DOI 10.1515/hmbci-2013-0056 Horm Mol Biol Clin Invest 2014; 18(3): 137–143
Marcia Kiyomi Koike* and Roberto Cardoso
Meditation can produce beneficial effects to prevent cardiovascular disease Abstract: Coronary heart disease is the major cause of global cardiovascular mortality and morbidity. Lifestyle behaviour contributes as a risk factor: unhealthy diet, sedentary lifestyle, tobacco, alcohol, hypertension, diabetes, dyslipidemia and psychosocial stress. Atherosclerosis pathologic mechanisms involving oxidative stress, dyslipidemia, inflammation and senescence are associated with arterial wall damage and plaque formation. Stress reduction was observed in several types of meditation. After meditation, hormonal orchestration modulates effects in the central nervous system and in the body. All types of meditation are associated with blood pressure control, enhancement in insulin resistance, reduction of lipid peroxidation and cellular senescence, independent of type of meditation. This review presents scientific evidence to explain how meditation can produce beneficial effects on the cardiovascular system, and particularly regarding vascular aspects. Keywords: atherosclerosis; meditation.
cardiovascular
disease;
*Corresponding author: Marcia Kiyomi Koike, IAMSPE, Programa de Pós-Graduação em Ciências da Saúde, Av Ibirapuera, 981, 2° andar, São Paulo, Brazil, 04029–000, Phone: +55 11 9 9964–8421, Fax: +55 11 3061–7170, E-mail: [email protected] Marcia Kiyomi Koike: Programa de Pós-graduação em Ciências da Saúde, Instituto de Assistência Médica do Servidor Publico Estadual (IAMSPE), São Paulo, Brazil; and LIM-51, Departamento de Clinica Médica, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, Brazil Roberto Cardoso: Núcleo de Medicina e Práticas Integrativas (NUMEPI), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Introduction Currently, the main causes of cardiovascular disease mortality and morbidly are coronary heart disease (CHD) and stroke. It is well known that CHD is associated with a western lifestyle, including tobacco use, unhealthy diet, irregular physical activity, abnormal lipid profile, hypertension, abdominal obesity, alcohol intake, diabetes,
and psychosocial stress [1]. Among possible strategies to manage physical and psychological stress, meditation has been proposed as an efficient and easy applicable procedure. Meditation is an ancient technique to promote modified state of consciousness and physical relaxation. Actually, the prevalent operational definition of meditation was proposed by Cardoso and collaborators [2]. They consider the procedure to be meditation when it has the following five operational parameters: (1) a specific technique clearly defined; (2) muscle relaxation somewhere during the process; (3) “logic relaxation”; (4) a self-induced state; and, (5) use of self-focus skill, termed “anchor”. A meditation technique can be classified using active (cathartic or movement), passive (concentrative or perceptive) or mixing techniques. Passive concentrative meditations are the most well-studied in medicine, and include transcendental meditation, Zazen, Zen and, Vipassana. These meditations have a specific “anchor” that permits total mental routing to a single focus, avoiding involvement with thought sequences and, getting “logic relaxation” [3]. Other meditations studied are Mindfulness, Love Kind Meditation, Raja Yoga, and QiGONG meditation. In 1971, Wallace, Benson & Wilson identified the “wakeful hypometabolic physiologic state” as the physiological condition resulting from meditation practice and characterised by the reduction of heart rate, respiratory frequency, oxygen consumption, carbon dioxide elimination and, an increase in electrodermic resistance and amplification of alpha wave intensity [4]. The wakeful hypometabolic physiologic state differs from the sleeping state [5] and it was similarly observed in different types of meditation technique [6]. Over the past four decades, physiological effects during and after long-term meditation have been demonstrated. Meditation can cause detectable effects in: 1. Central nervous system: a) activation of prefrontal cortex [7], cingulated gyrus [8], limbic system [7] and, corpus callosum [7, 8]; b) increase of secretion of inhibitory hypothalamic factors (somatostatin and dopamine) [9]; c) reduction of secretion of stimulatory factors (thyrotropin release hormone, growth hormone release factor, corticotrophin releasing hormone)
138 Koike and Cardoso: Meditation and the cardiovascular system [9]; d) Increase of secretion of beta endorphin [10], serotonin [11] and, metalonin [12]. 2. Autonomic nervous system: a) increase in heart rate variability [13], indicating activation of the parasympathetic system and reduction of activity of the sympathetic system; b) reduction of norepinephrine, epinephrine [14] and cortisol levels [15]. 3. Heart and vessels: a) reduction of arterial pressure by increasing nitric oxide [16] and, b) reduction of beta adrenergic sensibility [17]; c) reduction of vascular peripheral resistance [18]; d) reduction of aldosterone level [11]; e) reduction of lipid peroxidation levels [16]; and, f) inflammatory response [19]. We conducted this review because of the elevated incidence of cardiovascular disease and to possible further action to minimise them by meditation. This review presents recent evidence to explain beneficial effects of meditation that could prevent primordial, primary and secondarily cardiovascular disease. The review includes articles published in the last 10 years, obtained from the Medline electronic database using a combination of the following descriptors: meditation, cardiovascular disease, and atherosclerosis; and by sensitive and comprehensive searches and lateral searching including checking citations. Articles published before 2003 were considered only when related primarily to meditation. For clinical studies, we considered meditation-only techniques in agreement to operational definition [2] cited above and with well-established protocol.
Body of the review Stress is one of the most important contemporary events in global health. Cardiovascular damage is one of the main consequences. It is well known that regulation of stress response and reduction of risk factors of specific stress-decreasing approaches can be used in primordial prevention of illness and prevention of new events in cardiovascular disease. Thus, it seems clear that meditation can play an important role in this scenario, as it can be used as an approach to reduce stress hormonal response, blood pressure, insulin resistance, oxidative stress and to improve the balance of the autonomic nervous system and the immune system. In general, the biochemical changes found in meditators were the opposite to those found among chronically stressed individuals, such as better mood state, improvement of adrenal and renal functions [11].
The cardiovascular effects after meditation, such as reduction of arterial pressure and pulse, were firstly demonstrated in long-term meditators in a “meditation in groups” for 10 days by Dwivedi et al. in 1978 [20]. After the 1970s, other studies confirmed cardiovascular, respiratory, neuroendocrine and central nervous system modifications produced by meditation. In normal individuals, short-term meditation practice (5 days) has effects on neuroendocrine stress response, reducing cortisol levels [21]. As demonstrated by Walton and collaborators, transcendental long-term meditators (8.5 years) showed improvements in mood, adrenocortical activity and kidney function, with lower cortisol and aldosterone in serum, lower excretion of norepinephrine metabolite, higher dehydroepiandrosterone sulphate and serotonin metabolite [11]. Meditation may improve sleep quality because of psychological modifications [22] and increased melatonin releasing [12]. Gupta and collaborators showed improvement with healthy and happy lifestyle programmes (Mount Abu Open Heart Trial), based on principles of Raja Yoga, consisted of meditation, a vegetarian diet and, moderate aerobic exercise. All patients had CHD with angiographically documented stable coronary disease, > 50% of stenosis in at least one major epicardial artery, were included, and all participated in the 6.48-year follow-up. The authors found important health improvements (cardiovascular, metabolic and psychologic aspects), and a reduction in coronary stenosis and cardiac events. Adherence to the programme was an important aspect to benefit these patients [23]. Thus, cardiovascular disease patients may benefit from meditation. In a cohort study of 7.6 years, long-term effects of Transcendental meditation showed a decrease of 23% in primary outcome (all-cause mortality), a decrease of 30% in rate of cardiovascular mortality and a 49% decrease in rate of cancer mortality in hypertensive patients. In this study, Schneider and collaborators did not investigate the possible mechanisms involved [24]. Similarly, in another study using Transcendental meditation, the practice of meditation was effective to reduce the risk of mortality, myocardial infarction or stroke in CHD African American patients [25]. As demonstrated by Paul-Labrador and collaborators, a short-term protocol (16 weeks) promoted the reduction of systolic blood pressure, reduction of insulin resistance and increasing in heart rate variability by modulation of physiologic stress response [26]. Meditation may also balance the lipid profile. In a QiGONG meditation protocol, Lee and collaborators observed a reduction of blood pressure, total cholesterol
Koike and Cardoso: Meditation and the cardiovascular system 139
and elevation of high-density lipoprotein after 8 weeks of meditation [27]. Vyas and collaborators showed that Raja Yoga meditation, as behavioural intervention, is effective to reduce lipid profile (total and low-density lipoprotein) in pre- and post-menopausal women, with short-term (6 months to 5 years) or long-term ( > 5 years) meditation [28]. In another study, Zen meditation was effective to modulate cardiovascular risk factors, reducing lipid peroxidation caused by oxidative stress. The lipid peroxidation was estimated by tiobarbituric acid reactivity and higher nitric oxide level was estimated by measuring of nitrite and nitrate [16]. It is well known that altered lipid profile is a factor implied in vascular bed lesion. Other factors are oxidative stress and shear stress that contribute in the first event to the development of atherosclerotic plaques. Vascular bed is affected early in the structure and function in normal individuals whose parents had premature myocardial infarction: carotid media-intimae thickness is more pronounced and arterial reactivity is impaired [29]. In Transcendental meditation, reduced systolic arterial pressure was associated with reduction of peripheral resistance [18]. Moreover, vascular cell senescence has been appointed as important aspect to plaque formation. We agree that developing a translational study on in this theme would be unattainable. However, we selected interesting experimental articles for this review as presented below. The mobilisation of endothelial progenitor cells is associated with haematopoietic stem cells of bone marrow. In 2004, Landmesser and collaborators investigated statin treatment in endothelial nitric oxide synthase (eNO) knockout mice after myocardial infarction. They observed that eNO biodisponibility is mainly a mechanism to endothelial progenitor cells mobilisation, myocardial revascularisation, ventricular function, interstitial fibrosis and survival [30]. In humans, the migration capacity of endothelial progenitor cells was impaired in CHD patients, associated with ventricular dysfunction and worst ventricular remodelling [31, 32] and white blood cells (WBC) senescence [33]. In the last 10 years, shortening of WBC telomere length has been considered to be an ageing marker for conditions related to stress or chronic diseases. Telomeres are DNA sequences located at the ends of chromosomes to protect them during cellular replication. Telomere length shortens with chronological age and is shortened in people with age-related diseases such as work-related exhaustion [34], bad sleep quality in women [35], mood disorders [36], obesity [37], insulin resistance and diabetes [38, 39], osteoarthritis [40], osteoporosis [41], stroke [42], hypertension [43] and CHD [44].
An acceleration of telomere shortening in response to life stress is negatively associated with perceived stress [45]. Thus, the telomere length informs us about the biological age of an individual, and that it does not always correspond to chronological age. Differences between biological and chronological ageing may contribute to elevating the risk of cardiovascular disease and cellular senescence that participate in endothelial dysfunction and atherosclerosis. Chronologic ageing and cardiovascular risk factors are inversely related to WBC telomere length [43]. The WBC telomere length is related to a 3-fold increase in the risk of myocardial infarction occurrence [46, 47] and bone marrow dysfunction [33]. The shortening of WBC telomere length is related to the shortening of telomere length in vascular tissue. Coronary endothelial cells of CHD patients, in areas of atherosclerotic lesion, have shortened telomere length when compared to areas without lesions or patients without CHD [48]. A larger study conducted with offspring of Framingham patients showed that the shortened WBC telomere length was associated with the increase of carotid intimae-media thickness, mainly in obese men [49]. In addition, the shortening of WBC telomere length was observed in hypertensive patients [50] and in CHD patients [42], and it was associated to reduction of highdensity lipoprotein and increase of oxidative stress in diabetic CHD patients [38]. Experimental and clinical investigations indicate that stress-induced vascular senescence can be prevented by a telomere stabilising approach, such as physical exercise [51]. In the same way that physical exercise has shown a buffering effect on the senescence of immune system and vascular cells [52], meditation has shown effects on telomere length. The first study evaluating meditation (Buddhist) and telomere was conducted by Jacobs and collaborators in 2011 [53]. They demonstrated that intensive meditation training increased perceived psychological stress control and reduced neuroticism. These aspects implied in higher telomerase activity – cellular enzyme responsible to telomere length and maintenance – in WBC. Recently, Loving Kindness Meditation was associated to longer WBC telomere length in women [54]. On the one hand, this field still deserves to be explored further, as there is a lack of cohort studies to evaluate the role of meditation in the prevention of cardiovascular disease and to explain the mechanisms involved in this. On the other hand, molecular mechanisms begin to be elucidated. In higher states of consciousness of two long-term meditators (23 and 16 years of meditation), the response to stress was reduced and the genome-wide expression
140 Koike and Cardoso: Meditation and the cardiovascular system showed “general down regulation of metabolic and cell cycle processes, signalling, protein transport, regulation of gene expression, DNA repair, epigenetic mechanisms [55]. In healthy individuals, brief daily Yogic meditation modified the transcriptome related to immune system activity, reducing transcriptional via in expression of proinflammatory cytokines and innate antiviral response [56]. Bhasin and collaborators, applying a Kirtan Kriya meditation and other relaxation response approach among healthy long-term practitioners and even in novices (8 weeks), observed that relaxation response is the counterpart of the stress response by enhanced expression of genes associated with energy metabolism, mitochondrial ATP synthase, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways [57]. Another unexplored field is how meditation could affect the neuroendocrine balance in obese patients. Ghrelin is an endogenous peptide related to appetite and feeding. Ghrelin may induce weight gain not only by stimulating appetite but also by decreasing fat utilisation [58]. In experimental obesity, ghrelin level is elevated and is associated to anxiety-like behaviours. Short or longterm exercise training result in reduction of hypothalamic ghrelin in rats [59] and in humans [60]. Intravenous injection of synthetic ghrelin increased ACTH and cortisol level [61, 62] in volunteers, indicating an association of this peptide with stress conditions. The ghrelin level after exercise in humans is elevated when there is a reduction of body weight is present. Therefore, the ghrelin modulation on stress by exercise training and by meditation should be more carefully investigated. Despite these evidences, the use of meditation practice as an approach to complementary treatment of cardiovascular conditions is not as common as one would expect [63].
Expert opinion In 2005, The National Center for Complementary and Alternative Medicine (NCCAM) of National Institutes of Health (NIH), recognised meditation as an acceptable approach in the field of health. On that occasion, possible conditions to apply meditation as a therapeutic indication were presented: anxiety, pain, depression, stress, insomnia, cardiovascular disease, aids and cancer. Moreover, it was applied for mood and self-esteem, and wellness. In our opinion, considering the data presented in this review,
meditation can be a strategy to complement clinical treatment. The beneficial effects of meditation are beyond physical effects. Cognitive, memory, and mood alterations associated to reduced neuroticism can change behaviour and, consequently, improve lifestyle.
Outlook The World Health Organization has been focusing on improving the quality of life to promote health in general. Likewise, meditation can be a good way for those who adopt a western lifestyle to produce several benefits in their lives, including the reduction of cardiovascular damage. Cellular and molecular aspects must be investigated to elucidate the mechanism of how meditations act. In front of these evidences, genomic, transcriptomic, proteomic, metabolomic investigations are useful. The telomere lengths as predictor of future CHD could be considered.
Highlights –– Here we summarise the effects of meditation on physiology that could represent possible protector events to cardiovascular system. Meditation can:modulate the neuroendocrine axis, reduce stress, lower releases of cortisol and adrenaline; –– regulate the autonomic nervous system and generate reduction in blood pressure and cardiac frequency; –– reduce mortality and the risk of myocardial infarction and stroke by reducing resistance to insulin, lipid perodixation, and increase HDL; –– optimise biological age by acting on senescence mechanisms: increasing telomerase activity and preventing the shortening of telomeres of circulatory leukocytes or endothelial cells. In conclusion, among several other effects, meditation protects the neuroendocrine axis, vascular damage and senescence. Thus, for all the evidence presented, we are inclined to believe that the meditation practice may be clinically useful in primordial prevention of atherosclerosis and the secondary prevention of myocardial infarction and stroke. Received September 30, 2013; accepted April 17, 2014
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Marcia Kiyomi Koike* and Roberto Cardoso
Meditation can produce beneficial effects to prevent cardiovascular disease Abstract: Coronary heart disease is the major cause of global cardiovascular mortality and morbidity. Lifestyle behaviour contributes as a risk factor: unhealthy diet, sedentary lifestyle, tobacco, alcohol, hypertension, diabetes, dyslipidemia and psychosocial stress. Atherosclerosis pathologic mechanisms involving oxidative stress, dyslipidemia, inflammation and senescence are associated with arterial wall damage and plaque formation. Stress reduction was observed in several types of meditation. After meditation, hormonal orchestration modulates effects in the central nervous system and in the body. All types of meditation are associated with blood pressure control, enhancement in insulin resistance, reduction of lipid peroxidation and cellular senescence, independent of type of meditation. This review presents scientific evidence to explain how meditation can produce beneficial effects on the cardiovascular system, and particularly regarding vascular aspects. Keywords: atherosclerosis; meditation.
cardiovascular
disease;
*Corresponding author: Marcia Kiyomi Koike, IAMSPE, Programa de Pós-Graduação em Ciências da Saúde, Av Ibirapuera, 981, 2° andar, São Paulo, Brazil, 04029–000, Phone: +55 11 9 9964–8421, Fax: +55 11 3061–7170, E-mail: [email protected] Marcia Kiyomi Koike: Programa de Pós-graduação em Ciências da Saúde, Instituto de Assistência Médica do Servidor Publico Estadual (IAMSPE), São Paulo, Brazil; and LIM-51, Departamento de Clinica Médica, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, Brazil Roberto Cardoso: Núcleo de Medicina e Práticas Integrativas (NUMEPI), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
Introduction Currently, the main causes of cardiovascular disease mortality and morbidly are coronary heart disease (CHD) and stroke. It is well known that CHD is associated with a western lifestyle, including tobacco use, unhealthy diet, irregular physical activity, abnormal lipid profile, hypertension, abdominal obesity, alcohol intake, diabetes,
and psychosocial stress [1]. Among possible strategies to manage physical and psychological stress, meditation has been proposed as an efficient and easy applicable procedure. Meditation is an ancient technique to promote modified state of consciousness and physical relaxation. Actually, the prevalent operational definition of meditation was proposed by Cardoso and collaborators [2]. They consider the procedure to be meditation when it has the following five operational parameters: (1) a specific technique clearly defined; (2) muscle relaxation somewhere during the process; (3) “logic relaxation”; (4) a self-induced state; and, (5) use of self-focus skill, termed “anchor”. A meditation technique can be classified using active (cathartic or movement), passive (concentrative or perceptive) or mixing techniques. Passive concentrative meditations are the most well-studied in medicine, and include transcendental meditation, Zazen, Zen and, Vipassana. These meditations have a specific “anchor” that permits total mental routing to a single focus, avoiding involvement with thought sequences and, getting “logic relaxation” [3]. Other meditations studied are Mindfulness, Love Kind Meditation, Raja Yoga, and QiGONG meditation. In 1971, Wallace, Benson & Wilson identified the “wakeful hypometabolic physiologic state” as the physiological condition resulting from meditation practice and characterised by the reduction of heart rate, respiratory frequency, oxygen consumption, carbon dioxide elimination and, an increase in electrodermic resistance and amplification of alpha wave intensity [4]. The wakeful hypometabolic physiologic state differs from the sleeping state [5] and it was similarly observed in different types of meditation technique [6]. Over the past four decades, physiological effects during and after long-term meditation have been demonstrated. Meditation can cause detectable effects in: 1. Central nervous system: a) activation of prefrontal cortex [7], cingulated gyrus [8], limbic system [7] and, corpus callosum [7, 8]; b) increase of secretion of inhibitory hypothalamic factors (somatostatin and dopamine) [9]; c) reduction of secretion of stimulatory factors (thyrotropin release hormone, growth hormone release factor, corticotrophin releasing hormone)
138 Koike and Cardoso: Meditation and the cardiovascular system [9]; d) Increase of secretion of beta endorphin [10], serotonin [11] and, metalonin [12]. 2. Autonomic nervous system: a) increase in heart rate variability [13], indicating activation of the parasympathetic system and reduction of activity of the sympathetic system; b) reduction of norepinephrine, epinephrine [14] and cortisol levels [15]. 3. Heart and vessels: a) reduction of arterial pressure by increasing nitric oxide [16] and, b) reduction of beta adrenergic sensibility [17]; c) reduction of vascular peripheral resistance [18]; d) reduction of aldosterone level [11]; e) reduction of lipid peroxidation levels [16]; and, f) inflammatory response [19]. We conducted this review because of the elevated incidence of cardiovascular disease and to possible further action to minimise them by meditation. This review presents recent evidence to explain beneficial effects of meditation that could prevent primordial, primary and secondarily cardiovascular disease. The review includes articles published in the last 10 years, obtained from the Medline electronic database using a combination of the following descriptors: meditation, cardiovascular disease, and atherosclerosis; and by sensitive and comprehensive searches and lateral searching including checking citations. Articles published before 2003 were considered only when related primarily to meditation. For clinical studies, we considered meditation-only techniques in agreement to operational definition [2] cited above and with well-established protocol.
Body of the review Stress is one of the most important contemporary events in global health. Cardiovascular damage is one of the main consequences. It is well known that regulation of stress response and reduction of risk factors of specific stress-decreasing approaches can be used in primordial prevention of illness and prevention of new events in cardiovascular disease. Thus, it seems clear that meditation can play an important role in this scenario, as it can be used as an approach to reduce stress hormonal response, blood pressure, insulin resistance, oxidative stress and to improve the balance of the autonomic nervous system and the immune system. In general, the biochemical changes found in meditators were the opposite to those found among chronically stressed individuals, such as better mood state, improvement of adrenal and renal functions [11].
The cardiovascular effects after meditation, such as reduction of arterial pressure and pulse, were firstly demonstrated in long-term meditators in a “meditation in groups” for 10 days by Dwivedi et al. in 1978 [20]. After the 1970s, other studies confirmed cardiovascular, respiratory, neuroendocrine and central nervous system modifications produced by meditation. In normal individuals, short-term meditation practice (5 days) has effects on neuroendocrine stress response, reducing cortisol levels [21]. As demonstrated by Walton and collaborators, transcendental long-term meditators (8.5 years) showed improvements in mood, adrenocortical activity and kidney function, with lower cortisol and aldosterone in serum, lower excretion of norepinephrine metabolite, higher dehydroepiandrosterone sulphate and serotonin metabolite [11]. Meditation may improve sleep quality because of psychological modifications [22] and increased melatonin releasing [12]. Gupta and collaborators showed improvement with healthy and happy lifestyle programmes (Mount Abu Open Heart Trial), based on principles of Raja Yoga, consisted of meditation, a vegetarian diet and, moderate aerobic exercise. All patients had CHD with angiographically documented stable coronary disease, > 50% of stenosis in at least one major epicardial artery, were included, and all participated in the 6.48-year follow-up. The authors found important health improvements (cardiovascular, metabolic and psychologic aspects), and a reduction in coronary stenosis and cardiac events. Adherence to the programme was an important aspect to benefit these patients [23]. Thus, cardiovascular disease patients may benefit from meditation. In a cohort study of 7.6 years, long-term effects of Transcendental meditation showed a decrease of 23% in primary outcome (all-cause mortality), a decrease of 30% in rate of cardiovascular mortality and a 49% decrease in rate of cancer mortality in hypertensive patients. In this study, Schneider and collaborators did not investigate the possible mechanisms involved [24]. Similarly, in another study using Transcendental meditation, the practice of meditation was effective to reduce the risk of mortality, myocardial infarction or stroke in CHD African American patients [25]. As demonstrated by Paul-Labrador and collaborators, a short-term protocol (16 weeks) promoted the reduction of systolic blood pressure, reduction of insulin resistance and increasing in heart rate variability by modulation of physiologic stress response [26]. Meditation may also balance the lipid profile. In a QiGONG meditation protocol, Lee and collaborators observed a reduction of blood pressure, total cholesterol
Koike and Cardoso: Meditation and the cardiovascular system 139
and elevation of high-density lipoprotein after 8 weeks of meditation [27]. Vyas and collaborators showed that Raja Yoga meditation, as behavioural intervention, is effective to reduce lipid profile (total and low-density lipoprotein) in pre- and post-menopausal women, with short-term (6 months to 5 years) or long-term ( > 5 years) meditation [28]. In another study, Zen meditation was effective to modulate cardiovascular risk factors, reducing lipid peroxidation caused by oxidative stress. The lipid peroxidation was estimated by tiobarbituric acid reactivity and higher nitric oxide level was estimated by measuring of nitrite and nitrate [16]. It is well known that altered lipid profile is a factor implied in vascular bed lesion. Other factors are oxidative stress and shear stress that contribute in the first event to the development of atherosclerotic plaques. Vascular bed is affected early in the structure and function in normal individuals whose parents had premature myocardial infarction: carotid media-intimae thickness is more pronounced and arterial reactivity is impaired [29]. In Transcendental meditation, reduced systolic arterial pressure was associated with reduction of peripheral resistance [18]. Moreover, vascular cell senescence has been appointed as important aspect to plaque formation. We agree that developing a translational study on in this theme would be unattainable. However, we selected interesting experimental articles for this review as presented below. The mobilisation of endothelial progenitor cells is associated with haematopoietic stem cells of bone marrow. In 2004, Landmesser and collaborators investigated statin treatment in endothelial nitric oxide synthase (eNO) knockout mice after myocardial infarction. They observed that eNO biodisponibility is mainly a mechanism to endothelial progenitor cells mobilisation, myocardial revascularisation, ventricular function, interstitial fibrosis and survival [30]. In humans, the migration capacity of endothelial progenitor cells was impaired in CHD patients, associated with ventricular dysfunction and worst ventricular remodelling [31, 32] and white blood cells (WBC) senescence [33]. In the last 10 years, shortening of WBC telomere length has been considered to be an ageing marker for conditions related to stress or chronic diseases. Telomeres are DNA sequences located at the ends of chromosomes to protect them during cellular replication. Telomere length shortens with chronological age and is shortened in people with age-related diseases such as work-related exhaustion [34], bad sleep quality in women [35], mood disorders [36], obesity [37], insulin resistance and diabetes [38, 39], osteoarthritis [40], osteoporosis [41], stroke [42], hypertension [43] and CHD [44].
An acceleration of telomere shortening in response to life stress is negatively associated with perceived stress [45]. Thus, the telomere length informs us about the biological age of an individual, and that it does not always correspond to chronological age. Differences between biological and chronological ageing may contribute to elevating the risk of cardiovascular disease and cellular senescence that participate in endothelial dysfunction and atherosclerosis. Chronologic ageing and cardiovascular risk factors are inversely related to WBC telomere length [43]. The WBC telomere length is related to a 3-fold increase in the risk of myocardial infarction occurrence [46, 47] and bone marrow dysfunction [33]. The shortening of WBC telomere length is related to the shortening of telomere length in vascular tissue. Coronary endothelial cells of CHD patients, in areas of atherosclerotic lesion, have shortened telomere length when compared to areas without lesions or patients without CHD [48]. A larger study conducted with offspring of Framingham patients showed that the shortened WBC telomere length was associated with the increase of carotid intimae-media thickness, mainly in obese men [49]. In addition, the shortening of WBC telomere length was observed in hypertensive patients [50] and in CHD patients [42], and it was associated to reduction of highdensity lipoprotein and increase of oxidative stress in diabetic CHD patients [38]. Experimental and clinical investigations indicate that stress-induced vascular senescence can be prevented by a telomere stabilising approach, such as physical exercise [51]. In the same way that physical exercise has shown a buffering effect on the senescence of immune system and vascular cells [52], meditation has shown effects on telomere length. The first study evaluating meditation (Buddhist) and telomere was conducted by Jacobs and collaborators in 2011 [53]. They demonstrated that intensive meditation training increased perceived psychological stress control and reduced neuroticism. These aspects implied in higher telomerase activity – cellular enzyme responsible to telomere length and maintenance – in WBC. Recently, Loving Kindness Meditation was associated to longer WBC telomere length in women [54]. On the one hand, this field still deserves to be explored further, as there is a lack of cohort studies to evaluate the role of meditation in the prevention of cardiovascular disease and to explain the mechanisms involved in this. On the other hand, molecular mechanisms begin to be elucidated. In higher states of consciousness of two long-term meditators (23 and 16 years of meditation), the response to stress was reduced and the genome-wide expression
140 Koike and Cardoso: Meditation and the cardiovascular system showed “general down regulation of metabolic and cell cycle processes, signalling, protein transport, regulation of gene expression, DNA repair, epigenetic mechanisms [55]. In healthy individuals, brief daily Yogic meditation modified the transcriptome related to immune system activity, reducing transcriptional via in expression of proinflammatory cytokines and innate antiviral response [56]. Bhasin and collaborators, applying a Kirtan Kriya meditation and other relaxation response approach among healthy long-term practitioners and even in novices (8 weeks), observed that relaxation response is the counterpart of the stress response by enhanced expression of genes associated with energy metabolism, mitochondrial ATP synthase, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways [57]. Another unexplored field is how meditation could affect the neuroendocrine balance in obese patients. Ghrelin is an endogenous peptide related to appetite and feeding. Ghrelin may induce weight gain not only by stimulating appetite but also by decreasing fat utilisation [58]. In experimental obesity, ghrelin level is elevated and is associated to anxiety-like behaviours. Short or longterm exercise training result in reduction of hypothalamic ghrelin in rats [59] and in humans [60]. Intravenous injection of synthetic ghrelin increased ACTH and cortisol level [61, 62] in volunteers, indicating an association of this peptide with stress conditions. The ghrelin level after exercise in humans is elevated when there is a reduction of body weight is present. Therefore, the ghrelin modulation on stress by exercise training and by meditation should be more carefully investigated. Despite these evidences, the use of meditation practice as an approach to complementary treatment of cardiovascular conditions is not as common as one would expect [63].
Expert opinion In 2005, The National Center for Complementary and Alternative Medicine (NCCAM) of National Institutes of Health (NIH), recognised meditation as an acceptable approach in the field of health. On that occasion, possible conditions to apply meditation as a therapeutic indication were presented: anxiety, pain, depression, stress, insomnia, cardiovascular disease, aids and cancer. Moreover, it was applied for mood and self-esteem, and wellness. In our opinion, considering the data presented in this review,
meditation can be a strategy to complement clinical treatment. The beneficial effects of meditation are beyond physical effects. Cognitive, memory, and mood alterations associated to reduced neuroticism can change behaviour and, consequently, improve lifestyle.
Outlook The World Health Organization has been focusing on improving the quality of life to promote health in general. Likewise, meditation can be a good way for those who adopt a western lifestyle to produce several benefits in their lives, including the reduction of cardiovascular damage. Cellular and molecular aspects must be investigated to elucidate the mechanism of how meditations act. In front of these evidences, genomic, transcriptomic, proteomic, metabolomic investigations are useful. The telomere lengths as predictor of future CHD could be considered.
Highlights –– Here we summarise the effects of meditation on physiology that could represent possible protector events to cardiovascular system. Meditation can:modulate the neuroendocrine axis, reduce stress, lower releases of cortisol and adrenaline; –– regulate the autonomic nervous system and generate reduction in blood pressure and cardiac frequency; –– reduce mortality and the risk of myocardial infarction and stroke by reducing resistance to insulin, lipid perodixation, and increase HDL; –– optimise biological age by acting on senescence mechanisms: increasing telomerase activity and preventing the shortening of telomeres of circulatory leukocytes or endothelial cells. In conclusion, among several other effects, meditation protects the neuroendocrine axis, vascular damage and senescence. Thus, for all the evidence presented, we are inclined to believe that the meditation practice may be clinically useful in primordial prevention of atherosclerosis and the secondary prevention of myocardial infarction and stroke. Received September 30, 2013; accepted April 17, 2014
Koike and Cardoso: Meditation and the cardiovascular system 141
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