Hugh Tunstall-Pedoe on precursors to the WHO MONICA Project
The post-war epidemic
Peace and prosperity and the control of infections through antibiotics and vaccination all promised longer life expectancy after the Second World War. This promise was not fulfilled in many countries, particularly in men. A new form of heart disease, going under different names—degenerative, arteriosclerotic, atheromatous, ischaemic, or coronary heart disease—but basically one condition, was rapidly increasing. The most economically advanced and industrialized countries seemed at greatest risk. Large increases in such mortality had begun in many different countries, some as early as the 1920s, but others from a decade or two later. These countries, led by the United States of America, initiated studies to identify the causes of this disease, previously labelled as degenerative and, by implication, a manifestation, and therefore inevitable consequence, of increasing age.
The Framingham Study, the best-known study, and a model for many others, was launched in the early 1950s (1). Several thousand men and women in Framingham, Massachusetts, were examined for certain personal factors, suspected, and by this means subsequently shown, through many years of follow-up, to be powerful and consistent predictors of increased risk of coronary heart disease. The concept of risk factors was born. The most consistent and powerful of these in explaining coronary risk, the classic risk factors, were cigarette smoking, blood pressure and blood (serum or plasma, also known as total) cholesterol. Others were less common (diabetes mellitus), less consistent (obesity and exercise) or less readily measured (diet, alcohol and psychosocial factors).
Soon after the initiation of the Framingham Study came an international collaboration led from Minneapolis in the United States, the Seven Countries Study (2). It sought to explain the large variation in death rates from coronary heart disease in different countries. Study populations, some occupational, some residential, in seven countries, extended over the full range of mortality rates, from Finland (high) through the United States of America, the Netherlands, Italy, Yugoslavia, and Greece to Japan (low). This study found the classic Framingham risk factors to be of differing importance in determining variation in coronary risk between whole populations in different countries. Obesity and physical exercise accounted for little, as did cigarette smoking. Blood pressure was of some significance, but the dominant role went to cholesterol. The average blood cholesterol concentration varied significantly across populations. It correlated with the amount and type of fat in the diet and correlated strongly with population coronary disease rates.
Cardiovascular Survey Methods and Ten-day seminars
For cross-population comparability, studies in cardiovascular epidemiology needed standardized methods of ascertainment and people who knew how to use them. By the 1960s the former were sufficiently developed for the World Health Organization to publish a manual prepared by Henry Blackburn from Minneapolis and the Seven Countries Study, and Geoffrey Rose from the London School of Hygiene and the British Whitehall Study (3), the now classic Cardiovascular Survey Methods (4). Through the Research Committee and the Council on Epidemiology of what was then the International Society and Federation of Cardiology, an international faculty of teachers initiated annual ten-day teaching seminars. The first was in Makarska in Yugoslavia in 1968 (5). They continue to this day. They introduced the disciplines of cardiovascular epidemiology, and of managing field surveys, to likely candidates, often trainees in cardiology. The seminars produced a cadre of young initiates, and a network of contacts for international collaboration.
Coronary care and the European Myocardial Infarction Registers
During the 1950s and early 1960s ambulatory treatment of angina pectoris, the chronic symptom of coronary heart disease, consisted of pain relief with a limited range of nitrate drugs. For myocardial infarction (coronary thrombosis), an acute medical emergency, treatment was morphine, anticoagulants and extended bed-rest. Management was then revolutionized by electronic monitoring of patients with myocardial infarction in coronary care units (6), with potential resuscitation from cardiac arrest by electric defibrillation and mouth-to-mouth respiration. New drugs were being introduced. Claims that cardiac mortality was being halved in such units fitted strangely with rising population mortality rates. This led to an initiative from the European Regional Office of the World Health Organization in the late 1960s to establish Myocardial Infarction Community Registers (7) in which the incidence and outcome of acute coronary events would be studied on a whole-population basis. Both hospitalized myocardial infarction, and out of hospital coronary deaths would be studied together to assess the known and potential impact of coronary care. The registers established standardized techniques for heart attack registration not previously incorporated in Cardiovascular Survey Methods. They also confirmed that the great majority of coronary deaths were occurring in the community, outside hospital, and largely inaccessible to hospital-based acute coronary care.
The American decline and the Bethesda Conference
Concealed from immediate recognition by the instability of intermittent winter influenza epidemics, mortality rates from coronary heart disease in the United States of America began to decline in the early 1960s. Similar trends appeared in other New World countries such as Australia and Canada, while coronary disease mortality was still rising or stable elsewhere. The decline in mortality in the United States caused considerable excitement. It was analysed at a seminal conference organized by the US National Heart Lung and Blood Institute at Bethesda in Maryland, USA in 1978 (8). At this conference Písa of the World Health Organization in Geneva, with Epstein (later also important in MONICA) showed comparative data on trends in cardiovascular mortality after the Second World War for a number of different countries (8), work that Písa later extended with Uemura (9). The Bethesda conference demonstrated that the American decline was probably genuine, but inadequately explained. Despite thirty years of cardiovascular research, information on risk factors, morbidity and mortality was incompletely integrated. There had been variation and inconsistency in definitions and populations studied. What was needed was long-term monitoring of mortality, morbidity and risk factors in the same defined populations, experiencing different trends in mortality, to establish the underlying patterns and associations. This was the background to the WHO MONICA Project, first proposed after the Bethesda conference in 1979, and undertaken across four continents in the 1980s and 1990s, in parallel with similar studies in the United States of America (10-13). (Hugh Tunstall-Pedoe)
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13. Rosamond, W.D., A.R. Folsom, L.E. Chambless, C.H. Wang, ARIC Investigators, and Atherosclerosis Risk in Communities. 2001. Coronary heart disease trends in four United States communities. The Atherosclerosis Risk in Communities (ARIC) study 1987–1996. International Journal of Epidemiology Suppl 1:S17–22.
By permission from: Tunstall-Pedoe, H. 2003. MONICA monograph and multimedia sourcebook: The world’s largest study of heart disease, stroke, risk factors and population trends (1979–2002). Geneva: World Health Organization.