Global Risk Assessment

Global Risk Assessment for Coronary Artery Disease (CAD):

Need for New Guide Lines for South Asians

Gundu H. R. Rao, Ph.D
Professor, Laboratory Medicine and Pathology, Anesthesiology, Lillehei Heart Institute, and Biomedical Engineering Institute, Academic Health Center, University of Minnesota, Minneapolis, MN 55455.

S. Thanikachalam, M.D, D.M
Professor and Dean of the Faculties, Director, Cardiac Care Center, Sri Ramachandra Medical College and Research Institute, Porur, Chennai 600 016 India.

South Asians (Indians, Pakistanis, Bangladeshis and Sri Lankans) have the highest incidence of CAD compared to any other ethnic group in the world. It is estimated that they have four to five fold higher risk than Caucasians. To create awareness, develop early diagnostic techniques, educational and prevention programs, we started a society (South Asian Society on Atherosclerosis, SASAT) in 1993. Since then we have organized five international conferences in India on Atherosclerosis and Thrombosis. This society is unique, as it provides a wide platform for researchers, physicians, clinicians and health care providers to interact, develop and disseminate information needed to fight this chronic complex disease. In one of the earlier symposiums of SASAT we provided a position statement on Heart Health Care for South Asians. In this conference we would like to provide a brief overview on the global risk for CAD and the need for developing new guidelines for risk assessment and management.

Much of the data on CAD and risk promoters for CAD comes from research done in other countries, on the incidence and prevalence of this disease among South Asians living abroad and comparing that to the incidence in the native population of the country in which they reside. Known risk factors for CAD include smoking, hypertension, obesity, dyslipidemia, poorly regulated diabetes. Some of the other lesser know risk factors include, increased levels of homocysteine, low B12, lipoprotein remnants, lipoprotein (a), fibrinogen, hypercoagulable state, platelet hyperactivity, depleted antioxidants, infection and inflammation.

Framingham study initiated by the National Heart Institute of National Institutes of Health USA, some fifty years ago, with well-characterized 5,000 individuals, contributed significantly to our understanding of the risk factors for the development of CAD. Based on the information made available from this study and various other studies, health care organizations in the USA developed guidelines for early diagnosis and risk assessment, prevention and therapeutic modalities. As a result of this concerted effort, morbidity and mortality due to CAD has decreased significantly (40-50%) in the last three decades. However, this phenomenal improvement in the health of US population does not reflect in the South Asian groups settled in this country for the same length of time. From limited studies done so far, no specific risk factor can be singled out to explain this increased mortality due to CAD in South Asians.

Multiple risk promoters seem to pose potentially atherogenic condition. Some of these observations raise several important questions. Is this observed excessive risk for CAD in South Asians due to some altered endocrine metabolism? Is it due to frequent infections, inflammation or constant stress? Are the risk factors for the South Asians living abroad different from those of the Asians residing in the Indian subcontinent? Is there a role for the observed narrowness of the arteries and the smaller size of the circulating platelets in the early development of this disease? How about the role of genetic factors in predisposing this population to multiple metabolic disorders? Therefore, there is a great need to initiate multi-regional as well as multi-national community-based studies to follow the etiology of the pathogenesis of hypertension, obesity, diabetes and CAD in South Asians. Based on the results of such studies, we may be able to develop different new guidelines for risk assessment and management of CAD.

Global risk assessment is a key new feature in the latest US cholesterol guidelines (NCEP ATP 111). It is to a large extent based on the risk prediction equations that originated from the Framingham Heart Study. Relative risk for CAD in other populations from different regions or countries may differ from that of Caucasian and largely suburban subjects studied at Framingham. Indeed, similar studies done in other countries have developed risk predictor equations, compared with the original Framingham assessment program Framingham risk assessment, Procam risk calculator and have emphasized the need to determine the risk for CAD for different geographic and ethnic regions. The focus on single risk factor (cholesterol) or few common risk promoters has given way to an approach that accounts for the multi-factorial origin of CAD, and the need to develop newer guidelines and comprehensive management of patients at high risk. Researchers at the United Kingdom have developed risk predictor assays taking into account multiple risk promoters associated with CAD. The UKPD Risk Predictor Engine.

Researchers at the University of Minnesota (Rasmussen Center for the Cardiovascular. Disease Prevention), have developed a unique program, in which they focus on identifying the disease itself, instead of measuring risk factors. They hypothesize that myocardial ischemia, myocardial infarction and other cardiovascular events are precipitated by the dysfunction of the arterial wall. They believe that endothelial dysfunction, leading to the diminished availability of vasodilators such as adenosine, prostacyclin and nitric oxide probably precedes the end-organ failure associated with the cardiovascular diseases. They recommend a series of non-invasive tests to evaluate the relative state of the arterial disease. The tests used in this center for the early diagnosis of the arterial disease include, arterial elasticity measurement, fundus photography, forced vital capacity of the lungs, blood pressure activity response, electrocardiogram, cardiac ultrasound, and ankle-brachial pressure index.

By and large in majority of the heart disease prevention clinics emphasis has been to identify CAD risk promoters, both conventional as well as newer emerging risk factors. For lack of better guidelines, NCEP-ATP 111 guidelines are used as a reference point for comparison. However, there is increasing awareness that these guidelines may not be applicable for all the ethnic groups. In a limited hospital-based study, Chegu and Thanikachalam (personal communication), have shown the need to use lower cut off values for risk factors such as total cholesterol, LDL cholesterol, triglycerides and apolipoprotein B, compared to the values used in the NCEP guidelines. From these observations, it becomes clear, that both early diagnosis of the disease itself and the establishment of newer guidelines for CAD promoters play an important role in the risk assessment and effective management of CAD in South Asians at high risk. Additional population based studies are needed to compare the newer non-invasive methods with conventional risk factors using the newer guidelines, to identify and recommend appropriate protocols for risk assessment and management of CAD.

Jay N. Cohn, Professor of Cardiology at University of Minnesota in a recent article (Am. J. Hypertension 14: 258s-263s, 2001) advocates measurement of arterial compliance to identify patients at risk for cardiovascular events before disease becomes apparent. Pulse contour analysis (Hypertension Diagnostics, USA) is a newly developed noninvasive method that allows for easy, in-office measurements of arterial elasticity. Further studies are needed to find out how effective are these noninvasive methods in detecting the arterial disease in Indian men and women. A comparative community-based study will provide information on the suitability, benefits or otherwise of such methods over monitoring of conventional risk factor assessment.

There is a large body of evidence available to suggest that early diagnosis of the disease and appropriate interventions will make a big difference in the management of these chronic diseases. World Health Organization (WHO) for instance, is interested in developing screening for hypertension in the developing countries, so that appropriate cost effective therapeutic modalities can be developed to manage this disease (personal communication: Dr. Shanthi Mendis, WHO). Studies from the Madras Diabetes Research Foundation, Chennai, by Mohan and associates have demonstrated the ill effects of increased blood glucose levels on CAD risk even before the subjects develop full-blown diabetes. These observations suggest, that the intervention should start with those individuals who have demonstrable glucose intolerance and not after they become diabetics. Similarly the studies from Sri Ramachandra Medical College and Research Institute, Chennai, by Chegu and Thanikachalam, have demonstrated the need for the use of lower cut off for lipid risk promoters for CAD for the better management of CAD. By using the information from these new findings, a larger section of the population at high risk for CAD will obtain benefit.

Researchers at the University of Minnesota, USA and Chennai, India, have initiated preliminary studies to address some of these issues. They have started a dialogue with the national and international funding agencies to seek funds for long-range collaborative studies. They are also working with the medical industries to bring new diagnostic technologies to India for clinical trials. Results of such collaborative studies will yield new and useful information for the early risk assessment and effective management of CAD in Indians. Based on available scientific information, it is reasonable to suggest that reliable methods and ways exist to prevent cardiovascular disease as well as major risk promoters associated with these diseases. SASAT will make concerted efforts to develop position statement on Heart Health Care for Indians. It will facilitate the development of methodologies for the early diagnosis of the arterial disease. Furthermore, with the help of researchers and policy makers, it will develop new guidelines for CAD risk assessment and management. The advisory board of SASAT requests that the health, media, social service professionals, scientific researchers and various health care providers, join forces in eliminating this chronic complex disease by adopting appropriate policies and regulatory changes. Furthermore, we suggest that concerted effort should be made for facilitating greater awareness of risk factors for CAD and for encouraging the development of educational, diagnostic, preventive and therapeutic guidelines and implementing needed prevention programs.

For further information contact American Heart Association, Minnesota Affiliate, (Ph: 835 3300: Fax 835 5828); Heart Disease Prevention Clinic, U of M; Your personal physician; or Gundu H. R. Rao, Founder, Secretary General SASAT; Founder, President, South Asian Heart Foundation (Ph: 612-626-2717, Fax 612-625-0617); e-mail: