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OBJECTIVE: End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy volunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype.METHODS: Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3).RESULTS: Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 × 10(-8)) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 × 10(-186)), rs10665 with FVII (p = 2.4 × 10(-47)), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 × 10(-57)) and factor VIII (p = 1.2 × 10(-36)). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88-0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). INTERPRETATION: ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype.

Background The rate of coronary heart disease (CHD) mortality in eastern Finland has been the highest in the world. The official mortality statistics suggest, however, that it has declined by 60% during the past 20 years. The aim of the present study was to examine the contributions of incidence, recurrence, and case fatality of coronary events to the trends in CHD mortality in three areas of Finland. Methods and Results Population-based myocardial infarction registers have been operating in the provinces of North Karelia and Kuopio in eastern Finland and the Turku/Loimaa area in southwestern Finland from 1983 to 1992. During this 10-year period, each suspected coronary event in persons 35 to 64 years of age was evaluated for registration. Of these, 13 566 fulfilled the criteria of myocardial infarction or coronary death. Almost one fourth (22.4%) of the coronary events were sudden, out-of-hospital deaths. Among men, the average change in mortality was −7.1% per year (95% confidence interval, −8.4% to −5.8%) in North Karelia, −5.0% per year (−7.0% to −3.0%) in Kuopio, and −4.9% per year (−8.2% to −1.6%) in Turku/Loimaa. Among women, the corresponding changes were −5.6% (−11.1% to −0.1%), −4.4% (−8.1% to −0.7%), and −8.1% (−13.0% to −3.2%). In eastern Finland, the decline in CHD mortality was due to a decline in recurrent coronary events but also in the incidence of first coronary events, whereas in southwestern Finland, the decline in case-fatality rate had the major role. Conclusions The decline in CHD mortality rate in Finland appears to be the result of a successful combination of primary and secondary prevention measures and improvements in acute coronary care.

Objectives: To estimate the extent to which the changes in the main cardiovascular risk factors (blood pressure, smoking, and serum cholesterol concentration) can explain the observed changes in mortality from stroke in Finland during the past 20 years. Design: Predicted changes in mortality from cerebrovascular disease mortality were calculated by a proportional hazards model from data obtained in cross sectional population surveys in 1972, 1977, 1982, 1987, and 1992. Predicted changes were compared with the observed changes in mortality statistics. Setting: North Karelia and Kuopio provinces, Finland. Subjects: 16741 men and 16389 women aged 30-59 randomly selected from the national population register, of whom 14054 men and 14546 women participated. Main outcome measures: Levels of risk factors and predicted and observed changes in mortality from cerebrovascular disease. Results: The observed changes in diastolic blood pressure, total serum cholesterol concentration, and smoking in the population from 1972 to 1992 predicted a 44% fall in mortality from stroke in men and changes in diastolic blood pressure and smoking predicted a 34% fall in women. The observed fall in mortality from stroke was 66% in men and 60% in women. Conclusions: Two thirds of the fall in mortality from stroke in men and half in women can be explained by changes in the three main cardiovascular risk factors. Key messages Key messages In this study blood pressure and smoking were independent risk factors for stroke in both sexes and serum cholesterol concentration was also a risk factor in men Mortality fell by 62% in men and 63% in women over 20 years Changes in risk factors explained 71% of the fall in men and 54% in women Continued emphasis on promoting healthier lifestyles and effective treatment for hypertension are essential to maintain the fall in deaths

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.

Background and Purpose As part of the WHO MONICA Project (World Health Organization Moni toring Trends and Determinants in Ca rdiovascular Disease), mortality and incidence rates of acute stroke in 14 centers covering 21 populations from 11 countries were compared. Methods In this report, coverage and quality of the MONICA stroke registers were evaluated on five key indicators using data submitted to the MONICA Data Center. Results A low ratio of MONICA stroke register to routine statistics of stroke mortality and a low proportion of nonfatal out-of-hospital events were the most common biases; they indicate that identifications of fatal cases and/or case finding of nonfatal events occurring outside the hospital were inadequate in many MONICA centers. In 10 populations, the data quality analyses suggested that clarification of possible biases would be needed before these populations can be included in a comparative study. Data from the remaining 11 populations meet the data quality standards for multinational comparisons with respect to case ascertainment. Conclusions These results show that multinational comparisons of stroke incidence involve considerable problems in developing and maintaining appropriate standards of data quality. However, after considerable efforts to ensure quality, comparisons of stroke data within the MONICA Project are possible among a large number of the MONICA populations. Our observations also indicate that results from multinational comparisons of stroke mortality based on routine statistics must be interpreted with caution.

Objectives. To examine, whether the acute myocardial infarctions (AMIs) are becoming smaller. Design. Analysis of electrocardiogram (ECG) and enzyme findings of community-based AMI registers in three geographical areas of Finland during the 8-year period 1983–90. Setting. In the FINMONICA AMI Register, all suspected coronary events in persons aged 25–64 years have been registered since 1983 according to the protocol of the WHO MONICA project in the provinces of North Karelia and Kuopio in eastern Finland and Turku/Loimaa area in south-western Finland. Subjects. Each consecutive case of suspected AMI originating from the monitored populations. During the study period, 11487 definite or possible AMIs were registered. Main outcome measures. Trends in ECG findings classified as definite or probable, and trends in enzyme findings classified as abnormal or equivocal. Results. Of the registered AMIs, 8439 (73.5%) reached the hospital alive and survived ≥ 24 h from the beginning of the symptoms. They were included in the analyses of this report and divided further, to first ever AMIs (n = 5392) and to recurrent AMIs (3047). During the study period, the proportion of ECG findings classified as definite on the basis of the serial Minnesota coding declined in men 3.1% year−1 (P < 0.0001) on average for first AMIs and 1.9% year−1 (P = 0.004) for recurrent AMIs. In women, the corresponding declines were 1.9% year−1 (P = 0.007) and 1.6% year−1 (P = 0.02), respectively. Also, the proportion of enzymes classified as abnormal declined amongst men 2.2% year (P < 0.0001) for first AMIs and 2.8% year−1 (P < 0.0001) for recurrent AMIs. In women, the corresponding declines for abnormal enzymes was 1.3% year−1 (P = 0.13) and 3.0% year−1 (P = 0.02). These findings were consistent in all three areas with different registration teams and different laboratories. The proportion of definite ECG findings amongst patients hospitalized for AMI declined almost by half and the proportion of abnormal enzyme findings declined almost by one-third during the study period. Conclusions. Our findings are compatible with the clinical observation that the hospitalized AMIs are becoming smaller. The timing and magnitude of the changes suggest that they are mainly caused by decreased risk-factor levels in the population. Improved treatment of coronary heart disease and changed hospital admission policy are likely to be contributing factors.

We evaluated the reliability hospital discharge register data in the assessment of acute myocardial infarction trends. In the FINMONICA study areas, trends in age standardized attack rates for the ...

BackgroundMore accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design.MethodsUsing data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived.ResultsBoth scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events.ConclusionsGenetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.

Aims: Although socioeconomic status is a recognized independent risk factor for CVD mortality, the recommended European risk prediction equation for primary prevention does not consider it; an approach criticized by previous results in the UK and US. We aim to assess whether the SCORE project equation adequately estimates the risk in different educational classes, across several European populations. Methods: We considered 47 prospective population-based surveys from Nordic Countries (Finland, Denmark, Sweden), UK (Belfast and Scotland), Central Europe (France, Germany and Italy) and East Europe (Lithuania, Poland) and Russia. Baseline data collection and mortality follow-up (median time 10 years) adhered to standardized MONICA-like procedures. Three educational classes were derived from population-, sex- and birth year-specific tertiles of years of schooling. The individual SCORE risk was computed from age, total cholesterol, systolic blood pressure and smoking; the risk was recalibrated to the average observed risk in each population. We estimated age- and traditional risk factors-adjusted hazard ratios (HR) for 10 year CVD mortality (highest education as the reference), from Cox models. Moreover, the observed number of fatal CVD events by educational class was compared to the expected number, as estimated by the recalibrated SCORE function. Results: The cohorts summed-up 39,215 men and 29,240 women 40 to 64 years old and free from CVD event at baseline. Education was associated with CVD mortality in men (pooled age-adjusted HR for low vs high education: 1.6, 95% CI 1.4–1.9); the hazard ratios ranged from 1.3 (95%CI: 0.9–1.8) in Central Europe to 2.1 (1.6–2.7) in East Europe and Russia. The association attenuated after adjustment for SCORE risk factors and HDL-cholesterol. Among women, the association was significant in Nordic Countries only (age-adjusted HR for low vas high education: 1.7, 95% CI 1.1–2.6), but it was no more significant after adjustment for multiple risk factors. The original SCORE equation overestimated the risk at a population level, both in men and in women, except in East Europe and Russia. After recalibration, the SCORE equation overestimated the risk among the more educated men by 20% to 50% (in Central Europe, East Europe and Russia, respectively), but underestimated it in the less educated men by 7% to 23% (in Central Europe, East Europe and Russia, respectively). Conclusions: Our results, based on a well-harmonized study comprising several European populations, suggest the need to include country-specific socioeconomic status in the risk estimation equations.

The WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project has been established to measure 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 at the same time in defined communities in different countries. This cross-sectional study is based on data from the early part of the Project and assesses the association between mortality and population risk factor levels....Thirty-five populations of men and women aged 35-64 years are used in correlation analyses between four mortality measures (deaths from all causes cardiovascular diseases ischaemic heart disease and stroke) and three cardiovascular risk factors (regular cigarette smoking blood pressure and total cholesterol)....This analysis has shown that accepted cardiovascular mortality risk factors measured cross-sectionally at the population level do not reflect well the variation in mortality between populations. (EXCERPT)

The incidence and case fatality of stroke from 1983 to 1985 from the community-based stroke register of the FINMONICA study in Finland were compared with the corresponding rates in the hospital-based register of Akita in Japan collected during 1984-1986. The comparability of the two registers was assessed, and case fatality was compared only in hospitalized cases. In Akita, the age-standardized incidence of cerebral haemorrhage in people aged 25-74 was twice that in FINMONICA, while the reverse was true for incidence of cerebral infarction. Case fatality from stroke within 48 h of onset was higher in FINMONICA than in Akita in each stroke subtype. The incidence and mortality of subarachnoid haemorrhage were similar in the two populations. The differences in early case fatality are probably due to dissimilarities in the severity of the stroke attacks rather than discrepancies in early treatment. Coding practices and also a more unlikely selection bias due to the differential use of computerized brain tomography in the two countries may play a role in differences in incidence and case fatality between these two countries.

Aims: We assessed whether a cardiovascular risk model based on classic risk factors (e.g. cholesterol, blood pressure) could refine disease prediction if it included novel biomarkers (C-reactive protein, N-terminal pro-B-type natriuretic peptide, troponin I) using a decision curve approach which can incorporate clinical consequences. Methods and results: We evaluated whether a model including biomarkers and classic risk factors could improve prediction of 10 year risk of cardiovascular disease (CVD; chronic heart disease and ischaemic stroke) against a classic risk factor model using a decision curve approach in two prospective MORGAM cohorts. This included 7739 men and women with 457 CVD cases from the FINRISK97 cohort; and 2524 men with 259 CVD cases from PRIME Belfast. The biomarker model improved disease prediction in FINRISK across the high-risk group (20⊟40%) but not in the intermediate risk group, at the 23% risk threshold net benefit was 0.0033 (95% CI 0.0013−0.0052). However, in PRIME Belfast the net benefit of decisions guided by the decision curve was improved across intermediate risk thresholds (10⊟20%). At pt = 10% in PRIME, the net benefit was 0.0059 (95% CI 0.0007⊟0.0112) with a net increase in 6 true positive cases per 1000 people screened and net decrease of 53 false positive cases per 1000 potentially leading to 5% fewer treatments in patients not destined for an event. Conclusion: The biomarker model improves 10-year CVD prediction at intermediate and high-risk thresholds and in particular, could be clinically useful at advising middle-aged European males of their CVD risk.

The effect of different fat loads on postprandial lipemia and hemostatic activity was examined in 10 middle-aged men using 3 different meals. One meal was rich in saturated fatty acids (cream), the other rich in n-6 polyunsaturated fatty acids (sunflower oil) and the third was fat-free containing only carbohydrates. Lipoprotein lipids and hemostatic parameters were measured during fasting and 2, 4, 6 and 8 h after the test meal. In fasting samples, several hemostatic parameters were significantly associated with lipoprotein lipids. Most notable were the strong associations of fibrinolysis parameters tissue plasminogen activator antigen and plasminogen activator inhibitor activity (PAI-1) with total and very low density lipoprotein (VLDL) triglycerides. During lipemia, the associations were approximately similar or slightly weaker than in the fasting state. Both fat loads resulted in similar postprandial lipid responses: VLDL and high density lipoprotein (HDL) triglycerides reached maximum at 4 h after the meal. VLDL cholesterol also increased 4 and 6 h after the fat loads. HDL3 cholesterol declined after the fatty meals but no change was observed in the HDL2 fraction. The fat-free meal gave no significant lipid changes during the time course studied. Factor VII activity (F VII:C) increased 6 and 8 h after the fatty meals, whereas a decrease was observed after the fat-free meal. The changes (+/- S.D.) at 8 h after cream, sunflower oil and fat-free meal were 5.2 +/- 3.3, 3.3 +/- 4.2 and -5.8 +/- 7.9 percentage points, respectively, and the effect of the meal on the changes was statistically significant (F (8,99) = 2.99, P = 0.0048). F VII antigen (F VII:Ag) tended to decline during the day but there was no difference between the meals. Factor VIII activity (F VIII:C) was highest after the polyunsaturated fat meal and lowest after the fat-free meal. PAI-1 declined during the day and the decline tended to be steepest after the fat-free morning meal. The effect of the meal on the changes in lipoprotein lipids and hemostatic factors varied significantly between individuals. In conclusion, postprandial lipemia after a single fatty meal was associated with procoagulatory change in F VII:C but there was no difference between saturated fat and n-6 polyunsaturated fat.

Background Previous tools for stroke risk assessment have either been developed for specific populations or lack data on non-fatal events or uniform data collection. The purpose of this study was to develop a stepwise model for the estimation of 10 year risk of stroke in nine different countries across Europe. Methods Using data from the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project, sex-specific models estimating 10 year risk of stroke were developed using a Cox regression model stratified by country and including modelling of competing risks. Models were developed in a stepwise manner first using only data from questionnaires, and then adding data from physical examinations and finally data from blood samples. Results During 1 176 296 years of observation, 2928 incident fatal and non-fatal events of stroke were registered. The developed model showed good calibration and accuracy of prediction. The discrimination of the model varied between sex and country but increased with increasing number of variables used (area under the receiver operating characteristic curve between 0.77 and 0.79 in men and between 0.75 and 0.80 in women). Conclusion The present study shows that using a large multicountry cohort from nine European countries it is possible to develop a stepwise risk estimation model for 10 year risk of stroke tailored to different availability of risk factors and still obtain valid measures of risk even in the simplest form of the model, with increasing performance of the model following increasing complexity. The methods chosen which separate this model from previous models (competing risk and stepwise approach) should be considered for future risk estimation models.

Background WHO has played a leading role in the formulation and promulgation of standard criteria for the diagnosis of coronary heart disease and myocardial infarction since early 1970s. Methods The revised definition takes into consideration the following: well-resourced settings can use the ESC/ACC/AHA/WHF definition, which has new biomarkers as a compulsory feature; in resource-constrained settings, a typical biomarker pattern cannot be made a compulsory feature as the necessary assays may not be available; the definition must also have provision for diagnosing non-fatal events with incomplete information on cardiac biomarkers and the ECG; to facilitate epidemiologic monitoring definition must recognize fatal events with incomplete or no information on cardiac biomarkers and/or ECG and/or autopsy and/or coronary angiography. Results Category A definition is the same as ESC/ACC/AHA/WHF definition of MI, and can be applied to settings with no resource constraints. Category B definition of MI is to be applied whenever there is incomplete information on cardiac bio-markers together with symptoms of ischaemia and the development of unequivocal pathological Q waves. Category C definition (probable MI) is to be applied when individuals with MI may not satisfy Category A or B definitions because of delayed access to medical services and/or unavailability of electrocardiography and/or laboratory assay of cardiac biomarkers. In these situations, the term probable MI should be used when there is either ECG changes suggestive of MI or incomplete information on cardiac biomarkers in a person with symptoms of ischaemia with no evidence of a non-coronary reason. Conclusions This article presents the 2008-09 revision of the World Health Organization (WHO) definition of myocardial infarction (MI) developed at a WHO expert consultation.

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 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.

Background The prevalence of diabetes is increasing in all industrialized countries and its prevention has become a public health priority. However, the predictors of diabetes risk are insufficiently understood. We evaluated, whether 31 novel biomarkers could help to predict the risk of incident diabetes. Methods and Findings The biomarkers were evaluated primarily in the FINRISK97 cohort (n = 7,827; 417 cases of clinically incident diabetes during the follow-up). The findings were replicated in the Health 2000 cohort (n = 4,977; 179 cases of clinically incident diabetes during the follow-up). We used Cox proportional hazards models to calculate the relative risk of diabetes, after adjusting for the classic risk factors, separately for each biomarker. Next, we assessed the discriminatory ability of single biomarkers using receiver operating characteristic curves and C-statistics, integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Finally, we derived a biomarker score in the FINRISK97 cohort and validated it in the Health 2000 cohort. A score consisting of adiponectin, apolipoprotein B, C-reactive protein and ferritin almost doubled the relative risk of diabetes in the validation cohort (HR per one standard deviation increase 1.88, p = 2.8 e-5). It also improved discrimination of the model (IDI = 0.0149, p

Trends in the incidence of and mortality from coronary heart disease during the period 1983-1988 were assessed in the population aged 35-64 years in three areas of Finland. The official mortality statistics and the FINMONICA (Finnish portion of the World Health Organization MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) project) Acute Myocardial Infarction Register were used as data sources. They both showed that coronary heart disease mortality declined steeply in Finnish men and women. This marked decline in coronary heart disease mortality was associated with a decline in the number of out-of-hospital coronary deaths. The changes in the incidence of acute myocardial infarction in men did not parallel the changes in mortality. No decline in incidence was seen in women in any of the study areas. These results suggest that the routine mortality statistics alone may give an overly favorable picture of coronary heart disease trends. Data on incidence are necessary to assess the need for the treatment and prevention of coronary heart disease.

The acute myocardial infarction (AMI) register of the FINMONICA study, the Finnish part of the WHO-coordinated multinational MONICA project, operates in the provinces of North Karelia and Kuopio in eastern Finland and in Turku, Loimaa and in communities around Loimaa in southwestern Finland. The AMI register serves as an instrument for the assessment of trends in mortality from coronary heart disease (CHD) and of the incidence andattack rates of AMI among 25–64-year-old residents of the study areas. This report describes the methods used in the FINMONICA A MI register and the findings during the first 3 years of the study, in 1983–1985. The criteria of the multinational WHO MONICA project were used in the classification of fatal events and in the diagnosis of non-fatal definite AMI, but based on the experience within the FINMONICA study, stricter diagnostic criteria than those originally described in the WHO MONICA protocol were used for non-fatal possible AMI. This led to a marked improvement in the comparability of the data from the three study areas with regard to the incidence and attack rates of non-fatal AMI. During the 3-year period the total number of registered events was 6266 among men and 2092 among women. Among men the incidence and attack rates of AMI and mortality from CHD were higher in eastern than in southwestern Finland. Also among women the incidence and attack, rates of AMI were higher in eastern than in southwestern Finland, whereas there was no regional difference in mortality from CHD among women. The mortality findings of the FINMONICA AMI Register were in good agreement with the official CHD mortality statistics of Finland.

Background It is well known that increasing age is the strongest risk factor of stroke. Therefore, it has been a common belief in many countries including Finland that the numbers of stroke patients will increase considerably during the next two decades because the population is rapidly ageing. Methods The FINMONICA and FINSTROKE registers operated in Finland in the Kuopio area and city of Turku from 1983 to 1997. The results showed that the incidence, mortality and case fatality of stroke declined significantly during that period. Importantly, it was established that the trends in incidence and mortality were also declining among the elderly (>74 years). We used these results to create a model for the entire country. The model was based on the trends present in these registers from Turku and Kuopio area and age-specific population projections up to the year 2030 that were obtained from Statistics Finland. Results In the year 2000, the number of new first stroke cases was estimated to be 11500. If the declining trend were to level off totally after the year 2000, the number of new strokes would be 20100 in the year 2030 due to the ageing of the population. It would be 12100 if the trend continued as favourable as during the years 1983–1997. Conclusions Ageing of the population will not inevitably increase the burden of stroke in Finland if the present declining trends are maintained, but the annual number of cases will almost double if the incidence remains at the level of the year 2000.

Recently, genome wide association studies (GWAS) have identified a number of single nucleotide polymorphisms (SNPs) as being associated with coronary heart disease (CHD). We estimated the effect of these SNPs on incident CHD, stroke and total mortality in the prospective cohorts of the MORGAM Project. We studied cohorts from Finland, Sweden, France and Northern Ireland (total N = 33,282, including 1,436 incident CHD events and 571 incident stroke events). The lead SNPs at seven loci identified thus far and additional SNPs (in total 42) were genotyped using a case-cohort design. We estimated the effect of the SNPs on disease history at baseline, disease events during follow-up and classic risk factors. Multiple testing was taken into account using false discovery rate (FDR) analysis. SNP rs1333049 on chromosome 9p21.3 was associated with both CHD and stroke (HR = 1.20, 95% CI 1.08–1.34 for incident CHD events and 1.15, 0.99–1.34 for incident stroke). SNP rs11670734 (19q12) was associated with total mortality and stroke. SNP rs2146807 (10q11.21) showed some association with the fatality of acute coronary event. SNP rs2943634 (2q36.3) was associated with high density lipoprotein (HDL) cholesterol and SNPs rs599839, rs4970834 (1p13.3) and rs17228212 (15q22.23) were associated with non-HDL cholesterol. SNPs rs2943634 (2q36.3) and rs12525353 (6q25.1) were associated with blood pressure. These findings underline the need for replication studies in prospective settings and confirm the candidacy of several SNPs that may play a role in the etiology of cardiovascular disease.

BackgroundCardiovascular disease (CVD) incidence, complications and burden differ markedly between women and men. Although there is variation in the distribution of lifestyle factors between the genders, they do not fully explain the differences in CVD incidence and suggest the existence of gender-specific genetic risk factors. We aimed to estimate whether the genetic risk profiles of coronary heart disease (CHD), ischemic stroke and the composite end-point of CVD differ between the genders.Methodology/principal findingsWe studied in two Finnish population cohorts, using the case-cohort design the association between common variation in 46 candidate genes and CHD, ischemic stroke, CVD, and CVD-related quantitative risk factors. We analyzed men and women jointly and also conducted genotype-gender interaction analysis. Several allelic variants conferred disease risk for men and women jointly, including rs1801020 in coagulation factor XII (HR = 1.31 (1.08-1.60) for CVD, uncorrected p = 0.006 multiplicative model). Variant rs11673407 in the fucosyltransferase 3 gene was strongly associated with waist/hip ratio (uncorrected p = 0.00005) in joint analysis. In interaction analysis we found statistical evidence of variant-gender interaction conferring risk of CHD and CVD: rs3742264 in the carboxypeptidase B2 gene, p(interaction) = 0.009 for CHD, and rs2774279 in the upstream stimulatory factor 1 gene, p(interaction) = 0.007 for CHD and CVD, showed strong association in women but not in men, while rs2069840 in interleukin 6 gene, p(interaction) = 0.004 for CVD, showed strong association in men but not in women (uncorrected p-values). Also, two variants in the selenoprotein S gene conferred risk for ischemic stroke in women, p(interaction) = 0.003 and 0.007. Importantly, we identified a larger number of gender-specific effects for women than for men.Conclusions/significanceA false discovery rate analysis suggests that we may expect half of the reported findings for combined gender analysis to be true positives, while at least third of the reported genotype-gender interaction results are true positives. The asymmetry in positive findings between the genders could imply that genetic risk loci for CVD are more readily detectable in women, while for men they are more confounded by environmental/lifestyle risk factors. The possible differences in genetic risk profiles between the genders should be addressed in more detail in genetic studies of CVD, and more focus on female CVD risk is also warranted in genome-wide association studies.

The genetic background of complex diseases is proposed to consist of several low-penetrance risk loci. Addressing this complexity likely requires both large sample size and simultaneous analysis of different predisposing variants. We investigated the role of four thrombosis genes: coagulation factor V (F5), intercellular adhesion molecule 1 (ICAM1), protein C (PROC), and thrombomodulin (THBD) in cardiovascular diseases. Single allelic gene variants and their pair-wise combinations were analyzed in two independently sampled population cohorts from Finland. From among 14,140 FINRISK participants (FINRISK-92, n = 5,999 and FINRISK-97, n = 8,141), we selected for genotyping a sample of 2,222, including 528 incident cardiovascular disease (CVD) cases and random subcohorts totaling 786. To cover all known common haplotypes (>10%), 54 single nucleotide polymorphisms (SNPs) were genotyped. Classification-tree analysis identified 11 SNPs that were further analyzed in Cox's proportional hazard model as single variants and pair-wise combinations. Multiple testing was controlled by use of two independent cohorts and with false-discovery rate. Several CVD risk variants were identified: In women, the combination of F5 rs7542281 × THBD rs1042580, together with three single F5 SNPs, was associated with CVD events. Among men, PROC rs1041296, when combined with either ICAM1 rs5030341 or F5 rs2269648, was associated with total mortality. As a single variant, PROC rs1401296, together with the F5 Leiden mutation, was associated with ischemic stroke events. Our strategy to combine the classification-tree analysis with more traditional genetic models was successful in identifying SNPs—acting either in combination or as single variants—predisposing to CVD, and produced consistent results in two independent cohorts. These results suggest that variants in these four thrombosis genes contribute to arterial cardiovascular events at population level., Author Summary The genetic background of cardiovascular diseases is still largely unknown. As in other complex diseases, the genetic risk is thought to consist of several genetic variants and their possible interactions. Elucidation of the genetic component of any complex trait most likely requires simultaneous examination of various genes in large and well-characterized study samples. Our study explores the role in cardiovascular disease of four thrombosis genes: coagulation factor V, intercellular adhesion molecule 1, protein C, and thrombomodulin. These genes form a physiological pathway that is part of the coagulation cascade. Their defects, such as the Leiden mutation in factor V gene, predispose to venous thrombosis, making them tempting candidates for involvement with cardiovascular events. Given the interactions of these genes at the molecular level, a logical way to explore their genetic effects is simultanous rather than gene-specific analysis of all the four genes, aiming to illustrate their possible interplay. The study setting combines classification trees with classic genetic analyses and covers all known common variants of the genes. The results imply that the variants in these four genes contribute to disease risk either alone or in various allelic combinations.

OBJECTIVES: To quantify the association between systolic blood pressure and season, indoor and outdoor temperature and short-term trends in outdoor temperature. METHODS: The study used data from the WHO MONICA Project risk factors surveys from 25 populations in 16 countries. Random samples of men and women aged 35-64 years were invited to participate. Systolic blood pressure measurements were available for 115 434 participants. Hierarchical models were used to quantify the association between blood pressure and temperature, and account for differences in the associations between populations. RESULTS: Populations closer to the equator showed larger seasonal changes in blood pressure. A 1 degrees C increase in indoor temperature reduced systolic blood pressure by an average of 0.31 mmHg (95% posterior interval: -0.44, -0.19). A 1 degrees C increase in outdoor temperature reduced blood pressure by the smaller average of 0.19 mmHg (95% posterior interval: -0.26, -0.11). Increased outdoor, but not indoor, temperatures had a stronger effect in women than in men. The effect of outdoor temperature remained after controlling for indoor temperature. Short-term trends in temperature did not have a statistically signicant effect. CONCLUSIONS: Indoor and outdoor temperature have independent effects on systolic blood pressure, and both should be controlled for in studies that measure blood pressure. Improved protection against cold temperatures could lead to a reduction in the winter excess of cardiovascular mortality.

When the schooling years are compared between individuals having different birth years, the steep rise in schooling years in the 20th century must be taken into account. The problem has particular importance in large international population studies, such as the WHO MONICA Project and its successor, the MORGAM Project. We present an algorithm that divides the individuals into three groups on the basis of the schooling years while preserving smooth behavior of the cut-points between consecutive birth years. The usage of method is demonstrated with data from Finland, Italy, Lithuania, and Scotland, which have different patterns of the estimated tertiles of schooling years.

Aims The object of this study is to analyse the trends in coronary events in Finland during 1993–2002, correcting for the effect of troponins. Methods and results A population-based myocardial infarction register recorded all coronary events ( n =14 782) in four geographical areas of Finland during 1993–2002. Correction coefficients for the effect of troponins were calculated on the basis of 4359 coronary events, with simultaneous determination of troponins and the ‘old’ enzymatic markers of myocardial injury. Coronary mortality declined steeply, except in women aged ≥75 years. The incidence of first coronary events declined 2.0% (95% confidence interval −3.0, −0.9%) per year among men and 1.0% (−2.7, 0.6%) per year among women aged 35–74 years. After correcting for the effect of troponins, also the decline among women became statistically significant: 2.7% (−4.5, −0.8%) per year. The effect of troponins tended to be stronger in women and older individuals than in men and younger individuals. The 28-day case fatality declined among men, but not among women. The effect of troponins on case fatality trends was weak. Conclusion Declining trends in the incidence of coronary events in Finland during 1993–2002 were partly hidden by the effect of troponins. Both incidence and case fatality declines have contributed to the decline in mortality.

Objective To analyse the risk of coronary heart disease (CHD) events and total mortality among patients who had coronary artery bypass graft (CABG) surgery during 1988–1992. Methods A population-based myocardial infarction (MI) register included data on invasive cardiac procedures among residents of the study area. The subjects aged 35–64 years were followed-up for 12 years for non-fatal and fatal CHD events and all-cause mortality, excluding events within 30 days of the CABG operation. CABG was performed on 1158 men and 215 women. Results The overall survival of men who underwent CABG was similar to the survival of the corresponding background population for about ten years but started to worsen after that. At twelve years of follow-up, 23% ( n = 266, 95% CI 234–298) of the men who had undergone the operation had died, while the expected proportion, based on mortality in the background population, was 20% ( n = 231, 95% CI 226–237). The CHD mortality of men who had undergone the operation was clearly higher than in the background population. Among women, the mortality after CABG was about twice the expected mortality in the corresponding background population. In Cox proportional hazards models age, smoking, history of MI, body mass index and diabetes were significant predictors of mortality. Conclusions The prognosis of male CABG patients did not differ from the prognosis of the corresponding background population for about ten years, but started to deteriorate after that. History of MI prior to CABG and major cardiovascular risk factors was a predictor of an adverse outcome.

Upstream transcription factor 1 (USF1) is a ubiquitously expressed transcription factor controlling several critical genes in lipid and glucose metabolism. Of some 40 genes regulated by USF1, several are involved in the molecular pathogenesis of cardiovascular disease (CVD). Although the USF1 gene has been shown to have a critical role in the etiology of familial combined hyperlipidemia, which predisposes to early CVD, the gene's potential role as a risk factor for CVD events at the population level has not been established. Here we report the results from a prospective genetic–epidemiological study of the association between the USF1 variants, CVD, and mortality in two large Finnish cohorts. Haplotype-tagging single nucleotide polymorphisms exposing all common allelic variants of USF1 were genotyped in a prospective case-cohort design with two distinct cohorts followed up during 1992–2001 and 1997–2003. The total number of follow-up years was 112,435 in 14,140 individuals, of which 2,225 were selected for genotyping based on the case-cohort study strategy. After adjustment for conventional risk factors, we observed an association of USF1 with CVD and mortality among females. In combined analysis of the two cohorts, female carriers of a USF1 risk haplotype had a 2-fold risk of a CVD event (hazard ratio [HR] 2.02; 95% confidence interval [CI] 1.16–3.53; p = 0.01) and an increased risk of all-cause mortality (HR 2.52; 95% CI 1.46–4.35; p = 0.0009). A putative protective haplotype of USF1 was also identified. Our study shows how a gene identified in exceptional families proves to be important also at the population level, implying that allelic variants of USF1 significantly influence the prospective risk of CVD and even all-cause mortality in females., Synopsis Better characterization of molecular events resulting in cardiovascular disease (CVD) requires elucidation of genetic background of CVD. After a CVD candidate gene is identified in family-based studies or case-control studies, population-based prospective studies are needed to demonstrate any potential impact of allelic variants on the CVD risk at the population level. This study addresses the role of different alleles of the upstream transcription factor 1 (USF1) gene, encoding a transcription factor and originally associated with familial combined hyperlipidemia in rare families with multiple affected individuals. The product of USF1 regulates numerous genes of lipid and glucose metabolism, and the authors show in large population cohorts that specific alleles of USF1 are associated with the risk of CVD and all-cause mortality among females. The study implies an interesting female-specific risk effect, and should stimulate additional studies of the sex-specific CVD risk genes in different populations.

The amount of available DNA is often a limiting factor in pursuing genetic analyses of large-scale population cohorts. An association between higher DNA yield from blood and several phenotypes associated with inflammatory states has recently been demonstrated, suggesting that exclusion of samples with very low DNA yield may lead to biased results in statistical analyses. Whole genome amplification (WGA) could present a solution to the DNA concentration-dependent sample selection. The aim was to thoroughly assess WGA for samples with low DNA yield, using the multiply-primed rolling circle amplification method. Fifty-nine samples were selected with the lowest DNA yield (less than 7.5µg) among 799 samples obtained for one population cohort. The genotypes obtained from two replicate WGA samples and the original genomic DNA were compared by typing 24 single nucleotide polymorphisms (SNPs). Multiple genotype discrepancies were identified for 13 of the 59 samples. The largest portion of discrepancies was due to allele dropout in heterozygous genotypes in WGA samples. Pooling the WGA DNA replicates prior to genotyping markedly improved genotyping reproducibility for the samples, with only 7 discrepancies identified in 4 samples. The nature of discrepancies was mostly homozygote genotypes in the genomic DNA and heterozygote genotypes in the WGA sample, suggesting possible allele dropout in the genomic DNA sample due to very low amounts of DNA template. Thus, WGA is applicable for low DNA yield samples, especially if using pooled WGA samples. A higher rate of genotyping errors requires that increased attention be paid to genotyping quality control, and caution when interpreting results.

We compared the risk of acute coronary events in diabetic and non-diabetic persons with and without prior myocardial infarction (MI), stratified by age and sex.A Finnish MI-register study known as FINAMI recorded incident MIs and coronary deaths (n=6988) among people aged 45 to 74 years in four areas of Finland between 1993 and 2002. The population-based FINRISK surveys were used to estimate the numbers of persons with prior diabetes and prior MI in the population.Persons with diabetes but no prior MI and persons with prior MI but no diabetes had a markedly greater risk of a coronary event than persons without diabetes and without prior MI. The rate of recurrent MI among non-diabetic men with prior MI was higher than the incidence of first MI among diabetic men aged 45 to 54 years. The rate ratio was 2.14 (95% CI 1.40-3.27) among men aged 50. Among elderly men, diabetes conferred a higher risk than prior MI. Diabetic women had a similar risk of suffering a first MI as non-diabetic women with a prior MI had for suffering a recurrent MI.Both persons with diabetes but no prior MI, and persons with a prior MI but no diabetes are high-risk individuals. Among men, a prior MI conferred a higher risk of a coronary event than diabetes in the 45-54 year age group, but the situation was reversed in the elderly. Among diabetic women, the risk of suffering a first MI was similar to the risk that non-diabetic women with prior MI had of suffering a recurrent MI.

Background The estimation of population distribution of total cholesterol, as well as other blood lipids requires population surveys. Comparability of the estimates over time or between populations requires a predefined, standardized measurement protocol. This paper will assess the effect of variation in the pre-analytic procedures, on the estimation of population distribution of total cholesterol and the prevalence of hypercholesterolaemia. Implications of variation to real survey results are demonstrated on data collected during the WHO MONICA Project. Design and methods The extent (%) of pre-analytic variations were determined by literature review. Simulations were then used to estimate the effect of these variations on the distribution of total cholesterol values. Three populations were selected as examples for different population distributions of total cholesterol levels and variations resulting from seasonal and postural changes, use of tourniquet, and serum versus plasma collection were simulated both individually and in combinations. Results Depending on the population distribution of total cholesterol, differences in pre-analytic procedures can explain a difference of up to 1.12 mmol/l in the mean total cholesterol between populations, and a difference up to 41% in the prevalence of hypercholesterolaemia (> or =6.5 mmol/l). Conclusions Variation in results on measured total cholesterol levels due to differences in procedures during the pre-analytic stage can diminish substantially the reliability and comparability of measurements among surveys over time and between populations. The effect of pre-analytic variation in the population estimates of total cholesterol can be extensively reduced by standardization and training.

Background and Purpose— The purpose of this study was to analyze the incidence and mortality trends in stroke events among persons 25 to 74 years of age in Finland during 1983 to 1997. Methods— The population-based FINSTROKE register recorded 5650 new strokes among persons 25 to 74 years of age in 2 geographical areas of Finland: 2770 in the Kuopio area (east central Finland) and 2880 in Turku (southwestern Finland). Of these, 3065 were men and 2585 were women. Results— The rates of acute stroke events fell during the whole study period in both men and women. In both FINSTROKE areas combined, the average annual decline in the age-standardized incidence of first stroke events was 2.0% (95% confidence interval [CI], −2.8 to −1.2; P P P P P P P =0.07 among men, P =0.05 among women). Conclusions— Incidence and mortality of stroke events declined significantly in these 2 register areas in Finland during the 15-year period of 1983 to 1997.

It is common in the analysis of aggregate data in epidemiology that the variances of the aggregate observations are available. The analysis of such data leads to a measurement error situation, where the known variances of the measurement errors vary between the observations. Assuming multivariate normal distribution for the 'true' observations and normal distributions for the measurement errors, we derive a simple EM algorithm for obtaining maximum likelihood estimates of the parameters of the multivariate normal distributions. The results also facilitate the estimation of regression parameters between the variables as well as the 'true' values of the observations. The approach is applied to re-estimate recent results of the WHO MONICA Project on cardiovascular disease and its risk factors, where the original estimation of the regression coefficients did not adjust for the regression attenuation caused by the measurement errors.

Background and Purpose —It has been shown that low socioeconomic status is associated with death from stroke. More-detailed data have, however, remained scanty. The purpose of the present study was to examine the association of socioeconomic status with ischemic stroke. Besides mortality, we analyzed the incidence, case-fatality ratio, and prognosis of ischemic stroke events. Methods —Our population-based study included 6903 first stroke events registered by the FINMONICA Stroke Register in 3 areas of Finland during 1983 to 1992. Indicators of socioeconomic status, such as taxable income and education, were obtained by record linkage of the stroke register data with files of Statistics Finland. Results —Incidence, case-fatality ratio, and mortality rates for ischemic stroke were all inversely related to income. Furthermore, 28 days after the onset of symptoms, a greater proportion of patients with low income than of those with high income was still in institutionalized care and/or in need of help for their activities of daily living. Population-attributable risk of the incidence of first ischemic stroke due to low socioeconomic status was 36% for both sexes. For the death from first ischemic stroke, it was 56% for both sexes. Conclusions —Persons with low socioeconomic status have considerable excess rates of morbidity and mortality from ischemic stroke in Finland. A reduction in this excess could markedly decrease the burden of ischemic stroke to the society and thus constitute an important public health improvement.

OBJECTIVE—To examine socioeconomic differences in case fatality and prognosis of myocardial infarction (MI) events, and to estimate the contributions of incidence and case fatality to socioeconomic differences in coronary heart disease (CHD) mortality. DESIGN—A population-based MI register study. METHODS—The FINMONICA MI Register recorded all MI events among persons aged 35-64 years in three areas of Finland during 1983-1992. A record linkage of the MI Register data with the files of Statistics Finland was performed to obtain information on socioeconomic indicators for each individual registered. First MI events (n=8427) were included in the analyses. MAIN RESULTS—The adjusted risk ratio of prehospital coronary death was 2.11 (95% CI 1.82, 2.46) among men and 1.68 (1.14, 2.48) among women with low income compared with those with high income. Even among persons hospitalised alive the risk of death during the next 12 months was markedly higher in the low income group than in the high income group. Case fatality explained 51% of the CHD mortality difference between the low and the high income groups among men and 38% among women. Incidence contributed 49% and 62%, respectively. CONCLUSIONS—Considerable socioeconomic differences were observed in the case fatality of first coronary events both before hospitalisation and among patients hospitalised alive. Case fatality explained a half of the CHD mortality difference between the low and the high income groups among men and more than a third among women. Keywords: socioeconomic status; myocardial infarction; case fatality

Background —Low socioeconomic status (SES) is associated with increased coronary heart disease mortality rates. There are, however, very little data on the relation of SES to the incidence, recurrence, and prognosis of myocardial infarction (MI) events. Methods and Results —The FINMONICA MI Register recorded detailed information on all MI events among men and women aged 35 to 64 years in 3 areas of Finland during the period of 1983 to 1992. We carried out a record linkage of the MI register data with files of Statistics Finland to obtain information on indicators of SES, such as taxable income and education, for each individual who is registered. In the analyses, income was grouped into 3 categories (low, middle, and high), and education was grouped into 2 categories (basic and secondary or higher). Among men with their first MI event (n=6485), the adjusted incidence rate ratios were 1.67 (95% CI 1.57 to 1.78) and 1.84 (95% CI 1.73 to 1.95) in the low- and middle-income categories compared with the high-income category. For 28-day mortality rates, the corresponding rate ratios were 3.18 (95% CI 2.82 to 3.58) and 2.33 (95% CI 2.03 to 2.68). Significant differentials were observed for prehospital mortality rates, and they remained similar up to 1 year after the MI. Findings among the women were consistent with those among the men. Conclusions —The excess coronary heart disease mortality and morbidity rates among persons with low SES are considerable in Finland. To bring the mortality rates of low- and middle-SES groups down to the level of that of the high-SES group constitutes a major public health challenge.

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.

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 32000 men and women aged 25-64y 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 78-91cm in women. Mean hip circumference ranged from 94-105cm and from 97-108cm 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.

In the early to mid 1980s, the WHO MONICA Project conducted cardiovascular risk factor surveys in 41 study populations in 22 countries. Study populations aged 35-64 years comprised 32,422 men and 32,554 women. Blood pressures (BP) and body mass index (BMI) were measured according to a standard protocol. Participants were asked about antihypertensive medication. In men, the average age-standardized BPs ranged among the populations from 124 to 148 mm Hg for systolic (SBP) and from 75 to 93 mm Hg for diastolic (DBP). The corresponding values in women were 118-145 mm Hg for SBP and 74-90 mm Hg for DBP. In all populations, women had lower SBP than men in the age group 35-44. However, SBP in women rose more steeply with age so that in 34 of 41 populations women had higher SBP than men in the age group 55-64. The proportion of participants with untreated major elevation of BP ranged from 4.5% to 33.7% in men and from 1.9% to 22.3% in women. The proportions of participants receiving antihypertensive medication were 4.3-17.7% for men and 6.0-22.0% for women. These proportions were not correlated with the prevalence of untreated hypertensives. Age-adjusted BMI was associated with SBP and accounted for 14% of the SBP variance in men and 32% in women. We found a large difference in SBP among the MONICA study populations and conclude that the results represent a valid estimate of the public health problem posed by elevated BP. We also have shown that almost universally the problem of elevated BP is more prevalent in women than in men, especially in the older age groups.

The World Health Organization (WHO) MONICA Project is a 10-year study monitoring trends and determinants of cardiovascular disease in geographically defined populations. Data were collected from over 100 000 randomly selected participants in two risk factor surveys conducted approximately 5 years apart in 38 populations using standardized protocols. The net effects of changes in the risk factor levels were estimated using risk scores derived from longitudinal studies in the Nordic countries. The prevalence of cigarette smoking decreased among men in most populations, but the trends for women varied. The prevalence of hypertension declined in two-thirds of the populations. Changes in the prevalence of raised total cholesterol were small but highly correlated between the genders (r = 0.8). The prevalence of obesity increased in three-quarters of the populations for men and in more than half of the populations for women. In almost half of the populations there were statistically significant declines in the estimated coronary risk for both men and women, although for Beijing the risk score increased significantly for both genders. The net effect of the changes in the risk factor levels in the 1980s in most of the study populations of the WHO MONICA Project is that the rates of coronary disease are predicted to decline in the 1990s.

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.

One of the main hypotheses of the World Health Organization (WHO) MONICA Project is that trends in the major coronary disease risk factors are related to trends in rates of fatal and non-fatal coronary disease events. The units of study are populations rather than individuals. The WHO MONICA Project involves continuous monitoring of all coronary disease events in the populations over a 10-year period and periodic risk factor surveys in random samples of the same populations. Estimation of associations between average annual changes in mortality and risk factor levels is illustrated with the use of data from a subset of MONICA centers. Crude estimates of regression coefficients are compared with estimates obtained by weighting for standard errors in both the outcome and explanatory variables. The results show that the strength of association may be either underestimated or overestimated if these errors are not taken into account.

Background and Purpose The trends in stroke incidence reported so far have not been entirely consistent, although declining trends in mortality from stroke have been reported from a number of studies around the world. This study aims to evaluate the 10-year trends (from 1983 through 1992) in incidence, attack rate, and mortality of stroke in the Finnish population. Methods A population-based stroke register was set up in the early 1980s to collect data on all suspected events of acute stroke that occurred in the population aged 25 to 74 years permanently residing in three geographic areas of Finland: the provinces of Kuopio and North Karelia in eastern Finland and the Turku-Loimaa area in southwestern Finland. Trends in age-standardized attack rates, incidence, and mortality were calculated for the period studied. Results During the 10-year study period, 11 392 acute stroke events occurred in the monitored populations. A statistically significant decline was observed in the pooled FINMONICA data, both in the incidence of stroke (−1.7% with 95% confidence interval [CI], −3.0% to −0.5% per year in men; −2.2% with 95% CI, −3.6% to −0.7% per year in women) and in mortality from stroke (−5.2% with 95% CI, −8.2% to −2.2% per year; −4.7% with 95% CI, −8.2% to −1.2% per year). The attack rate of stroke also declined significantly in both sexes. When the areas were considered separately, the declining trends were observed within each area. The decline in incidence of stroke was, however, statistically significant only among men and women in Kuopio and among women in Turku/Loimaa. Mortality declined significantly in all three areas among men but among women only in Kuopio. The incidence to mortality rate ratio increased during the study period, indicating a steeper fall in mortality than in incidence. Conclusions A substantial decline in both stroke incidence and mortality was observed in the adult and elderly population in the FINMONICA study areas. Part but not all of the decline in stroke mortality, observed also in the official mortality statistics, can be attributed to the decline in stroke incidence during this 10-year period.

Because of the general inavailability of reference standards, there exist no common procedures to assess the quality of blood pressure measurements in epidemiological population surveys. To approach this problem within the collaborative international WHO MONICA Project, a standardized assessment of BP measurement quality was developed and applied to the forty-seven baseline surveys of that project. The entire assessments were carried out in retrospect, that is, only after each population survey had been completed. The assessment was focused on the procedures of quality assurance and control as reportedly applied in each survey, and on quality indicators which were derived from the recorded blood pressure values of each survey. The definitions of specific quality assessment items were based on the MONICA project protocol and on sources in the pertinent literature. The available information on quality assurance and control procedures depended solely on self-reports by local survey organizers and on site visits, and was occasionally found to be at variance with the actual blood pressure recordings. Therefore, quality indicators derived from actual blood pressure recordings were far more informative and comparable between surveys. Each survey was rated as optimal, satisfactory, or unsatisfactory with regard to single quality items and these single scores were used jointly to compute a summary score of blood pressure measurement quality for each survey. This summary score indicated that 39 out of 47 MONICA baseline surveys showed optimal or satisfactory BP measurement quality. Limitations and potentials for improvement of quality assessments became apparent. We conclude that a standardized assessment of BP measurement quality in epidemiological population surveys seems feasible and propose that quality assessment methods similar to the ones suggested here become a routine part of future epidemiological analyses of blood pressure values and hypertension in populations. This should facilitate valid study comparisons.

BACKGROUND 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 RESULTS Fatal 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 case-fatality 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. CONCLUSIONS The 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.

Objective —To compare the long-term trends in mortality and attack rate of ischaemic heart disease in North Karelia, Finland, and in Kaunas, Lithuania, from 1971 to 1987. Design —Data on routine mortality statistics were obtained from the Central Statistical Office of Finland and from the Central City Archives of Kaunas. In addition, data from the community based myocardial infarction registers were used. The registers used similar diagnostic criteria and had operated in both areas during the entire study period. Setting —The province of North Karelia in Finland and the city of Kaunas in Lithuania. Subjects —The target populations were the people of North Karelia and Kaunas aged 35–64 years. Main outcome measures —Mortality from ischaemic heart disease and the attack rate of acute myocardial infarction. Results —In North Karelia mortality from ischaemic heart disease and the attack rate of acute myocardial infarction declined steeply both in men and women. This decline was accompanied by a decrease in total mortality. In Kaunas, both mortality and the attack rate increased in men but remained unchanged in women. In 1985 to 1987, age standardised total mortality per 100 000 inhabitants was similar in the two populations in men (1081 (95% confidence interval (CI) 1013 to 1149), in North Karelia; 1082 (95% CI 1032 to 1132), in Kaunas). The proportional mortality from ischaemic heart disease was considerably higher in North Karelia (40%) than in Kaunas (28%). In women, age standardised total mortality was lower in North Karelia (350 (95% CI 312–388)) than in Kaunas (440 (95% CI 413 to 467)). The proportional mortality from ischaemic heart disease in women was also higher in North Karelia (28%) than in Kaunas (13%). Conclusions —Despite the remarkable decline in the occurrence of ischaemic heart disease, it still remains the most important cause of premature mortality in North Karelia. In Kaunas ischaemic heart disease mortality and attack rate increased in men. Experiences from successful cardiovascular disease prevention programmes in western countries, such as the North Karelia Project, should be exploited to prevent an increasing epidemic of ischaemic heart disease in eastern Europe.