Embargoed to Monday August 24^th 1998 12:30 Vienna time

Press Conference: European Congress of Cardiology, ESC Press Conference Centre Messe Vien,

WHO MONICA Project: preliminary analysis of final results
11:30 to 12:20, Monday 24th August 1998.

Participants: Dr Hugh Tunstall-Pedoe:Chairperson (Dundee, GB), Dr A Evans (Belfast, GB), Dr Ingrid Martin (WHO Geneva, CH), Dr U Keil (Münster, DE), Dr K Kuulasmaa (Helsinki, FI)

WORLD'S LARGEST AND LONGEST HEART STUDY PRODUCES SOME SURPRISES

The European Congress of Cardiology in Vienna this week is seeing preliminary analyses of the final ten-year results of the largest collaborative study of heart disease ever undertaken. These results - on the effects of treatments and risk factors in determining trends in coronary heart attack rates and mortality - which include some early surprises, will create considerable discussion and controversy amongst the world’s experts, although further analyses remain to be done. The near completion of this World Health Organization (Geneva) initiative is a remarkable feat of international research collaboration.

Background Twenty years ago investigators in 38 centres in 21 countries got together with the World Health Organization to answer key questions on coronary heart disease and stroke:

• Why were rates declining rapidly in some countries and increasing in others ?
• Were changes in disease rates driven directly by changes in factors known to be important in individuals - smoking, blood pressure, cholesterol and obesity ?
• How well could changing survival and mortality from heart attacks be related to changes in treatment ?
  • questions which are as topical today, when heart disease generates ever-increasing burdens and costs to the world’s ageing populations, as they were when they were first posed.

The Project The resulting collaboration was called the WHO MONICA Project (from MONItoring CArdiovascular disease). Participants, who were locally funded, used standardized methods to study trends in heart disease (and optionally stroke), trends in its treatment, and trends in coronary risk factors in their local populations, but copied their results to a Data Centre in Helsinki, for central analysis. Procedures and results were scrutinized by designated quality control centres, and by panels of international experts. Performances were scored, ranked and circulated. Serious failure led to exclusion from the study, but most investigators worked together for over ten years submitting data which met WHO MONICA Project requirements.

Preliminary results from 150 thousand heart attacks, and 180 thousand risk factor records were presented briefly at a "Hot-Line" session by Professor Hugh Tunstall-Pedoe (Dundee, Scotland, head of one of the quality control centres, and long-term member of the MONICA Steering Committee) on Sunday 23^rd August and with his MONICA colleagues (named above) at a press conference on the next day.

• Heart disease rates are declining in most of the populations studied but there is more decline in fatal than in nonfatal attacks and in men than in women. Rates are increasing in some Eastern populations.
• Survival rates from heart attacks are improving but to a lesser extent than event rates.
• Effective treatments are being adopted at very different rates in different countries.
• Improving heart attack rates do not always go with better survival.
• Blood pressure is coming down in most populations, as is smoking but there are differences by sex and age group in the latter.
• Cholesterol levels are difficult to measure and follow accurately over time, but they are changing little in most MONICA populations.
• Obesity is increasing in most MONICA populations.

AND WHEN THESE ARE PUT TOGETHER

• Those populations which, during the period of study, showed the most rapid increase in new treatments tended to be those in which heart attack survival and mortality were improving most – but this effect could be nonspecific. Many drugs were being adopted at the same time, and there were regional effects. It was therefore not possible in these preliminary analyses to say which treatments, if any, were the cause.
• Although there was more relationship in women than in men, changing rates of coronary heart disease in different populations did not appear to relate at all well to the change in the standard risk factors, considered one by one, or in a risk factor score. Large differences in the rate of decline occurred across populations with similar trends in risk factors.

Discussion and possible explanations The latter preliminary finding will cause surprise and controversy, as many had assumed a direct relationship. Professor Hugh Tunstall-Pedoe, speaking for the study, said:

"The WHO MONICA Project was set up in the early 1980s to see whether the engines driving the changes in heart disease rates were those known at that time to determine risk in individuals –smoking, blood pressure, cholesterol, and to a lesser extent, obesity. Our initial impression, - of no direct relationship overall in this study, despite reported results from individual centres- does not negate the importance of these factors to the individual and to health education. If you get eaten by a crocodile when you are expecting lions and tigers it does not mean that big cats have rubber teeth! We would not have done the study if we had been sure what it would show, and we needed international collaboration to make it possible. The preliminary results are a bit of surprise but not entirely so.

"There are several possible explanations for our findings, including problems of measurement, the fact that rates were declining in most populations anyway, and lack of linearity in trends associated with possible time-lags for which preliminary analyses do not allow. Another interesting possibility is that in population terms the contribution of the classical risk factors is swamped by that of other, dietary, behavioural, environmental or developmental factors, of which several have been proposed since the study was launched. Although many enthusiasts will now be staking claims for their favourite candidates, we cannot pass judgement on factors which were not included in the agreed core set of data for the original study. Some of these factors have been looked at in local and MONICA optional studies but will not have the power of a 38 population and ten-year evaluation. Further more sophisticated analysis of the central data that we do have will continue beyond these preliminary findings and will involve more use of our quality scores to weight the results."

Dr Ingrid Martin, responsible officer for cardiovascular diseases at the World Health Organization Headquarters in Geneva stated:

"The World Health Organization has facilitated, co-ordinated and helped to manage this study since 1979. MONICA has spread best practice in the technology of population surveys and disease monitoring through four continents. It has trained many young people in population aspects of cardiovascular disease. The findings on risk factors in no way diminish their importance for individuals and for public health. That the classical risk factors make major contributions to individual risk has been shown repeatedly in numerous studies, many involving MONICA investigators. They feature in ongoing WHO sponsored prevention programmes. The WHO MONICA Project is adding to our understanding of what is going on, and not taking away anything that was known before. It has generated high quality data for local use on what is happening to cardiovascular disease and major risk factors, and created an invaluable international resource. It is a model for other international research collaborations."

Enclosure: Press Pack consisting of:

• List of MONICA sites and principal investigators
• World Map to show MONICA sites
• *Ten-year trends in coronary death rates in MONICA populations using MONICA diagnostic criteria.
• *Ten-year trends in daily smoking in MONICA populations, smoking defined by MONICA criteria
           *Selected examples of WHO MONICA Project output

NOTE: 1: These findings will be the subject of a special evening discussion session outside the main Congress programme, organized by the WHO MONICA Project and by the European Society of Cardiology Working Group on Epidemiology and Prevention in Hall 16C Messe Vien, Tuesday 25th August 18:30-20:00

NOTE: 2 The WHO MONICA Project is sponsored and co-ordinated by the World Health Organization with contributions from NHLBI (USA) to data analysis and quality control, and European Union funding through BIOMED grants, plus donations from drug companies. The MONICA Data Centre has been supported by Finnish funds. Individual MONICA centres are funded by government bodies and by heart foundations.

NOTE: 3 Press release and results have been sent to individual Principal Investigators who can now comment both on the study and on their own local results for their national media and may put out their own statements.