Telephone-based mindfulness training to reduce stress in women with myocardial infarction: Rationale and design of a multicenter randomized controlled trial

Abstract

Background:

Elevated stress is associated with adverse cardiovascular disease outcomes and accounts in part for the poorer recovery experienced by women compared with men after myocardial infarction (MI). Psychosocial interventions improve outcomes overall but are less effective for women than for men with MI, suggesting the need for different approaches. Mindfulness-based cognitive therapy (MBCT) is an evidence-based intervention that targets key psychosocial vulnerabilities in women including rumination (i.e., repetitive negative thinking) and low social support. This article describes the rationale and design of a multicenter randomized controlled trial to test the effects of telephone-delivered MBCT (MBCT-T) in women with MI.

Methods:

We plan to randomize 144 women reporting elevated perceived stress at least two months after MI to MBCT-T or enhanced usual care (EUC), which each involve eight weekly telephone sessions. Perceived stress and a set of patient-centered health outcomes and potential mediators will be assessed before and after the 8-week telephone programs and at 6-month follow-up. We will test the hypothesis that MBCT-T will be associated with greater 6-month improvements in perceived stress (primary outcome), disease-specific health status, quality of life, depression and anxiety symptoms, and actigraphy-based sleep quality (secondary outcomes) compared with EUC. Changes in mindfulness, rumination and perceived social support will be evaluated as potential mediators in exploratory analyses.

Conclusions

If found to be effective, this innovative, scalable intervention may be a promising secondary prevention strategy for women with MI experiencing elevated perceived stress.

Myocardial infarction (MI) afflicts 325,000 women per year in the United States and is a major cause of morbidity and mortality.¹ Women experience poorer recovery and have higher mortality rates after MI compared with men, which are not fully explained by differences in biological and behavioral factors or differences in care.² Higher perceived stress may help to explain this disparity and is a promising target for interventions to improve health outcomes in women with MI. However, few psychosocial interventions tested in cardiac patients have directly addressed the unique experiences and needs of women. This study describes the rationale for an innovative stress management intervention for women with MI and the design of a randomized controlled trial (RCT) to evaluate its effects on perceived stress and mental and physical health outcomes over six months.

Association between stress and coronary heart disease in women

Perceived stress refers to the appraisal of one’s life as stressful or overwhelming and reflects the cumulative burden of stress from various sources such as work, relationships, caregiving, and finances.^3,4 Elevated levels of perceived stress have been associated with coronary heart disease (CHD) incidence⁵ and increased mortality and poorer health status in acute MI patients,⁶ independent of traditional risk factors. Many of the stressful life events and circumstances commonly experienced by women, including caregiving and marital discord, also influence their heart disease risk and outcomes. The Nurses’ Health Study found that women caring for a sick spouse had an almost doubled risk of incident CHD over 4 years of follow-up compared with noncaregivers.⁷ In the Stockholm Female Coronary Risk Study, marital stress increased the risk of recurrent cardiac events three-fold over five years among women with CHD.⁸ Although work stress alone was not a significant predictor, women reporting both marital and work stress had a 5.7-times greater risk of recurrent events compared with those reporting no stress.⁹ In a study of young and middle-aged acute MI patients, women were more likely than men to report stressful life events during the prior year and reported higher perceived stress than men throughout the first year after MI, which partially explained their worse recovery.^10–12 While the observed differences in recovery reflect multiple factors, the mediation effect of stress was independent of many potential confounders (e.g., sociodemographic characteristics, medical history, presentation characteristics, health status).

Both behavioral and physiological pathways contribute to the relationship between stress and CHD and may help explain poorer outcomes in women compared with men. Chronic stress is associated with poor diet, physical inactivity, and sleep disturbance, which predict risk of MI and poor prognosis after MI.^13,14 In a nationally representative sample of women surveyed about cardiovascular disease (CVD) awareness, 51% of respondents cited caregiving responsibilities as a significant barrier to CVD prevention due to the associated stress, sleep disruption, and lack of personal time.¹⁵ Acute and chronically elevated levels of stress are also associated with pathophysiological processes that increase risk for cardiac events, including impaired neuroendocrine function, platelet dysfunction, pro-inflammatory responses, impaired vagal control, and increased sympathetic nervous system activity.¹⁶ Sex differences in some of these stress-related mechanisms may help to explain poorer CHD outcomes in women. In particular, mental stress-induced myocardial ischemia and dysfunctional platelet reactivity to stress are more common in women with CHD than men.^17–20

Women also have greater psychosocial vulnerabilities than men. One difference is their greater tendency to ruminate, or engage in cyclical negative thinking about past, present and anticipated stressful experiences.²¹ Rumination prolongs adverse stress responses²² and has been associated with depression,²¹ disturbed sleep,²³ delayed blood pressure recovery after stress exposure,²⁴ and CHD incidence.²⁵ Women also report receiving less social support compared with men after MI.^26,27 Social relationships have important stress buffering effects, and the lack of supportive relationships leaves one without these resources and can itself be a major source of stress.²⁸ In two large observational studies of acute MI patients, low social support was associated with higher angina frequency, lower functional status, poorer QOL, and greater depressive symptoms up to one year after MI.^29,30 A qualitative meta-analysis of 43 studies of women’s experiences of CHD noted that many women with CHD reported disappointment in lack of support from others, but also guilt about needing help and being a burden.³¹ Qualitative studies also indicate that women with CHD desire social connection, particularly with other women with CHD.^31,32

Rationale for mindfulness training in women with MI

The need for psychosocial support among patients who have suffered a cardiac event is widely recognized and various interventions have been tested, including health education, stress management (eg, cognitive behavioral therapy, relaxation training, biofeedback), and other psychological therapies.^33–35 A meta-analysis of 43 RCTs in cardiac patients found that overall, psychosocial treatment reduced mortality by 27% over follow-up periods of up to 2 years and reduced event recurrence by 43% at follow-up beyond 2 years.³³ However, when stratified by gender, no benefit was observed for women for either time period. Importantly, successful reduction of distress was necessary for mortality benefits, and though not tested, it is possible that men experienced greater reductions in distress than women with the interventions studied. Consistent with this hypothesis, a secondary analysis of the Montreal Heart Attack Readjustment Trial (M-HART) found gender differences in the response to a nursing intervention such that collaborative approaches were more effective for reducing distress among women, while directive approaches were more effective among men.³⁶ These findings highlight the need for psychosocial interventions that address the experiences and needs of women with MI.

Mindfulness-based cognitive therapy (MBCT) is a program that combines mindfulness training and cognitive therapy to improve emotion regulation and reduce stress and negative emotions.³⁷ A core feature of the intervention is the cultivating of mindfulness, defined as a nonjudgmental awareness of present-moment experiences (e.g., thoughts, emotions, bodily sensations). MBCT also incorporates principles of Beck’s cognitive theory, which proposes that one’s thoughts and perceptions about situations influence one’s reactions.³⁸ Exaggerated or irrational thought patterns, or cognitive distortions (e.g., jumping to conclusions, all-or-nothing thinking), contribute to adverse emotional, behavioral and physiological reactions. Through simple meditation practices and cognitive techniques, MBCT promotes awareness and acceptance of one’s thoughts and emotions, including negative ones, as non-threatening experiences that are passing events rather than reflections of permanent reality (i.e., cognitive defusion). Learning to see thoughts as just thoughts, not facts, lessens reactivity to them. Paying attention to one’s automatic reactions to stressful events also helps one learn to deliberately respond to future stressors in more adaptive ways, including an improved ability to recognize and disengage from escalating patterns of negative thinking (i.e., rumination). MBCT is typically delivered in a group format, which provides an opportunity for social learning and support among participants. Decades of evidence have shown that mindfulness-based interventions reduce stress and emotional and physiological responses to stress,^39–43 and interest in these programs for patients with CVD is growing rapidly.^43,44 Though few studies have tested gender differences in response to mindfulness training, recent findings suggest that women have a greater interest in these approaches than men and may experience greater benefit from them.^45–48 Because MBCT targets key psychosocial vulnerabilities in women (i.e., rumination, low social support), we assert that it is a promising approach to reducing perceived stress in women with MI.

In its traditional form, MBCT is an intensive program delivered in eight weekly 2 to 2.5 hour in-person group sessions. Time and transportation can be significant barriers to participation, particularly among individuals suffering from acute or chronic health problems and those with busy or stressful lives. For example, a stress management program developed for women with CHD that was found effective was limited by the intensive, in-person format; almost 40% of eligible women declined to participate, most often due to the time commitment and inconvenience.³⁵ Therefore, we considered a number of alternative delivery methods for this population. Web- and app-based interventions are more convenient than in-person programs but often suffer from low engagement and poor adherence rates,^49,50 and may not address the need for meaningful connection with others expressed by women with MI.^31,32 A number of studies have shown that telephone-based psychosocial interventions (e.g., cognitive behavioral therapy) have comparable or higher adherence rates and similar efficacy compared with in-person protocols.^51,52 Further, the feasibility and efficacy of telephone-based mindfulness interventions has been demonstrated in other chronic disease populations.^53–57 Based on these considerations, we adapted MBCT for delivery to small groups by telephone (MBCT-T), which preserves real-time interaction and allows easy dissemination to patients whose health limits transportation or whose life circumstances (e.g., family and job roles) prevent participation. This RCT will evaluate whether MBCT-T can reduce perceived stress and improve physical and mental health outcomes over six months in women with recent MI.

Methods

Overview

This study is part of the Women’s Heart Attack Research Program (HARP) being conducted by the Sarah Ross Soter Center for Women’s Cardiovascular Research at the NYU School of Medicine. The overall aims of HARP are to investigate biological and psychosocial factors related to MI in women through three related research projects that share a common infrastructure and enrollment process. The HARP Stress Management Trial will test the effects of MBCT-T in 144 women with MI reporting elevated perceived stress after the acute recovery period. Women will be recruited from the HARP Clinical study, a multicenter cohort study of women with MI, and through self-referral in response to study advertisements. Following completion of baseline assessments (self-report questionnaires and one week of wrist actigraphy), women will be randomized to MBCT-T or enhanced usual care (EUC), which controls for the frequency of telephone contact. All assessments will be repeated at post-treatment (~8 weeks) and 6-month follow-up visits. The primary hypothesis is that 6-month perceived stress levels will be lower in women randomized to MBCT-T compared with those randomized to EUC. Figure shows the design of the HARP Stress Management Trial, which will be conducted at NYU Langone Health/Bellevue Hospital, Cedars-Sinai Medical Center, Ohio State University Medical Center, University of Pittsburgh Medical Center, and Johns Hopkins Medical Center. The study protocol has been approved by the Institutional Review Boards of all participating sites. Screening began at NYU/Belle-vue in December 2016 and at other sites in June, 2017. Implementation of study interventions began in November 2017.

Figure.

Study design. White box shows MI hospitalization at which time patients are screened and approached for the HARP Clinical study. Gray boxes show the HARP Stress Management Trial.

Participants

Eligibility criteria are listed in Table 1. Women aged ≥21 years with a diagnosis of MI⁵⁸ and a score of ≥6 on the 4-item Perceived Stress Scale (PSS-4), which is associated with poorer post-MI health status,⁶ are eligible. Screening at least two months post-MI reduces the likelihood of enrolling women whose stress levels would have improved without intervention.^11,33 Fluency in English is required, but we expect a diverse sample of women (≥35% racial and ethnic minorities). To ensure that telephone access and/or cost are not barriers to participation, cell phones and paid call plans will be provided for the duration of the study to women who do not have them. To enhance generalizability, we are not excluding women who are participating in cardiac rehabilitation programs or psychiatric treatment (medication and/or therapy). We are collecting data regarding concurrent treatments and expect similar rates across study arms. However, we exclude patients who require more intensive treatment (severe depression and/or suicidality), who are not appropriate for a group intervention (cognitive impairment, history of psychosis), or whose participation in another clinical trial may confound results.

Table 1.

Eligibility criteria

Inclusion criteria	Female Diagnosis of MI according to the Third Universal Definition of MI58 Age ≥ 21 years English-speaking Elevated perceived stress > 2 months after MI (PSS-4 ≥ 6) Willing to provide informed consent and comply with all aspects of the protocol
Exclusion criteria	Moderately severe or severe depressive symptoms (PHQ-9 ≥ 15) Active suicidal ideation (PHQ-9 item #9 or otherwise reported during screening) History of or current diagnosis of psychosis (EHR review) Significant cognitive impairment (EHR review or evident during screening) Current participation in another behavioral clinical trial

Study visits

Initial contact, screening and consent

Women with a diagnosis of MI based on the universal definition are identified at or around the time of referral to cardiac catheterization for evaluation and management and are approached by a research coordinator for consent for the HARP Clinical study (NCT02905357, clinicaltrials.gov). These women, as well as those who decline or are ineligible for the HARP Clinical study and those who self-refer, are screened and consented for the HARP Stress Management Trial at least two months after MI.

Baseline assessments

Once 12–14 eligible women are enrolled, baseline assessments are collected for the cohort over a 2-week period. A research coordinator administers self-report questionnaires, reviews the electronic health record (EHR), and provides an actigraph to each participant with instructions for the one-week sleep monitoring protocol. Participants are provided paid mailers to return the devices and sleep diaries upon completion of monitoring.

Randomization and blinding

After all baseline assessments for a cohort have been completed, participants are individually randomized to either MBCT-T or EUC. Randomization is stratified by CAD status (MI with and without obstructive coronary artery disease) given that an exploratory aim of the center is to compare baseline stress levels and effects of stress reduction in these two groups. Participants, intervention facilitators, and the study PI (who provides supervision) are aware of participants’ treatment assignments. However, other study investigators, biostatisticians, and research coordinators collecting outcome data are blinded and instruct participants not to reveal group assignments during their interactions.

Follow-up visits

Following completion of the 8-week MBCT-T or EUC program, the research coordinator schedules follow-up visits. Participants repeat the self-report measures and actigraphy protocol, and the research coordinator reviews the EHR to collect relevant medical and treatment data. All procedures are repeated at the 6-month visit.

Measures

We will test effects of MBCT-T on perceived stress (primary outcome) and a set of clinically meaningful secondary outcomes, including disease-specific health status and QOL, which predict subsequent health outcomes and healthcare utilization^59,60; depression and anxiety, which are common in MI patients and are associated with adverse outcomes^61–63; and poor sleep efficiency, an aspect of sleep that is influenced by stress and is associated with adverse health outcomes and mortality.^64,65 Changes in mindfulness, rumination, and perceived social support will be evaluated as potential mediators of MBCT-T-related changes in perceived stress and secondary outcomes. Validated measures of each outcome domain have been selected and are described below. The schedule of assessments is shown in Table 2.

Table 2.

Schedule of assessments

	MI hospitalization	Screening (2-months post-MI)	Baseline	Post-treatment	6-month Follow-up
Demographics	X*		X
Clinical lab results, vitals	X*
Medical history, medications	X*	X	X	X	X
Perceived stress (PSS)†	X*	X	X	X	X
Disease-specific health status (SAQ-7)			X	X	X
Quality of life (SF-12, PROMIS-10)			X	X	X
Depressive symptoms (PHQ-9)		X	X	X	X
Anxiety symptoms (HADS-A)			X	X	X
Sleep (actigraphy)			X	X	X
Mindfulness (FFMQ-SF)			X	X	X
Rumination (RRQ)			X	X	X
Perceived social support (ESSI)			X	X	X

^*Data collected as part of the HARP Clinical study.

^†The PSS-4 will be used at the MI hospitalization and 2-month screening visits; the PSS-10 will be used at the baseline and follow-up visits.

Sociodemographics and medical history

Demographic and socioeconomic data are collected via self-report and EHR review at the time of consent or baseline assessments. Prior history of CVD and procedures, CVD risk factors, and comorbidities are collected via EHR review at each time point. Medications (including psychiatric medications), participation in other programs (e.g., cardiac rehabilitation, psychotherapy), and hospitalizations and recurrent events are collected at each time point via self-report and EHR review. CAD status is classified based on results of clinically ordered cardiac catheterization (i.e., no stenosis ≥50% of any major epicardial vessel vs. stenosis ≥50% of any major epicardial vessel).

Self-report questionnaires

Perceived stress (primary outcome) is assessed with the 10-item Perceived Stress Scale (PSS-10), a widely used measure that assesses the degree to which situations in one’s life are appraised as overwhelming, uncontrollable, and unpredictable over the last month.⁴ Disease-specific health status is assessed with the Seattle Angina Questionnaire (SAQ).⁶⁶ We selected the recently developed 7-item short form (SAQ-7), which assesses functioning in three domains: angina-related physical limitation, angina frequency and angina-related QOL.⁶⁷ This short form has been validated in MI patients and has good psycho-metric properties, demonstrates excellent responsiveness to change and predicts mortality and readmission in CAD.⁶⁷ Physical and mental health-related QOL are assessed with the Short-Form Health Survey (SF-12), a widely used measure in health research,⁶⁸ and with the Patient-Reported Outcomes Measurement Information System (PROMIS)-Global Health, a 10-item measure recently developed by NIH as an indicator for Healthy People 2020.⁶⁹ Depressive symptoms are assessed with the PHQ-9, a validated measure that is based on DSM-IV diagnostic criteria for major depression and recommended for screening for depression in MI patients.⁷⁰ Anxiety is assessed with the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A), developed for and validated in patients with physical health problems.⁷¹

Self-report measures of three hypothesized mediators are also administered. The 15-item Five Facet of Mindfulness Scale Short Form (FFMQ-SF) assesses key dimensions of mindfulness: observing, describing, acting with awareness, non-judging and non-reactivity.⁷² The FFMQ-SF shows adequate construct validity, test–retest reliability, and sensitivity to change following mindfulness training.⁷² The 12-item rumination subscale of the Rumination-Reflection Questionnaire (RRQ) assesses the degree to which participants generally engage in ruminative thinking.⁷³ The 7-item ENRICHD Social Support Instrument (ESSI) assesses the perceived availability of emotional and instrumental support.⁷⁴ The ESSI was developed for MI patients and has been shown to be reliable, valid, and predictive of outcomes in cardiac patients.^29,75

Wrist actigraphy

Participants wear a validated actigraph (wGT3X-BT, ActiGraph Corp) on the non-dominant wrist for one week at each study time point to assess sleep.^76,77 The device is equipped with a highly sensitive accelerometer and quantifies the continuity and duration of sleep using validated algorithms. Data are stored in 1-minute epochs and processed with the Actilife 6 software. Self-reported sleep, wake, and nap times and sleep medications are collected using a daily diary to facilitate data processing. Sleep efficiency, defined as the percentage of time in bed spent sleeping, will be calculated for each night and averaged across the week for each study visit. Poor sleep efficiency is characterized by difficulty initiating and/or maintaining sleep and is associated with all-cause mortality.⁶⁵

Description of study arms

Enhanced usual care (EUC)

Given that usual care may vary significantly in a multicenter trial, we felt it important to provide consistent standard of care educational materials to all participants. Therefore, participants in both study arms receive a printed educational brochure developed by the American Heart Association and targeted to women: “Women, Heart Disease and Stroke.” To control for non-specific effects of attention, women in the EUC arm are contacted at the same frequency as those in the MBCT-T arm (8 weekly phone calls). The individual EUC calls are approximately 15 minutes each and follow a standardized protocol including a brief weekly check-in and review of brochure content as follows: Week 1: Facts about CVD in women; heart attack and stroke warning signs; Weeks 2–3: Review of CVD risk factors; Weeks 4–7: Strategies for management of key modifiable risk factors (hypertension, high cholesterol, smoking, physical inactivity, obesity and diabetes); Week 8: Other risk factors and considerations (e.g., alcohol, stress). Content related to stress is limited to communicating the importance of finding healthy ways to manage stress without suggesting specific strategies. We expect that the relevant EUC content will enhance treatment acceptability and credibility among women with recent MI without significantly influencing the study outcomes.

Stress management

MBCT-T is an 8-week manualized program that combines mindfulness training with cognitive therapy. The intervention is delivered to groups of about six patients by telephone using a conference line. Participants receive a workbook containing session content and home practice logs, and audio guides to support home practice. They complete individual orientation sessions with the MBCT-T facilitator by phone prior to the start of the group in which the rationale for the program is explained, questions are addressed, and motivation and anticipated barriers are discussed. Each subsequent weekly group session is approximately one hour long and is comprised of a brief check-in, teaching on the week’s topic, guided practice, inquiry and home practice assignment. Mindfulness training includes formal (e.g., body scan, mindfulness of breath) and informal (e.g., mindfulness of daily activities) practices, and cognitive approaches include thought monitoring, cognitive defusion, and skillful action. The final two sessions focus on developing individualized plans for sustainable daily mindfulness practice. Session topics and content areas are described in Table 3. Approximately 15 minutes per day of home practice is assigned between sessions. Participants who miss sessions are offered brief make-up sessions. Two measures of intervention adherence are collected for use in sensitivity analyses: (1) number of telephone sessions attended; (2) amount of home practice recorded on logs.

Table 3.

MBCT-T session content

Session	Topics
Orientation	Course outline, logistics Introduction to the stress response and mindfulness Setting intention, anticipating and addressing challenges
1: Awareness & Automatic Pilot	Recognizing automatic pilot Raisin exercise; awareness of multiple aspects of experience: thoughts, emotions, behaviors/impulses Non-judgmental awareness of routine daily activities
2: Living in Our Heads	links between thoughts, emotions, behavior and sensations Introduction of body scan Learning to place, hold, and shift attention
3: Gathering the Scattered Mind	Responding versus reacting Introduction of sitting meditation (mindfulness of breath)
4: Thoughts are Not Facts	Seeing thoughts as mental events, not facts (cognitive defusion) Importance of interpretation and cognitive distortions Introduction of mindfulness of thoughts meditation Halfway review
5: Allowing & Letting Be (Part I)	Recognizing and letting go of aversion (mental resistance) Introduction of working with difficulty meditation
6: Allowing & Letting Be (Part II)	Identifying distress signatures Introduction of responsive 3-minute breathing space (bringing mindfulness skills to daily stressors) Introduction of mindful movement
7: Taking Care of Myself	Using activity to cope Developing plans for sustainable meditation practice Developing action plan for managing future stress and distress
8: Maintenance	Review of skills Developing plan for daily formal and informal mindfulness practice

The MBCT-T program reflects a number of adaptations to the standard MBCT protocol.³⁷ It is delivered by phone rather than in-person, and involves shorter weekly sessions (1 hour vs 2–2.5 hours) and less home practice (~15 vs 45 min/d). The group format and core concepts of MBCT are retained, but several practices were dropped (seeing and hearing meditations, choiceless awareness in meditation, longer sitting meditations) to achieve the reduced time commitment. These adaptations were informed by prior studies and reviews of mindfulness-based interventions involving fewer and/or shorter sessions and reduced home practice,^{53–57,78–80} and our preliminary work with telephone-based mindfulness training in this and other patient populations.

Facilitator training and treatment fidelity

The MBCT-T program is delivered by certified MBCT instructors who have completed formal training and experience requirements. The EUC program is delivered by nursing students. All MBCT-T and EUC facilitators complete training in the study protocol with the Principal Investigator (TMS). All sessions are digitally audiotaped and approximately 30% will be reviewed to provide feedback and ongoing supervision to intervention facilitators. Facilitators’ degree of adherence to the MBCT-T protocol is rated using an adapted version of the validated MBCT Adherence Scale.⁸¹ A similar checklist has been developed to rate treatment fidelity of the EUC phone sessions.

Patient safety

Participants are referred back to their physicians for any medical questions that arise during telephone sessions. If a participant reports severe distress or suicidal ideation during a study visit or telephone session, the research team follows a detailed safety plan, which includes formal assessment of symptoms and depending on the severity, providing referrals, informing the treating physician, arranging emergency care, and reporting the event in accordance with the local IRB policy.

Statistical analysis plan

We hypothesize that participants randomized to MBCT-T will show greater 6-month improvements in perceived stress and secondary outcomes compared with those randomized to EUC. Intention to treat (ITT) will be the primary approach for all analyses. The basic analysis will compare the MBCT-T and EUC arms on 6-month changes in the study outcomes using mixed effects regression models. This analysis is suited to model repeated measurements nested on the same individuals and individuals clustered within study sites. In separate models, each of the primary and secondary outcome measures will be regressed onto assignment group, time, and the group × time interaction. Study site will be adjusted in the mixed effects model to account for potential dependence within the study site. A significant group × time interaction indicates that the change in outcome differs between the two groups and will be followed up by testing the simple slopes (change) for each group. In exploratory analyses, we will evaluate whether psychosocial factors targeted by MBCT-T (i.e., mindfulness, rumination, perceived social support) explain any observed improvements in perceived stress and secondary outcomes using mediation analysis techniques.

Sample size calculation

The primary outcome is the difference in 6-month change in perceived stress between the MBCT-T and EUC study arms. Sixty-five women per arm would provide 90% power to detect a difference of 4.0 in PSS-10 scores between arms at α=.05. This is consistent with published data⁸² and represents a ≈30% reduction in perceived stress given expected baseline scores.¹¹ We project 10% missing data at 6-months, given low mortality rates in this time frame and completion of follow-up assessments by phone.⁵² Based on these assumptions, we plan to enroll 144 women (72 per arm). Even if the group difference in PSS-10 change is as small as 3.5 or attrition approaches 15%, this sample size would still provide 80% power to detect a statistically significant difference.

Sources of funding

This study is part of the American Heart Association’s Go Red For Women Strategically Focused Research Network⁸³ and is funded by grants 16SFRN28850003 (Spruill), 16SFRN28730004 (Reynolds), 16SFRN28730002 (Berger) and 16SFRN27810006 (Hochman). The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the manuscript, and its final contents.

Discussion

Despite accumulating evidence of the adverse impact of elevated perceived stress on health outcomes after MI, the current standard of care does not include routine assessment or treatment of stress. Evidence-based stress management interventions are needed, particularly for women, who benefit less than men from psychosocial interventions that are not gender-tailored.^33,84 This trial will test the hypothesis that MBCT-T is an effective approach to reducing perceived stress in women with MI. Many stressful events and circumstances cannot be avoided, but the emotion regulation skills imparted in MBCT-T may mitigate the impact of current and future stressors on physiological processes that influence CVD risk.⁸⁵ The American Heart Association recently published a scientific statement based on a systematic review of studies of meditation suggesting a possible benefit on cardiovascular risk, and concluded that further research on this topic is warranted.⁴³ Although the HARP Stress Management Trial is not powered to test effects of MBCT-T on hard outcomes, improvements in perceived stress and the secondary outcomes we are assessing (i.e., general and disease-specific health, anxiety and depressive symptoms, sleep) would support future studies to evaluate the efficacy of this scalable intervention in preventing adverse psychological and cardiovascular outcomes in women with MI. The six month follow-up period will allow us to examine both short-term and sustained effects of MBCT-T, which has been identified as a priority area for future research in this area.^43,44 Repeated assessment of potential mediators will also inform future studies aimed at elucidating the effects and mechanisms of mindfulness training on CVD risk.