Meditation and Cardiovascular Risk Reduction

Despite numerous advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains a leading cause of morbidity and mortality. Novel and inexpensive interventions that can contribute to the primary and secondary prevention of cardiovascular disease are of interest. Numerous studies have reported on the benefits of meditation. Meditation instruction and practice is widely accessible and inexpensive and may thus be a potential attractive cost-effective adjunct to more traditional medical therapies. Accordingly, this American Heart Association scientific statement systematically reviewed the data on the potential benefits of meditation on cardiovascular risk. Neurophysiological and neuroanatomical studies demonstrate that meditation can have long-standing effects on the brain, which provide some biological plausibility for beneficial consequences on the physiological basal state and on cardiovascular risk. Studies of the effects of meditation on cardiovascular risk have included those investigating physiological response to stress, smoking cessation, blood pressure reduction, insulin resistance and metabolic syndrome, endothelial function, inducible myocardial ischemia, and primary and secondary prevention of cardiovascular disease. Overall, studies of meditation suggest a possible benefit on cardiovascular risk, although the overall quality and, in some cases, quantity of study data are modest. Given the low costs and low risks of this intervention, meditation may be considered as an adjunct to guideline-directed cardiovascular risk reduction by those interested in this lifestyle modification, with the understanding that the benefits of such intervention remain to be better established. Further research on meditation and cardiovascular risk is warranted. Such studies, to the degree possible, should utilize randomized study design, be adequately powered to meet the primary study outcome, strive to achieve low drop-out rates, include long-term follow-up, and be performed by those without inherent bias in outcome. ( J Am Heart Assoc. 2017;6:e002218.
inexpensive interventions that are of benefit to patients and can contribute to the primary and secondary prevention of CVD are of interest.
Dozens of studies have reported on the health benefits of meditation. According to the National Health Interview Survey, 8% of US adults practice some form of meditation. [bib_ref] Web-Based Mindfulness Intervention in Heart Disease: A Randomized Controlled Trial, Younge [/bib_ref] Up to 14% to 24% of patients with CVD have been reported to use or to have used some form of mind-body therapy, and 2% to 3% use or have used some form of meditation. [bib_ref] Heart rate variability is enhanced in controls but not maladaptive perfectionists during..., Azam [/bib_ref] [bib_ref] Decrease in blood pressure and improved psychological aspects through meditation training in..., De Fatima Rosas [/bib_ref] [bib_ref] Randomized controlled trial of Mindfulness-based cancer recovery versus supportive expressive group therapy..., Carlson [/bib_ref] [bib_ref] Mindfulness meditation alleviates fibromyalgia symptoms in women: results of a randomized clinical..., Cash [/bib_ref] In addition, half of CVD patients are interested in participating in a clinical trial of alternative therapies, and 17% are interested in participating in a clinical trial of meditation. [bib_ref] Heart rate variability is enhanced in controls but not maladaptive perfectionists during..., Azam [/bib_ref] [bib_ref] Decrease in blood pressure and improved psychological aspects through meditation training in..., De Fatima Rosas [/bib_ref] [bib_ref] Randomized controlled trial of Mindfulness-based cancer recovery versus supportive expressive group therapy..., Carlson [/bib_ref] [bib_ref] Mindfulness meditation alleviates fibromyalgia symptoms in women: results of a randomized clinical..., Cash [/bib_ref] Many forms of meditation can be learned from publications, the internet, and audio media. Many meditation courses are available for a modest fee or voluntary contribution. Hence, meditation may be an attractive costeffective adjunct to more traditional medical therapies. Accordingly, the American Heart Association commissioned this scientific statement to systematically and scientifically review the data on the potential benefits of meditation related to CVD.

# Methodology
Studies on meditation and cardiovascular risk reduction were searched for on PubMed using search terms including meditation, stress, blood pressure, hypertension, smoking, tobacco use, insulin resistance, metabolic syndrome, atherosclerosis, endothelial function, myocardial ischemia, primary prevention, and secondary prevention. Additional searches were performed on Google and Google Scholar, because some articles on meditation are not listed in PubMed.
Practices such as tai chi, qigong, and yoga, although involving inner focus and a concentration on breathing, consist of both mental and physical practices. Regular physical activity and exercise has itself been associated with cardiovascular risk reduction, [bib_ref] Mindfulness-Based Stress Reduction training reduces loneliness and pro-inflammatory gene expression in older..., Creswell [/bib_ref] [bib_ref] Self-compassion training modulates alpha-amylase, heart rate variability, and subjective responses to social..., Arch [/bib_ref] and thus findings from such studies would be confounded. Therefore, this review was restricted to practices of sitting meditation.
For all sections examining the effects of meditation on aspects of cardiovascular risk, a primary author without relationships with industry and a secondary reviewer drafted the initial text and conclusions. All sections, tables, and conclusions were then reviewed by all writing group members and the manuscript revised based on this review. The manuscript was then reviewed by 4 external reviewers and revised accordingly. The finalized manuscript was approved by all writing group members.

## Meditation
The practice of meditation dates as far back as 5000 BC. [bib_ref] Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators, Kaliman [/bib_ref] Although associated with Eastern philosophies and religion, including Buddhism and Hinduism, references or inferences regarding meditation and the meditative process can be found in Christianity, Judaism, and Islam. [bib_ref] Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators, Kaliman [/bib_ref] Over the past several decades, meditation is increasingly practiced as a secular and therapeutic activity.
In the traditional context, meditation refers to a family of mental practices that are designed to improve concentration, increase awareness of the present moment, and familiarize a person with the nature of their own mind. [bib_ref] Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators, Kaliman [/bib_ref] In a more general and contemporary context, meditation can be categorized as primarily focused attention, mindfulness, loving kindness and compassion, or mantra repetition, although there is usually overlap between the focuses. [bib_ref] Influence of mindfulness-based stress reduction (MBSR) on telomerase activity in women with..., Lengacher [/bib_ref] [bib_ref] Reduction in salivary alpha-amylase levels following a mind-body intervention in cancer survivors--an..., Lipschitz [/bib_ref] [bib_ref] Workplace based mindfulness practice and inflammation: a randomized trial, Malarkey [/bib_ref] With focused attention ("samatha" meditation), the practitioner may focus on the breath or on an object, sound, sensation, visualization, thought, or repeated word or phrase ("mantra"). When the mind wanders, the meditator notices the mind wandering and learns to bring the mind back to the present moment or the object of meditation. In mindful meditation, the individual strives to be in the present moment and aware of internal sensations, thoughts, and external stimuli, without becoming engrossed in or distracted by them. Mindfulness-based stress reduction is a program based primarily on mindful meditation, as well as yoga; other mindfulness-based programs are similarly based on mindful meditation. Insight ("vipassana") meditation can be considered a form of mindful meditation. In loving kindness and compassion, the meditator cultivates a feeling of benevolence toward oneself and others. In Vedic or transcendental meditation, repeated thought of a word is used to relax and clear the mind. The "relaxation response" technique similarly uses focused silent repetition of a word, sound, or phase. These practices may be used to: (1) increase concentration, insight, or awareness of the present moment;
(2) promote relaxation; (3) reduce stress; (4) settle the mind; (5) achieve a state of increased consciousness; and (6) reduce perceived suffering and increase happiness. [fig_ref] Table 1: Common Types of Meditation [/fig_ref] provides a summary of common types of meditation. Most forms of meditation are practiced 20 minutes or once or twice daily. Although meditation was first practiced millennia ago as part of Buddhist and Hindu religions, it has recently been introduced in the West as a stand-alone secular activity.

## Neurophysiology and neuroanatomy of meditation
Almost 2 decades of scientific studies, conducted at 20 universities, have identified the effects of meditation on the brain. [bib_ref] Reduction in salivary alpha-amylase levels following a mind-body intervention in cancer survivors--an..., Lipschitz [/bib_ref] Most forms of meditation engage regions in the brain that regulate attention and emotion. [bib_ref] Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to..., Pace [/bib_ref] The adult brain can undergo changes through a process called neuroplasticity, which may include development of new circuits ("rewiring") and/or neurons. [bib_ref] Effect of mindfulness based stress reduction on immune function, quality of life..., Witek-Janusek [/bib_ref] The different psychological targets of meditation are instantiated in distributed neural circuits that include different sectors of the prefrontal cortex and anterior cingulate cortex, the insula, and the midline regions that are important in default mode function. [bib_ref] One year pre-post intervention follow-up of psychological, immune, endocrine and blood pressure..., Carlson [/bib_ref] In addition, studies of loving-kindness and/or compassion meditation practices often lead to alterations in subcortical circuits directly implicated in emotional processing, such as the amygdala and ventral striatum. [bib_ref] Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to..., Pace [/bib_ref] [bib_ref] Short-term meditation training improves attention and self-regulation, Tang [/bib_ref] [bib_ref] A randomized controlled trial of mindfulness meditation versus relaxation training: effects on..., Jain [/bib_ref] Studies of the effects on meditation on the brain include those using electroencephalography, magnetic resonance imaging, and functional magnetic resonance imaging. Whereas numerous studies have reported on the acute neurophysiological effects of meditation, more relevant to this scientific statement are long-term neurophysiological and neuroanatomical changes. In 1 of the first reports on the longterm effects of meditation on the brain, a 2-month mindfulness meditation program resulted in increased left-sided anterior brain electrical activation, a pattern associated with positive affect and emotion, whereas no such changes occurred in a wait-listed control group. [bib_ref] A pilot study to examine the effects of a mindfulness-based stress-reduction and..., Mccomb [/bib_ref] A study of long-

## Samatha meditation
Samatha is translated to mean "calm" and samatha meditation is often referred to as calm, abiding meditation. Samatha meditation is the practice of calming the mind by practicing single-pointed meditation through mindful concentration focusing on the breath, image, or object.
Buddhist practice, dating to the time of the Buddha or even before

## Vipassana meditation (insight meditation)
Vipassana is translated to mean, "to see things as they really are." Vipassana emphasizes awareness of the breath, tuning into the air passing in and out through the nose. Vipassana teaches one to label thoughts and experiences as they arise, taking mental notes as one identifies objects that grab one's attention. Vipassana meditation is often taught at 10-day retreats.
Traditional Buddhist and Indian meditation. Well-known teachers include Mahasi Sayadaw, S.N. Goenka, Sharon Salzberg, Joseph Goldestein, Jack Kornfield, and Michael Stone
Mindful meditation An umbrella term for the category of techniques used to create awareness and insight by practicing focused attention, observing, and accepting all that arises without judgment. This type of meditation is also referred to as "open monitoring," in which one allows one's attention to flow freely without judgment or attachment.
Origins come from Buddhist teaching. Well-known Western teachers include Jon-Kabat Zinn, Tara Brach, Sharon Salzberg, Joseph Goldestein, Jack Kornfield, and Pema Chodron

## Zen meditation (zazen)
A type of meditation where one focuses one's awareness on one's breath and observes thoughts and experiences as they pass through the mind and environment. In some senses similar to Vipassana meditation, but with an emphasis on a focus of the breath at the level of the belly and on posture while sitting.
Buddhist meditation from Japan. Well-known teachers include Thich Nhat Hanh and Joan Halifax Roshi Raja yoga meditation Referred to also as "mental yoga," "yoga of the mind," or Kriya yoga. A practice of concentration to calm the mind and bring it to one point of focus. Includes a combination of mantra, breathing techniques, and meditation on the chakras/spinal cord focus points.
Hindu practice dating back thousands of years. Introduced to the West in 1893 by Swami Vivekananda. Further clarified and taught by Paramhansa Yogananda for the Western audience
Loving-kindness (metta) meditation
Loving-kindness meditation involves sending loving kindness to oneself, then continuing to send it to a friend or loved one, to someone who is neutral in your life, to a difficult person, and then out to the universe. Through this practice, the meditator cultivates a feeling of benevolence toward oneself and others.
Originates from Buddhist teachings, mainly Tibetan Buddhism. Well-known instructors include Sharon Saltzberg and Pema Chodron

## Transcendental meditation
Mantra-based meditation technique in which each practitioner is given a personal mantra that is used to help settle the mind inward. Transcendental meditation is taught by certified teachers through a standard 4-day course of instruction. Transcendental meditation is practiced for 20 minutes twice daily. standing Buddhist meditation practitioners demonstrated durable electroencephalographic changes, suggesting that the resting state of the brain may be altered by long-term meditative practices. [bib_ref] A randomized, wait-list controlled clinical trial: the effect of a mindfulness meditation-based..., Speca [/bib_ref] A brain magnetic resonance imaging study of experienced meditators found, when compared with age-matched controls, higher gray matter density in lower brainstem regions involved in the autonomic system and cardiorespiratory control. [bib_ref] Mindfulness training for smoking cessation: A meta-analysis of randomized-controlled trials, Oikonomou [/bib_ref] Some, though not all, longitudinal studies of 1 to 3 months of mindful meditation have demonstrated changes in brain structure and function not observed in control participants. [bib_ref] Effect of Brief Mindfulness Practice on Self-Reported Affect, Craving, and Smoking: A..., Ruscio [/bib_ref] A meta-analysis of 21 neuroimaging studies examining 300 meditation practitioners found 8 brain regions consistently altered in meditators, including areas key to meta-awareness, body awareness, and self-and emotion regulation. [bib_ref] Mindfulness training for smokers via web-based video instruction with phone support: a..., Davis [/bib_ref] Anatomical changes have been reported in the cerebral cortex, subcortical gray and white matter, brainstem, and cerebellum of meditators. [bib_ref] Effect of Brief Mindfulness Practice on Self-Reported Affect, Craving, and Smoking: A..., Ruscio [/bib_ref] Neurophysiological and neuroanatomical studies suggest that meditation can have long-standing effects on the brain, which may have beneficial consequences on the physiological basal state, physiological responses, and cardiovascular risk. However, these studies generally were nonrandomized and involved modest numbers of participants, some of whom were highly experienced (>10 000 hours) meditators. Additionally, different forms of meditation (eg, focused attention, mindfulness, and loving kindness) will have different psychological and neurological effects. Thus, the neurophysiological and neuroanatomical findings associated with 1 type of meditation cannot be extrapolated to all forms. Extrapolation of the findings in the aforementioned studies to the general population who engage in meditation must be done with caution.

## Meditation and cardiovascular risk reduction
A summary of the findings on meditation and cardiovascular risk reduction is provided in [fig_ref] Table 2: Summary of Findings on Studies of Meditations and Cardiovascular Risk Reduction* [/fig_ref]. Summaries of the individual studies, as well as their limitations, evaluated in this scientific statement are provided in Tables S1 through S9. These summary tables are not all-inclusive but summarize the findings of those studies deemed most relevant to this scientific statement. Findings on the effects of meditation on specific aspects of cardiovascular health are given in the following sections.

## Effects of meditation on psychological, psychosocial, and physiological responses to stress
Numerous studies, across both healthy and disease-based populations, have explored the effects of meditation on psychological and psychosocial outcomes. Most published studies report some improvements in levels of perceived stress, mood, anxiety, depression, quality of sleep, or overall wellbeing [bib_ref] Randomized trial comparing mindfulness training for smokers to a matched control, Davis [/bib_ref] [bib_ref] Randomized trial on mindfulness training for smokers targeted to a disadvantaged population, Davis [/bib_ref] [bib_ref] Brief meditation training induces smoking reduction, Tang [/bib_ref] [bib_ref] Mindfulness training for smoking cessation: results from a randomized controlled trial, Brewer [/bib_ref] [bib_ref] A pilot study on mindfulness based stress reduction for smokers, Davis [/bib_ref] [bib_ref] Effects of a randomized controlled trial of transcendental meditation on components of..., Paul-Labrador [/bib_ref] [bib_ref] Effects of yoga and meditation on clinical and biochemical parameters of metabolic..., Khatri [/bib_ref] [fig_ref] Table 1: Common Types of Meditation [/fig_ref]. A review by the Agency for Healthcare Research and Quality restricted to randomized, controlled trials with an active control concluded-with low strength of evidence-that mindfulness meditation programs show modest improvements in stress/distress and negative affect. [bib_ref] Effect of meditation on endothelial function in Black Americans with metabolic syndrome:..., Vaccarino [/bib_ref] Few studies have focused on patients with CVD. In a study of 60 patients recruited from a private cardiology clinic, those randomized to 8 weeks of mindfulness-based stress reduction (primarily using meditation techniques) had significantly lower perceived stress and anger 47 than a comparison control group. Similarly, a study of 59 elderly participants with stage I hypertension randomized to Zen meditation (20 minutes twice daily for 3 months) or a wait list found that meditation significantly improved psychological facets of and overall quality of life. [bib_ref] The effect of a six-week program of yoga and meditation on brachial..., Sivasankaran [/bib_ref] A growing body of research has examined the mechanisms by which meditation alters the physiological response to stress, with salivary cortisol the most commonly studied biomarker and a few exploring salivary amylase, [bib_ref] Association Between Mind-Body Practice and Cardiometabolic Risk Factors: The Rotterdam Study, Younge [/bib_ref] proinflammatory cytokines (ie, interleukin-6), or telomerase activity. Overall, findings from these studies have been mixed, with some demonstrating improvements in physiological parameters with meditation and others finding no changes. [bib_ref] Randomized trial comparing mindfulness training for smokers to a matched control, Davis [/bib_ref] [bib_ref] A pilot study on mindfulness based stress reduction for smokers, Davis [/bib_ref] [bib_ref] Effects of a randomized controlled trial of transcendental meditation on components of..., Paul-Labrador [/bib_ref] [bib_ref] Effects of combined traditional Chinese exercises on blood pressure and arterial function..., Zhang [/bib_ref] [bib_ref] Regression of coronary atherosclerosis through healthy lifestyle in coronary artery disease patients--Mount..., Gupta [/bib_ref] [bib_ref] Effect of a multimodality natural medicine program on carotid atherosclerosis in older..., Fields [/bib_ref] [bib_ref] Effects of stress reduction on carotid atherosclerosis in hypertensive African Americans, Castillo-Richmond [/bib_ref] [bib_ref] Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial, Ornish [/bib_ref] [bib_ref] Intensive lifestyle changes for reversal of coronary heart disease, Ornish [/bib_ref] [bib_ref] Effects of transcendental meditation on symptoms and electrocardiographic changes in patients with..., Cunningham [/bib_ref] Several recent studies have focused on the impact of meditation on proteomic and genomic regulators of the physiological stress response. [bib_ref] Regression of coronary atherosclerosis through healthy lifestyle in coronary artery disease patients--Mount..., Gupta [/bib_ref] [bib_ref] Usefulness of the transcendental meditation program in the treatment of patients with..., Zamarra [/bib_ref] [bib_ref] Effects of stress management training and dietary changes in treating ischemic heart..., Ornish [/bib_ref] Although unique gene expression profiles have been noted with meditation, their association with established physiological parameters is unknown. [bib_ref] Impact of transcendental meditation on mortality in older African Americans with hypertension..., Barnes [/bib_ref] One study of 40 patients reported that mindfulness-based stress reduction downregulated proinflammatory nuclear factor kappa B gene expression profile compared to wait-list control, with a trend-but no statistically significant reduction-in C-reactive protein levels. [bib_ref] Usefulness of the transcendental meditation program in the treatment of patients with..., Zamarra [/bib_ref] Overall, many, though not all, studies have reported that meditation is associated with improved psychological and psychosocial indices. Differences in study populations, control of potential confounders, and type and length of meditation evaluated may account for discrepant findings. Furthermore, small sample sizes and lack of randomization are common study limitations. Further study is needed on how meditation influences physiological processes associated with stress.

## Effects of meditation on blood pressure
Few high-quality, randomized trials of meditation and lowering of blood pressure have been published [fig_ref] Table 2: Summary of Findings on Studies of Meditations and Cardiovascular Risk Reduction* [/fig_ref]. The efficacy of mindfulness meditation for blood pressure reduction has been evaluated in a few studies. [bib_ref] The effect of a six-week program of yoga and meditation on brachial..., Sivasankaran [/bib_ref] [bib_ref] Long-term effects of stress reduction on mortality in persons > or =..., Schneider [/bib_ref] [bib_ref] Transcendental meditation, mindfulness, and longevity: an experimental study with the elderly, Alexander [/bib_ref] [bib_ref] A Prospective Trial of Ayurveda for Coronary Heart Disease: A Pilot Study, Dubroff [/bib_ref] The HARMONY (Hypertension Analysis of Stress Reduction Using Mindfulness Meditation and Yoga) trial assessed 24-hour ambulatory blood pressure measurements in patients with stage I hypertension randomized to an 8-week mindfulness-based stress reduction program or wait-list control and found no benefit of meditation. [bib_ref] Mind-body practices for patients with cardiac disease: a systematic review and meta-analysis, Younge [/bib_ref] In contrast, in a pilot study of 83 predominantly hypertensive blacks randomized to a mindful meditation program or control social support group, an 11/4 mm Hg decrease in systolic/diastolic blood pressure was observed in those randomized to 8 weeks of treatment and an analysisadjusted 22/17 mm Hg difference in blood pressure between the 2 groups at follow-up. [bib_ref] Mindfulness-based stress reduction program in coronary heart disease: A randomized control trial, Parswani [/bib_ref] Of note, this trial had 100% data ascertainment, over 80% compliance at each clinic visit, and measured blood pressure with an unattended manual device (a rigorous protocol with measurements 7-15 mm Hg lower than typical office readings). Other mind-body interventions that

## Neurophysiology and neuroanatomy
- Neurophysiological and neuroanatomical studies suggest that meditation can have long-standing effects on brain physiology and anatomy - Studies generally are nonrandomized and involve modest numbers of participants, sometimes performed under the direction of extremely experienced (>10 000 hours) meditators - Different forms of meditation have different psychological and neurological effects, and thus the neurophysiological and neuroanatomic findings of 1 type of meditation cannot be extrapolated to other forms of meditation Psychological, psychosocial, and physiological response to stress
- Many, although not all, studies report that meditation is associated with improved psychological and psychosocial indices - Differences in populations, control of potential confounders, and type and length of meditation evaluated may account for discrepant findings. Small sample sizes and lack of randomization are common study limitations - Further study is needed on how meditation influences physiological processes associated with the stress response Blood pressure
- Magnitude of reductions of systolic blood pressure varies widely - Study limitations including the methods of blood pressure measurements and bias in data ascertainment, high dropout rates, and different populations studied
Smoking and tobacco use - Some randomized data show that mindful meditation instruction improves smoking cessation rates Insulin resistance and metabolic syndrome
- Limited data on the effects of meditation on insulin resistance and metabolic syndrome Subclinical atherosclerosis - A few suboptimal studies of meditation and lifestyle intervention suggest the potential for benefit on atherosclerosis regression - Studies limited by multimodality approach, attrition, and incomplete follow-up - No firm conclusions can be drawn on the effects of meditation on atherosclerosis

## Endothelial function
- Three studies showed no benefit of meditation on brachial reactivity in the overall cohorts, although 1 study suggested a benefit in a subgroup of patients with coronary artery disease - No conclusions can be drawn on the effects of meditation on endothelial function

## Inducible myocardial ischemia
- Limited older studies suggest that meditation can lead to improvement in exercise duration and decreased myocardial ischemia - No contemporary studies have evaluated effects of meditation on myocardial blood flow or ischemia with advanced imaging techniques Primary prevention of CVD - Two studies of short-term intervention report surprising mortality reductions, and thus these findings need to be reproduced in larger, multicenter studies - Overall, because of the limited evidence to date, no conclusions can be drawn as to the effectiveness of meditation for the primary prevention of CVD Secondary prevention of CVD - Data on the potential benefits of meditation in patients with established coronary artery disease can best be characterized as generally of modest quality and as suggesting, but not definitely establishing, benefit - Because of generally limited follow-up time, there are more data on reduction of cardiac risk factors and psychological indices than on hard end points (eg, death, myocardial infarction) involve both a physical and mental component have been associated with significant reductions in blood pressure, [bib_ref] Comparison of cardiac rehabilitation programs combined with relaxation and meditation techniques on..., Delui [/bib_ref] [bib_ref] Stress reduction in the secondary prevention of cardiovascular disease: randomized, controlled trial..., Schneider [/bib_ref] [bib_ref] Mindfulness meditation, anxiety reduction, and heart disease: a pilot study, Tacon [/bib_ref] [bib_ref] The Support, Education, and Research in Chronic Heart Failure Study (SEARCH): a..., Sullivan [/bib_ref] but the specific contribution of meditation and meditation-like practices of inner focus and a concentration on the breath cannot be determined. The effects of transcendental meditation on blood pressure have also been reported. 70-73 A study of 298 university students randomized to transcendental meditation or wait-list control found at 3-month follow-up no significant changes in systolic or diastolic blood pressure, although significant reductions in blood pressure (5/3 mm Hg, respectively) did occur in those at high risk of the development of hypertension. In a randomized study of stress reduction in 201 black men and women with angiographically documented coronary artery disease randomized to transcendental meditation or health education, 5.4-year follow-up found a 4.9 mm Hg lower systolic blood pressure, 1 of numerous secondary study end points, in those randomized to transcendental meditation than in those randomized to health education, primarily because of an increase in blood pressure in the health education group. Numerous systematic reviews have been conducted on the effects of meditation on blood pressure. One 2007 systematic review assessed several methods of stress reduction in patients with hypertension and found modest benefit (ie, 5/ 3 mm Hg systolic/diastolic blood pressure reduction) with transcendental meditation; other popular types of meditation were not assessed. 74 Numerous meta-analyses in a 2007 Agency for Healthcare Research and Quality report on meditation and health generally found modest to no significant benefit with different meditation techniques when compared with active control groups (eg, health education), though the report also stated that meta-analyses based on low-quality studies and small numbers of hypertensive participants showed that transcendental meditation and Zen Buddhist meditation significantly reduced blood pressure. 75 A 2013 American Heart Association scientific statement on alternate approaches to lowering blood pressure concluded that transcendental meditation modestly lowers blood pressure and that its use may be considered. The writing group also concluded at that time that there were insufficient highquality studies assessing the benefit of other forms of meditative techniques to recommend them for blood pressure lowering. A 2015 analysis of 12 randomized, clinical trials of transcendental meditation involving a total of 996 predominantly black patients with or without hypertension found a mean reduction in blood pressure of 4/2 mm Hg (systolic/ diastolic) over the study duration of 2 to 60 months (mean 4 months) when compared with control participants. 72 Benefit in systolic blood pressure reduction seemed to persist up to 12 months. Of note, the completion rate (percentage of patients who completed all training and post-test) in these studies was a modest 63%.
The mechanism(s) whereby meditation lowers blood pressure when it occurs has not been fully elucidated. 77 Possibly, the long-term neurophysiological changes that occur with meditation [bib_ref] A randomized, wait-list controlled clinical trial: the effect of a mindfulness meditation-based..., Speca [/bib_ref] [bib_ref] Mindfulness training for smoking cessation: A meta-analysis of randomized-controlled trials, Oikonomou [/bib_ref] [bib_ref] Effect of Brief Mindfulness Practice on Self-Reported Affect, Craving, and Smoking: A..., Ruscio [/bib_ref] may lead to autonomic nervous systemmediated changes in blood pressure. One study of 15 participants with hypertension and chronic kidney disease reported a decrease in muscle sympathetic nerve activity and blood pressure during mindfulness meditation, 79 but no such long-term data exist. The impact of stress reduction on blood pressure remains to be better defined.
Reported reductions of systolic blood pressure with meditation vary widely. The heterogeneity in results reflects the various study populations, study designs, data ascertainment protocols, study duration, baseline blood pressure, and blood pressure measurement techniques used. Limitations to clinical interpretation include high drop-out rates, bias in data ascertainment, and lack of attention to statistical power, control participants, and methods of blood pressure measurements. [bib_ref] Effect of meditation on endothelial function in Black Americans with metabolic syndrome:..., Vaccarino [/bib_ref] The ability to generalize the findings is limited by the lack of reproducibility of results.

## Effects of meditation on smoking and tobacco use
Cigarette smoking is the leading cause of preventable disease and deaths in the United States, accounting for >480 000 deaths every year, or 1 of every 5 deaths. 81,82 Two thirds of American adults want to quit smoking, and yet only 6% achieve this goal annually. 83 Several types of meditation have been studied as interventions to facilitate smoking cessation [fig_ref] Table 3: Summary of Findings and Suggestions on Meditation and Cardiovascular Risk Reduction [/fig_ref]. Small studies 84-89 have shown that mindfulness training, a form of meditation, increases abstinence rates when compared with more traditional intervention programs. In 1 study of volunteers wishing to reduce stress, half of whom were smokers, who were randomized to either a 2week program of integrative body-mind technique-a form of mindfulness meditation-or relaxation training, a 60% reduction in smoking was observed among those instructed in integrative body-mind technique, with no reduction in those instructed in relaxation training. In this study, resting-state brain scans before and after intervention showed increased activity in the anterior cingulate and prefrontal cortex-areas of the brain that are related to self-control-for the meditation group, but not the relaxation training group. 90 A metaanalysis of 4 randomized, controlled trials of mindfulness training involving a total of 474 patients found that it was more effective than group counseling, with 25% of mindfulness training participants remaining abstinent from smoking for >4 months, compared with 14% of those receiving moretraditional cessation instruction. One study of transcendental meditation in 295 college students found no significant reduction in cigarette smoking at 3-month follow-up between those randomized to transcendental meditation and those in a wait-list control group. Thus, some randomized data show that mindful meditation instruction improves smoking cessation rates. Potential mechanisms include management of cravings and decreasing negative effect, which has been shown to be a potent stimulus for drug-seeking behavior and smoking relapse. Meditation may also affect smoking behavior through changes in urge intensity 87 and improved self-control. 90

## Effects of meditation on insulin resistance and metabolic syndrome
Metabolic syndrome, a cluster of conditions including hypertension, dyslipidemia, elevated fasting blood glucose, and abdominal obesity, is a risk factor for diabetes mellitus and CVD. 93-95 Data on the effects of meditation on insulin resistance and metabolic syndrome are sparse . In a study of 103 patients with coronary artery disease randomized to transcendental meditation or active control (health education), transcendental meditation improved insulin resistance. A study of the effects of meditation, yoga, and a vegetarian diet on parameters of metabolic syndrome 97 was too confounded by the multimodality approach to draw meaningful conclusions.
The relaxation response-the counterpart of the stress response-can be evoked by meditation. In 1 novel study, 98 20 minutes of listening to a relaxation response instructional CD reduced expression of genes linked to inflammatory response and the stress-related pathway-mechanisms that contribute to metabolic syndrome 99,100 -and enhanced expression of genes associated with energy metabolism, mitochondrial function, and insulin secretion. Changes in gene expression were more pronounced in experienced practitioners of relaxation techniques than in novices who had recently undergone 8 weeks of relaxation response training. The clinical effects of these changes in gene expression, if any, remain unknown.
A comprehensive review of metabolic syndrome and mindbody therapies identified only 3 relevant clinical trials, 2 of which are discussed above and the third of which involved restorative yoga as the primary intervention. In summary, data on the effects of meditation on insulin resistance and metabolic syndrome are limited.

## Effects of meditation on subclinical atherosclerosis
Limited evidence exists for the effects of meditation on subclinical atherosclerosis . Only 1 randomized, controlled trial was identified that studied the effects of a meditation intervention on atherosclerosis progression. In this study, carotid intimal thickness was assessed in 138 hypertensive blacks randomized to a transcendental meditation or control health education program and followed for a mean of 7 months. Attrition was high, with 57% of participants not completing follow-up. Among completers of the study, carotid intimal thickness regression was noted in the meditation group, whereas progression occurred in controls, with the difference between the 2 groups being statistically significant. In another randomized study, 57 healthy adults aged 65 years were randomized to 1 of 3 interventions: a transcendental meditation program that also included diet, exercise, and vitamin treatment; a diet/exercise/ vitamin arm without the meditation component; or a usual care arm. At 1 year, the meditation intervention group showed reduction in carotid intimal thickness that was not observed in the other groups.
Other studies on subclinical atherosclerosis evaluated more comprehensive multimodality lifestyle interventions that generally included components of dietary changes, exercise, and stress management (including components of meditative practice). 104-107 Study end points included changes in coronary artery atherosclerosis as assessed by quantitative coronary angiography 104-106 and ankle-brachial indices. Although these studies showed favorable effects of lifestyle intervention on atherosclerosis regression, given the multimodality approach, it is difficult to discern the effects of the meditation component alone. Study result interpretation is also limited by attrition and incomplete follow-up. In summary, although a few studies of meditation and lifestyle intervention suggest the potential for benefit on atherosclerosis progression, no firm conclusions can be made on the effects of meditation alone on atherosclerosis.

## Effects of meditation on endothelial function
Endothelial function can be indirectly assessed by evaluating brachial artery endothelial vasomotor response. In a pilot study of 41 participants (33 of whom completed the study), a 6-week combined yoga and meditation intervention failed to significantly improve endothelial function, although there was improvement in the cohort of 10 patients with coronary artery disease. 108 In a trial of 103 patients with coronary artery disease (84 of whom completed follow-up) randomized to 16 weeks of transcendental meditation or control health education, meditation had no significant effect on brachial artery reactivity testing. In a trial of 68 black Americans with metabolic syndrome risk factors, consciously resting meditation improved flow-mediated dilation at 12month follow-up, but compared with changes in the control health-education group, this improvement was not significantly different. 109 Only 38 participants (56%) completed the 12-month follow-up.
Limitations of these studies variably include modest sample size, relatively short durations of intervention, high attrition rates, and incomplete follow-up . Given these factors, as well as the different patient populations studied and variable findings in those with established coronary artery disease, no definitive conclusions on the effects of meditation on endothelial function can be made.

## Effects of meditation on inducible myocardial ischemia
A paucity of studies has examined the effects of meditation on inducible myocardial ischemia . In a 1996 study of 21 participants with coronary artery disease, 7.6 months of transcendental meditation led to significant increases in exercise duration (15%) and maximal workload (12%) compared with wait-listed controls, as well as lower rate-pressure products at given workloads and significantly delayed onset of ST depression. In a 1983 study of 46 patients with ischemic heart disease that combined stress management (meditation and stretching/relaxation exercises) and a veganbased diet, after 24 days those randomized to the lifestyleintervention group had a 44% increase in exercise duration, 55% increase in total work, and improved exercise ejection fraction and regional wall motion, whereas no significant changes occurred in those randomized to the control group. No contemporary studies have evaluated the impact of meditation on myocardial blood flow or ischemia with techniques such as stress echocardiography, single-photon emission computed tomography, cardiac positron emission tomography, or cardiac magnetic resonance imaging. Larger, randomized, clinical studies that evaluate the impact of meditation-based interventions on inducible myocardial ischemia, ideally using more sophisticated modalities to assess and quantify ischemia, are needed.

## Meditation and primary prevention of cvd
Although studies have assessed the effect of meditation on cardiovascular risk factors, recent Cochrane reviews have concluded that no properly conducted randomized, controlled trials have assessed its role in the primary prevention of cardiovascular mortality or nonfatal primary end points. This is largely because the relevant studies are small, with short-term follow-up and carried out in predominantly healthy participants.
One study 116 measured survival rate in 73 elderly participants randomly assigned to 3 months of transcendental meditation, mindfulness training, mental relaxation, or a no-treatment control group. The survival rate after 3 years for the transcendental meditation group was significantly better; 100% compared with 65% to 87% for other groups. In a second study, mortality and cause of death were assessed from vital statistics over 8 years of follow-up in 109 older black patients who had participated in a hypertension study. Participants were randomly assigned to 2 stress reduction approaches-either transcendental meditation or progressive muscle relaxation-or to a health education (ie, control) group for 3 months. The adjusted relative risk for CVD mortality was significantly reduced by 81% in the transcendental meditation group when compared with the control group. In both studies, mortality was assessed 3 to 8 years after the intervention period, so the results may not be attributed to transcendental meditation. This and other methodological issues raise concerns about the validity of their findings.
When patient data from the abovementioned 2 randomized, controlled trials were combined in a post-hoc analysis, [bib_ref] A meta-analytic review of the effects of mindfulness meditation on telomerase activity, Schutte [/bib_ref] the transcendental meditation group reportedly showed a 23% reduction in all-cause mortality compared with the control patients, a 30% reduction in cardiovascular mortality, and a nonstatistically significant 51% reduction in rate of cancer mortality . These studies of shortterm intervention applied to a limited number of participants report surprising mortality reductions that are on par with, or greater than, those observed in long-term intervention, large-scale, primary prevention studies of cholesterol therapy 118 and of blood pressure reduction. 119,120 Accordingly, these findings need to be reproduced in larger, multicenter studies.
In summary, data regarding the effectiveness of meditation for primary prevention of CVD are lacking, and because of the limited evidence to date, no conclusions can be drawn as to the effectiveness of meditation for the primary prevention of CVD.

## Meditation and secondary prevention of cvd
Limited and limited-quality data are available from studies of meditation for secondary prevention of CVD . Such studies, which generally have enrolled patients with stable coronary artery disease, have variably reported reductions in systolic blood pressure, insulin resistance, serum lipids, clinical symptoms, and anxiety and stress. 70,96,106,110,121-127 Most, although not all, studies randomized patients to either meditation or some type of "usual care." These studies are generally limited by modest sample size and limited duration follow-up, and a few assessed multifactorial interventions that combined meditation with other interventions (ie, yoga, diet). A systematic review and meta-analysis of randomized, controlled trials of mind-body practices, including meditation but other interventions as well, found that such interventions were associated with improvements in physical and mental quality of life, depression and anxiety, and systolic and diastolic blood pressure, but rated the overall quality of the studies as low. One commonly cited study involves 201 patients with angiographically documented coronary artery disease randomized to transcendental meditation or health education. After a mean of 5.4 years, the primary composite end point of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke was significantly lower in the meditation group (adjusted hazard ratio, 0.52). Post-hoc analysis found greater benefit (hazard ratio, 0.34) in those with high adherence. There was a nonsignificant 24% reduction in the broader secondary composite endpoint, which also included coronary revascularization or hospitalization for cardiac causes. The study, though, was conducted in 2 phases after a 1-year hiatus with 58 patients not participating in phase 2 of the study, and some concerns about analysis of the data have been raised. Overall, data on the potential benefits of meditation in patients with established coronary artery disease can best be characterized as of modest quality and suggesting, but not definitely establishing, benefit in secondary prevention. Because of the generally limited follow-up time, more data on reduction of cardiac risk factors and psychological indices (eg, stress, anxiety, and depression) exist than on hard end points (eg, death or myocardial infarction).

## Summary
Studies of meditation to date suggest a possible, though not definitively established, benefit of meditation on cardiovascular risk reduction. A 2008 review of >400 trials of meditation and health care rated the methodological quality of clinical trials as poor, but noted that the quality of these trials had significantly improved over time. Methodological issues in research to date include modest study size, limited and often incomplete followup, high drop-out rates, lack of randomization and/or appropriate control group, and unavoidable patient nonblinded study design. As with many other novel interventions, there is the possibility of publication bias toward positive studies of the beneficial effects of meditation. [bib_ref] Effect of Brief Mindfulness Practice on Self-Reported Affect, Craving, and Smoking: A..., Ruscio [/bib_ref] [bib_ref] Mindfulness training for smokers via web-based video instruction with phone support: a..., Davis [/bib_ref] Many investigators who conducted studies of meditation may have a strong belief in the benefits of meditation and may be enthusiastic meditators themselves, [bib_ref] Effect of Brief Mindfulness Practice on Self-Reported Affect, Craving, and Smoking: A..., Ruscio [/bib_ref] thereby introducing the possibility of unintended bias. Many studies of meditation techniques are performed by the same groups of researchers, so there is a need for independent verification of reported positive findings. Whereas these studies are important in that they serve to suggest that meditation may reduce cardiovascular risk, these limitations prevent definitive conclusions regarding efficacy of meditation on cardiovascular risk reduction.
Currently, the mainstay for primary and secondary prevention of CVD is American College of Cardiology/American Heart Association guideline-directed interventions. However, considering the generally low costs and risks associated with meditation, meditation may be considered as a reasonable adjunct to guideline-directed cardiovascular risk reduction by those so interested in this lifestyle modification, with the understanding that the benefits of such intervention remain to be better established.
Further research on meditation and cardiovascular risk is warranted. Such studies, to the degree possible, should utilize randomized study design, be adequately powered to detect clinically meaningful benefit, include long-term follow-up, and be performed by those without inherent bias in outcome. One such example is the ongoing Yoga-CaRe study for secondary prevention of myocardial infarction. 131 A summary of findings on meditation and cardiovascular risk reduction and on suggested methodology for future research are given in [fig_ref] Table 3: Summary of Findings and Suggestions on Meditation and Cardiovascular Risk Reduction [/fig_ref]. - Studies of meditation suggest a possible benefit on cardiovascular risk, although the overall quality and, in some cases, quantity of study data is modest - The mainstay for primary and secondary prevention of CVD is ACC/AHA guideline-directed interventions - Meditation may be considered as an adjunct to guideline-directed cardiovascular risk reduction by those interested in this lifestyle modification with the understanding that the benefits of such intervention remain to be better established - Further research on meditation and cardiovascular risk is warranted. Such studies, to the degree possible, should meet the following criteria:
- This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives $10 000 or more during any 12-month period, or 5% or more of the person's gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition. *Modest.  Significant.

# Reviewer disclosures
Reviewer Employment This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives $10 000 or more during any 12-month period, or 5% or more of the person's gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition. *Significant. - Single-blind randomized controlled trial to that assessed blood pressure, perceived stress, and anger in 60 cardiac patients. - Experimental group (N=30) received 8 weeks MBSR training while those in control group received no psychological training (wait-listed control group N=30).
- Systolic blood pressure, perceived stress, and ager were significantly improved (p<.01) in MBSR group as compared to control group. - University employees were randomized to a 6-week mindfulness-based stress release program (SRP) (N=50) or a waitlist control group (N=29) - SRP program is a structured program consisting of "practices using body, breath, and cognitive strategies and reflective activities to enhance professional and personal life" and is considered to be less intensive than MBSR - Perceived stress, workplace well-being, and engagement were measured at baseline and at completion of the program 
- Randomized trial that examined brief mindfulness-based intervention for younger female breast cancer survivors. - Women diagnosed with early stage breast cancer at or before age 50 who had completed cancer treatment were randomly assigned to a 6-week Mindful Awareness Practices (MAPS) intervention group (n = 39) or to a wait-list control group (n = 32). - Participants completed questionnaires before and after the intervention to assess stress and depressive symptoms (primary outcomes) as well as physical symptoms, cancerrelated distress, and positive outcomes. Blood samples were collected to examine genomic and circulating markers of inflammation. Participants also completed questionnaires at a 3-month follow-up assessment. - Meta-analysis of 4 clinical trials (total N=191) examining telomerase activity in association with meditation.
- A meta-analytic effect size of d = 0.46 indicated that mindfulness meditation leads to increased telomerase activity in peripheral blood mononuclear cells. These results
- Small number of studies included in analysis.
Younge, JO, PLoS One, 2015
- Randomized controlled single-blind trial that examined the physiological and psychological outcomes of a 12 weeks online mindfulness training program (N=215) as compared to usual care (N=109) in patients with cardiac disease - Primary outcome was exercise capacity as measured by a 6 min walk test. Other outcomes included heart rate, blood pressure, respiratory rate, NT-proBNP, subjective health status, perceived stress, psychological well-being, social support, and a composite end-point (all-cause mortality, heart failure, symptomatic arrhythmia, cardiac surgery, and percutaneous cardiac intervention). - Stratified-randomized trial - Following a laboratory cognitive stressor, participants (maladaptive perfectionists -N=21, and controls -N=39, were randomly assigned to a 10 min audio instructed mindfulness meditation condition or a 10 min rest condition with audio description of mindfulness meditation.
- Significant elevated heart rate variability (HRV) during meditation for controls but not for maladaptive perfectionists - Findings suggest that mindfulness meditation promotes relaxation following cognitive stress but the maladaptive perfectionist personality hinders relaxation possibly due to decreased cardiac vagal tone 
- Randomized controlled trial comparing Mindfulness Based Cancer Recovery program to a supportive-expressive group. A one day stress management seminar was used for the control group. - 88 distressed cancer survivors with a diagnosis of stage 1 or stage 11 cancer who completed treatment at least three months prior participated.
- No differences were found in regards to telomere length between the mindfulness group and the supportive expressive group -but a trend was observed in the combined intervention group as compared to the control group - Examined the extent to which a brief mindfulness training intervention buffered self-reported psychological and cortisol responses to TSST in 66 young adults. - Participants were randomly assigned to either a 3 day (25 min per day) mindfulness meditation training or an analytic cognitive training control program. - Controlled for treatment expectancies.
- Perceived stress was reduced in brief mindfulness training group however demonstrated increased cortisol reactivity to TSST as compared to the control group. - No changes were observed in systolic or diastolic blood pressure between the two groups.
- Did not include a validated state mindfulness measure - Since blood pressures were not taken continuously during/after the TSST, BP reactivity may not have been fully captured. - Examined impact of a day of intensive mindfulness meditation in experienced individuals (N=19) on expression of circadian, chromatin modulatory, and inflammatory genes in peripheral blood mononuclear cells compared to a control group (N=21) of individuals with no meditation experience who engaged in leisure activities in the same environment as intervention group - Blood was collected before and after the intervention for analysis of gene expression. In addition, individuals underwent the Trier Social Stress Test (TSST).
- Core clock gene expression at baseline was similar between groups and their rhythmicity was not influenced by meditation. - Epigenetic regulatory enzymes and inflammatory genes were similar at baseline for the two groups. - Reduced expression of histone deacetylase genes (HDAC 2, 3, and 9), alterations in global modification of histones , and decreased expression of proinflammatory genes (RIPK2 and COX2 were found in meditators as compared to controls. - Faster recovery of cortisol levels after the TSST was associated with lower gene expression levels of RIPK2 and HDAC2
- Small sample size
Lengacher CA, Biol Res Nursing 2014 [bib_ref] Influence of mindfulness-based stress reduction (MBSR) on telomerase activity in women with..., Lengacher [/bib_ref] - 162 breast cancer survivors were randomized or wait-listed. [bib_ref] Mindfulness meditation and improvement in sleep quality and daytime impairment among older..., Black [/bib_ref] week Mindfulness-based stress reduction (MBSR) on telomere length (TL) and telomerase activity (TA) at 6 and 12 weeks.
- MBSR led to increased telomerase activity but no increase in telomere length
- Small-modest sample size - Mindfulness-based stress reduction influenced telomerase activity in women with breast cancer - Prospective study of 26 healthy subjects who had no prior relaxation response training (RR; diaphragmatic breathing, mantra repetition, and mindfulness meditation)-eliciting experience (Novices, N1) who underwent 8 weeks of RReliciting training (Short-term Practitioners, N2). - Parallel cross-sectional study of another 26 healthy subjects with significant prior RR-practice (4-20 years; Long-Term Practitioners, M) and compared with novices either before or after their 8-week RR training.
- Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the longterm practitioners as compared to novices. RR practice enhanced gene expression related to energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stressrelated pathways.
- Small sample size - Quasi-experimental design - Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways. Some genes were modified only in long-term practitioners, whereas others were modified in both short-and long-term practitioners with a greater intensity in the latter. Rosenkranz, MA, Brain Behav Immun, 2013 [bib_ref] A comparison of mindfulness-based stress reduction and an active control in modulation..., Rosenkranz [/bib_ref] - Randomized controlled trial (N=49) comparing 8 weeks MBSR program to Health Enhancement Program (HEP) - Psychological stress and endocrine response were measured before and after the Trier Social Stress Test. - Inflammation was measured by using capsaicin topical cream to induce inflammation before and after intervention
- Cortisol responses to TSST were similar between MBSR and HEP groups. - Reduction in psychological distress and symptoms in response to TSST were similar between groups - Those randomized to MBSR group had significantly smaller post-stress inflammatory response as compare to HEP.
- Generalizability to populations with chronic illness - Unable to determine interaction between stress and inflammation because, due to potential participant burden, stress condition was not employed in the absence of inflammation and an inflammation condition was not tested in the absence of stress. Qu S, PLoS ONE 2013 [bib_ref] Rapid gene expression changes in peripheral blood lymphocytes upon practice of a..., Qu [/bib_ref] - Ten health adults did two courses of 4 consecutive days of a comprehensive yoga program, at the same time of the day (6.30 am -8.30 am) or yoga and related practices or nature walk with relaxing music.
- Gene expression changes were noted as early as 2 hours. 97 unique genes were affected by yoga and related practices vs. 24 by the control regimen. 36% of the control group genes were also influenced by the yoga regimen, suggesting overlap in effect on biological processes. Nyklicek, L, Health Psychol, 2013 (23)
- 88 community-dwelling volunteers reporting elevated levels of perceived stress were randomly assigned to a MBSR program or waitlist control group. - Participants underwent a social stressor consisting of mental math and making a speech before and after the intervention. - Measurements before, during and after the social stressor included heart rate variability, blood pressure, and salivary cortisol.
- Controlling for age, body mass index, and beta blockers, participants in the MBSR group demonstrated larger decreases in systolic blood pressure, diastolic blood pressure. - No effect was obtained for other physiological measures.
- Absence of critical committee during TSST could have reduced cortisol response to stressor. - Recovery period after social stressor was only 10 minutes which may have limited the ability to capture changes during recovery. Carlson, J Clin Oncol, 2013 [bib_ref] Randomized controlled trial of Mindfulness-based cancer recovery versus supportive expressive group therapy..., Carlson [/bib_ref] - Randomized controlled trial to compare mindfulness -based cancer recovery (MBCR) program to supportive-expressive group therapy (SET) in distressed survivors of stage 1 to III breast cancer (N=271) - 1-day stress management class was used as a control condition - Measures (mood, diurnal salivary cortisol, stress, quality of life, and social support) were collected at baseline and after the intervention by evaluators blinded to the study condition.
- Cortisol slopes were maintained in MBCR (p=.011) and SET group (p=.002) participants in comparison to those in the control group whose cortisol slopes became flatter. - Stress symptoms were improved in MBCR group compared to SET (p=.009) and control (p=.024) groups. - Those participating in the MBCR group demonstrated greater improvements in quality of life compared to the control group (p=.005) and social support compared to those in the SET group (p=.012).
- Only breast cancer patients in study -findings may not be generalizable. - High attrition (34.5% in MBCR group).
Jacobs, TL, Health Psychol, 2013 (24)
- Observational study examining self-reported mindfulness and evening cortisol at the beginning and after a 3 month Shamatha meditation retreat (N=57) - The group met 2/day for 1-hr sessions to engage in guided meditations and dialogue but primarily practiced solitary meditation for much of the day (M = 6.3 hr/day, SD = 1.34). - To allow for acclimatization, cortisol measures were taken 2 weeks after arrival to the retreat site, which meant that participants had already been meditating for up to 9 days before the initial cortisol measure was - Blinded design -48 young, healthy meditation novices were randomly assigned to MBSR, non-MBSR, or inactive control group. - At posttest, those in the inactive control group were randomly split into incentive and non-incentive controls - Attention, self-report of mindfulness, perceived stress, and salivary cortisol were measured at pre and post intervention.
- Attentional effects of MBSR, non-MBSR, and the financial incentive were comparable or significantly larger in the incentive group. - 33 women who had completed treatment for breast cancer participated in the study' - MBSR group met weekly for 2.5 hours for 8 consecutive weeks - Cortisol Awakening Response (CAR) was assessed at three days prior to the MBSR program and three days after. - Depressive symptoms, perceived stress, and medical symptoms were measured pre and post intervention.
- Cortisol levels demonstrated a prolonged increase after awakening at the post MBSR assessment. This was accompanied by significant improvements in self-reported stress, depressive symptoms, and medical symptoms.
- Small sample size 
- University employees and staff randomized to a low dose MBSR program (N=24 or wait list control group (N=24). - Low dose MBSR program consisted of 1 hour weekly sessions for 6 consecutive weeks with 20 minutes of daily practice. - Perceived stress, sleep quality and mindfulness assessed at baseline and at end of 6 weeks intervention. - Salivary cortisol was collected three times a day for 2 consecutive days every week for the duration of the intervention.
- Participants in the low dose MBSR group had significant reduction of perceived stress (p=.0025) and increase in mindfulness (p=.0149). - No changes in average daily salivary cortisol levels over time for participants in both groups and no differences from the pretest to the posttest were found.
- Small sample size - Psychological measures (i.e. perceived stress) only measured at baseline and end of intervention. - Wait list control group Pace, TW, Psychoneuroendocrinology, 2009 [bib_ref] Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to..., Pace [/bib_ref] - Examined the effect of compassion meditation on innate immune, neuroendocrine, and behavioral responses to psychosocial stress and examined the degree to which meditation practice influenced stress reactivity in 61 healthy adults randomized to 6 weeks of training in compassion meditation (N=33) or in a health discussion control group (N=28). - Response to TSST was measured by repeated measures of interleukin -6 (IL-6), cortisol and total distress scores on the Profile of Mood States (POMS).
- No main effect of group assignment on TSST responses was found for IL-6, cortisol, or POMS scores. - Increase meditation practice was correlated with decreased TSSTinduced IL-6 (p=.0008) and POMS distress scores (p=.014).
- Small sample size - Did not perform TSST prior to intervention -may be possible that individuals who had reduced inflammatory response to social stress may have been more willing or able to engage in meditation practice. - Those randomized to the meditation group may have had higher expectations of outcomes than those randomized to the control group. Witek-Janusek, Brain Behav Immun, 2008
- Non randomized controlled design to evaluate the effect of MBSR on immune function, quality of life, and coping in women recently diagnosed with breast cancer - Participants self-selected into the MBSR group (N=44) or control group (usual care) (N=31). - Data was collected from a cancer free group of women (N=30) for comparison of immune measures.
- Over time, women in MBSR group reestablished NKCA and cytokine production levels while women in the usual care group demonstrated continued reductions in NKCA and IFN-gamma. IL4, IL-6, and IL-10 increased. - Women in MBSR group had reduced cortisol levels and improved QOL and coping effectiveness compared to those in the usual care group.
- Small sample size - Non-randomization of participants
[formula] Carlson, LE, Brain Behav Immun, 2007(31) [/formula]
- 49 women with breast cancer and 10 men with prostate cancer were enrolled in an 8 weeks MBSR program. - Health behaviors, quality of life, mood, stress, salivary cortisol levels, immune cell counts, intracellular cytokine production, blood pressure and heart rate were assessed at baseline, post-intervention, and 6 and 12 months post intervention.
- Symptoms and stress were significantly improved after the intervention and improvements were maintained at 12 months post intervention. - Cortisol and proinflammatory cytokines decreased over follow up period - Blood pressure significantly decreased from baseline to post intervention. 
- Randomized controlled trial examining the effects of a 1month mindfulness meditation to a somatic relaxation training to a control group in 83 students.
- Both meditation and relaxation groups demonstrated improvements in mood and decreases in distress when controlling for social desirability as compared to the control group (p>.05). - Meditation group demonstrated significant pre-post decreases in distractive and ruminative thoughts compared to control group (p<.04).
- Small sample size Robert MacComb, JJ, J Altern Complement Med, 2004 (34)
- Women with documented histories of cardiovascular disease were randomly assigned to a MBSR group (N=9) or control group (N=9). - Pre-post hormonal measures and physical functioning were collected - Submaximal exercise responses were measured after the 8 weeks intervention.
- No significant main effects or interaction for resting levels of stress hormones or physical functioning, or submaximal exercise responses - Significant differences in breathing patterns (p<.01).
- Small sample size
[formula] Speca, M. Psychosomatic Medicine, 2000(35) [/formula]
- 90 outpatient cancer patients were randomized to a weekly meditation group lasting 1.5 hours or 7 weeks with home meditation practice or a wait-list control group. - Participants completed the Profile of Mood States and the Symptoms of Stress Inventory before and after the intervention
- Participants in meditation group reported significantly lower total mood disturbance and fewer overall symptoms of stress (p<.05).
- Wait list control group - Prospective Cohort study with 2 cohort of subjects with and without established CAD. - 6 weeks of yoga and meditation on hemodynamic and laboratory parameters as well as on endothelial function were studied.
- Significant reductions in blood pressure, heart rate, and BMI in the total cohort with yoga. - Design: RCT - Population: 138 hypertensive African Americans enrolled but only 60 completed post-test carotid ultrasound. - Intervention: Transcendental Meditation vs a Health Education program. TM is a mental technique practiced twice a day for 20 minutes. Initial teaching instructions conducted in both groups within 1 weeks, follow-up meetings 1 weeks later, than every 2 weeks for 2 months, and once a month for 3 months.
- Outcome: carotid intimal medial thickness (cIMT) by B-mode U/S. - Follow-up: 6-9 months (mean 6.81.3 months)
- TM group showed a significant decrease of -0.098 mm (95% CI -0. 198 to 0.003 mm) in cIMT compared with an increase of 0.054 mm (95% CI -0.05 to 0.158 mm) in the control group (P=0.038 for between group difference). - Correlation between attendance rates of meetings and change in cIMT scores was significant for TM group but not health education group - TM group also had statistically significant within-group changes in SBP, DBP, pulse and pulse pressure while health education group improved only SBP and DBP. - - TM reduced carotid atherosclerosis among African American hypertensive adults - High rate of attrition questions the generalizability of these findings. 170 participants were randomized but only 60 had completed posttest interpretable cIMT scans, although attrition was equal in both groups. - Design: RCT - Population: 28 patients with CAD - Intervention: randomized to a lifestyle intervention vs control. Lifestyle intervention included a very low fat vegetarian diet, moderate aerobic exercise, stopping smoking, stress management program (that included stretching, breathing techniques, meditation, progressive relaxation, and imagery) which they were asked to practice at least 1 hour per day, and group therapy - Outcome: Coronary atherosclerosis by quantitative coronary angiography - Follow-up: 1 yr and 5 years
- At 1 yr, 82% overall experienced some regression of their CAD. Average % diameter stenosis regressed from 40% to 38% in intervention group, yet progressed from 43% to 46% in controls. - More regression of atherosclerosis occurred at patients in the intervention group at 5 years followup than was seen at the 1 yr followup. There was a 4.5% and 7.9% relative improvement in coronary stenosis in the intervention arm at 1 and 5 years, respectively vs. 5.4% and 28% relative worsening at 1 and 5 years in control.
- A multi-modality lifestyle intervention (that includes meditation stress management as one component) confers coronary atherosclerosis regression - Small sample size. And only 20 out of 28 (71%) had 5 yr follow-up data - Intervention not blinded - Multi-modality of the lifestyle intervention limits the ability to discern the effects of mediation vs. the other components such as the extremely low fat vegetarian diet.
- Randomized study of 30 male patients with a diagnosis of coronary artery disease treated with either mindfulness based stress reduction (mindfulness meditation) consisting of 8 weekly instructional session and 30 minutes meditation daily at home or "treatment as usual" - Mindfulness based stress reduction including training in different variants of mindfulness meditation including body scan meditation, sitting meditation, mindful walking and mindful eating - All patients in both groups instructed on health behaviors including regular exercise for at least 30 minutes and suggested diet
- At the end of the intervention, for the mindfulness based stress reduction group, there were significant within group and between group decreases in anxiety, depression, perceived stress, and systolic blood pressure - At 3 month follow-up, there was a further significant reduction in blood pressure - Specific independent contribution of meditation to study findings cannot be determined
[fig] : Wait97 Healthy women aged 30-60 entered into 1 week spa retreat: 30 regular meditators and 64 non meditators (31 vacation only and 33 vacation + meditation) with post intervention 1 and 10 month follow up  Regular meditators had lower telomerase at baseline, and a significant increase in peripheral blood cell telomerase activity post treatment not observed in the other two groups. [/fig]
[fig] : Perceived stress reduced (p=.004) post intervention, Decreased pro-inflammatory gene expression (P = .009) and inflammatory signaling (P = .001) at post intervention. Intervention effects on psychological and behavioral measures not maintained at 3 month follow up. Small sample size Use of wait-list control group Levine et al. Meditation and Cardiovascular Risk Reduction: A Scientific Statement From the American Heart Association  2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. [/fig]
[table] Table 1: Common Types of Meditation [/table]
[table] Table 2: Summary of Findings on Studies of Meditations and Cardiovascular Risk Reduction* [/table]
[table] Table 3: Summary of Findings and Suggestions on Meditation and Cardiovascular Risk Reduction [/table]