Indian Heart Journal article by ProCOR founder Bernard Lown, MD

Bernard Lown, MD
2001-05-31

Dr. Lown publishes article entitled �Cardiology at a Crossroad: Challenge for India.� The full text of the article is now available here.

Cardiology at a Crossroad: Challenge for India

Bernard Lown, MD*

Cardiology is now at a critical crossroad globally. We are living in an age of unprecedented medical progress. The innovations in cardiology, at times bordering on the miraculous, are compelled by inexorable advances in scientific knowledge. The present trajectory, though heady, is not sustainable and furthermore threatens to denature the moral core of our professionalism. Three developments have brought the issue into prominence. First is the emerging global pandemic of cardiovascular disease that will impact most decisively on poor developing countries. Second, is the burgeoning cost of health care in rich countries that forces rationing of medical care along class lines. Third is the growing public discontent with and alienation from a technology centered medical profession. These issues are interrelated and demand critical analysis. As is true of crises wrought by human agency, they challenge new thinking and offer opportunities for reaching a higher plateau of human service and development.

The CVD Pandemic in Developing Countries.

While unable to shake the disease of poverty, a mounting epidemic of cardiovascular disease (CVD) is now sweeping the urban areas of the developing world. For the first time chronic degenerative ailments, generally associated with affluent societies, constitute a major cause of death in impoverished countries of the South. In 1990, two thirds of the 14 million cardiovascular fatalities worldwide occurred in developing countries.(1-3) These numbers are likely to increase as more than half the population is under 15. Furthermore in the developing world, CVD is emerging at an earlier age. In 1990 the proportion of CVD deaths occurring below the age of 70 years was 26.5% in rich countries as compared to 46.7% in poor countries (1). While the medical and socioeconomic consequences may prove ruinous, astonishingly the CVD epidemic in the South has received scant notice among physicians and public health professionals.(4)

Reasons for the increase in CVD are not mysterious. One important factor is rising life expectancy. Other factors relate to rapid and chaotic urbanization with accompanying life style changes and to the powerful economic and cultural influences of globalization.(5) The shift in agricultural production from small farmer to large corporation, distribution from shopkeeper to supermarket, consumption from fresh to processed foods, promote drastic changes in nutrition. Junk food replaces dietary fiber and the complex carbohydrates of fruits and vegetables. Consumption of fat and salt increase and that of micronutrients diminish. Calorie intake multiplies while physical activity lessens. The mismatch between energy intake and energy output manifests in a pandemic of obesity.(6) Crowding, mass unemployment and wanton violence engender social and psychological stresses which are additional risk factors for CVD and diabetes. When to this witches brew is added the rising consumption of tobacco, the outcome is as tragic as it is preordained.

The mounting scourge of cigarette smoking deserves a further comment. During the 1990's, the retreat of cigarette companies has become a near route in some industrialized nations. To make up for lost revenue, the tobacco companies forged a long range global strategy to maintain sales roughly constant where they were under siege, while investing mammoth resources to increase market share in the Third World. In the past decade United States tobacco consumption dropped 17 percent while exports have skyrocketed 259 percent.(7) Tobacco promotion is pursued aggressively in less -developed countries, with advertising budgets frequently surpassing national funds appropriated for leading disease. Among the primary targets are women and children. These vulnerable groups are ill equipped to cope with the slick marketing techniques and the dirty tricks perfected by the tobacco industry.

Most developing countries have no advertising controls, lack adequate health warning requirements, and have a dearth of pressure groups campaigning for stricter tobacco controls. They have set no age limits, nor imposed restrictions on smoking in public places. Their populations are poorly educated on the health hazards, nor is information being provided to the burgeoning numbers of teen-agers who are most susceptible to advertising hype.(8) The higher tar and nicotine content purveyed to the developing world makes their cigarettes far more addictive and therefore more lethal. When the spreading tobacco habit is coupled with the rapid rising prevalence of obesity and high blood pressure, guaranteed is the fire storm spread of ischemic heart disease.

How will India respond to this challenge? Current developments suggest that it will follow stereotypically the pattern evident world-wide. The role models are the industrial nations, particularly the USA. The emulation is in part driven by the fact that most developing countries have weak or nonexistent public health infrastructures (9), by their embrace of medical residency training programs aimed to impart proficiency in interventional technologies, and by the high incomes offered to those servicing wealthy clienteles in super-specialized sectors. Corporate sponsored medical emporia are now mushrooming in urban centers all over the developing world. Interventional cardiology is a lucrative business. To attract "customers" no costs are spared in acquiring cutting edge equipment serviced by highly trained professionals. Highlighted in these centers is specialized tertiary care treatment for those with ischemic heart disease while preventive strategies are largely ignored. In addition to the exorbitant social cost of such medical practice, it short changes the individual patient by promoting unnecessary procedures which exact inevitable and unjustified burdens of morbidity as well as death.

Momentary reflection indicates that half way technologies applied to advanced stages of disease are counter productive strategies for containing an ever mounting epidemic. An important warning sign about the road not to travel is now being provided by the USA, the chief advocate of a technological approach to health. The American people are now grappling with a health care crisis without seeming exit.

USA - A Health System in Crisis

A glance at any American cardiological journal convinces one that a majority of communications relate to promoting high tech solutions. One unexceptional example, that of percutanous transluminal coronary artery angioplasty(PTCA), is illustrative of some of the underlying factors in the present health care crisis. In 1978, Gruntzig et al launched the era of interventional cardiology with introduction of this revolutionary approach.(10) In 1991, a mere thirteen years later, more than 300,000 PTCA's were performed annually in the USA at an estimated cost of $7 billion (USA).(11) In the ensuing eight years, the number of coronary artery angioplasties more than doubled and now exceeds 700,000 annually.(12) This near exponential dissemination of PTCA occurred before safety and efficacy of the procedure had been established. Though balloon dilatation effectively widens the caliber of a narrowed vessel in up to 90% of cases, it presents problems as yet unsolved. Foremost is the fact that restenosis occurs within six months in 30-50 percent of patients. (11, 13) Furthermore, PTCA does not protect against plaque rupture, the major cause of ischemic heart disease mortality, nor does it deal with minor stenosis which constitute the nidus for abrupt closures and resulting myocardial infarction. In fact such unexpected closures occur after 2-5 percent of successful angioplasties.

The response to these limitations has been added technologies such as stenting. In some countries intracoronary stent placement is used in 60% of percutaneous recanalization procedures.(14) While stents reduce the restenosis rate of angioplasty by 30 or more percent, this is at a cost of neointimal proliferation. As could be expected novel technologies are now on the ready to respond to this yet newer complication. Various types of endoluminal beta-and gamma-radiation therapies are purported to lessen neointimal growth (15, 16), but not without additional complications which indubitably will beget still newer and costlier technologies.

When first introduced it was assumed that PTCA would reduce the far more expansive coronary bypass operation. This proved wrong. PTCA, by virtue of high rates of restenosis, did not affect the anticipated large cost savings, nor was there a decrease in the number of bypass procedures. In fact the two have continued to increase in parallel. Furthermore the exponential growth of PTCA, irrespective of its limitation, is driven by the fact that cardiologists who decide on its indication are the very ones who perform the lucrative procedure. Such self-referral is invariably associated with overuse of diagnostic or therapeutic interventions.(17) Fueling the run away exponential rise in these procedures relates to is the fact that cardiology subspecialty academic programs overtrain residents in interventional techniques. It is not unexpected that those proficient in financially rewarding procedures try to maximize their performance. The enormous enrichment that awaits medical specialists has skewed the distribution of doctors in the USA away from primary care, with 70 percent now providing specialty care.

The consequences of uncontrolled technology usage in the USA, driven by other than evidence supported medical indications, when multiplied across disciplines has powered astronomic health cost escalation. Last year health expenditures exceeded one trillion dollars (USA). My home state of Massachusetts, with only 6.3 million inhabitants, spends $5,900 per person per year, or more for health care than is budgeted by Indian government with a population of one billion.

One would anticipate that with such mammoth expenditures every single American would be receiving first class health care resulting in the best outcomes anywhere in the world. This is not the case. Forty-four million Americans are bereft of any health insurance and many more millions have inadequate health protection. In terms of outcomes USA ranks an embarrassing 37th among 191 countries according to the World Health organization. (18) The ranking is based on such indicators as life expectancy, child survival to age five, out-of-pocket health expenditures and on a number of other factors which define high quality of care. In fact a technological focused approach neither provides universal nor high quality health care.

The point is that the richest country in the world can not afford these enormous expenditures which are projected to double to 2.1 trillion dollars by the year 2007- a whopping 16.6% of America's gross domestic product.(19) To stem the inflation of costs, the USA has promoted the marketization of health services under the aegis of investor-owned health maintenance organizations(HMO). The intent is to enforce financial discipline by subjecting health care to the efficiencies of industrialization. Ignored is the commonsense fact that human beings can not be standardized; overlooked is the fact that health care is a customized service resisting commodification and therefore incompatible with the efficiencies of industrialized assembly line or other mass production technologies.

The market solution is now widely acknowledged to have failed. It has not contained costs, nor promoted universal access, nor maintained the quality of care. These outcomes have not been unexpected. As in any business enterprise, a paramount objective is to meet the profit expectations of investors. To achieve this objective, HMO's have recruited the healthy and short-shrifted the sick, have markedly curtailed hospital stays, and have down-sized hospital staff especially by reducing the cadre of experienced nurses. At the same time doctors have been inundated with a glut of paper work responding to Draconian measures to enhance efficiency and profitability. Less money has been made available for patient care as a large percentage of insurance premiums have been diverted from health related programs to dividends for investors, to increased market share through costly promotion campaigns and for egregious executive salaries, commonly in excess of one million dollars annually.

Limiting physician autonomy in patient management has undermined doctor morale and reduced it to an all time low. The lack of professional satisfaction has lead to early burn out among increasing numbers of doctors.

There is a growing appreciation that the present direction of health care in the USA is untenable. It is widely agreed that though the American gross national product is $8 trillion annually, the growth in the level of health expenditures in the long run is unaffordable. A curative approach based on high technological investment surely is not an appropriate direction for poor developing countries.

Preventive Cardiology

Far more attractive practically as well as fiscally is a preventive strategy. Epidemiological studies extending over a half a century have unearthed a wealth of information as well as forged an effective strategy for containing the epidemic of ischemic heart disease. The initial impetus was provided by the surveillance of nearly an entire population in the small Massachusetts community of Framingham. As a result of the accumulated evidence primary prevention is now a challenging possibility. The essential concept is straight forward -- readily identifiable risk factors long antedate the emergence of CHD.(20) Cardiovascular death strikes not as an unexpected bolt of lightning but as the culmination of a slowly evolving process marked by readily recognizable signposts.

Much of the burden of heart disease is propelled by four easily recognized and modifiable factors such as elevated cholesterol, high blood pressure, cigarette smoking and physical inactivity. Early attention focused on lipids. Extensive population studies demonstrate a continuous association between plasma cholesterol levels and the risk of coronary artery disease.(21, 22) Multiple clinical trials have also established that treating hypertension reduces the toll of cardiovascular disorders.(23) This is true as well for smoking cessation and physical inactivity.

Availing themselves of these new insights, industrialized societies have effected a substantial reduction in cardiovascular mortality during the last half of the 20th century. In the USA, during the three decades from 1960 -1990, CHD incidence receded about 1% annually with a concomitant decline in CHD mortality. In large measure the decline relates to modification of CHD risk factors.(24-26) While improvement in treatment has contributed to this trend, the onset of the decline antedates the high volume of high tech medical interventions.

That a concerted national effort can affect a striking change in CVD mortality has been dramatically demonstrated in Finland. Heart disease mortality there, the highest in the world, exhibited the steepest decline anywhere recorded.(27,28) Within a single generation risk factor profile of the Finnish people has been changed. Dietary alteration involving lower fat consumption has decreased mean levels of serum cholesterol, at the same time smoking has diminished among men while control of hypertension has been improved. The exemplary health dividend has been a 50% cut in cardiovascular mortality in both middle aged men and women.(29)

Primary prevention is indispensable to reduce the cardiovascular burden. Although considering the big canvas, more promising is a population based strategy to prevent the emergence of risk factors rather than their amelioration in individual patients.(30) Primordial prevention was first suggested by Strasser in 1980, to focus on preventing the emergence of major risk factors as a prominent component of public health strategy for containing the toll of CVD.(31) As elegantly argued by Geoffrey Rose, a small shift in the population mean of a particular risk factor is associated with a large change in the prevalence of high values.(32) For example, if the mean of a cholesterol distribution in a population is reduced by 6-7%, the prevalence of hypercholesterolemia (defined by the top decile) will be halved. Likewise a reduction in the population mean of systolic blood pressure of 8 mm will reduce the prevalence of hypertension by 50%. Rose cogently reasoned that a population based approach is likely to be far larger, less costly, much safer and better sustained than current practice of dealing with the individual patient. Primordial and primary prevention are complementary. Their essence is the promotion of healthier life styles goals for entire populations.

For cardiologists the principal responsibility is the optimal management of individual patients entrusted to their care. But I would maintain that our professional commitment to health mandates also a leadership role in community education on the optimal thoroughfare to healthy living. These are interrelated mutually reinforcing strategies.

Even in managing the individual patient a higher premium has to be given to secondary prevention. Here the cardiologist confronts a pharmacological revolution that has drastically improved the prognosis of heart disease and has reduced the need for costly hospital based interventions. Novel therapies are being introduced for each of the multifactorial elements contributing to the disease, such as beta blockers, aspirin, anti- hypertensives, ace inhibitors, antidiabetic agents, etc. Introduction of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) has been among the most effective. It is clear that treating hypercholesterolemic patients with statins reduces the incidence of fatal and non fatal myocardial infarction by 30-35%, as well as lowering the incidence of strokes and the need for bypass surgical procedures (33-36.)

The Lown Cardiovascular Group, over many years focused on secondary prevention and has shown that it is possible to reduce by a formidable 80% the need for coronary bypass, angioplasty, and stenting in patients with multivessel coronary artery disease. Long range outcomes in survival, incidence of myocardial infarction, as well as the quality of life have been of an order achieved with far more costly interventions. (37-39)

Whether focusing on the individual patient or on the larger community, the objective is a changed life style. Central to its achievement is an informed public. Health education, therefore, can no longer be viewed as a discretionary component of care, rather, it needs to be considered essential to a comprehensive approach to CVD.(39) In this respect a basis for hope is the ongoing digital information revolution, a social transformation of true epic proportions. In public imagination the information age is embodied in the Internet promising new vistas for democracy, education, and personal enrichment. Indeed nothing in prior human history has provided a potential for making readily available more information for more people at lower cost. In the USA the most popular are health web sites. The existing 100,000 such sites are visited by 30 million Americans.

New Directions

Since the North has lived with the cardiovascular epidemic for a half a century, the broad contours of this experience should prove instructive as the developing world confronts its own epidemic of CVD. Exploiting the new possibilities of the digital age is the unique, dynamic international forum, ProCOR, an ongoing, e-mail- and web-based (www.procor.org) electronic conference intent on fostering a global dialogue. This is to be a dialogue of equals where members of diverse constituencies from the medical profession, from among health care providers, from among those responsible for shaping and implementing health policy, and from community groups involved with health care, share know how, timely information, experience, ideas, and proposals. Among key goals is to stimulate research in areas where there exists but a paucity of reliable epidemiological data about incidence and trends in CHD risk factor prevalence. A further objective is to rouse awareness of the cardiovascular community in the industrialized world far too long blinded to the plight of the majority of humankind.

ProCOR is a joint undertaking of the Lown Cardiovascular Research Foundation and SatelLife (40) a leading provider of health information and communication services to health workers in developing countries. ProCOR is guided by a distinguished advisory committee comprised of colleagues from internationally recognized institutions. Moderators ensure high scientific quality of content and discussion by screening incoming messages, posting relevant current research publications, and fostering meaningful dialogue.

To respond to the specific problems in particular countries, regional and national AmiCOR groups, (friends of ProCOR) have been promoted. In this global enterprise AmiCOR-India (registered domain name is http://www.amicorindia.org) of special significance. Directed by Dr. S. Reddy and moderated by Dr. D. Prabhakaran, it has an advisory committee representative of many areas of expertise and headed by Dr. Ramalingaswami. A key objective will be to popularize preventive and cost-effective care of cardiovascular diseases among the healthcare providers, policy makers and the general public. "The dialogue is intended to nurture and facilitate opinion makers who are committed to bring about changes in the existing paradigm of technology based curative medicine, and make preventive and cost-effective care a popular choice."(41) AmiCOR-India will aim to identify and nurture young researchers to investigate local conditions related to CVD and how best to contain the epidemic.

To launch an effective preventive strategy will mandate training a cadre of cardiovascular professionals who are sensitized to the issues and possess the appropriate public health tools. The Lown Cardiovascular Group has accepted a small role in confronting this challenge. For the past 44 years the Lown Group has sponsored a nationally accredited three year postdoctoral fellowship training program. This is now being terminated and with the collaboration of the Brigham and Women's Hospital and the Harvard School of Public Health a new program is being initiated for the exclusive training of cardiologists from the developing world.

A novel curriculum will foster competence in both an holistic as well as a resource conserving approach to patient management. Competence will be promoted in a number of disciplines related to identification of cardiovascular risk factors as well as community based cardiovascular prevention programs. In addition to classical cardiovascular subjects, the curriculum will hone proficiency in an array of subjects; among these epidemiology, nutrition, biostatistics, cost-effectiveness analyses, informatics, medical technology assessment, socioeconomic determinants of health, and such unique areas as the utilization of mass communication to affect behavioral changes as well as reshape cultural norms relating to health. Trainees will be encouraged to carry out research relevant to the particular needs in their countries. The program is to begin this year and the first recipient of a fully funded two year fellowship is from India.

A growing understanding in the rich countries of the North is that without good health there can not be economic development, a prerequisite for a stable world order. An important expression of that understanding is the CVD Research Initiative for the Developing Countries. Launched in 1998 through a partnership of Global Forum for Health Research (GFHR) and the World Health Organization among its key goals is to promote research that will help direct policies and programs for controlling cardiovascular disease. (42) One focus in on high blood pressure. While hypertension is a growing problem in the developing world, it is a key risk factor in India where one out of three deaths is due to heart disease.

Preventive cardiology has now come of age. It is no longer tolerable to our conscience as health professionals to ignore this effective strategy. The stakes are not to be measured merely in unaffordable economic costs, but in preventing untold misery and denying people a longer life span. The cardiology profession is challenged to lead this important campaign for promoting good health for all segments of society. We have just crossed the threshold of a new century. The start of a new millennium is reason for innovative and determined resolve.

*Professor Emeritus Harvard School of Public Health; Senior physician Brigham and Women's Hospital, Boston; Former Co-Founder and Co-Chairman of International Physicians for the Prevention of Nuclear War (IPPNW); Founder and Chairman of SATELLIFE; Chairman of ProCOR; Co-recipient UNESCO Peace Award 1984; Co-recipient of Nobel Peace Prize on behalf of IPPNW, 1985; and Indira Gandhi Memorial Lecturer New Delhi, 1993

#The author acknowledges gratefully the constructive comments of R.S.Vasan, MD, DM Framingham Heart Study (USA), and A. Chockalingam Ph.D. Ottawa (Canada)

Bibliography

1. Murray CJL, Lopez AD: Global Comparative Assesements in the Health Sector. Geneva, Switzerland. World Health Organization, 1994.

2. Dodu SRA: Emergence of cardiovascular disease in developing countries. Cardiology 1988;75:56-64.

3. Chockalingam A, Balaguer-Vintro I: Impending global pandemic of Cardiovascular Disease World Heart Federation. Prous Science,SA. 1999. Barcelona, Spain.

4. Reddy KS, Yusuf S: Emerging epidemic of cardiovascular disease in developing countries. Circ. 1998;97:596-601.

5. Reddy KS: Can we telescope the transition? Chronic disease epidemics in developing countries. ProCOR. Commentary. www.ProCOR.org , 1997; November.

6. Drewnowski A, Popkin BM: The nutrition transition: New trends in the global diet. Nutrition Reviews, 1997;55:31-34

7. Weissman R: Tobacco's global reach. The Nation. 1997; July 7, p 5.

8. Lown B: The Opium wars of the 21st Century:Tobacco and the Developing World. ProCOR Commentary, www.ProCOR.org, 1997; September.

9. Garrett L: Betrayal of Trust; The Collapse of Global Public Health Hyperion, New York, 2000

10. Gruntzig AR: Transluminal dilatation of coronary-artery stenosis. Lancet 1978;1:263.

10. Nicod P, Scherrer U: Explosive growth of coronary angioplasty: Success story of less than a perfect procedure. Circulation 1993;87:1749-1750.

11. Sapirstein W, Zuckerman B, Dillard J: FDA approval of coronary artery Brachytherapy. New Eng J Med 2001; 344:297-299.

12. Frischman DL,Leon MB, Baim DS et al. A randomized comparison of coronary-stent placement and baloon angioplasty in treatment of coronary artery disease. N Eng J Med 1994;331:496-501.

13. Schwartz L, Blew B,Bui S: Intracoronary-stent placement for coronary artery disease. Lancet 1997;350:113.

14. Verin V, Popwski Y, Bruyne De B, et al: Endoluminal beta-radiation therapy for the prevention of coronary restenosis after baloon angioplasty N Eng J Med 2001;344:243-249.

15. Leon MB, Paul S, Teirstein PS, et al: Localized intracoronary gamma-radiationtherapy to inhibit the recurrence of restenosis after stenting. N Eng J Med 2001;344:250-256.

16. Relman AS: "Self-referral": What's at stake? N Engl J Med 1992;327:1521- 1524.

17. World Health Organization. The WHO report 2000 health systems performance. Geneva:WHO, 2000.

18. Ginzberg E: Ten encounters with the US health sector, 1930-1999. JAMA 1999;282: 1665-1668.

19. Kannell WB, DawberTR, Friedman GD,et al: Risk factors in coronary heart disease. Ann Intern Med 1964; 61:888-899.

20. Stamler J, Wentworth D, Neaton JD: Is the relationship between serum cholesterol and risk of premature death from coronary artery disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT) JAMA 1986;256-2823 1828.

21. Chen Z, Peto R, Collins R et al: Serun cholesterol concentration and coronary heart disease in populations with low cholesterol concentrations. BMJ 1991;303:276-282.

22. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure . Arch Inern Med 1997;157:2413-2445

23. Cooper R, Stamler J, Dyer A. Garside D: The decline in mortality from coronary disease. U.S.A. 1968-1975. J Chronic Dis 1978;31:709-20.

24. Feinleib M: The downward trend and nature of the decrease in coronary artery disease mortality rate. Am J Cardiol 1984;54:2C-6C.

25. National Center for Health Statistics. Vital Statitstics of the United States , 1988 Volume II: Mortality. Part A. Hyatsville, Md: US Dept of Health and Human Services, Public Health Services, Center for Disease Control; 1991.

26. Pyorala K Salonen JT, Valkonen T Trends in coronary heart disease mortality and morbidity and related factors in Finland. Cardiology 1985;72:35-51.

27. Salomaa V, Miettinen H, Kuulamaa K et al: Decline of coronary heart disease mortlaity in Finland during 1983 to 1992: roles of incidence , recurrence and case fatality :The FINNMONICA MI Register Study Circulation. 1996;94:3130- 3137.

28. Vartiinen E, Korhonen HJ, Pietinen P et al Fifteen year trends in coronary risk factors in Finland withspecial reference to North Karelia. Int J Epidemiol 1991;20:651-662.

29. Labarthe DR: Prevention of CVD Risk Factors in the First Place, www.Procor.org, ProCOR Commentary Sept 2000.

30. Strasser T: Reflections on cardiovascular diseases. Interdisc Sci Rev 1978; 3:225-230.

31. Rose G. Ancel Keys Lecture. Circulation 1991;84:1405-1409.

32. Scandinavian Simvastatin Survival Study Group: Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease. Scandinavian Simvastatin Survival Study(4S). Lancet. 1994;1383-1389.

33. Shepherd J, Cobbe SM, Ford I, et al: for the West of Scotland Coronary Preventive Study Group. Prevention of coronary heart disease with pravastatin in men with hypcrcholcserolemia. N Eng J Med. I995:33:l3O1-l3O7.

34. Sacks FM. Pfeffer MA. Moye LA. Et al for the Cholesterol and Recurrent Events Trial Investigators: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. NEng J Med. 1996:335:1001-1009.

35. Hebert PR, Gaziano JM, Chan SN et al: Cholesterol lowering with statin drugs, risk of stroke and total mortality. JAMA;1997;278:313-321.

36. Podrid PJ, Graboys TB, Lown B: Prognosis of medically treated coronary disease patients with profound ST segment depression during exercise testing. N Eng J Med 1981;305:1111-1116.

37. Graboys TB, Headley A, Lown B: Results of a second opinion program for coronary artery bypass graft surgery. JAMA 1987;258:1611-1614.

38. Graboys TB, Biegelman B, Lampert S et al : Results of a second opinion trial among patients recommended for coronary angiography. JAMA 1992;268:2537-2540.

39. Chockalingam A: The maturation of patient education. www.Procor.org, ProCOR Commentary Sept 1999

40. Lown B, Bukachi, F, Xavier R: Health Information in the developing world. Lancet 1998;352:SII34-38.

41. Prabhakaran D, Rddy S: Mission statement for Amicor-India. 2001; Jan.

42. The Institute of Medicine Report and Summary. Control of Cardiovascular Diseases in Developing Countries. Research, Development and Institutional Strengthening. 1998 National Academy Press, Washington, DC, USA.