Kari Kuulasmaa

Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents.

The WHO MONICA Project is a 10-year study that monitors deaths due to coronary heart disease (CHD), acute myocardial infarction, coronary care, and risk factors in men and women aged 35 to 64 years in defined communities. This analysis of methods and results of coronary event registration in 1985 through 1987 provides data on the relation between CHD morbidity and mortality. Methods and ResultsFatal and nonfatal coronary events were monitored through population-based registers. Hospital cases were found by pursuing admissions (“hot pursuit”) or by retrospective analysis of discharges (“cold pursuit”). Availability of diagnostic data on identified nonfatal myocardial infarction was good. Information on fatal events (deaths occurring within 28 days) was limited and constrained in some populations by problems with access to sources such as death certificates. Age-standardized annual event rates for the main diagnostic group in men aged 35 to 64 covered a 12-fold range from 915 per 100 000 for North Karelia, Finland, to 76 per 100 000 for Beijing, China. For women, rates covered an 8.5-fold range from 256 per 100 000 for Glasgow, UK, to 30 per 100 000 for Catalonia, Spain. Twenty-eight-day casefatality rates ranged from 37% to 81% for men (average, 48% to 49%), and from 31% to 91% for women (average, 54%). There was no significant correlation across populations for men between coronary event and case-fatality rates (r= −.04), the percentages of coronary deaths known to have occurred within 1 hour of onset (r = .08), or the percentages of known first events (r= −.23). Event and case-fatality rates for women correlated strongly with those for men in the same populations (r = .85, r = .80). Case-fatality rates for women were not consistently higher than those for men. For women, there was a significant inverse correlation between event and case-fatality rates (r= −.33, P < .05), suggesting that nonfatal events were being missed where event rates were low. Rankings based on MONICA categories of fatal events placed some middle- and low-mortality populations, such as the French, systematically higher than they would be based on official CHD mortality rates. However, rates for nonfatal myocardial infarction correlated quite well with the official mortality rates for CHD for the same populations. For men (age 35 to 64 years), approximately 1.5 (at low event rates) to 1 (at high event rates) episode of hospitalized, nonfatal, definite myocardial infarction was registered for every death due to CHD. The problem in categorizing deaths due to CHD was the large proportion of deaths with no relevant clinical or autopsy information. Unclassifiable deaths averaged 22% across the 38 populations but represented half of all registered deaths in 2 populations and a third or more of all deaths in 15 populations. ConclusionsThe WHO MONICA Project, although designed to study longitudinal trends within populations, provides the opportunity for relating rates of validated CHD deaths to nonfatal myocardial infarction across populations. There are major differences between populations in nonfatal as well as fatal coronary event rates. They refute suggestions that high CHD mortality rates are associated with high case-fatality rates or a relative excess of sudden deaths. The high proportion of CHD deaths for which no diagnostic information is available is a cause for concern.

Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality : 10-year results from 37 WHO MONICA Project populations

Summary Background The WHO MONICA (monitoring trends and determinants in cardiovascular disease) Project monitored, from the early 1980s, trends over 10 years in coronary heart disease (CHD) across 37 populations in 21 countries. We aimed to validate trends in mortality, partitioning responsibility between changing coronary-event rates and changing survival. Methods Registers identified non-fatal definite myocardial infarction and definite, possible, or unclassifiable coronary deaths in men and women aged 35–64 years, followed up for 28 days in or out of hospital. We calculated rates from population denominators to estimate trends in age-standardised rates and case fatality (percentage of 28-day fatalities=[100-survival percentage]). Findings During 371 population-years, 166 000 events were registered. Official CHD mortality rates, based on death certification, fell (annual changes: men −4·0% [range −10·8 to 3·2]; women −4·0% [-12·7 to 3·0]). By MONICA criteria, CHD mortality rates were higher, but fell less (-2·7% [-8·0 to 4·2] and −2·1% [-8·5 to 4·1]). Changes in non-fatal rates were smaller (-2·1%, [-6·9 to 2·8] and −0·8% [-9·8 to 6·8]). MONICA coronary-event rates (fatal and non-fatal combined) fell more (-2·1% [-6·5 to 2·8] and −1·4% [-6·7 to 2·8]) than case fatality (-0·6% [-4·2 to 3·1] and −0·8% [-4·8 to 2·9]). Contribution to changing CHD mortality varied, but in populations in which mortality decreased, coronary-event rates contributed two thirds and case fatality one third. Interpretation Over the decade studied, the 37 populations in the WHO MONICA Project showed substantial contributions from changes in survival, but the major determinant of decline in CHD mortality is whatever drives changing coronary-event rates.

Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations

BACKGROUND From the mid-1980s to mid-1990s, the WHO MONICA Project monitored coronary events and classic risk factors for coronary heart disease (CHD) in 38 populations from 21 countries. We assessed the extent to which changes in these risk factors explain the variation in the trends in coronary-event rates across the populations. METHODS In men and women aged 35-64 years, non-fatal myocardial infarction and coronary deaths were registered continuously to assess trends in rates of coronary events. We carried out population surveys to estimate trends in risk factors. Trends in event rates were regressed on trends in risk score and in individual risk factors. FINDINGS Smoking rates decreased in most male populations but trends were mixed in women; mean blood pressures and cholesterol concentrations decreased, bodymass index increased, and overall risk scores and coronary-event rates decreased. The model of trends in 10-year coronary-event rates against risk scores and single risk factors showed a poor fit, but this was improved with a 4-year time lag for coronary events. The explanatory power of the analyses was limited by imprecision of the estimates and homogeneity of trends in the study populations. INTERPRETATION Changes in the classic risk factors seem to partly explain the variation in population trends in CHD. Residual variance is attributable to difficulties in measurement and analysis, including time lag, and to factors that were not included, such as medical interventions. The results support prevention policies based on the classic risk factors but suggest potential for prevention beyond these.

Estimation of contribution of changes in coronary care to improving survival, event rates, and coronary heart disease mortality across the WHO MONICA Project populations

BACKGROUND The revolution in coronary care in the mid-1980s to mid-1990s corresponded with monitoring of coronary heart disease (CHD) in 31 populations of the WHO MONICA Project. We studied the impact of this revolution on coronary endpoints. METHODS Case fatality, coronary-event rates, and CHD mortality were monitored in men and women aged 35-64 years in two separate 3-4-year periods. In each period, we recorded percentage use of eight treatments: coronary-artery reperfusion before, thrombolytics during, and beta-blockers, antiplatelet drugs, and angiotensin-converting-enzyme (ACE) inhibitors before and during non-fatal myocardial infarction. Values were averaged to produce treatment scores. We correlated changes across populations, and regressed changes in coronary endpoints on changes in treatment scores. FINDINGS Treatment changes correlated positively with each other but inversely with change in coronary endpoints. By regression, for the common average treatment change of 20, case fatality fell by 19% (95% CI 12-26) in men and 16% (5-27) in women; coronary-event rates fell by 25% (16-35) and 23% (7-39); and CHD mortality rates fell by 42% (31-53) and 34% (17-50). The regression model explained an estimated 61% and 41% of variance for men and women in trends for case fatality, 52% and 30% for coronary-event rates, and 72% and 56% for CHD mortality. INTERPRETATION Changes in coronary care and secondary prevention were strongly linked with declining coronary endpoints. Scores and benefits followed a geographical east-to-west gradient. The apparent effects of the treatment might be exaggerated by other changes in economically successful populations, so their specificity needs further assessment.

Stroke Incidence, Case Fatality, and Mortality in the WHO MONICA Project

BACKGROUND AND PURPOSE This report compares stroke incidence, case fatality, and mortality rates during the first years of the WHO MONICA Project in 16 European and 2 Asian populations. METHODS In the stroke component of the WHO MONICA Project, stroke registers were established with uniform and standardized rules for case ascertainment and validation of events. RESULTS A total of 13,597 stroke events were registered from 1985 through 1987 in a total background population of 2.9 million people aged 35 to 64 years. Age-standardized stroke incidence rates per 100,000 varied from 101 to 285 in men and from 47 to 198 in women. The combined stroke attack rates for first and recurrent events were approximately 20% higher than incidence rates in most populations and varied to the same extent. Stroke incidence rates were very high among the population of Finnish men tested. The incidence of stroke was, in general, higher among populations in eastern than in western Europe. It was also relatively high in the Chinese population studied, particularly among women. The case-fatality rates at 28 days varied from 15% to 49% among men and from 18% to 57% among women. In half of the populations studied, there were only minor differences between official stroke mortality rates and rates measured on the basis of fatal events registered and validated for the WHO MONICA stroke study. CONCLUSIONS The WHO MONICA Project provides a unique opportunity to perform cross-sectional and longitudinal comparisons of stroke epidemiology in many populations. The present data show how large differences in stroke incidence and case-fatality rates contribute to the more than threefold differences in stroke mortality rates among populations.

Educational level, relative body weight, and changes in their association over 10 years : an international perspective from the WHO MONICA Project

OBJECTIVES This study assessed the consistency and magnitude of the association between educational level and relative body weight in populations with widely different prevalences of over-weight and investigated possible changes in the association over 10 years. METHODS Differences in age-adjusted mean body mass index (BMI) between the highest and the lowest tertiles of years of schooling were calculated for 26 populations in the initial and final surveys of the World Health Organization (WHO) MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Project. The data are derived from random population samples, including more than 42,000 men and women aged 35 to 64 years in the initial survey (1979-1989) and almost 35,000 in the final survey (1989-1996). RESULTS For women, almost all populations showed a statistically significant inverse association between educational level and BMI; the difference between the highest and the lowest educational tertiles ranged from -3.3 to 0.4 kg/m2. For men, the difference ranged from -1.5 to 2.2 kg/m2. In about two thirds of the populations, the differences in BMI between the educational levels increased over the 10-year period. CONCLUSION Lower education was associated with higher BMI in about half of the male and in almost all of the female populations, and the differences in relative body weight between educational levels increased over the study period. Thus, socioeconomic inequality in health consequences of obesity may increase in many countries.

Population Versus Clinical View of Case Fatality From Acute Coronary Heart Disease Results From the WHO MONICA Project 1985–1990

BACKGROUND The clinical view of case fatality (CF) from acute myocardial infarction (AMI) in those reaching the hospital alive is different from the population view. Registration of both hospitalized AMI cases and out-of-hospital coronary heart disease (CHD) deaths in the WHO MONICA Project allows both views to be reconciled. The WHO MONICA Project provides the largest data set worldwide to explore the relationship between CHD CF and age, sex, coronary event rate, and first versus recurrent event. METHODS AND RESULTS All 79,669 events of definite AMI or possible coronary death, occurring from 1985 to 90 among 5,725,762 people, 35 to 64 years of age, in 29 MONICA populations are the basis for CF calculations. Age-adjusted CF (percentage of CHD events that were fatal) was calculated across populations, stratified for different time periods, and related to age, sex, and CHD event rate. Median 28-day population CF was 49% (range, 35% to 60%) in men and 51% (range, 34% to 70%) in women and was particularly higher in women than men in populations in which CHD event rates were low. Median 28-day CF for hospitalized events was much lower: in men 22% (range, 15% to 36%) and in women 27% (range, 19% to 46%). Among hospitalized events CF was twice as high for recurrent as for first events. CONCLUSIONS Overall 28-day CF is halved for hospitalized events compared with all events and again nearly halved for hospitalized 24-hour survivors. Because approximately two thirds of 28-day CHD deaths in men and women occurred before reaching the hospital, opportunities for reducing CF through improved care in the acute event are limited. Major emphasis should be on primary and secondary prevention.

Contribution of 30 Biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: The MONICA, risk, genetics, archiving and monograph (MORGAM) biomarker project

Background— Cardiovascular risk estimation by novel biomarkers needs assessment in disease-free population cohorts, followed up for incident cardiovascular events, assaying the serum and plasma archived at baseline. We report results from 2 cohorts in such a continuing study. Methods and Results— Thirty novel biomarkers from different pathophysiological pathways were evaluated in 7915 men and women of the FINRISK97 population cohort with 538 incident cardiovascular events at 10 years (fatal or nonfatal coronary or stroke events), from which a biomarker score was developed and then validated in the 2551 men of the Belfast Prospective Epidemiological Study of Myocardial Infarction (PRIME) cohort (260 events). No single biomarker consistently improved risk estimation in FINRISK97 men and FINRISK97 women and the Belfast PRIME Men cohort after allowing for confounding factors; however, the strongest associations (with hazard ratio per SD in FINRISK97 men) were found for N-terminal pro-brain natriuretic peptide (1.23), C-reactive protein (1.23), B-type natriuretic peptide (1.19), and sensitive troponin I (1.18). A biomarker score was developed from the FINRISK97 cohort with the use of regression coefficients and lasso methods, with selection of troponin I, C-reactive protein, and N-terminal pro-brain natriuretic peptide. Adding this score to a conventional risk factor model in the Belfast PRIME Men cohort validated it by improved c-statistics (P=0.004) and integrated discrimination (P<0.0001) and led to significant reclassification of individuals into risk categories (P=0.0008). Conclusions— The addition of a biomarker score including N-terminal pro-brain natriuretic peptide, C-reactive protein, and sensitive troponin I to a conventional risk model improved 10-year risk estimation for cardiovascular events in 2 middle-aged European populations. Further validation is needed in other populations and age groups.

Trends in obesity and energy supply in the WHO MONICA Project.

OBJECTIVE: To examine the relationship between secular trends in energy supply and body mass index (BMI) among several countries.DESIGN: Aggregate level analyses of annually reported country food data against anthropometric data collected in independent cross-sectional samples from 34 populations in 21 countries from the early 1980s to the mid-1990s.SUBJECTS: Population randomly selected participants aged 35–64 y.MEASUREMENTS: BMI data were obtained from the WHO MONICA Project. Food energy supply data were derived from the Food Balance Sheet of the Food and Agriculture Organization of the United Nations.RESULTS: Mean BMI as well as the prevalence of overweight (BMI ≥25 kg/m2) increased in virtually all Western European countries, Australia, the USA, and China. Decreasing trends in BMI were seen in Central and Eastern European countries. Increasing trends in total energy supply per capita were found in most high-income countries and China while decreasing trends existed in Eastern European countries. Between country differences in temporal trends of total energy supply per capita explained 41% of the variation of trends in mean BMI; the effect was similar upon the prevalence of overweight and obesity. Trends in percent of energy supply from total fat per capita had a slight effect on the trends in mean BMI (+7% increment in R 2) when the total energy supply per capita was adjusted for, while energy supply from total sweeteners per capita had no additional effect.CONCLUSION: Increasing energy supply is closely associated with the increase of overweight and obesity in western countries. This emphasizes the importance of dietary issues when coping with the obesity epidemic.

Waist and hip circumferences, and waist-hip ratio in 19 populations of the WHO MONICA Project

OBJECTIVE: To assess differences in waist and hip circumferences and waist-to-hip ratio (WHR) measured using a standard protocol among populations with different prevalences of overweight. In addition, to quantify the associations of these anthropometric measures with age and degree of overweight.DESIGN: Cross-sectional study of random population samples.SUBJECTS: More than 32 000 men and women aged 25–64 y from 19 (18 in women) populations participating in the second MONItoring trends and determinants in CArdiovascular disease (MONICA) survey from 1987–1992.RESULTS: Age standardized mean waist circumference range between populations from 83–98 cm in men and from 78–91 cm in women. Mean hip circumference ranged from 94–105 cm and from 97–108 cm in men and women, respectively, and mean WHR from 0.87–0.99 and from 0.76–0.84, respectively. Together, height, body mass index (BMI), age group and population explained about 80% of the variance in waist circumference. BMI was the predominant determinant (77% in men, 75% women). Similar results were obtained for hip circumference. However, height, BMI, age group and population, accounted only for 49% (men) and 30% (women) the variation in WHR.CONCLUSION: Considerable variation in waist and hip circumferences and WHR were observed among the study populations. Waist circumference and WHR, both of which are used as indicators of abdominal obesity, seem to measure different aspects of the human body: waist circumference reflects mainly the degree of overweight whereas WHR does not.