Fatalities from myocardial infarction in Nordic Countries and Lithuania

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1 European Heart Journal (997) 8, 9-98 ities from myocardial infarction in Nordic Countries and Lithuania V. V. Salomaa*, V. Lundbergf, U. Agnarsson±, R. Radisauskas, M. Kirchhoff and L. WilhelmsenH for the MONICA investigators** in Nordic countries and Lithuania *National Public Health Institute, Helsinki, Finland; tkali.x Hospital, Kalix, Sweden; \Heart Preventive Clinic, Reykjavik, Iceland; ^Institute of Cardiology, Kaunas, Lithuania; \\Glostrup Population Studies, Copenhagen, Denmark; *\G6teborg University, Goteborg, Sweden Aim To investigate fatalities from myocardial infarction at 8 days and one-year among patients aged years in the Nordic and Lithuanian centres participating in the World Health Organization MONICA (Monitoring of Trends and Determinants of Cardiovascular Disease) Project. Methods and results Altogether 9 myocardial infarction events registered according to the protocol of the MONICA Project were included in the study. For these events, one-year follow-up was carried out using routine mortality statistics. ities were expressed as agestandardized means per year for a 3-year period from the mid-98s. The myocardial infarction fatalities at 8 days (including out-of-hospital deaths) in the eight participating populations varied among men, between 36-5% (95% confidence interval %) in Iceland and 54-6% ( %) in Kaunas, Lithuania. Among women, it varied from 3-4% ( %) in Iceland to 57-5% ( %) in Glostrup, Denmark. More than half of this mortality Introduction Myocardial infarction is one of the most important causes of mortality in industrialized countries '. The mortality rates depend both on the incidence and fatality of the myocardial infarction. However, the majority of coronary mortality occurs outside hospital and therefore the fatality rates are difficult to establish. Estimates of myocardial infarction fatalities vary widely depending on the population studied and the criteria of myocardial infarction 7. Although there are few studies on the **Key investigators in participating centres are listed in the Appendix. Revision submitted 4 June 996 and accepted 9 June 996. Correspondence: Dr Veikko Salomaa, National Public Health Institute, Department of Epidemiology and Health Promotion, Mannerheimintie 66, FIN-3 Helsinki, Finland. occurred suddenly and the patient did not reach hospital alive. ities for the period from day 8 to one year varied among men, from 5-3% (-9-7-6%) in Iceland to -9% (8-3-8%) in North Karelia, Finland, and among women from 3-5% (-4-6-5%) in Kuopio, Finland, to 3-5% (7--9-7%) in Glostrup, Denmark. Conclusions Approximately half of the myocardial infarction patients died within one year after the onset of the attack and half of those who died, died out-of-hospital. While the myocardial infarction fatalities differed considerably between the participating populations, differences of this magnitude are unlikely to be toty explained by differences in the registration procedures. Further comparisons of acute coronary care and secondary prevention measures are warranted. (Eur Heart J 997; 8: 9-98) Key Words: Myocardial infarction, coronary heart disease, case-fatality, MONICA Project. above, even fewer have been published on the long-term prognosis of myocardial infarction patients. It is important, however, to obtain reliable information on deaths that occur both in the short- and long-term from myocardial infarction, since there are powerful measures of reducing fatality of hospitalized patients. Thrombolytic treatment can be used to reduce deaths that occur in the short-term and lowering low density lipoprotein cholesterol for those that occur in the long-term' 8 ". Comparison of fatality figures between populations could indicate whether these treatment modalities are effective or whether there is room for improvement. Cross-sectional comparison of fatality figures between populations is problematic, because it requires a carefully standardized methodology and complete coverage of both fatal and non-fatal events. The World Health Organization's MONICA (Monitoring Trends and Determinants of Cardiovascular Disease) Project Downloaded from by guest on January X/97/9+8 $8./ tj 997 the European Society of Cardiology

2 9 V. V. Salomaa et al. has established such a methodology for registration of myocardial infarction events'"' and this, together with stable populations and reliable mortality statistics in Nordic countries, provide a sound basis for examining and comparing fatalities from myocardial infarction. Kaunas in Lithuania has a long and successful tradition in cardiovascular epidemiology ' 3 and their myocardial infarction register has been functioning since the beginning of the 97s' 4. Interestingly, the trend in coronary mortality has been increasing in Lithuania, whereas the Nordic populations show a declining trend. The 8-day fatality rates from myocardial infarction for populations taking part in the WHO MONICA Project have been published previously in a paper describing the registration procedures and baseline findings in 38 populations from countries'". The aim of the present paper is to analyse these data for Nordic countries and Lithuania in more detail and to discuss possible reasons for observed differences. Furthermore, we have extended our study beyond the 8-day limit of the MONICA project and carried out one-year follow-up after the infarct in relation to total and coronary mortality. Material and methods The registration procedures and participating populations of the myocardial infarction registers in the WHO MONICA Project have been described recently'". Among others, seven populations from Nordic countries and one from Lithuania are taking part in the study. These populations are: Glostrup, Denmark; Kuopio Province, Finland; North Karelia, Finland; Turku/ Loimaa, Finland; Iceland; Kaunas, Lithuania; Gothenburg, Sweden; and Northern Sweden. The population sizes within the age group years ranged from 63 9 in North Karelia, Finland, to 9 in Northern Sweden. Every coronary event occurring in the monitored populations was registered and assessed according to the MONICA protocol'". Data for the 3-year period were used for other populations, but were used for Gothenburg, Sweden, and for Northern Sweden. The autopsy rates in populations included in the present study were high, varying from 9% in Gothenburg, Sweden, to 45% in Glostrup, Denmark. The coronary event rates were calculated according to 'MONICA Definition ', which includes 'definite myocardial infarctions', 'fatal possible myocardial infarctions' and 'fatal unclassifiable events' expressed per per year'". It is considered to give the best comparability for event rates in different populations. Diagnostic criteria for definite myocardial infarction, fatal possible myocardial infarction and fatal unclassifiable events have been published'". Briefly, definite myocardial infarction consists of events with (a) definite ECG, or (b) typical, atypical or inadequately Eur Heart J, Vol. 8, January 997 described symptoms, together with probable ECG and abnormal cardiac enzymes, or (c) typical symptoms and abnormal enzymes with ischaemic or non-codable ECG or ECG unavailable, or (d) fatal case which, on visual inspection, appears to be fresh myocardial infarction, and/or recent coronary occlusion found at necropsy. The category fatal possible myocardial infarction or coronary death consists of fatal cases where there is no good evidence for another cause of death, clinicy or at necropsy, (a) with symptoms typical or atypical or inadequately described, or (b) without typical or atypical or inadequately described symptoms, but with evidence of chronic coronary occlusion or stenosis or old myocardial scarring at necropsy, or (c) with a good history of chronic ischaemic heart disease. unclassifiable events consist of cases with no necropsy, no history of typical or atypical or inadequately described symptoms, no previous history of chronic ischaemic heart disease and no other diagnosis. The MONICA Project pays particular attention to the coverage of fatal coronary events. The number of registered fatal events in each area should match or exceed the number of coronary deaths in the routine mortality statistics for that area. No such reference exists for non-fatal events, but the MONICA protocol requires that centres develop registration procedures, which cover at least definite non-fatal myocardial infarctions. Accordingly, centres included in the present study have tested their registration procedures in pilot studies and found the coverage adequate. Details of the registration and case finding procedures have been described in the main publication of the MONICA Project'" and in individual publications of the participating centres' 5 " 7. Statistical methods The time frame for one event in MONICA is 8 days. Thus, multiple symptoms occurring during the same 8-day period are considered to belong to the same event. Twenty-eight day fatalities are the proportion of events (%) which are fatal within 8 days. The one-year follow-up was carried out using routine mortality statistics from each country. Total mortality and ischaemic heart disease mortality (4-44) were used as the end points. We defined one-year fatalities as the proportion of events (%) which were fatal within 365 days after the onset of the attack. Multiple non-fatal events occurring in the same person during this 365-day period would, however, inflate the denominator of the one-year fatalities, thus biasing the results lower. Since the MONICA database does not contain a unique personal identifier, we had no way of identifying multiple non-fatal events in the same person. We could, however, use the Finnish social security number for calculating the magnitude of this bias in the Finnish populations. Deleting the 'extra' non-fatal events in the same person brought about a 6% increase in the one-year fatalities in the Finnish populations. We therefore multiplied the one-year fatalities in Downloaded from by guest on January 9

3 ities from myocardial infarction in Nordic countries 93 other populations by 6. This removes the bias, assuming that the number of multiple non-fatal events is similar in participating populations. Another way to deal with this problem is to calculate the one-year fatalities for first events only. This approach was, however, complicated by the fact that in some populations the history of previous myocardial infarction was not known for a certain proportion of events (maximum 7% of non-fatal events in Glostrup, Denmark). When calculating one-year fatalities, we combined these events with the category of 'no previous myocardial infarction', i.e. they were considered as first myocardial infarctions. The fatalities were age-standardized to the age distribution of coronary events in MONICA. Thus the weights were, 3 and 7 for the age-groups 35-44, and 55-64, respectively. The 95% confidence intervals were calculated on the basis of the normal approximation of binomial distribution. Among women, the agespecific fatalities are presented with the two lowest age groups combined because of the sm number of events in young women. The statistical analyses were carried out using SAS [I8]. Results Altogether, 9 fatal and non-fatal myocardial infarction events fulfilling the inclusion criteria were registered during the study period. Their distribution by centre, sex and age group is presented in Table. The number of fatal unclassifiable events was very sm in most populations, but some occurred in Kaunas, Lithuania, and in Glostrup, Denmark. The information on whether the myocardial infarction was first or recurrent was also well recorded in most populations, but some missing information on previous infarcts occurred especiy on fatal events in Glostrup, Denmark; Kaunas, Lithuania; and Northern Sweden. The age-specific 8-day fatalities increased with increasing age among men (Table ). Among women, the increase was less consistent due to the smer number of events. The age-standardized 8-day fatalities varied among men from 36-5% (95% Cl %) in Iceland to 54-6% ( %) in Kaunas, Lithuania (Table ). Among women, the lowest 8-day fatalities were observed in Kuopio, Finland, 3-4% ( %) closely followed by Iceland, 3-9% (3--4-5%). The highest 8 day fatalities in women was observed in Glostrup, Denmark, 575% ( %). In three out of the eight participating populations the 8-day fatalities were higher in women than in men, but in the majority of populations it was higher in men than in women. As expected, the 8-day fatalities were higher for recurrent myocardial infarctions than for the initial occurrence (Table 3), but the rank order of the populations remained approximately similar both for first and recurrent infarcts. Every third or every fourth myocardial infarction patient died out of hospital. Among men, this proportion was highest in Kaunas, Lithuania, 4-% (38-3^*4-%), and lowest in Iceland, 4-3% ( -7-5%) (Table 4). Among women, the out-of-hospital fatalities were highest in Glostrup, Denmark, 36-8% (3--4-3%) and lowest in Northern Sweden, 7-3% (3-5%). The total in-hospital fatality among men was highest in Glostrup, Denmark, 33-7% (3--37-%) of those who had arrived at hospital alive, and lowest in Iceland, 6% (-7-9-6%). Early (<4 h since the beginning of symptoms) in-hospital fatalities were higher in Glostrup, Denmark, than elsewhere. In women, the total inhospital fatalities were also highest in Glostrup, 3-8% ( %) of those who arrived at hospital alive, and lowest in Iceland, 7-7% ( %). However, the confidence intervals were wide among women. After the first 8 days, mortality was low. For the period between day 8 and one year the highest fatalities among men were observed in the Finnish centres, North Karelia, -9% (8--3-8%), and Turku/ Loimaa 9% ( %) (Table 5). In Iceland, the corresponding figure was 5-3% (-8-7-6%), less than half that observed in North Karelia and Turku/Loimaa. Among women, fatalities for the period from day 8 to one year was highest in Glostrup, Denmark, 3-5% (7--9-7%) and lowest in Kuopio, Finland, 3-5% (-4-6-5%). The total one-year fatality among men was highest in Kaunas, Lithuania, 58 4% ( %) and lowest in Iceland, 4% (36-44%) (Table 5). In women, the highest one-year fatalities were observed in Glostrup, Denmark, 6-% ( %), and the lowest in Iceland, 35-4% (6-^4-8%). When broken down to first and recurrent myocardial infarctions, the findings remained approximately similar to those of total fatalities. Coronary heart disease was by far the most common cause of death during the period between 8 days and one year after the myocardial infarction. Among men, the proportion of coronary heart disease deaths of deaths varied from 77-% in Iceland to 98-% in Northern Sweden. Among women, the proportion of coronary heart disease deaths varied between 57-% of deaths in Turku/Loimaa, Finland, and 98-% in Northern Sweden. Discussion Our study revealed considerable differences both in 8-day and in one-year myocardial infarction fatalities. However, the key question is, to what extent are these differences real and to what extent are they brought about by differences in registration procedures. The data of the myocardial infarction registers in the WHO MONICA Project are primarily collected for longitudinal within-centre trend estimation " 9 and not for cross-sectional between-population comparisons. Therefore, the observed differences between populations should be interpreted with caution. There are, however, several reasons to believe that the numbers in the present study are reasonably comparable. Eur Heart J, Vol. 8, January 997 Downloaded from by guest on January 9

4 / Numbers of fatal and myocardial infarction events in Nordic and Lithuanian MONICA populations by age group and sex e in years) classifiable events s Ml not known (age in years) nclassifiable events s MI not known ocardial infarction; DEN GLO=Denmark, Glostrup; = Finland, North Karelia, = Finland, province of Kuopio; FN-TUL= Finland, Turk E=lceland, whole country; = Lithuania, Kaunas; =Sweden, Gothenburg; =Sweden, Northern Sweden Downloaded from by guest on January 9 SW

5 ities from myocardial infarction in Nordic countries 95 Table Age-specific and age-standardized 8-day myocardial infarction case fatalities (%) in men and women aged years in Nordic and Lithuanian MONICA populations Men (age in years) Age-st (95% CI) Women Age-st (95% CI) CI = confidence interval ( ) ( ) ( ) ( ) (44-5-5) ( ) ( ) ( ) ( ) (3--4-5) ( ) ( ) (39-45) ( ) ( ) ( ) Table 3 Age-standardized 8-day first and recurrent myocardial infarction case-fatalities in men and women aged years in Nordic and Lithuanian MONICA populations Men (age in years) First Recurrent Women (age in years) First Recurrent In the WHO MONICA Project, the number of fatal events registered in a particular area must be similar to, or greater than, the number of coronary deaths in the routine mortality statistics for that area. Therefore, it is unlikely that a significant number of fatal events would have been missed in the present study. Furthermore, the standardized coding practice and strict quality control of MONICA, together with the high autopsy rates in populations taking part in the present study, make substantial misclassification unlikely. Of the non-fatal events, we chose to include definite myocardial infarctions only, since in previous studies they have turned out to be reasonably comparable' 3 ' '. The one-year follow-up was carried out using routine mortality statistics of each country. Coding of the causes of death is not standardized in the routine mortality statistics and therefore some caution is warranted with regard to specific causes of death. However, total mortality is free of coding problems and can be reliably identified in countries participating in the present study. Furthermore, it is known that the vast majority of postmyocardial infarction deaths are due to coronary heart disease and our findings are in agreement with this previous literature - 3 '. On the basis of the above, it seems unlikely that the observed differences in myocardial infarction fatalities could be due toty to differences in the registration procedures. Accordingly, there must be important differences between the participating populations either in the severity of the infarct or in the administration of acute coronary care and in secondary prevention measures. At the time of the present study, thrombolytic treatment was still rare and cannot explain the observed differences in fatalities. However, drug consumption statistics show some potentiy interesting differences between the Scandinavian countries. For example, the use of beta-blockers in Denmark was only half that in Iceland, Sweden or Finland, while the consumption of diuretics was considerably more frequent in Denmark than in other Scandinavian countries' 4 '. The evidence of the potential impact of different drug treatments has been recently reviewed and it is plausible that the use of beta-blockers could be one reason for the observed differences in the present study' 5. However, the country-wide statistics are directly applicable to MONICA areas only in Iceland, where the monitored area included the whole country. Data on acute coronary care and medications prescribed after myocardial infarction have been collected in each participating population as a part of the MONICA Project. These may provide clues on how to reduce fatalities from myocardial infarction in the future. It should be kept in mind, however, that differences in acute coronary care can only effect the mortality of those patients who reach hospital alive. This should be most marked in late (>4 h) in-hospital mortality. In Glostrup, Denmark, early (<4 h) in-hospital mortality was high. This may, in part, reflect the fact that Glostrup is a suburban area Downloaded from by guest on January 9 Eur Heart J, Vol. 8, January 997

6 96 V. V. Salomaa et al. Table 4 Age-standardized pre-hospital and in-hospital of myocardial infarction case-fatalities in men and women aged years in Nordic and Lithuanian MONICA populations Population % Pre-hospital (95% CI) <4h* In hospital >4hf Total (95% CI) Men FN-TUL Women LTU-K.AU ( ) (7-4-3-) ( ) ( ) (--7-5) ( ) ( ) (4-5-9-) (3--4-3) (3---9) (9-3) (--35-3) (-6-5-3) (9-^-4) (3--33-) (3---5) ( ) (6-7-) (6-5-3-) (8--5-8) (-7-9-6) ( ) (-8-6-9) (6--) ( ) (3-4) ( ) (-9^3-9) ( ) (5-8-9) (7--3-) (4--4-8) *<4 h since the beginning of symptoms; case-fatality expressed as a percentage of patients who have reached the hospital alive. t>4 h since the beginning of symptoms; case-fatality expressed as a percentage of patients who have reached the hospital alive and survived first 4 h since the beginning of symptoms. Table 5 Age-standardized one year myocardial infarction case-fatalities in men and women aged years in Nordic and Lithuanian MONICA populations Population Men Women 8-day to -year case-fatalities* First Recurrent Total (95% CI) 8-8(6---5) 8-3 (6--5) -9 (8-3-8) -9 ( ) 5-3 (-9-7-6) 8-4 (5-3--6) 5-6 ( ) 8 (6-) 3-5 (7--9-7) 3-5 (-4-6-5) 9-6(4--5-) -9 (-5-9-3) 5-9 (-4--3) 4-3 (--8-3) 9-5 ( ) 7 (3--) First day to -year case-fatalities Recurrent Total (95% CI) 54-5( ) 47-6 ( ) 5-9 ( ) 54-4 ( ) 4 (36-44-) 58-4 (55-6-7) 44-7 ( ) 43.4 ( ) 6 ( ) 37- (3-3^4-) 47- ( ) 56-6 ( ) 35-4 ( ) 5- ( ) 47-7 ( ) 35/89 ( ) Downloaded from by guest on January 9 *Case-fatalities expressed as a percentage of patients who were alive after 8 days of symptoms. close to Copenhagen and some criticy ill patients, who die out of hospital in more rural areas, may reach hospital alive in Glostrup. The average 8-day myocardial infarction fatalities in the myocardial infarction registers of the WHO MONICA Project is 48% among men and 54% among women'". The populations participating in the present study are close to the average level among men, but somewhat below average among women. Lowel and co-workers have recently described the 8-day fatality for a subgroup of MONICA populations' 3. They found that fatalities ranged from 37% for men in Perth, Eur Heart J, Vol. 8, January' 997

7 ities from myocardial infarction in Nordic countries 97 Australia, to 58% for women in Augsburg, Germany. This is similar to the range observed in the present study. French investigators have reported 8-day fatalities for hospitalized patients, ranging from 9-9% in Toulouse to 7-5% in Strasbourg and 3-6% in Lille 4. The inhospital fatalities of the present study were close to the level of Strasbourg in most populations, but in Glostrup, Denmark, the numbers were higher, exceeding even those of Lille. In addition to confirming these previous numbers in greater detail, the present study provides new information on one-year myocardial infarction fatalities. Although the mortality for the period between day 8 and one year was considerably lower than the mortality during the acute phase of myocardial infarction, it is not negligible. Since these numbers originate from the era before the widespread use of thrombolytic and acetylsalicylic acid treatment, they can serve as baseline numbers for future comparisons. It is anticipated that these treatments should also improve the long-term prognosis of myocardial infarction. In conclusion, the one-year myocardial infarction fatalities were approximately 5% in most of the participating populations, and about 6% of those who died, died out of hospital. These two features of the present study emphasize once more the extremely serious nature of myocardial infarction and the need for its prevention. Only preventive efforts, including both primary and secondary prevention, can reach the majority of patients who die suddenly before reaching hospital. References [] Uemura K, Pisa Z. Recent trends in cardiovascular disease mortality in 7 industrialized countries. World Health Stat Q 987; 38: 4-6. [] De Vreede JJ, Gorgelsen AP, Verstraaten GM, Vermer F, Dassen WR, Wellens HJ. Did prognosis after acute myocardial infarction change during the past 3 years? A metaanalysis. J Am Coll Cardiol 99; 8: [3] Lowel H, Dobson A, Keil U et al. for the Acute Myocardial Infarction Register Teams of Auckland, Augsburg, Bremen, FINMONICA, Newcastle, and Perth. Coronary heart disease case fatality in four countries. A community study. Circulation 993; [4] Amouyel P, Arveiler D, Cambou J-P el al. Myocardial infarction case-fatality gradient in three French regions: the influence of acute coronary care. Int J Epidemiol 994; 3: 7-9. [5] Burke GL, Sprafka JM, Folsom AR, Luepker RV, Norsted SW, Blackburn H. Trends in CHD mortality, morbidity and risk factor levels from 96 to 986: The Minnesota heart survey. Int J Epidemiol 989; 8 (Suppl ): S73-S8. [6] Wilhelmsen L, Johansson S, Ulvenstam G el al. CHDin Sweden: mortality, incidence and risk factors over years in Gothenburg. Int J Epidemiol 989; 8 (Suppl ): SO-S8. [7] Goff DC Jr, Ramsey DJ, Labarthe DR, Nichaman MZ. 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(Proceedings of The nd International MONICA Congress, Helsinki, Finland, August 4-5, 987.) Acta Med Scand 988 (Suupl 78): 4-7. [] Beaglehole R, Dobson A, Hobbs M et al. Comparison of event rates among three MONICA centres. (Proceedings of The nd International MONICA Congress, Helsinki, Finland, August 4-5, 987.) Acta Med Scand 988 (Suppl 78): [] Aberg A, Berstrand R, Johansson S et al. Declining trend in mortality after myocardial infarction. Br Heart J 984; 5: [3] Pohjola S, Siltanen P, Romo M. Five-year survival of 78 patients after myocardial infarction. A community study. Br Heart J 98; 43: [4] Nordic statistics on medicines Nordic Council on Medicines. Uppsala 988. NLN Publication No. [5] Wilhelmsen L, Johansson S. Secondary prevention of coronary heart disease: drug intervention and life-style modification. In: Marmot M, Elliott P, eds. Coronary heart disease epidemiology. From aetiology to public health. Oxford: Oxford University Press, 99: Appendix Key personnel of myocardial infarction registers in participating centres: Glostrup, Denmark: Marianne Kirchhoff, Marianne Schroll, Lise Stener Eriksen. Eur Heart J. Vol. 8, January 997 Downloaded from by guest on January 9

8 98 V. V. Salomaa et al. Kuopio, Finland: Heikki Miettinen, Seppo Lehto, Iceland: Nikulas Sigfusson, Ingibjorg Stefansdottir, Pertti Palomaki, Kalevi Pyorala, Seija Apell, Marjatta Inga I. Gudmundsdottir, Uggi Agnarsson. Selkainaho, Pirkko Koljonen. Kaunas, Lithuania: J. Bluzhas, R. Radisauskas, North Karelia, Finland: Harri Mustaniemi, Matti D. Rasteniene, D. Rastenyte, R. Grazuleviciene, I. Ketonen, Paula Korhonen, Eira Laiste. Adomaviciene. TurkulLoimaa, Finland: Matti Arstila, Tapio Gothenburg, Sweden: Lars Wilhelmsen, Saga Johansson, Vuorenmaa, Pirjo Immonen-Raiha, Esko Kaarsalo, Mona Falkman, Georg Lappas. Matti Niemela, Anu Mononen, Aino-Maija Kantee. Northern Sweden: Fritz Huhtasaari, Bo Wikstrorh, Stina National Public Health Institute-KTL, Helsinki, Finland: Bostrom, Vivan Lundberg, Elsy Jagare-Westerberg. Markku Mahonen, Veikko Salomaa, Matti Romo, Pekka Puska, Jorma Torppa, Jaakko Tuomilehto. Downloaded from by guest on January 9 Eur Heart J, Vol. 8, January 997