Title:Impact of yoga on blood pressure and quality of life in patients with hypertension - a matched controlled trial in primary care

Transcription

1 Author's response to reviews Title:Impact of yoga on blood pressure and quality of life in patients with hypertension - a matched controlled trial in primary care Authors: Moa Wolff (moa.wolff@med.lu.se) Kristina Sundquist (kristina.sundquist@med.lu.se) Sara Larsson Lönn (sara.larsson_lonn@med.lu.se) Patrik Midlöv (patrik.midlov@med.lu.se) Version:2Date:18 October 2013 Author's response to reviews: see over

2 October 16, 2013 Title: Impact of yoga on blood pressure and quality of life in patients with hypertension - a controlled trial in primary care matched for systolic blood pressure Dear Editor, Thank you for inviting us to revise our manuscript. We appreciate the reviewers feedback and the thoughtful suggestions of ways to strengthen the paper further. We have attempted to answer all the comments in full and enclose a pointby-point list of our responses below. Yours sincerely, Dr. Moa Wolff Center for Primary Health Care Research Clinical Research Centre (CRC), building 28, floor 11 Jan Waldenströms gata 35 Skåne University Hospital SE Malmö Sweden 1

3 Reviewer 1 Reviewer: Elmarie Terblanche Reviewer's report: The effect of yoga on the blood pressure responses of hypertensive individuals is a worthy topic to explore, as there are many individuals who may not like higher impact exercises or for whom this type of exercises are contra- indicated. Major compulsory revisions: 1. I found the Background to the study very superficial, with extremely limited and well-motivated reasons for the study. The reader is also not suitably informed on the outcomes of previous studies where yoga was used as an intervention, neither has the importance or necessity to do this study in a primary care setting been adequately motivated. Response: We acknowledge that our quest to write a readable and accessible article has provided a background section that is too brief and superficial. We have added information to give well-motivated reasons for the study, and reasons to why it should be performed in primary care. We also added information on the outcome of previous yoga studies. Page 3, paragraph 1-3, 5 p3, Background, line 4: There are many additional strategies, especially exercise interventions that have been investigated before. As it is stated here the impression is created that there are no other strategies for reducing BP other than pharmacological treatment. The authors should briefly explain what other strategies have been explored so far, especially in terms of exercise, and what the general outcomes of these interventions were. Were the results from other yoga studies clinically significant? Results from these studies should be discussed, so that the results of the current study can be seen in context. Response: We agree that there are many additional strategies to lower blood pressure than drugs and we have added information about this and about the results from other yoga studies in the background. Page 3, paragraph 2-3 To what extent the results from other yoga studies were clinically significant remains an unanswered question and this is now stated in page 3, paragraph 3. p3, Background, line 7-8: has it been shown previously that complementary treatments have an effect on medicine intake and side effects? This is a very broad statement to make which is not limited to yoga in particular. This sentence should be reformulated or explained why yoga specifically would have this effect. Response: The sentence has been reformulated to moderate the message. Page 3, paragraph 4 2. With regards to the two interventions, it seems that the main difference was not so much that one group exercised at home and the other had one class per week. The difference was rather in the volume of information and assistance that the two groups received. The class group met once per week and received 2 2

4 CD s and 2 manuals, and were asked to exercise for 30 min a day. The other group had an appointment with a doctor, received 1 CD and 1 manual and were asked to exercise for 15 min a day. The two interventions thus differed on more than one level, not only in terms of exercising at home or not. Furthermore, no results are reported on the amount of training that the groups actually did and without any evidence on the quantity of exercise it cannot be concluded that home-based yoga training gives better results. The authors should therefore rethink the true question of this study. Response: We agree that the wording yoga class vs. yoga at home is a simplified description. It could also be presented as long yoga program vs. short yoga program, demanding yoga program vs. simple yoga program etc. In table 2 we present the compliance of the two groups. The yoga class group participants did their yoga on average 47 times during the intervention period (47 x 30 minutes = 24 hours). The yoga at home group participants did their yoga program on average 63 times (63 x 15 = 16 hours). Page 11, paragraph 1 A weakness of the study, of course, concerns the validity of self-reported data, which is a problem in all studies of this kind. This in now explained in discussion on page 13, paragraph p7, Measurements: It is unclear why the methods for the measurement of metabolic biomarkers were included in this manuscript, as well as the results on these variables in Table 1. These biomarkers were not part of the stated aim of the study, neither was it discussed. Response: We agree that this might be information of limited interest, and we have shortened the method section regarding blood samples. Page 8, paragraph 3 We still do think that it is of some interest to present the metabolic biomarkers as part of the baseline information. 4. Similarly to my concerns about the Background, I also find that the Discussion lack any depth and fails to provide any new insight on the effect of an exercise intervention on resting BP. The Discussion should be amended in light of the concerns raised. Response: We acknowledge your concerns, and we have tried to change the discussion accordingly. Page 11, discussion paragraph 3, Page 12, paragraph 2-4, Page 13, paragraph 1-2, 5, Page 14, paragraph p 11, Conclusion, line 3 4: The conclusion that a yoga program may reduce medical costs etc cannot be made from this study, as the study was limited to a once-off, acute measurement of post-intervention BP. Medical costs and side-effects will only be reduced if the reduction in BP lasts a significant period during the day (i.e. a significant PEH response). Thus to make this conclusion, BP should be monitored for at least 24 hours after the intervention to see if it is a long-lasting effect. 3

5 Response: It is true that we cannot draw conclusions regarding medical costs and side-effect reduction from our study. The sentence has been reformulated to moderate the message. Page 14, paragraph3 24 hour BP monitoring is indeed the best method to investigate BP over time. Nevertheless, studies on medicine effects on BP are usually not made with 24 hour ambulatory BP measurement, since it is complicated, time-consuming and expensive. Page 14, paragraph 1 6. The yoga at home group already did better at baseline in terms of quality of life. The authors must speculate why, as this could also explain why they did better on the intervention. It is known that individuals how are more positive about their life and health, will be more motivated to try something new, exercise regularly and further improve their health. This matter is not discussed at all. Response: This is interesting and important to highlight. We have addressed the topic in the discussion. Page 12, paragraph 3 Minor essential revisions: 1. p 3, Design, line 1: This study was. (not is) Response: Of course. Thank you very much. 2. p5, Procedure: No mention is made of the activity levels of the participants prior to the yoga intervention, neither was this accounted for in the analysis of the results, or the Discussion. Did participants partake in any other activities during the intervention? Was the recorded or monitored? Could it be that the yoga at home group engaged in other activities as well, even if it was only more household activities (since the majority were women)? Response: In the lifestyle survey we did ask the patients about their habits regarding sports and other physical activities. There were no significant changes between the groups or pre/post-intervention. Page 9, paragraph 2. Page 10, paragraph 2 3. It wasn t specified what information was given to the Control group. This should be mentioned, as well as steps taken to ensure that this group complied with the requirements of the project, i.e no exercise/yoga. Response: The control group was told not to change their medicine and to continue living as usual. They did not get any restrictions regarding physical activities. 4. p8, line 4-5: It seems that the goals were not clear in terms of training frequency. On the one hand participants were encouraged to exercise every day, but the goal was to train at least once a week. Weren t the participants confused about what was actually expected of them? 4

6 Response: We agree that the manuscript is a bit unclear at this point. The patients were only informed about the goal of performing yoga 15 and 30 minutes respectively. The other goal (yoga in nine of 12 weeks) was set up together with the IMY-founder, to be able to sort observed cases from per protocol set. We did not want to influence the patient compliance by letting them know about this goal. We have tried to clarify the text. Page 8, paragraph 5 5. p8, Statistical analysis: it should be verified from the literature why a difference of 5 mmhg in SBP was used to calculate the power of the study. On what is this number based? Response: We based the 5 mmhg assumption partly on information from a Swedish literature review [12], which shows a mean reduction of BP of 10/5 mmhg from antihypertensive drugs, when used alone. The effect of an additional drug is mostly lower. This assumption is also in line with results from other yoga studies. Page 9, paragraph 3 6. Table 1: Please check the results for WHO1 and WHO 2. According to my calculations there was also a significant difference between the 2 intervention groups. Response: We regret this error and appreciate that you pointed it out. The table text states that we measured a significant change compared to control (WHO1 and WHO2). However, the calculations were made using ANOVA, implying that the significance derives from comparisons between mean values of all three groups. We have changed the table text accordingly. Table 3 7. Figure 1: To what does arms refer at the bottom of the diagram? Response: Since this expression is not used otherwise in the manuscript we agree that it may be confusing. We have changed arms to groups. Figure 1 Reviewer 2 Reviewer: Lisa Ware Reviewer's report: The manuscript addresses the important issues of whether complimentary therapies can improve treatment of hypertension and if these therapies can be administered effectively by primary care staff. While the conclusion that this complimentary therapy may be able to reduce anti-hypertensive medication intake appears premature, the article presents some interesting data. Specific recommendations are listed below. Discretionary Revisions A short description of the enrolment procedure would be helpful in the abstract. 5

7 Response: We agree and we have added some text to describe the enrolment procedure more accurate. Page 2, methods What was the rationale for basing power on the difference between the at home and control groups, especially if the class was assumed to be the more intensive treatment arm? The estimated drop-out rate is very high, what was this 30% based on? Response: When we did our power-calculation, we assumed that the yoga at home group would have less effect than the yoga class group. Since we wanted to be able to detect significant change even for the less effective treatment, we chose to base our power on the difference between yoga at home and control groups. The 30 % drop-out rate is often used in intervention studies. Was the same yoga instructor used throughout? Response: The yoga instructor was the same in 11 of 12 classes. In one class she was replaced by another yoga instructor due to illness. Minor Essential Revisions Abstract: Give the numbers in each of the treatment arms. Be clear that BP was measured in clinic, not at home. Give the percentage of patients on medication. Response: OK, done. Page 2, methods Methods: What was the rationale for the two different types of yoga used? Why was the same CD and manual not used in both treatment arms? Response: The design of the intervention in the yoga class group had been used previously in an inpatient care study in Stockholm with positive effect on blood pressure (unpublished data). We wanted to see if we could demonstrate this favorable effect in a primary care setting. The intervention for group two (yoga at home group) was designed in collaboration with the founder of the Institute for Medical Yoga in Stockholm, Sweden (IMY). We wanted to compare the effect of two different yoga concepts on primary care patients, rather than comparing the effect of the different yoga programs. This has been clarified in the text. Page 4, paragraph 3, 5, Page 5, paragraph 1 The approach used resulted in significant differences in the exposure between the two treatment groups, for example; o Being told to do the yoga by a physician versus a yoga instructor could have had a huge effect. This is acknowledged but could be explored further. 6

8 Response: Yes, maybe. We have added reasoning about this. Page 12, paragraph 4 o Significant barriers may have existed for the yoga group approach that did not exist for the yoga at home group such as travelling to the centre each week and the level of difficulty/time which have been acknowledged. But were there other barriers? Was any additional material required (mats, clothing etc.) and how did patients feel about being in a class environment with other patients, especially if living with body dissatisfaction? Describe the environment where yoga was practiced. Was it private, comfortable, did primary care staff see who was attending or not attending? Response: There were probably several additional barriers to the yoga class patients. On the other hand, one could also speculate that these barriers would be balanced by a rewarding interaction with the other group members? Page 13, paragraph 1 The yoga was taught in a room, specially arranged for the purpose, with yoga mats, pillows, blankets and chairs for the patients to use. The entrance was separated from the health care center. Page 7, paragraph 2 Describing the yoga at home as an easier intervention and requiring less time and effort for the [ ] physician does not appear accurate. Although the at home intervention used simpler exercises, it cannot be concluded this was easier for patients as, for example, they did not have the class structure or peer support of the class and data was not collected on how easy they felt the exercises to be. Additionally, it appears that the at home intervention was prescribed by the physician resulting in more time and effort on their part. Perhaps the at home was less resource intensive because of overall staff time involvement or use of facilities although this is not clear in the manuscript. We agree that the wording is somewhat unclear, and we have tried to make it more accurate. Page 5, paragraph 1, Page 14, paragraph 3 Give the rationale for your exclusions based on SBP and DBP. Response: When we did our review on medical records, we did not want to select patients with extreme BP values, since these would probably be under medical adjustments. We used the ESC hypertension definition and picked patients with normal-, normal high- and grade 1 hypertension- levels at their last control. At the baseline control we were eager to include as many patients as possible in the study. We thought it seemed unlikely that we would have any BP lowering effect on patients with SBP <120 mmhg. However, we often see DBP values <80 mmhg in our hypertensive patients. Regarding the upper limit, >180/110, we thought it would be unethical to leave their medication unchanged for twelve weeks. 7

9 What was the reason patients were excluded based on BP written in their records when later baseline testing showed around 10% of these recorded BPs incorrectly classified the patient s eligibility? Repeating BP measures in patients without a recent assessment with random selection from the pool of participants in which you were more certain of their eligibility may have given a larger final sample size. Randomised allocation to treatment arm with minimisation would have been a better strategy to use and this is a potential limitation of the study (resulting possibly in differences between the groups, albeit not statistically significant in this sample size). Response: By looking at the last BP-values in the medical records, we wanted to ensure that we would not get patients with extreme values, but we can t be sure that it would have been different if we had invited all patients with hypertension. We agree that random allocation is superior to matching of group. Our rationale for this was that we wanted to ensure similar SBP-values at baseline. We have now addressed this topic in the discussion. Page 14, paragraph 2 Avoid use of the term (see below) and try to make the methods more concise. Refer to Figure 2 in the results, not the methods. Rephrase the sentence even if they are older or have not exercised for a long time. I would suggest something like suitable for all ages and levels of fitness. In the sections on each intervention, avoid repetition. FBG (fasting blood glucose) and TC (total cholesterol) are more commonly used abbreviations. Once your sample is described as fasted in methods it is unnecessary to repeat this with the FP abbreviation. Response: Thank you. We have made the proposed changes. However, the blood glucose was measured in plasma and not in blood. Split the measurements section to clinical and self-report. The section on self-report data (yoga calendars) could be more concise with clear indication this was how you assessed adherence. Also describe the questionnaires used here. Was there any validation of the health status and lifestyle survey for this study? Response: We have split the measurements section. Page 8, measurements The health care status and life style survey questionnaire was made for this study and is not validated. We have added information on the contents of the questionnaires. Page 9, paragraph 1-2 The methods state patients who changed their medication were excluded. In contrast, the abstract states medication remained unchanged during the study. Response: We agree that this is a bit confusing and we have changed the abstract text. Page 2, methods State how you assessed the data followed a normal distribution. 8

10 Response: We assessed that data followed a normal distribution by studying the residuals. We have added a sentence about this in the statistical method section. Page 9, paragraph 3 For blood pressure, measured as a continuous variable, the residuals were approximated well by a normal distribution. The same applies for the QoL domains when summed. For the single items QoL, WHO 1 and WHO 2 the ANCOVA model and normality assumption can be questioned as they rank from 1 to 5. Nevertheless, the residuals are symmetric and we think it can be valuable to use the same approach for these analyses, and have no reason to believe that the interpretation of the results will change with another model. Figure 2 is unnecessary as the results are described in the text. Response: Yes perhaps, but we think that figure 2 is justified since it demonstrates differences between the two groups. Results: Give the percentage of patients in each group on medication in Table 1 with data on how many were well controlled. Specific frequency of drugs used could be discussed in the text e.g. the most common single or combination treatment was... Response: Since there are less than 100 patients in each group, we chose to present the data in absolute numbers (n) instead of percent (%). We have now changed this regarding number of patients on medication. We have also added information in Table 1 on how many were well controlled at baseline. Table 1 In the results section we have added some information about frequency of drugs. Page 10, paragraph 2 Discussion: Avoid referring to tables and figures within the discussion. Response: OK, done. While it may be reasonable to speculate that time may have been one of the barriers to treatment adherence, there is no evidence to support your statement hypertensive patients in primary care generally perceive themselves as relatively healthy and patients feel that 30 minutes per day is too big a commitment. Support or remove these statements. Response: We agree, and we have removed this statement. Major Compulsory Revisions The aim of the study could be more clearly defined as it is unclear if the aim is to look at yoga per se, or yoga at home versus group, or compare different types of yoga or examine if a less resource intensive method of prescribing yoga is effective. Also review the title as the groups were only matched on SBP and not 9

11 on other variables that may have influenced the results or adherence such as gender, age, presence of comorbidities etc. Response: We have changed the wording in the background to clarify the aim of the study. Page 4, paragraph 3 We have also changed the title according to your suggestion. Page 1 Abstract: Referring to yoga as an alternative method to medical treatment of hypertension may result in misinterpretation by healthcare providers and patients. It would be better presented as a supplementary therapy in addition to medical treatment. Response: OK, done. Page 2, background Suggesting in the conclusions that yoga may reduce medicine intake, side effects and drug costs is far too premature without data to support this. Rather suggest that simple yoga exercises may be useful as a complimentary therapy in addition to medical treatment when prescribed by primary care physicians. Rephrase also in the Background and Conclusion sections. Response: We have changed this according to your suggestion. Page 2, conclusion, Page 3, background paragraph 4, Page 14, conclusions Methods: The methods section is much too long and requires significant shortening. For example, there is much repetition and the sections patients and recruitment, and intervention and allocation to treatment arm could be combined. Response: We have tried to shorten the methods section. What was the rationale for including well controlled hypertension patients? Are patients with a SBP of 120 mmhg expected to achieve as much of a change as those with poorly controlled hypertension? Response: Of course, this level could be discussed. We also considered 130 and 135 mmhg as a SBP limit. In the control group, did the medical examination take place during the study period for any of the patients? If so, did other groups receive a medical examination also. Response: Normally, hypertensive patients in Sweden have medical examination by their physician once a year. This was not influenced by their participation in the study for any of the group members. Was only a single BP measure taken or two with the average/ last measure used? Please give more detail. 10

12 Response: BP measurement was standardized in a sitting position, right arm, two readings (three readings when the first and second readings differed by >5 mmhg), and was carried out by nurses using a validated BP monitor (Omron i- C10). This is now explained in clinical measurements, page 8. Results: Intervention group 2 had significantly higher scores for QOL1 and 2 at baseline. Discuss how this may have influenced the results obtained. Could it reflect a difference in their physical capabilities, the presence of co-morbidities or their readiness to change for example? Response: This topic is now discussed. Page 12, paragraph 2 Discussion: One major limitation is the use of self-report data to assess adherence to the intervention and the influence of social desirability on the patient s responses. Would patients self-report differently about doing something a doctor told them to do versus another person? If the self-report data is correct, the results obtained may possibly indicate that the number of sessions completed is key as adherence appears to be poorer in the group treatment arm. Response: We agree that self-reported data has its limitations, as in all studies of this kind. It is likely that patients tend to adhere more to a doctors advice about yoga, when yoga is used as a supplementary therapy. On the other hand, the patients in the yoga at home group only met the doctor for 20 minutes, while the yoga class group patients met their instructor for 12 hours during the intervention period. We have added discussions about this. Page 13, paragraph 2, Page 12, paragraph 3 It s true that the number of sessions may be a key factor. On the other hand the yoga class group spent on average about 50% more time doing yoga than the yoga at home group. Page 12, paragraph 4 Yoga should not be promoted as a treatment alternative. Justify your statement that yoga at home is more cost effective especially if physician time is used to explain the intervention and the manual and CD are still required. Response: We have changed the expression to supplementary therapy. We have moderated the message that yoga is more cost effective. Page 11, discussion paragraph 3 The limitations of the study could be clearer e.g. differences between treatment arms; recruitment, randomization procedures and allocation to treatment arms; reliance on self-report to assess adherence; and a single clinic BP measure for your primary outcome. We have deepened the discussion part for limitations, and made comments in various places in the text, for example on page 12, paragraph 3, page 13, paragraph 3-5, page, paragraph 1, 2, 5 11

13 Reviewer 3 Reviewer: Debbie Stein Reviewer's report: This is a study assessing the effects of yoga on hypertension. subjects are divided into 3 groups including 1 group who has 1 class a week in a yoga studio, 1 group who does daily home practice and a control group. Only the group that practices yoga at home shows a reduction in DBP and improvement in quality of life. Overall the study is well done for a lifestyle intervention study. I think there are some weaknesses in the design and these should be acknowledged in the discussion. 1. subjects are matched for SBP at entry but not for number of medications so it is possible that some subjects had more severe htn and were not well matched Response: This is a good point and we have added this reasoning to the discussion. Page 12, paragraph 5 2. there is no mention of underlying comorbidities so it is also difficult to determine if groups were well matched Response: The groups were not matched for comorbidities since it is methodologically difficult to match for multiple variables. However, in the health status survey the subjects were asked about their comorbidities regarding diabetes and CVD. There were no significant differences between the groups. We have added this information about this in the methods and results section. Page 9, paragraph 2, page 10, paragraph 2 3. the group that had a instructional class in yoga only met once a week and were encouraged to practice yoga daily at home wheras the home practice group were instructed to do daily practice so it may be that the lack of effect in the group taught once a week in the class is that they had less exposure to yoga overall and this is why this intervention was less effective, also 12 weeks may be too short to see an effect Response: Patients in both yoga intervention groups were encouraged to perform yoga daily at home. Thus, there was no difference in this matter between the yoga intervention groups. However, the compliance in the yoga class group was poorer, which may have affected the results. Page 12, paragraph ambulatory BP measurements ideally should be done to improve accuracy Response: We have added a comment about this in the discussion. Page 14, paragraph 1 5. also need to acknowledge that these studies are difficult to perform but important as yoga is increasingly popular and practiced by many people so it is worth conducting better designed trials to try assess if there are real benefits to yoga practice on BP reduction 12

14 Response: We agree, and we have added reasoning about this in the discussion. Page 13, paragraph 2 13