Medical, Socialogical and environmental issues in cardiovascular disease epidemiology, prevention and rehabilitation.

AYURVEDA, CHOLESTEROL AND CORONARY HEART DISEASE

Rajeev Gupta, Arvind Gupta
Monilek Hospital and Research Centre, Jaipur 302004; and Mahatma Gandhi National Institute of Medical Sciences, Jaipur 302022 India

The ancient Indian medical system of ayurveda was well developed and akin to the contemporary European medicine. For almost two thousand years there were parallel developments in field of understanding and treatment of various disorders and heart diseases. During the renaissance period, while in Europe there were tremendous developments in fields of anatomy and physiology of cardiovascular diseases, in India the developments slowed. As a consequence, the understanding of physiology of the circulation and diseases affecting the heart and the arteries were not part of mainstream Indian medicine. Ayurvedic diagnostic methods of these diseases and treatment also did not progresses as well as in conventional medicine. This tardiness could also be due to the fact that atherosclerosis and coronary heart diseases were rare in India up to the early twentieth century. Current literature of ayurveda focuses on use of pulse in diagnosis of heart diseases. Therapeutic modalities include comprehensive lifestyle change, yoga and herbo-mineral compositions. Many herbal products available in India, such as Allium sativum, Commiphora .mukul, Emblica officinalis, Terminalia arjuna, Trigonella foenum-graecum, Ocimum sanctum, Withania somnifera and Zingiber officinale, hold great promise for development and use as novel strategies in prevention and treatment of atherosclerosis and coronary heart disease. These modalities need to be scientifically evaluated using currently available research techniques.

A couplet in the Bhagwad Gita, one of the most ancient of Indian scriptures, clearly describes the virtues of healthy lifestyle in prevention of infirmity and ill-health.1 The couplet states that those who combine a balanced diet, regular physical activity, regular hours, maintain equanimity, and are balanced in thoughts and action, are away from infirmity. This couplet matches with the current recommendations for coronary artery disease prevention propounded by the World Health Organization and various international societies.2,3 Current recommendations for primordial prevention of vascular diseases include a balanced diet, regular physical activity, smoking cessation and stress management.4,5

Whether ancient Indians knew of coronary heart disease is conjectural.6 As in European civilizations, ancient Indian physicians considered that disease occurrence resulted from a mismatch of the three humors in the body (vata-air, pitta-bile and kafa-phlegm). Circulatory disorders were considered to be due to imbalance of vata or air and kapha or phlegm. Some recent authors have highlighted the fact that coronary heart disease was well known to ancient Indian sages and scholars.6,7 They have speculated that hritshoola was the name given to angina and descriptions of character of angina was well known. It has also been postulated that circulation of blood with heart as its principal reservoir and force was known to ancient Indian scientists much before the discoveries of William Harvey.

Ayurveda as a science of life emerged in the millennium BC. Charaka Samhita (compendium) and Susruta compendium are the most detailed treatises of the ayurvedic method of health promotion and treatment. These encyclopaedias are not efforts of a single author, but developed as knowledge emerged from careful observations of practitioners of ancient system of Indian medicine.8

The Charaka compendium describes the basic object of ayurveda to protect health of the healthy and to alleviate disorders of the diseased. Though all the organs and systems in the human body are given due importance in ayurveda, the heart has been given a special importance in the maintenance of life processes. Charaka compendium states that the heart specialists regard the heart as the central pivot of the body like the central pillar supporting the house, one gets fainting on its injury and death on its severe painful conditions.8 The advantages of preventive and promotional treatment have been summed as by Charaka as- from promotive treatment one attains longevity, memory, intelligence, freedom from disorder, youth, exence of lustre and voice, optimum strength of physique and sense organs, successful words, respectability and brilliance.6 Promotive treatment is the way for attaining exent life. In this review we shall concentrate on recent developments in the science of ayurveda that pertain to prevention and treatment of coronary artery disease.

The aim of the present chapter on ayurvedic text is to provide introduction to some of the ideas and preoccupations of the ancient medical tradition of ayurveda.6,8,9 There are literally hundreds of medical textbooks in Sanskrit and they all have their special reasons for existing: each includes some ideas, diseases, herbs, remedies or diagnostic techniques not mentioned by other authors.

The early medical writer, Charaka, tells us that when setting out to learn about Indian medicine we should have certain criteria in mind for choosing the text we wish to study:10

A discerning person who wants to become a physician should start by selecting a text based on a consideration of his ability to cope with hard or easy tasks, the results he is after, the likely aftermath, the place and the time. After all there are numerous physicians' manuals in circulation in the world, so he should apply himself only to a text which is used by scholars, which covers a lot of topics, and is respected by qualified people. It has to be good for pupils of all three levels of ability, and it should not be flawed by repetitiousness. It should be derived from the traditions of the saints. The connection and sequence of its text and commentary should be well organised. It should be solidly based, and have no corrupt or missing words. It should be full of significance, its ideas should follow in sequence and is should give importance to the exactness of what ideas really refer to. Its ideas should be coherent, and its topics should not be haphazard. It should communicate its meaning rapidly, and it should have both definitions and examples. This type of text is like a flawless sun: it dispels darkness and throws light on everything.

The obvious starting places in ayurvedic literature are the compendia of Charaka10 and Susruta11. These works are absolutely fundamental to ayurveda, and no selection would be complete without passages from them. These two works are traditionally taken together with a third text, the Heart of Medicine by Vagbhatta, and called the great threesome of ayurveda.8 There is a lesser threesome also consisting of the more recent books by Madhava (c. 700), Sarangdhara (c. 1300) and Bhavamisra (c. 1500). All these books contain long discourses on diagnosis and management of various diseases. There are also long pharmacological passages in all the major works which detail many, many herbal recipes, along with a well developed literature of herbal dictionaries and texts on materia medica.

The origins of classical Indian medicine, i.e., ayurveda, is shrouded in mystery. There is much earlier religious literature in India- the vedas. These texts are not about medicine as classically conceived, but about religion. They form the surviving liturgy of extremely ancient Indo-aryan ritual practices. There are parts of these texts, especially the Atharvaveda, which bear on the early history of medicine in India. However, if we look more closely at the medical ideas and practices in the early Vedic religious literature, we find that for the most part they do not form an obvious precursor to the system of classical ayurveda. Indeed, such medical literature is remarkable more for its differences from classical ayurveda rather than the similarities. For example, there is no clear mention in Vedic literature of the system of three humours or dosas, one of the centrepieces of ayurveda. It has been argued that protagonists of ayurveda who say that ayurveda is derived from the vedas is to provide social acceptance and religious sanction to this form of medicine.

At the end of the nineteenth century it was fashionable in some circles to claim that the roots of ayurveda lay in Greek medicine, but this point of view was discarded by serious researchers long time ago.9 Zysk has provided concrete evidence for the historical roots of ayurveda.12 He sees ayurveda as a medical tradition emerging from the ascetic milieu which existed in North India in fifth century BC. Zysk has found evidence in the earliest literature preserved by Buddhist monks, who were part of the milieu, which meshes almost perfectly with early ayurveda as represented by the compendia of Susruta and Charaka. The Buddhist evidence, however, is still embedded within a religious discourse.8 Thus very simply in the compendia of Charaka and Susruta which form the earliest purely medical literature in India and it is in these works that we find the first presentation of the classical system of ayurveda.

In common with many other ancient and classical Indian sciences, such as grammar, logic, and philosophy, Indian medicine has a technical vocabulary of its own. However, although there have been many attempts to plunder it to provide modern medical and scientific terminology for contemporary Indian languages, this vocabulary has not yet been the subject of an adequate systematic and historical study, and many basic questions remain unanswered.

Ayurveda is often erroneously associated with herbs only. In actual fact it has a huge canvas that includes among other things, yoga and panchkarma. Diet and digestion are the pivots on which most of the ayurvedic theories are based. The basic philosophy of ayurveda is based on the five-elements (panchmahabhoota) theory. These elements are derived from inter-play of doshas, dhatus and mala. Character of these elements is governed by dietary habits, lifestyle, environment and the mental state of the individual and ill health results due to disturbances in any of these factors. An important concept of ayurveda is that each individual is genetically different, this gives him a very specific constitution and also a very individual way of interacting with the environment. To promote health each individual must modify his lifestyle to optimise bodily functions. If for some reason illness occurs, then ayurveda describes remedies based on herbs, minerals and other therapeutic procedures such as panchkarma.

One of the bete noires of ayurvedic studies is the interpretation and translation of the word dosa. As the Sanskrit texts make clear, a dosa is a substance which flows or circulates within the body, bringing disease through excess or deficiency. The vata or 'wind' dosa is localised mainly in the large intestine, the pitta, 'bile' or 'choler' dosa is localised mainly around the navel, and the kapha or "phlegm" dosa is localised mainly in the chest. All the dosas have secondary locations too. If a dosa remains in a peaceful state, then no diseases manifest, but if a dosa builds up in one of its locations, or spreads to an area that is not its own, then illness can result.8

This account of disease aetiology is mainly a matter of displacement, rather than imbalance. Disease arises when a humoral substance collects in the wrong part of the body, and becomes irritated or inflamed. While the idea of balance is certainly present in ayurveda, the platitude that one finds repeated numbingly without exception in all secondary sources on ancient Indian medicine namely, 'disease is caused by an imbalance of the humours', is not an adequate characterisation of disease causation as described in the original ayurvedic text. The excessive focus on this statement, usually presented as the cornerstone of Indian medicine, the very essence of Indian humoral view, is a reading back into Indian medical history of Hippocratic or Galenic thinking, in the Aristotelian interpretation.9

Too much has been speculated from the present knowledge of cardiology, especially cardiovascular pharmacology, and the ancient Indian scriptures. Stephen Hawking, the famous physicist, speculates whether ancient Indians knew of the modern developments in science, especially in fields of physics, chemistry, medicine and physiology.13 He concluded that a lot of reverse speculation has been done by the modernists, scientists and philosophers, who have tried to find the current knowledge in ancient scriptures. The Indian scriptures are especially more difficult to interpret as there could be multiple meanings and interpretations of a single word. We believe that the knowledge available in the ancient Indian scriptures should be analysed keeping the time when these were written in consideration.

The Charaka compendium is the text with which classical medicine in India really begins.8,10 The physician Charaka is mentioned in Chinese texts of the late fifth century AD. The texts report that Charaka was a contemporary of Kanishka, a Buddhist king of India, living at the end of the first or second century AD. It has also been speculated that there is a strong link between Charaka's compendium and Buddhism and the current evidence places the composition of the earliest version of the compendium in third or second centuries BC.

The Charaka compendium consists of 120 chapters divided into eight parts as follows:

Each of these texts cover large divisions and the compendium is a composite work. The study of heart diseases is not a major part of the compendium possibly because this disease was uncommon in the times of Charaka, his predecessors and followers. This observation is similar to the Greek and other ancient medical sciences who also do not highlight the symptoms of coronary heart disease or atherosclerotic diseases of other organs in the body.

Charaka compendium has not described the heart and blood vessels in great detail but the importance of pulse in diagnosis of various diseases has been well described in ayurveda. Charaka's compendium described three paths of disease: the extremities, the trunk, and the junction of bones with lethal points. Heart is included in the lethal points and blood in the extremities. The ancient physicians and surgeons were aware of the network of vessels and tendons in the body. There are a number of different names for these, such as shira, dhamani, srota, nadi, snayu and kandara. There are descriptions of the heart as an important organ that controls life and afflictions of the heart, vata or kapha related, can be fatal. The heart was not considered a pump in the ayurvedic view of the body, not did the blood circulate in the post-Harveian sense. There was no concept of the contrast between the venous and the arterial circulation and several of the vessels are most commonly seen as being rooted in the navel and not in the heart. There is no description of the process of hardening of the arteries and it is difficult to speculate whether ancient Indians or Europeans knew of atherosclerosis.8,9

The Charaka compendium describes epidemics of various forms related to corrupt air, corrupt water, corrupt locale, corrupt time and corrupt rulers. These relate with the epidemic of communicable diseases as we now understand. Whether these factors were also considered important in non-communicable disease epidemic is not clear from Charaka compendium. Charaka compendium advised that people who wished to live long should have good behaviour because "life is rooted in good behaviour and death comes from the opposite".

Like Charaka's compendium, that of Susruta also is a composition that consists of several historical layers and was the work of several hands.8,11 This compendium is definitely a work before the fifth century AD and the date can be pushed further back in time, since the Indian grammarian Katyayana, roughly datable to c. 250 BC. It is possible that the seeds of this work started at this time and continued to AD 500.

The Susruta compendium consists of six large parts as follows:

Again, this is an encyclopaedic work akin the Charaka compendium. Susruta is considered the father of surgery and a major part of the compendium is devoted to this aspect.

Susruta compendium describes the importance of blood and its role in various diseases. He delves on food and describes that good food is converted in the nutritive juice or blood. It is located in the heart. There is some attempt to describe the circulation. The vital fluid (blood) enters twenty-four pipes from the heart, ten go up, ten are horizontal and ten go down. The nutritive juice flows throughout the whole body like a tiny particle, in a manner similar to the propagation of sound, light and water.8

Blood letting as a therapy has been elaborated. However, no mention of impurities of the blood and afflictions of organs such as heart or brain is mentioned. We are thus not sure whether these physicians knew of blood circulation, blood impurities in the contemporary sense, or circulation.

The Susruta compendium also described various types of winds and their afflictions. The winds are: fore-breath (prana), up-breath (udana), mid-breath (samana), intra-breath (vyana),and down-breath (apana). The intra-breath is considered to be associated with blood movement. Various disorders of the wind are discussed but a clear description of heart disease or angina is lacking. There is a description of influence of kapha or phlegm on wind. It has been described that the mixture of these two humours is dangerous and can lead to mingled diseases including chest pain and paralysis. "When the intra-breath is coupled with choler there is a burning feeling, one limbs flail about, and one feels exhausted. When the intra-breath is covered by phlegm the symptoms are a heaviness in chest and all limbs, stiff bones and joints and paralysis". This description is the closest one can get to the current definitions of angina or stroke.

There is no doubt that Vagbhata's Astangahradaya, or Heart of Medicine, is the greatest synthesis of Indian medicine ever produced. It towers over lesser works and in practice even eclipsed the ancient compendia of Charaka and Susruta.

This stands in relation to the South Asian medical tradition very much as Avicenna's Canon stands to that of the Middle East and Europe. The best current scholarship places its composition at about AD 600. The Chinese pilgrim I-Tsing, who travelled in India from AD 672-688 said that it has been composed only recently and that: "all physicians in the five parts of India practise according to this book, and any physician who is well versed in it never fails to live by the official pay". Thus Vagbhatta's work profoundly influenced the medical tradition of the whole of Asia.

Survey of medicine is the first chapter of Vagbhata's Heart of Medicine and presents the whole of ayurvedic medicine in a nutshell. Other chapters are daily regimen, seasonal regimen, the six savours, the system of humours, lethal points on the body, and insanity. Survey of medicine lists eight parts of medicine: the body, children, possession, head, arrows, scalpel, old age, and virility. These are considered the basics of science of medicine. Causes of diseases are summarised as the under-use, wrong use, or overuse of time, the objects of sense, and action, are known to be one and only cause of illness. Their proper use is one and the only cause of health. Illness is an imbalance of humours and freedom from illness in a balance of humours. He thus moved away from the Charaka's and Susruta's concept of ill-health and propounded the theory of balance of various systems.

Vagbhata's treatise has thirty chapters that form the rules section dealing with the philosophy of medicine, six sections on body and sixteen sections on aetiology of various diseases. Diabetes is included but no description of heart diseases is presented. There are twenty-two chapters on treatment and preventive care has forty chapters. Thus there are one hundred and twenty chapters divided into six sections. Heart is described as doorway to the stomach and the seat of mind and of life. It is located between the breasts, the chest, and the belly.

Sarngadhara's compendium was composed probably about AD 1300. It was very popular and remained ayurveda's major text for almost five hundred years. In the twentieth century this work has attracted increased attention from the ayurvedic pharmaceutical industry which frequently uses recipes from this work. This work is relatively short and is well organised.

Earlier treatises of medicine were very exhaustive and dealt with philosophy and observational study. In Sarngadhara's compendium the medieval Indian doctor could find for the first time a learned Sanskrit exposition of many previously undocumented medical procedures that had been creeping into his normal practice. In particular, there were verses on pulse diagnosis and the use of metals in compounds. These techniques were virtually unknown to ancient authors. Sarngadhara's compendium is also the first to mention medical uses of opium and is free with many poisons in his recipes. He recommends wolfsbane, datura, strychnine, as well as mercury, opium and cannabis.

The development of science of ayurveda was thus a dynamic process till the middle of last millennium. Newer diseases, diagnostic methods and treatment modalities were included in successive compendia. This was similar to the developments in European medical systems. However, heart diseases as separate entity was not well described and no mention of typical angina pectoris was present. The development of ayurveda slowed down after this time, possibly because of Islamic and European influences.

Eristratus in Greece about 250 BC described heart as a pump, with ingress and egress controlled by the valves. Galen of Pergamum (129-216 AD) is considered the central figure of the western tradition of medicine. He could be the European contemporary of Charaka. His book On the Causes of Pulsation provides one of the earliest descriptions of physiology of arteries and heart. He was convinced that arteries contained blood coming from the heart but opined that heart and arteries contracted simultaneously producing the pulse and resulted in imbibing vital pneuma or spirit. His views were essentially those of the medical fraternity in those times. Praxagoras and Alexandrian Greek physicians around 320 BC had initially suggested that there was a strong link between the heart, arteries, veins and illness. The Galenic views persisted till the middle-ages and examination of the pulse was considered an important part of physicians' examination. Circulation of blood and central importance of the heart and blood vessels was not discovered till the middle of the last millennium by William Harvey.

In Europe also the renaissance period showed slow development of basics of anatomy and physiology. The last achievement of renaissance anatomy was perhaps its greatest, the discovery of the circulation of blood by William Harvey in Britain. Harvey's experience in Padua (Italy) placed him at the innovative end of learned medicine, where Aristotelian ideas were challenging Galenic ones and new approaches to anatomy were being developed.9

His treatise named De Motu Cordis is brief and to the point.9 Harvey began by pointing out the inconsistencies and contradictions of Galen's view of the movement of air and blood to the heart. He wondered how mitral valve allows sooty vapours back along the pulmonary vein but not blood, and how the air and the sooty vapours are kept separate in the pulmonary vein, and he stresses that if the vein was opened only blood was found. Harvey then proceeded, more positively to demonstrate, in the anatomical sense of pointing out ot the eye, the action of auricles and the ventricles of the heart and the existence of the pulmonary transit of the blood. In later chapters of this monograph Harvey cautiously announced his discovery of the circulation of the blood. He argued that blood must move continuously in a circuit otherwise the arteries and the body would burst. The problem was to show the pathways of the circular movement. This he showed by tying an upper limb with a tourniquet and showing successive movement of blood through the artery and vein as the tourniquet is released.

All his conclusions were supported by experiments and quantitative research.14 Both were constituents of the new science of the seventeenth century which replaced the qualitative Aristotelian view of the nature by a mechanical and quantitative natural philosophy and science. For the ancient ayurvedic science, we have argued previously that the qualitative science could not mature into quantitative science due to lack of social and peer support.15

The roots16 of cardiovascular pathology and importance of atherosclerosis date to 1700's when atheroma was first identified. In 1727, Brunner described necropsy findings in aorta of a 75-year old scientist "the internal coat (of aorta) in several places was ruptured, lacerated and rotten like fruit". In 1755 von Haller studied aortic plaques. On opening into these at autopsy he found yellow mush effusing between the muscular fibers and the intima. He described this material as soft and pultaceous, not dissimilar to that seen in atheromata (from Greek athere, meaning mush or gruel). In latter half of the eighteenth century coronary arteries entered medical thought and literature with a belief that these vessels were closely associated with angina pectoris. By mid-1850's it was shown that atherosclerotic plaques consisted of cholesterol. Virchow, von Rokitansky and Anitschkow defined the ular pathology of atherosclerosis and were successful in producing experimental atherosclerosis using cholesterol-feeding in experiments.

Geographical pathology emerged as a research discipline in late 19th and early 20th century.16 A treatise by Hirsch of Berlin in late 19th century concluded that data on heart diseases around the world was practically non-existent. Awareness of atherosclerosis as pathological condition was, however, gradually increasing. In 1906, Mackenzie wrote of atherosclerosis "in recent articles on the subject there is one very important aspect which has not been considered- that is the beginning of the conditions that lead on to arteriosclerosis.17 The case is generally considered when mischief is done, and the cause can usually be attributed to an agency that suits the particular fancy of the examining medical man". In the early 1930's, Rosenthal reviewed the low prevalence of atherosclerosis in populations in Africa, Asia and Latin America and compared these with a high prevalence in Europe and USA. He inferred that "...in no race for which a high cholesterol intake and fat intake are recorded is atherosclerosis absent ... where a high protein diet is consumed, which naturally contains small quantities of cholesterol, but where the neutral fat is low, atherosclerosis is not prevalent".

Investigating geographical differences has always been the mainstay of epidemiological research.16 Anitschkow reported in 1934 that there was a significant geographical variation in frequency of atherosclerosis determined by social class and occupation. In the 1930's also, Wilhelm Raab in Vienna related geographical differences in coronary heart disease frequency to dietary differences, in particular dietary fat. The early data available on the relationship between atherosclerosis and diet were reviewed by Rosenthal in 1934 who also stressed the importance of fatty foods and excess calories in genesis of atherosclerosis and hypertension.

Cardiovascular diseases account for a large proportion of all deaths and disability worldwide. Global Burden of Disease Study18 reported that in 1990 there were 5.2 million deaths from cardiovascular diseases in economically developed countries and 9.1 million deaths from the same causes in developing countries. However, whereas about one-quarter of all cardiovascular disease deaths occurred in persons who were less than 70 years of age in the developed world, more than about half of these deaths occurred in those less than 70 years in the developing world. It has been predicted that by the year 2020 there will be an increase by almost 75% in the global cardiovascular disease burden. Almost all of this increase will occur in developing countries.19

The situation in India is more alarming. Reddy reported that mortality from cardiovascular diseases was projected to decline in the developed countries from 1970 to 2015 while it was projected to almost double in the developing countries.20,21 In the Global Burden of Diseases Study it was reported that of a total of 9.4 million deaths in India in 1990, cardiovascular diseases caused 2.3 million deaths (25%). 1.2 million deaths were due to coronary heart disease and 0.5 million due to stroke. It has been predicted that by 2020 there would be a 111% increase in cardiovascular deaths in India. This increase is much more than 77% for China, 106% for other Asian countries and 15% for economically developed countries.19

The cause for this increase of cardiovascular disease and atherosclerotic coronary heart disease (CHD) in developing countries has been described as epidemiological transition, a term initially suggested by Omran.22 At any given time different countries of the world and even parts within a country are in different phases of this transition and we classified this transition into seven phases.23

Table 1: Stages of Epidemiological Transition as Pertains to Cardiovascular Diseases

Stage of Developemnt Deaths from CVD (% of total) Predominant CVD and Risk factors Regional Example
1. Stage of pestilence and famine 5-10 Rheumatic heart disease, infection and nutritional Sub-Saharan Africa, rural India, South America
2.Age of receding pandemics 10-35 As above and hypertensive heart disease and haemorrhagic stroke China
3. Age of degenerative and man-made diseases 35-65 All forms of strokes, ischaemic heart disease at young ages, increasing obesity and diabetes Urban India, former socialist economies, aboriginalcommunities
4. Stage of delayed degenerative diseases ~ 50 Stroke and ischaemic heart disease t old age Western Europe, North America, Australia
5. Age of health regression and social upheaval 35-55 Re-emergence of deaths from ischaemic heart disease, infections, alcoholism and violence with increase in the young Russia

Yusuf et al recently reclassified the transition into 5 phases (Table 1).24 Accordingly, in the first phase of transition the predominant cardiovascular diseases are rheumatic heart diseases and other infection and nutrition related cardiovascular diseases. As the socioeconomic development takes place, in the second phase, infectious burden is reduced, nutrition improves and diseases related to hypertension become more important. With continuing change in diet, adoption of sedentary lifestyle and increasing smoking, atherosclerotic diseases increase related to cardiovascular system increase. The fourth stage is characterised by increasing public response to the epidemic in form of increased prevention efforts associated with decline in mortality. The fifth phase has been added to describe a new development in Eastern Europe where socioeconomic upheaval has been linked to increased cardiovascular mortality in these countries. Rural India is currently in between phase I and II of the epidemiological transition thus described with predominant cardiovascular disease being nutrition related, rheumatic heart disease and hypertension with a low prevalence of coronary heart disease. However, the urban India has progressed to stage II-III of this transition and there is a massive coronary heart disease epidemic. In some parts of rural and urban India transition to stage IV has occurred.

Lessons learnt from epidemiological research are important in formulating prevention guidelines.25 Prevention of CHD has become a reality following successes in high-risk populations as in Finland and USA in 1970's. Age-adjusted CHD mortality has decreased by more than 40% in the last 25 years in USA.26 This has been attributed to population-based preventive measures coupled with high-risk treatment approach employing suitable primary prevention techniques, better treatment of these conditions, and secondary prevention strategies late in the recovery phase of the illness.

Control of the predicted increase in cardiovascular diseases will require modification of risk factors that have two characteristics. First, the risk factors must have high attributable risk or high prevalence, or both. Second, most or all of the risks must be reversible cost effectively. Many of the coronary risk factors such as smoking, high cholesterol, and high blood pressure (BP) are directly associated with risks of several types of cardiovascular disease, and the associations with disease risk are continuous. Moreover, most or all of smoking, cholesterol or blood pressure related risk appears to be reversible within a few years with inexpensive interventions.

Whether ancient Indians knew CHD is conjectural. As in European civilizations, ancient Indian physicians considered that disease occurrence resulted from a mismatch of the three humors in the body (vata-air, pitta-bile and kafa-phlegm). Circulatory disorders were considered to be due to imbalance of vata or air. Some recent authors have highlighted the fact that coronary heart disease was well known to ancient Indian sages and scholars. They have speculated that hritshoola was the name given to angina and descriptions of character of angina was well known. It has also been postulated that circulation of blood with heart as its principal reservoir and force was known to ancient Indian scientists much before the discoveries of William Harvey. Although as we have discussed above all these are statements are speculative and probably not true.

The incidence of coronary heart disease in any population is associated with the relative shifts in its biological characteristics -serum lipids, blood pressure, blood glucose, insulin, thrombogenic factors and others.27 This hypothesis is based on Pickering's observation that sick individuals are just the extreme of a continuous distribution28 and Rose's postulation of sick individuals and sick populations.27 These shifts are a consequence of changes in life-styles -smoking, physical activity, alcohol intake and rich diet as well as psychosocial influences that accompany economic transition.23,25 Hence, to understand the epidemiology of coronary heart disease it is important to review the economic and related transition in India and its effect on diet and life-style.29

Whether ayurvedic therapies shall prove effective in controlling the cardiovascular disease epidemic in India and elsewhere is a moot question.30 Much more epidemiological, interventional and basic studies are needed.

Two basic tenets of ayurveda- lifestyle change and herbal supplementation could be important and need major attention in reduction of coronary risk factors. We need to identify studies that have systematically evaluated influence of these interventions on coronary risk factors.

YOGA AND MEDITATION

Yoga and techniques of meditation have been known for centuries to improve physical stamina and provide mental relaxation. Recent studies have shown than these techniques can lower systemic blood pressure, decrease resting heart rate, decrease noradrenaline production in brain and other tissues and have an indirect effect on metabolism of glucose, lipids and many neurotransmitters.31 All these factors are important in genesis of coronary artery disease. Ayurvedic techniques are presumed to cause prevention and cure of coronary heart disease . One study has shown a trend to reduction of hypertension and coronary risk.32 However as a proof, concrete scientific evidence in form of results of outcomes research should be available instead of anecdotal data or seductive theories.

Role of exercise in prevention of coronary artery disease is well defined.33 Studies have shown that exercise is useful in improving myocardial metabolism at the level of adnyl cyclase system. It also decreases platelet aggregability, normalises lipid concentrations and causes regression of atherosclerosis in experimental models. Analysis of epidemiological data has shown that there is a significant and graded relation between physical inactivity and the risk of coronary heart disease. A meta-analysis shows that there is a 90% excess coronary heart disease risk among physically inactive persons.33 Habitual physical activity is also inversely related to death from all causes. Both in primary and secondary prevention trials, the beneficial effect of exercise remains after adjusting for confounding variables. In Seven Countries Study, however, it was shown that exercise helps persons with hyperlipidemias only.34 The duration, frequency and intensity of physical activity that me be protective against coronary disease remain the issue. Recent studies show that expenditure of 150 to 300 calories per day as in walking and working around the house may be equally beneficial as moderate to severe exercise.35 Indeed severe exertion may be a risk factor for sudden death. Thus, mild physical exercise is recommended to all individuals for primary prevention of coronary heart disease. Persons of middle age and above, who are not used to exercise are advised physician guided exercise prescription.

Role of exercise in secondary prevention and regression of coronary atherosclerosis in humans is not clear.33 Exercise can lead to development of collateral channels in coronary system and retard progression of atherosclerosis.36 Studies have shown that regression of coronary atherosclerosis due to exercise may be related to decrease in cholesterol levels, increase in insulin receptors, fibrinolysis or modification of endorphin and dopamine levels. Further studies are needed to clarify this issue. We postulate that both the ancient and modern forms of yoga have substantial benefits related to mild to moderate exercise in these techniques.31

Mental stress has been known to have adverse effects on metabolism of noradrenaline, acetylcholine, lipids and glucose- insulin.37 Mental stress can also lead to abnormalities in platelet function and clotting mechanisms. All these are important in genesis and aggravation of atherosclerosclerotic coronary heart disease. Mental stress can produce electrocardiographic abnormalities and left ventricular wall motion abnormalities in persons with coronary heart disease and may be important in genesis of silent ischemia.38 It has also been shown that personality subtypes, especially type A or hostile personalities, can predispose to coronary artery disease.39 However, it is difficult to quantify mental stress, and type and amount of mental stress which causes atherosclerotic cardiovascular events is not known. Added to this is the problem that majority of stress inducing psychological tests are not standardised and fail to provide a repetitive experimental model.40

What is not known is whether mental relaxation techniques as currently available can reverse the biochemical processes induced by mental stress and whether selective techniques of Indian system of medicine to induce mental relaxation can stand the results of scientific investigation. This stems from the fact that no consistent experimental models exist to induce mental stress and test like math test or reading have a low sensitivity. The measurement of stress induced changes is also difficult and imprecise. Electrocardiography, including Holter analysis, is an insensitive tool to detect changes induced by mental stress. Presently non-invasive investigations like stress echocardiography, and radionuclide studies are being investigated for measuring mental stress induced changes on heart.40

According to Brhadaranyaka and Chhandyoga Upanishads the ultimate aim of pranayama and yogic techniques is to control life (Prana).41 This target is difficult to achieve, but mental peace and relaxation thus achieved could be used as a therapeutic tool. Studies of yoga and transcendental meditation (TM) have shown that it causes a decrease in blood pressure and pulse rate.31 This effect is seen in normal volunteers and in patients with hypertension. Patel and others in Britain have shown that meditation techniques lower blood pressure on a short term and long term basis.32 This factor may be important in primary prevention of coronary atherosclerosis. On metabolic level it causes a decrease in various biochemical inducers and aggravators of atherogenesis.42 Among the effects seen are on pulse rate, respiration, blood pressure, lean body mass, basal metabolic rate and biochemical parameters like glucose intolerance, lipids, norepinephrine and epinephrine.42,43

Clinical studies about effectiveness of yoga in coronary heart disease based on scientific randomisation protocols are lacking. And even after great effort we could not find many randomised clinical trials focussing on yoga published in peer-reviewed journals.

Lifestyle Heart Trial by Ornish et al in USA was the first randomised trial demonstrating usefulness of yoga and allied life-pattern changes in reversing atherosclerosis in patients with mild to moderate coronary artery disease.44 Aim of the study was to see whether regression of coronary atherosclerosis can occur as a result of lifestyle changes alone. The changes suggested were low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise. Stress management techniques included stretching exercises (Yogic exercises), breathing techniques (Pranayama), meditation (Dhyana), progressive relaxation (Shavasana), and imagery (Sankalpa); the purpose of these was to increase the patient's sense of relaxation, concentration and awareness. Group support was also provided to all patients to help patients adhere to lifestyle changes. Evaluation of serial coronary arteriograms was performed to evaluate efficacy. After a short follow-up period of one year it was seen that in 28 patients assigned to this programme there was a significant decline in all the major coronary risk factors. Coronary angiograms showed that, on average, lesions of more than 50% regressed by 6% whereas they increased by 3% in control group of 20 patients. Overall, a regression was seen in 82% of patients and was statistically significant.

Ornish et al also published the results of five-year follow-up of this cohort.45 In the active intervention (yoga) group the absolute average percent diameter stenosis of coronary arteries decreased by 1.75% after 1 year (a 4.5% relative improvement) and by 3.1% after 5 years (a 7.9% relative improvement). In the control group the average absolute coronary diameter increased by 2.3% after 1 year (a 5.4% relative worsening) and by11.8% after 5 years (a 27.7% relative worsening) (p=0.001). Twenty five cardiac events occurred in the yoga group patients versus 45 events in 20 control group patients during the five year follow-up (risk ratio 2.47 times).

Table 2: Influence of Yoga on Coronary Risk Factors (Manchanda et al)

Variables Control Group (n=21) Intervention Group (n=21)
  Baseline After 1 year Baseline After 1 year
Angina episodes/week 4.1±2.1 5.4±2.3 6.7±2.9 2.1±2.7*
Weight (Kg) 73±10 72±10 72±12 66±8*
Total cholesterol 237±40 236±35 257±44 203±45*
LDL cholesterol 145±30 142±27 156±33 118±30*
HDL cholesterol 38.8±4 39.8±6 40.8±6 41.3±4
Triglycerides 169±47 174±51 193±58 148±50*
Exercise duration 430±119 374±151 349±147 413±132*
Mean lesion severity (% diameter stenosis) 50.7±18 68.4±16* 62.4±14 60.9±16

* significant change

Manchanda et al46 in India studied influence of yoga and comprehensive lifestyle intervention in patients with coronary artery disease. In a prospective randomised controlled trial 42 patients were enrolled, 21 as controls and 21 in yoga intervention group. Lifestyle changes were smoking cessation, regular walking, diet control and yoga exercises included health rejuvenating exercises, breathing exercises, yogic postures for stretch relaxation, relaxation, meditation, and reflection and contemplation. After one year of follow-up there was a significant decrease in weight, total cholesterol, LDL cholesterol and triglycerides (Table 2). Progression of coronary atherosclerosis in these patients with severe coronary artery disease was evaluated by serial coronary angiograms. Coronary arteriography repeated at one year showed that significantly more lesions regressed in the yoga group as compared to controls (20% vs. 2%), and less lesions progressed (5% vs. 37%). Yoga group subjects also required less revascularisation procedures.

Although these small studies have revealed interesting conclusions, the results need to be substantiated by larger studies.47 Similar studies with various non-invasive and invasive parameters of coronary heart disease need to be performed to substantiate the role of yoga and Indian style of living. These studies would include epidemiological, hemorheological, experimental and clinical investigations in field of coronary heart disease.

All the pharmacoepias of ayurveda contain large number of herbal preparations. Ayurvedic texts are rife with large number of herbal preparations that can be safely and successfully used for treatment of chronic disorders.48 Use of herbal medicines is widespread all over the world.49

Initial compendia of Charaka, Susruta and Vagbhata did not highlight herb based therapies. Anyway, the definition of heart diseases, especially the process of atherosclerosis was inadequate in these compendia and to derive substantial conclusions for usefulness of ayurvedic herbo-mineral preparations in coronary atherosclerosis or coronary artery disease from these texts is not justified.

Large number of substances are highlighted for control of phlegm- or wind-related diseases. The Bower manuscript (Yasomitra manuscript) that dates to about AD 400-500 is the first treatise that highlights medicinal uses of garlic.8,12 Vagbhata says of garlic that:

It is very sharply hot and has the pungent savour. It is penetrating, cordial, it helps one's hair grow, and is a powerful aphrodisiac. It is smooth, appetising and digestive. It helps fractures to heal up, it increases strength, and it inflames blood and bile. It destroys vitiligo, pallid skin disease, abdominal lumps, piles, urinary disorder, worms, phlegm, and wind. It also cues hiccups, catarrh, wheezing, and cough. It is also a rejuvenant.

A variety of garlic based recipes are given in the texts. These include, garlic juice recipe, crushed garlic recipe, fried garlic recipe, garlic and meat recipe, garlic and barley balls, stewed juice of garlic, and garlic cough paste. Later day ayurvedic texts, especially in the last years of nineteenth century and the twentieth century are more specific regarding diagnosis and treatment of heart diseases. These, however, appear to be subsequent addition to the ancient texts.

According to the ayurvedic texts, a mere collection of herbs does not constitute an ayurvedic remedy. A herbal product containing the same ingredients as an ayurvedic product may not deliver the same degree of safety and efficacy, as ayurveda prescribes specific processing that enhances both safety and efficacy. This sentence summarises the essential difference between herbal and ayurvedic medicine. According to the later-date ayurvedic manuscripts, a particular composition and complicated processing characteristics of an ayurvedic remedy aim at achieving comprehensive treatment with no side effects.48

The principles of treatment for various diseases and ailments have been precisely laid out in ayurvedic text. They involve formulation of various herbs and minerals in precise proportions with specific processing methods. A careful choice of the right plant is followed by prudent selection of the parts to be processed, i.e., the leaves, seeds, stem, bark or roots. Each step is vital and may cause unsatisfactory pharmacological results when not executed with care.

Table 3: Cardiovascular Active Herbs Mentioned in Ayurvedic Texts

Various plants have been mentioned in ayurvedic texts to have importance cardiovascular effects, in alphabetic order, are shown in Table 3.50 A large number of Indian ayurvedic preparations contain all of these herbal medications or a combination of these. Single herb formulations are also available in the market. A large benefit in reducing cardiovascular risks is attributed to these herbs and many articles listing benefits have been published in peer-reviewed and other journals. To separate grain from chaff is difficult. Most of these studies have been small, single-centre based, and performed on animals and humans. Large prospective randomised controlled trials are lacking.51,52

Notable among plants studied for cardiovascular benefits and in reducing atherosclerotic risks are Terminalia arjuna, Commiphora .mukul, Allium sativum, Emblica officinalis, Trigonella foenum-graecum, Ocimum sanctum, Withania somnifera and Zingiber officinale (Table 4).30,50 A brief account of these plants and a summary of their clinical activities are given below.

Table 4: Cardiovascular Effects of Selected Herbs

Plants Effects Observed
Allium sativum Fibrinolytic, antithrombotic, inhibits platelet aggregation, reduces release of arachidonic acid, reduces thromboxane production, prolongsbleeding time, hypolipidemic in healthy as well as CAD subjects, hypoglycemic, diuretic, and antioxidant.
Commiphora mukul Increases coagulationand prothrombin time in hyperlipidemic subjects, increases fibrinolysis, decreases platelet adhesion, prolongs clotting time, hypocholesterolemic, raises HDL cholesterol, reduces weight, resolves xanthomas, antioxidant.
Emblica officinalis Diuretic, antioxidant, hypolipidemic, and cytoprotective.
Ocimum sanctum Hypotensive and cardiac depressant activity, hypoglycemic, antistress, hypolipidemic, anti-inflammatory.
Terminalia arjuna Diuretic, anti-anginal, improves congestive heartfailure, antioxidant, prolongs prothrombin time, enhances PGE2 like activity, inhibits platelet aggregation, antihypertensive, hypocholesterolemic and HDL raising effect.
Trigonella foenum-graecum Hypoglycemic, hypocholesterolemic, hypotriacylglycerolemic.

It is a perennial evergreen plant found in abundance throughout Indian subcontinent mainly in sub-himalayan tracts of Uttar Pradesh, South Bihar, Madhya Pradesh, Delhi and Deccan region. It is also found in forests of Sri Lanka, Burma and Mauritius. It belongs to Combretaceae family and is a large deciduous tree with buttrressed trunk and spreading crown with drooping branches attaining a height of upto 20 metres. Its bark is used as medicine since 600 BC and it is mentioned in both Charaka and Susruta compendia. Vagbhata for the first time indicated its usefulness in treating heart diseases. The main constituents of its bark stem powder include glycosides viz. arjunine, arjunetin, arjunoside-1, arjunoside-2, triterpeno-glycoside, bioflavonoids and minerals such as calcium, magnesium, zinc and copper.50

It was Chaturvedi who first reported that alcoholic decoction of this drug significantly increases euglobulin lysis time, prolongs prothrombin time and lowers serum cholesterol levels in coronary aretry disease patients.53 It also inhibits platelet aggregation. Further, intravenous administration of Terminalia arjuna extract in experimental animals led to dose dependent decrease in blood pressure and heart rate which was considered to be centrally mediated. It has also been demonstrated to posses antihypertensive and antiarrhythmic activity.54

In an experimental study, hypercholesterolemic rabbits receiving Terminalia arjuna treatment showed more marked reduction in total cholesterol and triglycerides and elevation in HDL-cholesterol than hypercholesterolemic control rabbits.54-56 Administration of aqueous extracts of Terminalia arjuna produced marked fall in cholesterol levels associated with decreased aortic and tissue atherosclerosis.54 In addition to its anti-ischaemia and lipid lowering effects it also possesses antioxidant effects.57 Its antioxidant property may be beneficial in reducing LDL oxidation. Anti-oxidant benefits have also been demonstrated in a randomised controlled trial in patients with coronary artery disease.58

Powdered stem bark of Terminalia arjuna was found to modify various known coronary risk factors like obesity, hypertension, diabetes mellitus and circulating catecholamines.55 In a double blind study of rheumatic heart disease patients with congestive heart failure, administration of Terminalia arjuna, 500 mg 8 hourly, resulted in significant improvement of exercise duration (89±44 seconds to 179±6 seconds), left ventricular ejection fraction (41.5+91% to 54.5+12%) and decrease in heart size.59 The effect of Terminalia arjuna in 15 stable cases of angina were found to reduce the intensity and frequency of angina pectoris and improved effort tolerance.60 The drug lowered systolic blood pressure and body mass index and increased HDL-cholesterol. Same group of workers reported the beneficial effects of Terminalia arjuna in stable angina patients using treadmill and echocardiographic parameters wherein improvement in tolerance of exercise, blood pressure response and left ventricular ejection fraction was observed after 4 weeks of therapy.61

More recently Dwivedi et al studied the effect of Terminalia arjuna on anginal frequency, left ventricular ejection fraction (LVEF) and left ventricular mass in coronary artery disease patients.61 A significant reduction in anginal frequency (3.5±2.0 to 1.1±1.1), improvement in LVEF (42.3±10% to 52.7±12%) and reduction in left ventricular mass (159 gm/m2±56 to 141±56 gm/m2) following 3 months of adjuvant Terminalia arjuna therapy was reported. In various clinical studies, Terminalia arjuna was used in the dose of 1-2g per day which has been found to be the optimum dose in patients of coronary artery disease. At this dosage it is well-tolerated. However, some patients complain of mild gastritis, headache and constipation. No metabolic, renal and hepatic toxicity has been reported even when patients were administered Terminalia arjuna for more than 24 months.

The anti-anginal activity of Terminalia arjuna coupled with enhancement of prostaglandin E2 like activity, negative chronotropic, anti-arrhythmic, anti-hypertensive, hypolipidemic, HDL cholesterol raising, and antioxidant properties and its potential to improve LVEF and reduce left ventricular mass makes it eminently cardioprotective drug in overall management of coronary artery disease.50,55

Commiphora mukul also known as Indian bdellium tree and is distributed in rocky tracts of Rajasthan, Gujarat, Mysore, Sindh and Baluchistan in South Asia. It is a small armed tree with spinescent branches and ash-colored rough branches. The guggul of commerce is the pale yellow or brown aromatic gum resin obtained from the bark. The gum resin consists of irregular roundish masses of varying sizes. It is opaque, reddish brown in color and has a dusty surface. A number of studies on hypocholestrolemic properties of this resin have emanated from Central Drug Research Institute, Lucknow.30,62

The active alkaloid in Commiphora mukul has been identified as guggulsterone.63 It has a significant cholesterol and triglyceride reducing effect. A multi-centre controlled clinical trial reported that the cholesterol lowering efficacy is mild to moderate.64,65 It has been released for clinical use in India but is not very popular.

Emblica officinalis belongs to Euphorbuiaceae family. It is small or middle sized deciduous tree. Leaves are small, closely set in pinnate fashion, branchlets look rather feathery in general appearance. Fruits are small 1.5-2.5 cm in diameter, fleshy, roundish, rather indistinctly marked into six lobes, pale green or yellowish. The plant occurs throughout tropical and subtropical India; it is found abundantly in deciduous forests of Madhya Pradesh. Though all of its parts including dried fruit seeds, leaves, root, bark and flowers are used for medicinal purposes, mostly its dried fruit seeds have been in use for therapeutic purposes. The fruits are one of the three constituents of the well-known Indian preparation triphala. Flowers, root and bark of the tree are also used for medicinal purposes.30

Emblica officinalis is very rich in vitamin C. Vitamin C has been claimed to possess antioxidant and hypolipidemic property. It has been found to reduce serum total cholesterol, aortic cholesterol and hepatic cholesterol significantly, without any effect on serum triglyceride levels in both normal and cholesterol induced hypercholesterolemic rabbits.66 The effect of Emblica officinalis on total serum cholesterol and its lipoprotein fraction was also studied In normal and hypercholesterolemic men aged 35-55 years.67 The supplement was given for a period of 28 days in the raw form. Both the normal and hypercholesterolemic subjects showed a decrease in cholesterol levels. Two weeks after withdrawing the supplement, the total serum cholesterol levels rose significantly almost to initial levels. Dietary administration of a crude aqueous extract of Emblica officinalis fruit reduced significantly the cytotoxic effects of sodium arsenite administered orally to Swiss albino mice.68

Ocimum sanctum commonly known as tulsee belongs to Lamiaceae family. It is a much branched erect herb, up to 75 cm high, hairy all over. Its leaves seeds and roots are used for medicinal purposes. It is found throughout India upto an altitude of 1,800 meters in the Himalayas. Gas liquid chromatography of the essential oil of Ocimum sanctum yields eugenol (76%) as major constituent, besides methyl eugenol, caryophylline, calcium, phosphorus and insoluble oxalate.30

Crude watery extract of Ocimum sanctum leaves shows transient hypotensive effect in anesthetized dogs and cats and negative inotropic and chronotropic effect on rabbit heart.69 Ocimum sanctum is said to possess hypotensive and anti-stress activity as well as lipid lowering activity in rabbits.70-72 Anti-inflammatory and anti-thrombotic properties of an alcoholic extract of basil leaves have been reported.73

Trigonella foenum-graecum (fenugreek) is an annual herb widely used for culinary and medicinal purposes for centuries in many parts of the world. Its seeds, whose name has appeared in Greek and Latin pharmacopoeias, are reported to have anti-diabetic activity.8,9

Uses of Trigonella foenum-graecum leaves and seeds in traditional medicine include as hypoglycemic, as appetite stimulant, tonic, reconstituent, laxative, emollient, blood cleanser and against aortic palpitation.30 Seeds are known to exhibit hypoglycemic activity when taken orally.74,75 The hypoglycemic effect of seeds, and the major alkaloid Trigonelline was first described by Fournier and Nadkarni.30 Ajabnoor and Tilmisany74 reported the hypoglycemic effect of its seeds on the serum glucose level. Intraperitoneal administration of water extract of leaves produced a statistically significant decrease in blood glucose concentration for both normoglycemic and alloxan-induced hyperglycemic rats.74 According to the same group of workers, oral administration of the extract produced a statistically significant decrease in blood glucose levels only in the hyperglycemic rat.74 Alloxan treated animals receiving the aqueous extract of leaves showed rapid normalization of blood glucose levels in comparison to the control and this could possibly be due to still surviving B-cells and their possible regeneration.

In addition to its lipid lowering and hypoglycemic activities there are few reports indicating its antioxidant properties. Pre-treatment with Trigonella foenum-graecum seeds in alloxan induced diabetic rats prevented rise in blood lipid peroxidation in addition to lowering down of sugar to a near normal level.76 The intensity of peroxidative damage was also reduced as indicated by reduction in thio-barbituric acid reactivity.76

Studies on clinical uses of Trigonella in coronary artery disease and atherosclerosis are limited. Ganguly et al77 reported beneficial effects in dyslipidaemia associated with coronary artery disease and Gupta et al78 reported usefulness of this drug in mitigating insulin resistance and important component of coronary artery disease in Indians.79

Withania somnifera belongs to family Solanaceae. This is a small or medium sized shrub up to 1.5 meters high. Stem and branches are covered with minute star shaped hairs. The plant occurs in drier regions of India. The dried root of the plant is used for medicinal purposes. Its roots possesses diuretic activities. It acts as an anti-stress, adaptogen and also possesses its hypotensive and cardiotonic properties. Fruits of this plant has been found to have adaptogenic (anti-chronic stress) activity in Wistar rats on behavioral, physiological, immunological and biochemical perturbations, qualitatively similar to those exhibited by Panax ginseng. It has also been found to possess antioxidant properties.30 In a study, a combination of Terminalia arjuna, Ocimum sanctum, Withania somnifera and Boerhavia diffusa was effective in reducing the clinical manifestations of stable angina pectoris and 75% reduction in sublingual isosorbide dinitrate use in treadmill-positive coronary artery disease cases. No significant side effects were observed after 60 days treatment with this combination.80

Dried ginger powder 500-1000 mg, or fresh ginger, 2-4 gm, is used for nausea. Ginger's alleged vitalizing effect on the heart and blood is attributed to decreased platelet aggregation and inhibition of thromboxane synthesis observed in in vitro studies. In vitro antiplatelet activity varies by form (dried, raw, cooked or extract).50,80 Clinical studies, however, using raw, cooked or dried ginger do not shown an effect on bleeding time, platelet aggregation or thromboxane production.80 Compounds isolated form ginger including shogaol and gingerol have been studied for positive inotropic and pressor effects; however, no clinical trials currently support these effects. Neither adverse effects not drug interactions have been reported.

A compendium of Indian medicinal plants published from Arya Vaidya Sala in Kottakkal, Kerala has described properties and uses of 500 plants found in India.81 Cardiovascular benefits have been described for more than 300 of these. Detailed mechanisms of action of the plants in providing cardiovascular benefits are not reported. Thus it is difficult to critically evaluate the cardiovascular friendly herbs and plant materials. Many other plants and herbs have been evaluated for cardiovascular beneficial properties. Many have undergone animal experiments and some small clinical trials.

Critical evaluation of these plants and their exact role in primary and secondary prevention of atherosclerotic cardiovascular disorder needs to be explored in double blind randomized clinical trials in multicentric studies. Recently, both Indian Council of Medical Research and Department of Indian Systems of Medicine has initiated some studies on Terminalia arjuna, Emblica officinalis, Inula racemosa, and N. jatamanshi. Till the results of these studies are available to us it is prudent to include Terminalia arjuna, Trigonella foenum-graecum, Ocimum sanctum and Emblica officinalis in our armamentarium and harness their cardiovascular beneficial effects on the basis of studies made so far.

The use of herbal therapies is escalating in the US and other developed countries49 and there has been a recent focus on benefits and harms of these preparations. Most of the ayurvedic herbs are not available in India and these herbs have not been extensively investigated there. Valli and Giardina recently reviewed the benefits, adverse effects and drug interactions of herbal therapies with cardiovascular effects available in the USA.82

In USA and almost all the countries of the world herbal products are marketed without proof of efficacy or safety that is required of conventional drugs. In the USA, the Dietary Supplement and Health Education Act of 1994 assigns responsibility for ensuring safety and efficacy to manufacturers with no requirement to submit documentation of product testing. It also does not set standards for quality control nor require approval before supplements enter the market. Manufacturers may not make claims for treatment or cure of a disease but may state a product's physiologic effects. Consumers have little information to make decisions about safety, adverse effects, contraindications, interactions or effectiveness and must rely on manufacturers to provide ingredients that are accurately labelled. Many herbal remedies cannot be patented, and manufacturers do not expect to recoup the estimated $ 350 million to confirm safety and efficacy. The National Centre for Complementary and Alternative Medicine, established in 1998 at the National Institutes of Health, is mandated to conduct and advocate research into complementary medicines and techniques.

Several herbs offer potential for cardiovascular conditions including venous insufficiency, intermittent claudication, hyperlipidemia, hypertension and congestive heart failure in the US (Table 6).49 Varying mechanisms, including antioxidant, antiplatelet, fibrinolytic, antiatherosclerostic, antihyperlipidemia, antiarrhythmic, and vasodilatory actions, are ascribed to herbs.83 Data from epidemiological studies support the potential of dietary antioxidants and flavonoids present in several herbs to improve cardiovascular health.84 To date however, clinical trials with antioxidants such as vitamin E, vitamin A and beta-carotene failed to show any clinical benefit.85,86 Herbal remedies may induce adverse cardiac effects including sympathomimetic activity, hypertension and arrhythmias (Table 5).87 Many interfere with platelet function and patients at risk for bleeding or taking antiplatelet drugs should be cautioned about specific herbs.83 Physicians must be attuned to interactions between herbs and drugs with a narrow therapeutic window, such as warfarain and digoxin.

Table 6: Herbs for Cardiovascular Indications Commonly Available in USA

Herb Indication Evidence Comments
Garlic Hyperlipidemia
Hypertension
Atherosclerosis
Claudication
RCT
RCT
RCT
RCT
Reduces serum cholesterol 5-15%.
Weak evidence for modest effect
Single-trial evidence
No significant improvement.
Gingko Cerebrovascular
Claudication
Anti-oxidation
RCT
RCT
RCT
Conflicting evidence.
Modest improvement in walking.
Experimental evidence, no clinical difference
Ginseng Heart failure
Hypertension
NBNRCT
NBNRCT
Improvement in cardiac function.
Small improvements in systolic BP. Hypertensive effects also described.
Hawthorn Heart failure RCT Improvement in symptoms of fatigue and measures of cardiac function. Large trials under way

RCT: randomised controlled clinical trial. NBNRCT: Trials that were not blinded or placebo-controlled

Adverse effect data is almost exclusively available as case-reports, and as a result may be vastly underreported. Lack of regulation and quality control and of product standardization makes it difficult to establish safe doses of herbal products. Active compounds may vary 200-fold between manufacturers and batches. Additives and contaminants including caffeine, indomethacin, and heavy metals such as lead, mercury and arsenic have been found in herbal remedies.88 Misidentification of plants has led to serious adverse events including renal failure. Considering that the growing appeal of herbal remedies is likely to continue, physicians, particularly cardiologists, must become familiar with available cardiovascular information on herbs.49,82

Garlic has been described in ancient Indian ayurvedic literature as a very useful plant.8 Current research has shown multiple benefits of garlic.49,80 It is believed to thin the blood, reduce cholesterol , decrease blood pressure, inhibit atherosclerosis and improve circulation. Randomised clinical trials have been conducted for antihypertensive, antiatherosclerostic and antiplatelet action, and intermittent claudication. A recent summary of the data supporting garlic's potential in modifying cardiovascular risks, while generally supporting its usefulness, also emphasize a lack of knowledge about active compounds and mechanisms of action.89 Though garlic is believed to be beneficial for conditions for which approved drugs are available, such as hyperlipidemia90 and hypertension91 few studies compare it to pharmacological treatments.92

Studies of garlic are plagued by methodological problems related to active compounds. The active substance is allicin, formed by the action of alliinase on alliin when garlic is crushed. Alliinase is activated by acid pH, heat and extraction inorganic solvents. Thus garlic's effects are dependent on whether it is cooked in aqueous, oil or organic extracts. In addition to allicin, other active compounds ingarlic include methy allyl trisulfide, diallyl trisulfide, diallyl disulfide, and ajoene. Its characteristic odour is associated with the active compounds, which limits blinding in clinical trials. Most studies use commercially available dried garlic powder standardised for allicin content, in doses of 300-900 mg/day. However, even standardised products may yield different qualities of allicin owing to differences in tablet composition. Few trials indicate whether placebo could be differentiated form active treatment.82

Garlic is generally safe and well tolerated; however, serous adverse events including central nervous system bleeding and skin burns from topical application, have been reported. Effects such as flatulence, dyspepsia, allergic dermatitis, and asthma have been described. Increases in the prothrombin time in subjects previously stable on warfarin have been attributed to garlic; however, there is little to substantiate the mechanism of the interaction.

The antihyperlipidemic efect of garlic has been extensively studied.89-94 Early trials lacked controls, adequate blinding and dietary monitoring; they were underpowered or did not analyze results based on intention to treat. Recent trials have produced negative findings, possibly resulting from preparations with reduced bioavailability of allicin. Several meta-analyses have summarized data from clinical trials. Each has used different inclusion criteria, yet the results are consistent across analyses: garlic modestly reduces lipids 15 to 25 mg/dl (5% to 15%). The earliest rneta-analyses included studies with deficiencies. Warshafsky et al93 reported a reduction in serum cholesterol of 23 mg/dl (-9% from baseline). Silagy and Neil94 reported lipid reduction of 12% and provided a subgroup analysis of trials that utilized non-powder forms (i.e., raw, oil or extract). Lipids were reduced by 15% in this subgroup; however, three of five studies were not double-blind and two were not placebo-controlled. Stevinson et al95 selected only randomized, placebo-controlled trials of hypercholesterolemic subjects and reported a reduction of only 15.7 mg/dl (4% to 6% reduction).

Most recently, Ackermann et al89 reported a comprehensive meta-analysis of garlic trials showing a reduction in cholesterol of 17 mg/dl. Subgroup analyses of trials including only hyperlipidemic subjects and double-blind trials did not differ. In contrast to Silagy and Neil94 subgroup analysis of trials employing standardized dried garlic powder preparations showed a slightly improved reduction in cholesterol of 19 mg/dl. This analysis also reported a dose duration effect of garlic. A trial of garlic versus a fibrate drug for hyperlipidemia reported similar efficacy.96 Treatment with dried garlic powder tablets (900 mg/day) reduced total serum cholesterol levels from 282 mg/dl to 210 mg/dl over 12 weeks while bezafibrate (600 mg/day) reduced cholesterol from 287 mg/dl to 208 mg/dl. Both treatments produced parallel reductions in low-density lipoprotein (LDL) and increases in high-density lipoprotein (HDL) cholesterol. There was a trend toward greater reduction in serum triglycerides with bezafibrate (42% vs. 29%).

In vitro evidence suggests garlic reduces blood pressure by inhibiting platelet nitric oxide synthase.97 Many clinical trials, however, find no significant antihypertensive effect despite form, dose or duration of treatment. Studies evaluating hypertensive subjects report a modest reduction in diastolic pressure.98 A small, open-label trial reported that large doses of garlic powder (2,400 mg) lowered blood pressure 7/16 mm Hg. Only the diastolic pressure decreased significantly. In a placebo-controlled trial only the diastolic pressure decrease (13 mm Hg) was significant. A meta-analysis reported a modest systolic blood pressure reduction of 7.7 mm Hg and diastolic reduction of 5.0 mm Hg, but only two trials involved hypertensive subjects.98

Blood-thinning properties are attributed to enhanced fibrinolytic and antiplatelet activity.80 There is no consensus as to the mechanism of fibrinolytic activity. In vitro and animal studies support several mechanisms for garlic's antiplatelet effects. Diallyl disuffide and diallyl trisulfiide inhibit thromboxane synthesis, possibly by inhibiting phospholipase-A and mobilizing arachidonic acid. Extract of raw garlic contains compounds that inhibit cyclooxygenase and ajoene, a compound in alcohol extracts of garlic, may inhibit binding of fibrinogen to pIatelet receptors.99,100,101

Garlic's anticoagulant properties have been linked to reports of bleeding, however, clinical trials find conflicting results. Dried garlic powder decreased platelet aggregation in three controlled trials. Several trials describe increased fibrinolytic activity, and two report elevation of tissue plasminogen activator. However a trial using garlic powder in patients with hyperlipoproteinemia found no change in bleeding time, fibrin split products or lysis time.99

The antiatherosclerotic activity of garlic is attributed to cholesterol lowering, but in vitro and animal studies also have been linked to clinical trials also support effects independent of lipid levels, possibly by inhibition of lipid peroxidation.102 Modest benefits in atherosclerotic conditions has been reported. Garlic administered for 48 months reduced atherosclerotic plaque at the femoral artery or carotid bifurcation by 5% to 18%, however, 23% subjects taking garlic versus 3% on placebo withdrew from the study due to odor.

A large number of herbs, mainly reported in Chinese literature have been investigated in US for cardiovascular benefits.82 These are not ayurvedic herbs, nor are these present in Indian subcontinent and hence not discussed. Salvia miltiorrhiza (danshen) is used for promotion of blood flow and treat cardiovascular disorders. It is administered in Chinese hospitals for angina and acute myocardial infarction. The active compounds are tanshinones and phenoliccompounds. Panax (ginseng) refers to roots of Panax species. Ginseng is believed to promote vigor, potency, well being and longevity. In China it is used for angina pectoris, myocardial infarction and congestive heart failure. Crataegus species (Hawthorn). This shrub is native to North America and Europe. This has been used in congestive heart failure and proposed mechanisms of action include antioxidant, inotropic, vasodilatory and antihypertensive actions. Aesculus hippocastanum (horse chestnut seed) has been approved for venous insufficiency. The active compound, aescin, is a mixture of triterpene glycosides. Ephedra sinica (Ma huang) is a natural source of ephedrine and has potent sympathomimetic activity. It is a constituent of herbal remedies and soft drinks for weight loss and a large number of cases of adverse events with this herb have been reported (Table 6).

The growing of herbal remedies all over the world has far exceeded the increase in available information on their benefits, adverse effects and drug interactions (Table 7).49,82 Coherent, easily accessible data on remedies is lacking. Although there is little existing data comparing herbal therapy to approve drugs, major trials are under way and the SPICE trial in USA is a landmark investigation of comparison of a herbal remedy with standard therapy.

With only modest evidence-based data, physicians may opt to put off interactive questions or refrain from prescribing herbal remedies. Considering that the escalating appeal of herbal remedies is likely to continue, such a stance is impractical and potentially risky for patients. Rather, another option is that physicians and other health-care providers become familiar with the data and advocate for greater research and access to information.

Table 6: Herbs with Adverse Cardiovascular Effects

Herb Adverse Effect Comments
Belladonna Tachycardia Herbal source of atropine
Feverfew Platelet dysfunction In vitro evidence of platelet antagonism not supported in clinical trials
Garlic Increased bleeding tendency Case reports of hemorrhage. In vitro evidence of platelet dysfunction but conflicting anti-platelet and fibrinolytic activity in clinical trials.
Ginger Platelet dysfunction
Hypertension
Conflicting results in human trials.
Animal studies report pressor effect.
Ginkgo Increased bleeding tendency, platelet dysfunction Case reports of cerebral hemorrhage, pharmacological evidence of platelet antagonism
Ginseng Hypertension An abuse syndrome involving hypertension is described in chronic users.
Hellebore Hypotension, bradycardia Accidental ingestion
Kava Platelet dysfunction Limited in vitro evidence
Licorice Hypertension, pulmonary edema, cardiomyopathy Decreased inactivation of cortisol causing symptoms of mineralocorticoid excess.
Ma huang Stroke, myocardial infarction, arrhythmia, hypertension Numerous case reports of adverse effects.
Oleander Arrhythmia Cardiac glycosides cause symptoms similar to digitalis toxicity.
Yohimbine Hypertension, arrhythmia Increases norepinephrine levels and central sympathetic outflow.

Table 7: Important Cardiovascular Drug Interactions

Drug Herb
Warfarin Danshen, garlic, gingko, ginseng
Antiplatelet drugs (NSAIDs, ticlopidine, others) Dong quai, feverfew, garlic, ginger, gingko
Digitalis Kava, hawthorne, herbal laxatives, oleander, St. John's wort, Siberian ginseng
Clonidine Yohimbine
Tricyclic antidepressants Yohimbine
Methysergide, other serotonin antagonists Feverfew

What is there about ayurveda and other forms of alternative medicine that sets them apart from ordinary medicine? An editorial in the New England Journal summarizes the conflict. 103 The term refers to a remarkably heterogeneous group of theories and practices, as disparate as homeopathy, therapeutic touch, imagery, and herbal medicine. What unites them?

Eisenberg et al104. defined alternative medicine (now often called complementary medicine) as "medical interventions not taught widely at the medical schools or generally available at hospitals." That is not a very satisfactory definition, especially since many alternative remedies have recently found their way into the medical mainstream. In India and many developing countries of Asia and Africa there is a widespread use of herbal preparations in almost all diseases.

What most sets different forms of alternative medicine apart is that it has not been scientifically tested52,105 and its advocates largely deny the need for such testing. By testing, we mean the marshaling of rigorous evidence of safety and efficacy as required by many regulatory agencies for the approval of drugs and by the best peer-reviewed medical journals for the publication of research reports. Of course, many treatments used in conventional medicine have not been rigorously tested, either, but the scientific community generally acknowledges that this is a failing that needs to be remedied. Many advocates of alternative medicine, in contrast, believe the scientific method is simply not applicable to their remedies. They rely instead on anecdotes and theories.105,106

It might be argued that conventional medicine relies on anecdotes, too, some of which are published as case reports in peer-reviewed journals. But these case reports differ from the anecdotes of alternative medicine. They describe a well-documented new finding in a defined setting and suggest a hypothesis that should be tested in a proper clinical trial. In contrast, anecdotes about alternative remedies (usually published in books and magazines for the public) have no such documentation and are considered sufficient in themselves as support for therapeutic claims.

Alternative medicine also distinguishes itself by an ideology that largely ignores biologic mechanisms, often disparages modern science, and relies on what are purported to be ancient practices and natural remedies (which are seen as somehow being simultaneously more potent and less toxic than conventional medicine). Accordingly, herbs or mixtures of herbs are considered superior to the active compounds isolated in the laboratory as propounded in the recent ayurvedic texts. These scholars often forget that ayurveda has been a dynamic science and serial evaluation of various compendia have shown that it grew with current knowledge till the eighteenth century.

In India, of all forms of alternative treatment the most common is ayurveda. Until the 20th century, most remedies were botanicals, a few of which were found through trial and error to be helpful. For example, purple foxglove was found to be helpful for dropsy, the opium poppy for pain, cough, and diarrhea, and cinchona bark for fever. All that began to change in the 20th century as a result of rapid advances in medical science. The emergence of sophisticated chemical and pharmacologic methods meant that we could identify and purify the active ingredients in botanicals and study them. Digitalis was extracted from the purple foxglove, morphine from the opium poppy, and quinine from cinchona bark. Furthermore, once the chemistry was understood, it was possible to synthesize related molecules with more desirable properties. For example, penicillin was fortuitously discovered when penicillium mold contaminated some bacterial cultures. Isolating and characterizing it permitted the synthesis of a wide variety of related antibiotics with different spectrums of activity.

The results of these advances have been spectacular. As examples, we now know that treatment with aspirin, heparin, thrombolytic agents, angiotensin converting enzyme inhibitors and beta-adrenergic blockers greatly reduces mortality from myocardial infarction;107 antibiotics heal peptic ulcers; and a cocktail of cytotoxic drugs can cure most cases of childhood leukemia. Also in the last century, we have developed and tested vaccines against a great many infectious scourges, including measles, poliomyelitis, pertussis, diphtheria, hepatitis B, some forms of meningitis, and pneumococcal pneumonia, and we have a vast arsenal of effective antibiotics for many others. In less than a century, life expectancy in the many countries has increased by three decades, in part because of better sanitation and living standards, but in large part because of advances in medicine. Primary prevention of coronary heart disease and a significant decline from cardiovascular disease related mortality has been largely achieved by control of coronary risk factors using population-based and high-risk approaches.108,109 Changes in diet and physical activity status have led to decline in all the major non-communicable diseases in the developing world.110 The major potential of ayurveda and traditional Indian system of medicine is in primary and secondary prevention of coronary heart disease and dyslipidemia.

There cannot be two kinds of medicine - conventional and alternative. There is only medicine that has been adequately tested and medicine that has not, medicine that works and medicine that may or may not work. Once a treatment has been tested rigorously, it no longer matters whether it was considered alternative at the outset. If it is found to be reasonably safe and effective, it will be accepted. But assertions, speculation, and testimonials do not substitute for evidence. Alternative treatments, including ayurveda, should be subjected to scientific testing no less rigorous than that required for conventional treatments. A world-wide effort has begun in this direction but there is still a long way to go.

  • Bhagwad Gita. Circa 2000 BC. Chapter 6:verse 17
  • Beaglehole R. Global cardiovascular disease prevention: time to get serious. Lancet 2001; 358:661-663
  • Pearson TA, Blair SN, Daniels SR, et al. AHA guidelines for primary prevention of cardiovascular disease and stroke: 2002 update. Circulation 2002; 106:388-391
  • Assman G, Carmena R, Cullen P, et al. Coronary heart disease: reducing the risk a worldwide view. Circulation 1999; 100:1930-1938
  • Gupta R, Jain P, Kaul U, Reddy KS, Kumar A. Prevention of coronary heart disease in India: Cardiological Society of India guidelines. In: Gupta R. Editor. Current Advances in Atherosclerosis Research. 2001; 4:135-159
  • Wasir HS. Traditional wisdom for heart care. New Delhi. Vikas Publishing House. 1995
  • Dwivedi S. Ayurveda and coronary heart disease. Indian Practitioner 2000;
  • Wujastyk D. The roots of ayurveda. New Delhi. Penguin Books. 1998
  • Conrad LI, Neve M, Nutton V, Porter R, Wear A. The Western Medical Tradition: 800 BC to AD 1800. Cambridge. Cambridge University Press.1995
  • Charaka Samhita.
  • Susruta Samhita.
  • Zysk KG. Ascetism and healing in ancient India. New York. Oxford University Press. 1991
  • Hawking S. A brief history of time. Bantam Books. 1984
  • WHO Study group. Health Research Methodology.
  • Gupta R. Coronary heart disease epidemiology in India: lessons learnt and future directions. In: Kumar A. Editor. Current perspectives in cardiology. Chennai. Cardiological Society of India. 2000; 97-108
  • Stamler J. Established major coronary risk factors. In: Marmot M, Elliot P. Editors. Coronary Heart Disease Epidemiology. Oxford. Oxford University Press. 1992; 35-66
  • Mackenzie J. Arteriosclerosis. BMJ 1906; I:319
  • Murray CJL, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 1997 349:1269-1276
  • Rodgers A, Lawes C, MacMahon S. Reducing the global burden of blood pressure related cardiovascular disease. J Hypertens 2000; 18(Suppl 1):S3-S6
  • Reddy KS. Why is preventive cardiology essential in the Indian context? In: Wasir HS. Editor. Preventive Cardiology: An Introduction. New Delhi. Vikas Publishing. 1991; 1-14
  • Reddy KS. Cardiovascular disease in India. WHO Stat Q 1993; 46:101-107
  • Omran AR. The epidemiological transition: a theory of the epidemiology of population change. Milbank Mem Fund Q 1971; 49:509-538
  • Gupta R. Epidemiological transition and increase in coronary heart disease in India. South Asian J Prev Cardiol 1997 1:14-22
  • Yusuf S, Reddy KS, Ounpuu S, Anand S. Global burden of cardiovascular diseases: Part I: General considerations, the epidemiological transition, risk factors and impact of urbanisation. Circulation 2001; 104:2746-2753
  • Yusuf S, Reddy KS, Ounpuu S, Anand S. Global burden of cardiovascular diseases: Part II: Variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 2001; 104:2855-2864
  • Cooper R, Cutler J, Desvigne-Nickens P, et al. Trends and disparities in coronary heart disesae, stroke, and other cardiovascular diseases in the Unites States. Findings of the national conference on cardiovascular disease prevention. Circulation 2000; 102:3137-3147
  • Rose G. Ancel Keys' Lecture. Circulation 1991; 84:1405-1409
  • Pickering G. Hypertension: definition, natural histories and consequences. Am J Med 1972; 52:331-338
  • Gupta R. Coronary heart disease epidemiology in India: the past, present and future. . In: Rao GHR, Kakkar VV. Editors. Coronary artery disease in South Asians. New Delhi. Jaypee Brothers. 2001; 6-28
  • Dwivedi S, Giri S, Srivastava DK. Coronary artery disease in Indians and non-resident Indians with special reference to lipids and their modification by medicinal plants. In: Rao GHR, Kakkar VV. Editors. Coronary artery disease in South Asians. New Delhi. Jaypee Brothers. 2001; 278-296
  • Gupta R. Regression of coronary atherosclerosis induced by drugs, diet and lifestyle changes. In: Gupta R, Madan BR. Editors. Contemporary Medicine-1. New Delhi. Jaypee Brothers. 1993;54-74
  • Patel C, Marmot MG, Terry DJ, Carruthers M, Hunt B, Patel M. Trial of relaxation in reducing coronary risk: four year follow-up. BMJ 1985; 290:1103-1106
  • Berlin JA, Colditz GA. A meta-analysis of physical activity in the prevention of coronary heart disease. Am J Epidemiol 1990; 132:612-628
  • Menotti A, Puddu V. Ten-year mortality from coronary heart disease among 172,000 men classified by occupational physical activity. Scand J Work Environ Health 1979; 5:100-108
  • Fletcher GF, Balady G, Blair SN, et al. Statement on exercise: benefits and recommendations for physical activity programs for all Americans. Circulation 1996; 94:857-862
  • Schuler G, Hambrecht R, Schlierf G, et al. Regular physical exercise and low fat diet: effects on progression of coronary artery disease. Circulation 1992; 86:1-11
  • Carpeggiani C, Skinner JE. Coronary flow and mental stress: experimental findings. Circulation 1991; 83(Suppl II):90-93
  • Specchia G, Falcone C, Traversi E, et al. Mental stress as a provocative test in patients with various clinical syndromes of coronary heart disease. Circulation 1991; 83(Suppl II):115-127
  • Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 1999; 99:2192-2217
  • Rozanski A, Krantz DS, Bairey N. Ventricular responses to mental stress testing in patients with coronary artery disease: pathophysiological implications. Circulation 1991; 83(Suppl II):137-144
  • Gupta SB. Metaphysical effect of ancient yoga. South Asian J Prev Cardiol 1999; 3:119-123
  • Udupa KN, Singh RH, Settiwar RM. Physiological and biochemical studies on the effect of yogic and certain other exercises. Indian J Med Res 1975; 63:620-624
  • Bagga OP, Gandhi A. A comparative study of effect of transcendental meditation and shavasana practices on cardiovascular system. Indian Heart J 1983; 35:39-45
  • Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse heart disease? The lifestyle heart trial. Lancet 1990; 336:129-133
  • Ornish D, Scherwitz LW, Billings JH, et al. Intensive lifestyle changes for reversal of coronary heart disease. JAMA. 1998;280:2001-2007
  • Manchanda SC, Narang R, Reddy KS, et al. Retardation of coronary atherosclerosis with yoga lifestyle intervention. J Assoc Physicians India 2000; 48:687-694
  • Ornish D. Avoiding revascularization with lifestyle changes: the Multicenter Lifestyle Demonstration Project. Am J Cardiol. 1998;82:72T-76T
  • Dahanukar S, Thatte U. Ayurveda Unravelled. New Delhi. National Book Trust. 1996
  • Miller LG. Herbal medicinals. Arch Intern Med 1998; 158:2200-2211
  • Dwivedi S. Putative uses of Indian cardiovascular friendly plants in preventive cardiology. Ann Natl Acad Med Sci (India) 1996; 32:159-175
  • Nahin RL, Straus SE. Research into complementary and alternative medicine: problems and potentials. BMJ 2001; 322:161-164
  • Talalay P, Talalay P. The importance of using scientific principles in the development of medicinal agents from plants. Acad Med 2001; 76:238-247
  • Chaturvedi PN. A study n the effect of an indigenous drug Arjuna (Terminalia arjuna) on arterial thrombosis and ischemic heart disease. Thesis for MD (Ayurveda). Banaras Hindu University. 1967
  • Singh N, Kapur KK, Singh SP, et al. Mechanism of cardiovascular action of Terminalia arjuna. Planta Med 1982; 45:102-104
  • Dwivedi S, Udupa N. Terminalia arjuna: pharmacognosy, phytochemistry, pharmacology and clinical use- a review. Fitoterpia 1989; 60:413-420
  • Ram A, Lauria P, Gupta R, et al. Hypocholesterolaemia effects of Terminalia arjuna tree bark. J Ethnopharmacol 1997; 55:165-169
  • Nair S, Nagar R, Gupta R. Anti-oxidant phenolics and flavonoids in common Indian foods. J Assoc Physicians India 1998; 46:708-710
  • Gupta R, Singhal S, Goyle A, Sharma VN. Antioxidant and hypo-cholesterolaemic effects of Terminalia arjuna tree-bark powder: a randomised placebo-controlled trial. J Assoc Physicians India. 2001; 49:231-235
  • Bharani A, Ganguly A, Bhargava KD. Salutaryeffect of Terminalia arjuna in patients with severe refractory heartf ailure. Int J Cardiol 1995; 49:191-199
  • Dwivedi S, Agarwal MP. Anti-anginal and cardioprotective effects of Terminalia arjuna- an indigenous drug in coronary artery disease. J Assoc Physicians Ind 1994; 42:287-289
  • Dwivedi S, Johri R. Beneficial effects of Terminalia arjuna in coronary artery disease. Indian Heart J 1997; 49:507-510
  • Satyawati GV, Dwarkanath C, Tripathi SN. Experimental studies on the hypocholesterolemic effect of Commiphora mukul. Indian J Med Res 1969; 57:1950-1962
  • Wu J, Xia C, Meier J, Hu X, Lala DS. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol Endocrinol 2002; 16:1590-1597
  • Satyawati GV. Gum guggul (Commiphora mukul): the success story of an ancient insight leading to modern discovery. Indian J Med Res 1988; 87:327-335
  • Verma SK, Bordia A. Effect of Commiphora mukul in patients with hyperlipidemia with special reference to HDL cholesterol. Indian J Med Res 1988; 87:356-360
  • Thakur CP. Emblica officinalis reduces serum, aortic and heaptic cholesterol in rabbits. Experientia 1985; 41:423-424
  • Jacob A, Pandey M, Kapoor S, Saroja R. Effect of Indian gooseberry on serum cholesterol levels in men aged 35-55 years. Eur J Clin Nutr 1988; 42:939-944
  • Biswas S, Talukdar G, Sharma A. Protection against cytotoxic effects of arsenic by dietary supplementation with crude extract of Emblica officinalis fruit. Phytother Res 1999; 13:513-514
  • Singh TJ, Gupta PD, Khan SY, Misra KC. Pharmacological investigation of Ocimum sanctum. Indian J Pharmacol 1970; 32:93-96
  • Chattopadhyay RR. Hypoglycemic effect of Ocimum sanctum leaf extract in normal and streptozotocin diabetic rats. Indian J Exp Biol 1993; 31:891-893
  • Sarkar A, Lavania SC, Pandey DN, Pant MC. Changes in blood lipid profile after administration of Ocimum snactum leaves in the normal albino rabbits. Indian J Physiol Pharmacol 1994; 38:311-312
  • Bhargava KC, Singh N. Anti-stress activity of Ocimum sanctum. Indian J Med Res 1981; 73:443-451
  • Singh S, Sharma VN. Anti-thrombotic effects of Ocimum sanctum leaf extract. Thesis submitted for PhD (Pharmacy), University of Rajasthan. 2000
  • Ajabnoor MA, Timisany AR. Effect of Trigonella foenum graecum on blood glucose levels in normal and alloxan diabetic mice. J Ethnopharmacol 1988; 22:45-49
  • Puri D, Prabhu KM, Murthy PS. Hypocholesterolaemic effect of hypoglycemic principle of fenugreek seeds. Indian J Clin Biochem 1994; 9:16-19
  • Ravikumar P, Anuradha CV. Effect of fenugreek seeds on blood lipid peroxidation and antioxidants in diabetic rats. Phytother Res 1999; 13:197-199
  • Ganguly MJ, Dwivedi S, Khanna N, Sharma KK. Effect of Terminalia arjuna and fenugreek in patients of coronary artery disease as an adjuvant therapy. In: Gupta SR. Editor. Current Advances in Atherosclerosis Research. Indian Society for Atherosclerosis Research. 2000; 3:90-100
  • Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum seeds on glycaemic control and insulin resistance in type-2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India 2001; 49:1057-1061
  • McKeigue PM, Shah B, Marmot MG. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet 1991; 337:382-386
  • Srivastava KC, Verma SK, Bordia A. Spices: a source of phytochemicals protective of human health with special reference to cardiovascular disease. South Asian J Prev Cardiol 1999; 3:95-102
  • Warrier PK, Nambiar VPK, Ramankutty C. Editors. Indian medicinal plants: a compendium of 500 species. Volumes 1-5. Madras. Orient Longman. 1994
  • Valli G, Giardina E-G V. Benefits, adverse effects and drug interactions of herbal therapies with cardiovascular effects. J Am Coll Cardiol 2002; 39:1083-1095
  • Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355:134-138
  • Muldoon MF, Kritchevsky SB. Flavonoids and heart disease. BMJ 1996; 312:458-459
  • ATBC Study Group. The effect of vitamin E and beta-carotene ontheincidence of lung cancer and other cancers inmale smokers. N Engl J Med 1994; 330:1029-1035
  • HOPE Study Investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000; 342:154-160
  • Ernst E. Harmless herbs? A review of recent literature. Am J Med 1998; 104:170-178
  • Ko RJ. Adulterants in Asian patent medicines. Letter. N Engl J Med 1998; 339:847
  • Ackerman RT, Mulrow CD, Ramirez G, Gardner CD, Morbidoni L, Lawrence VA. Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med 2001; 161:813-824
  • Neil HAW, Silagy CA, Lancaster T, et al. Garlic powder in the treatment of moderate hyperlipidemia: a controlled trial and meta-analysis. J R Coll Physicians Lond 1996; 30:329-334
  • Silagy CA, Neil HAW. A meta-analysis of the garlic on blood pressure. J Hypertens 1994; 12:463-468
  • Agarwal KC. Therapeutic actions of garlic constituents. Med Res Rev 1996; 16:111-124
  • Warshafsky s, Kamer RS, Sivak SL. Effect of garlic on totalserum cholesterol. A meta-analysis. Ann Intern Med 1993; 119:599-605
  • Silagy C, Neil A. Garlic as a lipid lowering agent- a meta-analysis. J R Coll Physicians Lond 1994; 28:39-45
  • Stevinson C, Pittler MH, Ernst E. Garlic for treating hypercholesterolemia. Ann Intern Med 2000; 133:420-429
  • Holzgartner H, schmidt U, Kuhn U. Comparison of the efficacy and tolerability of a garlic preparation vs. bezafibrate. Azneimittelforschung 1992; 42:1473-1477
  • Das I, Khan NS, Soorana SR. Potent activation of nitric oxide synthase by garlic: a basis for its therapeutic applications. Curr Med Res Opin 1995; 13:257-263
  • McMahon FG, Vargas R. Cab garlic lower blood pressure? Pharmacotherapy 1993; 13:406-407
  • Bordia A, Mohammed N, Thomson M, Ali M. An evaluation of garlic and onion as antithrombotic agents. Prostaglandins Leukot Essent Fatty Acids 1996; 54:183-186
  • Bordia A, Verma SK, Srivastava KC. Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1998; 58:257-263
  • Krishnakumar K, Helen A, Rajasree CR, Vijayammal PL, Augusti KT. Supplementation of garlic and onion oils on nicotine induced lipid peroxidation. In: Dwivedi S. Editor. Current Advances in Atherosclerosis Research. Indian Society for Atherosclerosis Research. 1999; 2:87-94
  • Orekhov AN, Grunwald J. effects of garlic on atherosclerosis. Nutrition 1997; 13:656-663
  • Angell M, Kassirer JP. Alterntive medicine- the risks of untested and unregulated remedies. N Engl J Med 1998; 339:839-841
  • Eisenberg DM, Kessler RC, Foster C, et al. Unconventional medicine in the United States - prevalence, costs, and patterns of use. N Engl J Med 1993; 328:246-252
  • Kannel WB. Clinical misconceptions dispelled by epidemiological research. Circulation 1995; 92:3350-3360
  • Eaton SB, Konner M, Shostak M. Stone-agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am J Med. 1988; 84:739-749
  • Yusuf S. Two decades of progress in preventing vascular disease. Lancet 2002; 360:2-3
  • Grundy SM, Balady GJ, Criqui MH, et al. Primary prevention of coronary heart disease: guidance from Framingham. Circulation 1998; 97:1876-1887
  • Deedwania P, Gupta R. Prevention of coronary heart disease in Asian populations. In: Wong ND, Black HR, Gardin JM. Preventive Cardiology. New York. McGraw Hill. 2000; 503-516
  • Mann JI. Diet and risk of coronary heart disease and type 2 diabetes. Lancet 2002; 360:783-789