical, relaxing or slow music, no clear recommendations exist on how music interventions should be administered in the treatment of high blood pressure. A systematic review on music interventions in anxiety and pain relief in clinical practice provide some insights on which music may be most beneficial [36]. The authors recommend patient-preferred slow and flowing music, approximately 60 to 80 beats per minute, with a minimum duration of 30 min in length. Research in hypertensive animal models found music containing high-frequency sounds to stimulate dopamine synthesis leading to blood pressure reduction [37]. Moreover, music interventions may be greatly enhanced by preference and familiarity of the patients. Anxiety- and pain reducing effects appear to be greatest when people are given a choice of music to listen to or listen to their own favorite music and other research suggests patient-preferred music, as opposed to prescribed music, to be a critical factor in the effectiveness of music interventions [5, 10, 35, 38]. The observed large variation in the types of music used, the applications of music interventions, and the outcomes studied, illustrate the complexity of the topic, and pose a major challenge for future studies.
Limitations
As with any meta-analysis, the general limitations inherent to meta-analyses should be taken into account [39]. Since the number of patients included in each study is very small and no formal comparison of the treatment effect between the music intervention- and control group was possible, no hard conclusions can be drawn concerning the effect of music interventions on hypertension. As described above, the inherent limitations of both fixed- and random-effects models in the case of a very small, heterogeneous sample of studies rendered our subgroup analysis inconclusive. There was significant heterogeneity in the reported outcomes, which is most likely the result of the large methodological variation among the included studies with regard to patient characteristics, the type of music administered, the duration of each intervention and the follow-up time.
Randomization was mentioned in all trials, though specific information on trial conduct, such as allocation concealment and blinding, was reported poorly and therefore quality assessment of the included studies was limited (see Additional file 2). This, as well as incomplete outcome data, gave rise to a moderate to high risk of bias in the included studies. Publication bias may have affected the outcomes, as some abstracts were unavailable as full-text articles (Fig. 1).
Perspectives
Our results show that current studies on the effect of music interventions on lowering blood pressure in hypertensive patients do not provide evidence on a possible cause-effect relationship. Since music interventions may be of beneficial value in hypertensive patients, presenting a potential adjuvant to standard pharmacological treatment, there is a need for further high quality research on the subject. Music interventions could not only be of value in case of multidrug therapy or treatment resistant hypertension, but might also be offered as a durable treatment modality in developing countries. However, well-designed high-quality, sufficiently powered randomized controlled trials are first required to establish a cause-effect relationship between music interventions and blood pressure reduction in hypertensive patients.
This research, ideally in the form of large, well-reported randomized controlled trials following the CONSORT statement for nonpharmacological trials with clearly-defined interventions and controls and adequate statistical analyses, could explore the ability of music interventions in lowering blood pressure in a large population, examine the permanence of the reduction in blood pressure and elucidate which patients could benefit most [40]. The influence of different forms of music intervention, with regard to factors such as genre and patient-preference, should be investigated. In addition both music therapy and recorded music interventions could be analyzed to obtain more knowledge on the manner of administration of music interventions in the treatment of hypertension. Finally, evaluation of factors that may play a role in the sensitivity to corrections of elevated blood pressure, such as baroreflex sensitivity, can be explored.