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(Stroke. 1997;28:500-506.)
© 1997 American Heart Association, Inc.

Articles

Stroke Trends in the WHO MONICA Project

WHO MONICA Project prepared by; Per Thorvaldsen, MD; Kari Kuulasmaa, PhD; Anna-Maija Rajakangas, MSc; Daiva Rastenyte, MD; Cinzia Sarti, MD; Lars Wilhelmsen, MD

From the Annex of the WHO MONICA Project; Glostrup Population Studies, Glostrup University Hospital, Denmark (P.T.); the Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland (MONICA Data Center) (K.K., A.-M.R., D.R., C.S.); and the Department of Medicine, Östra University Hospital, Gothenburg, Sweden (L.W.).

Correspondence to Dr Per Thorvaldsen, Department of Neurology, Gentofte Hospital, DK-2900 Hellerup, Denmark. E-mail thorvald{at}inet.uni-c.dk.

	Abstract

Top Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
Background and Purpose Stroke registers were established as part of the international collaborative World Health Organization Monitoring of Trends and Determinants in Cardiovascular Disease (WHO MONICA) Project in 17 centers in 10 countries. The aim of the present analyses was to estimate and compare temporal stroke trends across the MONICA populations.

Methods All stroke events in defined populations were ascertained and validated according to a common protocol and uniform criteria. Almost 25 000 stroke events in more than 15 million person-years were analyzed. Age-standardized rates for fatal stroke and for all stroke events were calculated for whole calendar years for each of the populations. Temporal stroke trends were estimated using annual rates for 5 to 6 years.

Results Annual stroke attack rates decreased among men in 13 populations and among women in 15 of the 17 MONICA populations. Stroke mortality rates declined among men in 11 populations and among women in 14 of the populations studied. The estimated trends reached the level of statistical significance at the 5% level in only a small number of populations. The trends in official cerebrovascular death rates were in agreement with those estimated on the basis of MONICA data in the majority of the populations studied.

Conclusions Decreasing stroke mortality and attack rates in a large proportion of populations studied can be interpreted as an indication of declining stroke rates in most of the populations studied. The numbers of populations with statistically significant trends were small, and it is therefore not possible to determine with certainty in which of the populations were the changes real.

Key Words: cerebrovascular disorders • epidemiology • incidence • mortality

	Introduction

Top Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
Stroke trends were first analyzed using stroke mortality data showing that stroke mortality had declined for several decades in the United States.^{1 2 3} For the years 1970 through 1985 a decline of stroke mortality was observed in 25 countries,^{4 5} most substantially in Japan, North America, and western Europe. In most industrialized countries, a parallel decline occurred in coronary heart disease mortality.^{6 7} In contrast to the decline in the western industrialized world, stroke mortality increased in eastern European countries.

Stroke register data have contributed evidence that the changes also involve stroke morbidity.⁸ However, the data on stroke incidence trends drawn from population-based stroke registers have been less clear than trend data obtained from national vital statistics on cerebrovascular mortality. A decline in stroke incidence has been reported in the United States,^{9 10 11 12} Asia,^{13 14 15} and Europe,^{16 17} but in some of the populations studied there were no significant changes^{18 19 20 21 22 23} or increasing rates were found in women,²⁴ men,²⁵ or both sexes.^{26 27}

WHO MONICA collaborative publications have previously described the basis for this multinational comparison of stroke epidemiology²⁸ and analyzed stroke incidence and mortality rates across the populations.²⁹ This collaborative study compares temporal trends in stroke rates for 5 to 6 years across 17 MONICA populations in 10 countries.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
The WHO MONICA Project was started in the first half of the 1980s. The objective was to continuously register the occurrence of myocardial infarction and stroke in many populations and to analyze the relationship between temporal trends in morbidity and mortality rates and changes over time in major cardiovascular risk factors.^{30 31} MCCs were established and began data collection between 1982 and 1985. The MCCs registered stroke events in the community using uniform criteria for case ascertainment and validation. Core data were reported to the MONICA Data Center in Helsinki, Finland, according to a common protocol.

Study Populations
The MONICA populations were defined as all residents of selected areas delineated by clear geographic and administrative boundaries. Stroke events were registered for the subpopulation aged 25 to 64 years. The populations were dynamic in the sense that subjects entered the population by reaching the study age range or by moving into the area. Likewise, subjects left the population when they moved out of the area, exceeded the upper age limit, or died. A description of the populations has been given elsewhere.³²

Table 1 shows the average midyear population size for men and women aged 35 to 64 years obtained from population registers, censuses, or intercensal estimates. The total number of person-years studied was more than 15 million.

View this table: [in this window] [in a new window]   Table 1. WHO MONICA Populations, Average Midyear Population Size, and Numbers of Stroke Events for Men and Women Aged 35-64 Years

Definition of Stroke
Stroke was defined as rapidly developing signs of focal (or global) disturbance of cerebral function lasting more than 24 hours (unless interrupted by surgery or death), with no apparent nonvascular cause; the definition included patients presenting with clinical signs and symptoms suggestive of subarachnoid hemorrhage, intracerebral hemorrhage, or cerebral infarction. Hence, the study is based on clinical diagnoses, which have been shown to be reliable.³³ In this article, we will report cases with ICD codes 430 through 434 or 436. The MCCs used the 8th or 9th revised version of the ICD, which both cover the same range of acute cerebrovascular diseases by the codes used.

Events were categorized as either definite stroke, not stroke, or unclassifiable. Criteria for definite stroke were fulfilled when the available information permitted a clinical stroke diagnosis. Unclassifiable was used when no diagnosis other than stroke was present to explain the event but the available information was insufficient for determining whether symptoms and duration fully met the MONICA criteria for definite stroke. The term unclassifiable was restricted to fatal events, with very few exceptions. Stroke events were subdivided into first or recurrent and into fatal or nonfatal. A period of 28 days was used to define case fatality and to distinguish one event from another.

In the present study, we have included both definite and unclassifiable stroke, as well as first and recurrent events, in the analyses. Transient ischemic attacks and silent brain infarction (cases without clinical symptoms or signs) were not included. Neither were events associated with trauma, blood disease, or malignancy.

Case Ascertainment
The MONICA stroke study is community based, and all events occurring in the populations studied were registered and assigned to a diagnostic category irrespective of survival status and place of occurrence and management. Details of case ascertainment have been described elsewhere.^{28 29 30 31 32}

The major source of information on fatal events was death certificates. All deaths with a stroke diagnosis in the death certificate or that otherwise could have been caused by stroke were registered, and the cause was validated according to the MONICA criteria. Hospitalized cases were identified from hospital admission lists (hot pursuit) or discharge diagnoses (cold pursuit). All suspected stroke cases were retrieved and validated. Events were validated on the basis of medical records for the admission relating to the event. Records from previous admissions, outpatient clinics, and other medical services were scrutinized when available and pertinent to the determination of diagnostic category or order of event.

A variety of procedures, which were adjusted to conform with local conditions, were used to identify nonfatal cases that occurred and were managed outside the hospitals.

Statistical Methods
Stroke attack rate refers to all strokes, both first and recurrent events. Case fatality is defined as the proportion of events fatal within 28 days of onset. Mortality rate is the number of fatal events (within 28 days) within a year per 100 000 population.

A comparison of stroke rates across the MONICA populations²⁹ showed that on average 20% (range, 8% to 26%) of the stroke events were recurrent events, and first-ever stroke incidence rates were correspondingly lower than the attack rates. In the present report, we have chosen to use stroke attack rates for the calculations of temporal trends. The estimates of the trends in attack rates for the periods considered will have a large variance. The estimates based on first stroke only or recurrent events would be even less accurate because of the smaller numbers of events and therefore would not bring important additional information.

Age-standardized attack and mortality rates were calculated on the basis of 5-year age groups in the range of 35 to 64 years. The data used for calculation of mortality rates were grouped by year and age determined by the day of death to obtain rates comparable with official statistics. The weights 6, 6, 6, 5, 4, and 4 were derived from the age distribution of Segi's World Population³⁴ and used for the age groups 35 to 39, 40 to 44, 45 to 49, 50 to 54, 55 to 59, and 60 to 64 years, respectively.

Confidence intervals (95%) of the age-standardized attack and mortality rates were calculated using the relationship between the Poisson and ² distributions to derive the CIs for weighted sums of Poisson parameters.³⁵

Age-standardized case-fatality rates were calculated on the basis of 10-year age groups using weights 1, 3, and 7 for the age groups 35-44, 45-54, and 55-64 years, respectively, reflecting the age distribution of all stroke events, derived from the pooled stroke events in the MONICA populations.

Temporal trends were calculated using data for the populations and years that were of acceptable quality. The trends in event rates were calculated from age-standardized annual event rates using the regression model log r_t=a+bt+e_t, assuming that the annual numbers of events within age groups follow Poisson distribution and allowing for additional deviation from the regression line.³⁶ The instantaneous change rate per year at the time point t is a constant proportion, 100b percent of the event rate at t. The 100b is printed in the tables. The estimated yearly change is exp(b)-1, which is approximately b for small changes.³⁷

The trends in case fatality were calculated from the annual age-standardized case fatality using linear regression, assuming that the annual case-fatality rates within age groups follow the binomial distribution and allowing for additional deviation from the regression line in the same way as in the calculation of the trends in event rates.

Data Quality
The quality of stroke data has been evaluated during the course of data collection by test-case coding.³⁸ Data submitted to the MONICA Data Center were checked for completeness and logical consistency and scrutinized for deviant distributions of key variables. Details of the data quality assessment have been reported elsewhere.²⁸ Except for official stroke mortality data, there has been no external source for comparison with MONICA stroke register data.

In this report, stroke mortality rates have been calculated on the basis of (1) fatal events registered and validated for the MONICA Project and (2) the official numbers of cerebrovascular deaths. The numbers of officially registered cerebrovascular deaths (ICD codes 430-438) could exceed the numbers of fatal events (ICD codes 430-436) in the stroke register because of the wider range of diagnoses. On the other hand, all possible stroke deaths should be validated and registered even if they are classified as "not stroke" according to MONICA criteria; the range of diagnosis that could possibly hide stroke cases (eg, hypertension and other cardiovascular diagnosis) was determined locally. The ratio of the numbers of fatal events in all categories in the MONICA stroke register to the number of stroke deaths in the official statistics would therefore exceed 1.0 when more events were validated and registered for the MONICA Project than were officially coded as cerebrovascular deaths. In nine of the populations studied, this ratio was greater than 1.0 for all years included in the present analysis. The register-to-official statistics ratio was between 0.75 and 1.0 for 1 calendar year in three MONICA stroke registers (Glostrup, Denmark; Kuopio, Finland; and Warsaw, Poland) and for more than 1 year in the remaining five registers (Beijing, China; Moscow (intervention), Moscow (control), Novosibirsk (intervention), Russian Federation; and Novi Sad, Yugoslavia), which could be due to underreporting of events validated and classified as "not stroke," underreporting of fatal stroke events, or a combination of both. A ratio lower than 0.75 was interpreted as an indication of inadequate ascertainment of fatal events. For this reason, data for the calendar year 1985 from the SWE-GOT register and data for the years 1986 and 1988-1990 from the RUS-NOI register were excluded from the analyses, since these data were subject to further validation by the time the data were compiled. Four of the 21 populations considered in the earlier publication²⁸ on the quality assessment were not included in this analysis at all because data of adequate quality were not available for a sufficient number of years.

	Results

Top Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
The average annual attack rates for all stroke events are shown in Table 2. The lowest rates among men and women in the MONICA populations were found in Friuli (Italy) and the highest in Novosibirsk (Russian Federation). Stroke attack rates varied threefold among men and fivefold among women in the populations studied.

View this table: [in this window] [in a new window]   Table 2. Age-Standardized Stroke Attack Rates per 100 000 and Their Trends in Men and Women Aged 35-64 Years in the MONICA Populations

In both men and women, stroke occurrence was higher in the MONICA populations in Finland, Lithuania, the Russian Federation, and China than in those in the Scandinavian and west and central European countries. Overall, stroke was almost twice as frequent in men aged 35 to 64 years as in women of the same age.

Stroke mortality rates calculated on the basis of stroke events registered for the MONICA Project and documented to be fatal within 28 days of onset are shown in Table 3 together with age-standardized mortality rates derived from official statistics (ICD codes 430-438). Both sources (MONICA stroke registers and official statistics) show that stroke mortality was higher in the MONICA populations in Yugoslavia, Poland, Lithuania, Finland, and the Russian Federation than in Italy, Germany, Denmark, and Sweden.

View this table: [in this window] [in a new window]   Table 3. Age-Standardized Stroke Mortality Rates per 100 000 and Their Trends in Men and Women Aged 35-64 Years in the MONICA Populations and in Routine Mortality Statistics

The proportions of events that were fatal within 28 days of stroke onset were more than one third in both men and women in the MONICA populations in Halle County (East Germany), Friuli (Italy), Warsaw (Poland), and Moscow (Russian Federation) (Table 4). The average case-fatality rates were higher in women than in men in 12 of the 17 populations studied.

View this table: [in this window] [in a new window]   Table 4. Overall Age-Standardized Stroke Case Fatality and Linear Trend in Men and Women Aged 35-64 Years in the MONICA Populations

In the populations in which stroke attack rates declined, the annual changes were between -0.4% and -6.5% in men and between -0.3% and -13.8% in women. Few of the individual trends were statistically significant at the 5% level, but the trends were negative among men in 13 and among women in 15 of the 17 populations in this study, indicating an overall decrease of the occurrence of stroke in the MONICA populations. The downward trend was particularly clear for men in Glostrup (Denmark) and northern Sweden and for women in Kuopio (Finland) and in Moscow (Russian Federation), indicating that these populations are likely to be among those with real changes.

The mortality rates calculated on the basis of MONICA data decreased among women in 14 of the populations studied and among men in 12 of the populations. In almost all of the populations in which MONICA stroke mortality showed a decrease, the official cerebrovascular death rates declined accordingly.

The trend estimates point to men and women in North Karelia (Finland) and Friuli (Italy) and to women in Kuopio (Finland) and Moscow (Russian Federation) as the MONICA populations most likely to be among those with a real decline of stroke mortality.

In 11 female and 8 male populations, both stroke attack rates and 28-day case-fatality rates declined. Consequently, MONICA stroke mortality rates also declined in these populations. Similarly, the estimated stroke mortality trends were positive when both stroke attack rates and case fatality increased. This was seen for men and women in the MONICA population in Kaunas (Lithuania) and for men in Gothenburg (Sweden).

Increasing case-fatality rates could in some populations have the effect of increased calculated mortality rates despite declining attack rates. This was seen in particular among men in Moscow (Russian Federation), where the estimated stroke mortality rates increased by 5.1% in the MONICA register and by 6.8% according to official statistics despite a 2.2% yearly decline in stroke attack rates. Neither of these changes, however, were statistically significant.

The direction (negative versus positive) of the stroke mortality trend in official statistics was in agreement with that observed in the MONICA register in the majority of the populations studied. Divergent trends (MONICA stroke register versus official statistics) were observed for men in Moscow (Russian Federation), where the official stroke mortality declined in contrast to increasing mortality in the MONICA registers; in Glostrup (Denmark), official mortality rates for men and women increased, whereas stroke mortality declined in the MONICA register.

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
The present results indicate that stroke mortality declined in most of the populations studied. The results also show that declining stroke mortality rates were not only due to improved survival but must also be attributable in part to a concomitant incidence decline. The downward trend that was observed in most centers reached the level of statistical significance among men in two and among women in three MONICA populations. This reflects the low statistical precision of the trend estimates. Therefore, the period considered (ie, 5 to 6 years) does not seem long enough to categorize the populations into those with high or low trends. However, the overall picture is that of a decline in stroke attack rates, with downward trends among men in 13 of the 17 populations and among women in 15. These proportions of negative trends are not likely to be coincidental. Rather, they must be seen as an indication of declining stroke rates among men and women in the populations studied.

Studies of stroke mortality have been based mostly on official vital statistics. However, it is difficult to draw conclusions on stroke incidence from studies of stroke mortality because case fatality may vary between populations and change over time within populations. Also, other sources of routine registration (eg, hospital admission lists and hospital discharge registers) may be used to estimate stroke incidence rates, but their coverage and reliability are often insufficient and may vary widely between countries. Population-based stroke registers can provide more accurate data on stroke incidence^{8 39 40 41 42} than routine statistics and also more valid measures of stroke trends when maintained according to standardized procedures for case ascertainment and validation, as in the MONICA Project. In this way, the MONICA Project has obtained stroke rates that are comparable across the populations studied, whereas up to now only comparisons of rates from studies with different designs have been possible, with many difficulties.⁴⁰

Stroke was defined by the clinical presentation, and this definition has been applied throughout the study period. Therefore, in principle case ascertainment should not be affected by the introduction of CT. This, unfortunately, does not guarantee that the results were not confounded by the introduction of new diagnostic procedures. Declining stroke rates could be slightly underestimated because increasing use of neuroimaging improved case finding. On the other hand, this could be balanced by improved specificity of the diagnosis.

The classification of cases into first or recurrent events requires valid information on the medical history and previous stroke, which was not always available. Data on previous stroke were missing in only a small percentage of the nonfatal events, but as many as one third of the fatal events were of unknown order (first or recurrent) in some of the populations studied.²⁹ We did not distinguish between first and recurrent strokes in the present study because for the individual populations the trends in the rates of first and recurrent events are even less accurate statistically than the trends in attack rates. Consequently, on the basis of the present data, it is impossible to determine the extent to which declining stroke occurrence can be ascribed to primary stroke prevention in the population and the extent to which it was due to more successful secondary prevention in stroke survivors.

On average, one third of the stroke events registered for the MONICA Project among men and women 35 to 64 years old were fatal within 28 days of onset. The official mortality data covered a wider range of cerebrovascular disorders and could include cases that were fatal after the 28th day from the stroke onset. For this reason, the rates in the MONICA register will unavoidably be different from the official mortality rates for the same population. However, this should not prohibit comparisons of trends, provided registration procedures and diagnostic criteria were kept constant. In all populations except Glostrup (Denmark), the trends were similar in both registers; in Glostrup, a nonsignificant decline of the mortality rates was observed in the MONICA register, while routine statistics tended to show an increase in stroke mortality (also statistically nonsignificant). The small number of events in this area limits the statistical power of these analyses and underlines the need for longer registration time and for caution when interpreting these results. In men and women in Warsaw (Poland), stroke mortality declined slightly, whereas stroke attack rates increased. If these trends reflect real and oppositely directed changes, then the decreased mortality in this population was solely due to improved case fatality. However, improved ascertainment of nonfatal events could lead to similar changes in case-fatality, attack, and mortality rates, but local validation of case finding did not support suspicion of such bias.

Changing stroke rates should be analyzed in relation to changes in cardiovascular risk factors in the population. Declining stroke rates have been attributed in part to improved hypertension control,⁹ and increasing stroke incidence has similarly been considered a likely effect of deteriorating lifestyle factors in the population.²⁶ Obviously, the ultimate goal of stroke epidemiology is stroke prevention. Continuing research is therefore needed to facilitate efforts toward stroke prevention. The WHO MONICA collaborative study on stroke, coronary heart disease, and cardiovascular risk factors has the potential to add a significant contribution to current knowledge in the field of cardiovascular epidemiology.

The present results are preliminary in the sense that the MONICA Project has been planned to analyze changes over 10 years. A few centers have completed the registration of stroke, coronary events, and risk factors for the full 10-year period; others are still in the process of completing their data.

	Selected Abbreviations and Acronyms

 

CI = confidence interval ICD = International Classification of Diseases MCC = MONICA Collaborating Center MONICA = Multinational Monitoring of Trends and Determinants in Cardiovascular Disease WHO = World Health Organization

	Acknowledgments

 
MONICA Centers are funded predominantly by regional and national governments, research councils, and research charities. Coordination is the responsibility of the WHO, assisted by local fundraising for congresses and workshops. The WHO also supports the MONICA Data Center (MDC) in Helsinki, Finland. Not covered by this general description is the ongoing generous support of the MDC by the National Public Health Institute of Finland and a contribution to WHO from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md, for support of the MDC and the Quality Control Center for Event Registration in Dundee, Scotland. Likewise appreciated are grants from ASTRA Häsle AB, Sweden; Hoechst AG, Germany; Hoffmann-La Roche AG, Switzerland; and the Institut de Recherches Internationales Servier (IRIS), France, to support data analysis and preparation of publications.

	Appendix 1

Top Abstract Introduction Materials and Methods Results Discussion Appendix 1 References

 
Annex 1: Sites and Key Personnel of Contributing WHO MONICA Centers
China. Beijing Heart, Lung, and Blood Vessel Research Institute: Wu Zhaosu (Principal Investigator) and Wu Yingkai (former Principal Investigator). Denmark. Glostrup Population Studies, Glostrup University Hospital: M. Schroll (Principal Investigator), H. Kirkby, S. Henriksen, D. Jeppesen, G. Vincents, and P. Thorvaldsen. Finland. National Public Health Institute, Helsinki: P. Immonen-Räihä, E. Kaarsalo, E.V. Narva, P. Puska (former Principal Investigator), K. Salmi, V. Salomaa, C. Sarti, J. Sivenius, J. Torppa, and J. Tuomilehto (Principal Investigator). Germany. Centre for Epidemiology and Health Research, Berlin: D. Eisenblätter, L. Heinemann (Principal Investigator), E. Claßen, and W. Barth (Principal Investigator). Italy. Institute of Cardiology, Regional Hospital, Udine: D. Vanuzzo (Principal Investigator), L. Pilotto, G.B. Cignacco, M. Scarpa, R. Mazini, and G. Zilio. Lithuania. Kaunas Medical Academy, Institute of Cardiology: J. Bluzhas (Principal Investigator) and D. Rastenyte. Poland. National Institute of Cardiology, Warsaw, Department of Cardiovascular Epidemiology and Prevention: S.L. Ryvik (Principal Investigator), M. Polakowska (Co-Principal Investigator), G. Broda (Co-Principal Investigator), B. Jasinski, A. Pytlak, and H. Wagrowska. Russian Federation. National Research Centre for Preventive Medicine, Moscow: T. Varlamova (Principal Investigator); Institute of Internal Medicine, Academy of Medical Sciences, Novosibirsk: Y. Nikitin (Principal Investigator), V. Feigin, S. Molijutina, T. Vinogradova, and A. Tarasov. Sweden. Östra Hospital Preventive Cardiology Unit, Göteborg: L. Wilhelmsen (Principal Investigator), P. Harmsen, K. Romanus, and G. Lappas; Department of Internal Medicine, Kalix Lasarett, Kalix: F. Huhtasaari (Principal Investigator) and V. Lundberg; Umeå University Hospital, Department of Medicine: K. Asplund (Principal Investigator), B. Stegmayr, and P.O. Wester (former Principal Investigator). Yugoslavia. Novi Sad Health Centre: M. Planojevic (Principal Investigator) and D.J. Jacovljevic (former Principal Investigator), M. Zikic, and T. Djapic.

MONICA Management Center, WHO, Geneva, Switzerland. I. Gyarfas (former Responsible Officer), Z. Pisa (former Responsible Officer), S.R.A. Dodu (former Responsible Officer), S. Böthig (former Responsible Officer), I. Martin (Responsible Officer), M.J. Watson, and M. Hill. MONICA Stroke Advisory Group. K. Asplund, R. Bonita, D. Eisenblätter, S. Hatano, M. Schroll, P.O. Wester, Wu Zhaosu, H. Tunstall-Pedoe, and J. Tuomilehto. MONICA Data Center. National Public Health Institute, Helsinki, Finland: K. Kuulasmaa (Responsible Officer), J. Tuomilehto (former Responsible Officer), A.-M. Rajakangas, E. Ruokokoski, M. Mähönen, V. Moltchanov, and J. Torppa. MONICA Quality Control Center for Event Registration. University of Dundee, Scotland: H. Tunstall-Pedoe (Responsible Officer), K. Barret, and C. Brown. MONICA Steering Committee. A. Evans (Chair), M. Hobbs (Chair, Publications Subcommittee), M. Ferrario, H. Tunstall-Pedoe (Rapporteur), I. Gyarfas, K. Kuulasmaa, and A. Shatchkute; consultants: A. Dobson, Z. Pisa, and O.D. Williams; previous Steering Committee members: S. Sans, F. Gutzwiller, R. Beaglehole, U. Keil, S. Rywik, S. Fortmann, P. Puska, and A. Menotti; former consultants: M.J. Karvonen, R.J. Prineas, M. Feinleib, and F.H. Epstein.

Received October 21, 1996; revision received December 5, 1996; accepted December 6, 1996.

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