November 1990
This section provides information about the background, objectives, hypotheses, major components, organization and management, of the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA Project).
Although cardiovascular disease accounts for approximately half of all deaths in developed countries, the mortality rates show wide variation from one country to another. In the past considerable research effort has been expended, with rich results, on investigating national, regional, ethnic and individual differences in cardiovascular risk considered as a static attribute. Yet mortality rates are changing. In several countries a major decline in coronary heart disease mortality has occurred since the 1960s and smaller declines have occurred in a few other countries while rates elsewhere are stationary or rising.[1,2] Stroke mortality is declining in many countries but the trends vary considerably. In most cases these trends in mortality rates are isolated observations unsupported by any validation of death certificates, or by data on trends in non-fatal cardiovascular disease (or incidence), or by systematic observations on cardiovascular risk factor levels, or socio-cultural behaviour such as diet and exercise. It is not possible, therefore, to attribute changes in mortality with confidence either to a change in disease incidence or to a change in its natural history; yet such information is fundamental to the development and monitoring of strategies for prevention and control.
The purpose of the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA Project) is to complement the older cross-sectional studies of differences in disease rates by longitudinal investigation of the dynamics of change. The MONICA Project will initiate the simultaneous monitoring of cardiovascular mortality, morbidity, case fatality, risk-factor levels and social and behavioural trends within defined communities over a period of years so that these variables may be interrelated. By replicating the same core of observations in many contrasting communities, and by thus monitoring multiple similar and dissimilar trends, there is a potential for the investigation of the determinants of cardiovascular disease which would be beyond the scope of any single research unit or nation acting alone.
This manual covers the minimum core requirements for a Collaborating Centre that are obligatory.
The objectives of the MONICA Project are to measure the trends in cardiovascular mortality and coronary heart disease and cerebrovascular disease morbidity and to assess the extent to which these trends are related to changes in known risk factors, daily living habits, health care, or major socioeconomic features measured at the same time in defined communities in different countries. Collaborating Centres may wish to cover all these areas, but the basic protocol covers key items only, leaving the rest as local options.
Changes in cardiovascular mortality rates might be related to: a change in disease incidence, or change in case fatality, or change in both disease incidence and case fatality. The alternative explanations, therefore, relate to whether the trends in fatal and non-fatal incidence attack rates are parallel, convergent or divergent, and whether the resultant case fatality rate is changing or not.
A change in incidence could be related to known etiological factors such as:
A change in case-fatality rates could be related to changes either in medical care in the population affected, or in the natural history of the disease, or in both.
The MONICA study will involve measurement of:
These four variables can be used to test six possible associations:
The replication of the study in several contrasting Centres with different trends should demonstrate the consistent associations despite the varying experiences; something that studies within one country, where trends may be uniform, are less likely to achieve.
Although the six associations described previously can be tested within the MONICA Project for both coronary heart disease and stroke, a small number of main null hypotheses have been formulated:
CORONARY HEART DISEASE
Main null hypothesis: For the population reporting units there is no relationship between:
- 10-year trends in the major CVD risk factors of serum cholesterol, blood pressure and cigarette consumption; and
- 10-year trends in incidence rate1 (fatal plus non-fatal attack rates) of coronary heart disease.
Second main null hypothesis: For the population reporting units there is no relationship between:
- 10-year trends in case fatality rate (percentage of attacks that are fatal within 28 days); and
- 10-year trends in acute coronary care.
STROKE
Main null hypothesis: For the population reporting units there is no relationship between:
- 10-year trends in the major CVD risk factors of serum cholesterol, blood pressure and cigarette consumption; and
- 10-year trends in incidence rate1 of stroke.
Second main null hypothesis: For the population reporting units there is no difference in 10-year trends in event rates or mortality rates between stroke and coronary events.
Note: 1The phrase "incidence rate" more typically refers to first-ever events, while "attack rate" refers to the occurrence of an event, recurrent or not. In terms of assessing causality, it would be preferable to analyse changes in the rate of occurrence of first events; however, the complete and accurate documentation required to differentiate between first and subsequent events will not always be available for all events for all Centres. Thus, it will be necessary to analyse the data on attack rates and also, where the data permit, on "incidence rates for first event."
Four basic sources of information are to be utilized in the core study over a period of 10 years, three involving special studies:
For the defined population each Centre should be able to obtain:
The balance has to be struck between the ideal and the practical. If only one Centre is to be established in a country it is hoped that the Centre will be typical, in its morbidity and mortality and risk factors levels and trends, of the country as a whole. Some of this information will be unavailable when the choice is made, and other considerations such as the accessibility and compactness of the population may go against the choice of a particular population, even though its mortality rates are average for the country concerned.
Where a country has greatly contrasting regions the possibility of setting up several Centres should be considered. Similarly, if a Centre is being established in a population in which an intensive campaign of cardiovascular disease control and prevention is being mounted thought should be given to the study of an additional population elsewhere. Insofar as mortality, morbidity and risk factor trends within the population studied are being related to each other, the representativeness of that population of a nation or region is of less importance to the collaborative study than that a variety of contrasting populations and trends are included. The choice of a typical or representative population may, therefore, be more of an issue in obtaining national funding for projects than it is a primary requirement of the collaborative study. As few Centres in any country can undertake the present study, populations may be chosen more for their accessibility to the Collaborating Centre and the local knowledge and contacts already made.
Reporting Units are the population group for which trends in cardiovascular and cerebrovascular disease and risk factors will be directly measured. An official MONICA Reporting Unit is defined as the residents of an area delineated by clear geopolitical boundaries. It is this area which is the object of the MONICA data collection activities, i.e. for which annual demographic and mortality data are reported, to which the event registration process is applied and within which the population survey is conducted. A given MONICA Collaborating Centre may have more than one official MONICA Reporting Unit.
The number of subjects screened in the study population will be under the control of the investigators but the number of morbid or fatal events is determined by the size of the population and the event rate in the age group concerned. The event rate in most cases for coronary heart disease will be greater than for stroke, and male mortality will be higher than female mortality.
In order to monitor mortality trends in middle-age with the same degree of precision, the study population would need to be much larger for stroke or female coronary heart disease mortality than for male coronary heart disease mortality.
The problem of the population size for monitoring time trends in event rates is critical and limits the number of possible Collaborating Centres able to produce very accurate trend estimates. The annual number of events is what matters, not the population size; in high incidence Centres smaller populations can be studied and in low incidence Centres larger ones would be needed.
No Centre will be rejected from the project just because the population size is rather small but this factor will be considered with any others that might make a Centre unsuitable. In populations generating less than 200 fatal coronary events in men per year, it will be difficult to establish trends in fatal event rates with confidence.
The study population should be an administrative unit or units both for local government and for medical services. This will ensure that routinely collected information on the size and age and sex breakdown, emigration and immigration, and provision and utilization of medical services apply to the same population as that being investigated; Collaborating Centres should not have to conduct their own censuses but should take advantage of the available information.
Diurnal. Populations are enumerated on the basis of residence but may be composed of commuters working elsewhere. Study populations should be investigated to find methods of finding victims of vascular illnesses who fall ill while at work outside the study area. This problem arises particularly if part of a city is being studied; it is less important if a total community is involved.
Seasonal. Migration to the country for holidays or other purposes may affect recording of events. Methods for tracing both deaths and illnesses occurring at distant places should be investigated.
Permanent migration in and out. The turnover of the population does not create the same problems for the core study as it would for registration and long-term follow-up of persons or for the interpretation of the results of record linkage. However, there are potential problems in populations with a high turnover, namely:
The denominator for the study will be persons with their chief residence in the study area, which will be defined geographically to correspond with administrative and census boundaries. The decennial censuses in 1980 or 1981 will be used to provide the age and sex breakdown of the population. These figures should be revised to give the best available estimates of the midyear (30 June) population size and structure for each year of the study. It is possible that the 1990 and 1991 census results will be employed to validate these estimates retrospectively as inaccurate population trends could account for spurious trends in mortality and morbidity rates. Populations for which it is not possible to obtain census data or intercensal estimates cannot be used.
The numerator will be persons with their chief residence in the study area, however recently they have moved in, who suffer an illness or death satisfying study criteria after arrival. Events in non-residents occurring in the study area or admitted to hospital in the area do not qualify. Events in residents occurring out of the area do qualify. Efforts must be made to find them; or to estimate the potential loss and whether over a period of years it could be changing and interfering with the validity of the observed trends in rates.
Inevitably the core study will be extended to include data of local interest. Additionally there are areas of general interest which are not included in the core study. The core study has concentrated on basic items which can be standardized cross-culturally. Many of the local options are of great importance, but the lack of a good method of investigation (or the presence of too many competing ones which are not standardized for international use) prevented their inclusion as an obligatory component of the core study.
Centres interested in specific items will be encouraged to develop new methods and to share their techniques, and for certain key items to report on local methods of measurement and on trends. Reference Centres have been established for diet, exercise and drug monitoring, and the WHO Regional Office for Europe in Copenhagen is responsible for coordinating studies on socioeconomic and behavioural factors.