In Croatia, every fifth death is due to ischemic heart disease (IHD) (1), and the standardized death rate from IHD is twofold the average reported from the European Union (EU) countries. (2) Acute coronary syndrome (ACS) is the leading manifestation of IHD. ACS episode is not only associated with mortality, recurrent major ischemic events or disability but it also results in reduced quality of life and considerable burden upon healthcare system. According to the results of a recent study conducted in EU countries, ACS episode leads to the loss of working capacity for 70 workdays on average, along with indirect disease related cost of 13,953 €. (3)

In the past two decades, the Croatian Cardiac Society in collaboration with other key healthcare policymakers has gradually optimized medicamentous and invasive treatment of ACS, similar to other EU countries, all this in order to ensure timely and efficacious ACS treatment based on appropriate guidelines. Besides numerous scientific, professional, preventive and promotional activities, regionalization of cardiologic care was performed in 2005. By launching the Croatian Network of Interventional Treatment of Acute Myocardial Infarction and establishment of new centers of interventional cardiology (4-6), modern revascularization treatment (7) by the method of percutaneous coronary intervention (PCI) has been gradually ensured all over the country.

The aim of this study was to analyze trends in the IHD and acute myocardial infarction (AMI) mortality and hospitalizations in the City of Zagreb (Zagreb) and Republic of Croatia (Croatia).

Data on mortality and in-hospital morbidity collected at the Croatian Institute of Public Health for Zagreb and Croatia were retrospectively analyzed. The analysis included data on the number of deaths due to IHD (International Classification of Diseases-10^th Revision (ICD-10) code I20-I25) and deaths due to AMI (ICD-10 code I21) from January 1, 2001 until December 31, 2016. Results were expressed according to gender and age groups (<45, 45-64 and >64 years) and cumulative.

Age-standardized death rates (ASDR) were calculated for each year according to population estimates. Standardization was based on the 2011 census to make ASDR as close as possible to the real values of general rates.

Data on the prevalence of hospitalization for AMI (ICD-10 code I21) were analyzed for the 2009-2016 period, since when the diagnostic-therapeutic system has been used in hospitals as the only and formal mode of recording, accounting and billing healthcare services.

During the 2001-2016 period, the IHD group of syndromes was the cause of 164,473 deaths in Croatia, while the average number of deaths per year was 10,280 (Table 1). In Zagreb, there were 24,322 deaths from IHD or 1520 per year on average during the study period (Table 2).

In Croatia, there were 61,480 deaths from AMI (7.5% of all-cause deaths), 40.2% of them women, during the 2001-2016 period. Of these, 1317 (2.1% of all deaths) persons were aged <45, 14,906 (24.2%) were aged 45-64, and 45,257 (73.6%) were aged >65. The number of deaths from AMI and their proportion according to gender and age groups for Croatia are shown in Table 3.

In Zagreb, there were 9018 deaths due to AMI (6.7% of all-cause deaths), 39.6% of them women, during the 2001-2016 period. Of 9018 deaths from AMI, 166 (1.8%) were recorded in persons aged <45, 2164 (24.0%) in those aged 45-64, and 6688 (74.2%) in persons aged >65. The number of deaths due to AMI and their proportion according to gender and age groups in Zagreb are presented in Table 4.

Trends in ASDR due to AMI in Zagreb and Croatia are illustrated in Figure 1. There was a continuous ASDR decline during the 2001-2016 period. In 2001, the ASDR from AMI in Zagreb was 114.7/100,000 and was comparable to the results recorded for Croatia (117.7/100,000 population). In 2016, the ASDR from AMI showed substantial decline, i.e. 75.8/100,000 and 50.9/100,000 for Croatia and Zagreb, respectively, yielding a decrease by 55.6% in Zagreb and 35.6% in Croatia.

Figure 2 shows trends in ASDR due to AMI for the population aged 0-64. In Zagreb, death rate from AMI was 38.9/100,000 for active population and was slightly lower than the national rate of 40.5/100,000. Analysis of ASDR from AMI in active population in 2016 showed it to be 16.3/100,000 and 24.5/100,000 for Zagreb and Croatia, respectively. In comparison to 2001, the ASDR from AMI was reduced by 58.1% in Zagreb and 39.5% in Croatia.

Hospitalization for AMI was found to be on an increase both in Zagreb and in Croatia. Data on the number of respective hospitalizations during the 2009-2016 period are shown in Figure 3. At the beginning of the study period, 1151 (15.4%) hospitalizations for AMI were recorded in Zagreb, whereas their percentage declined to 12.5% in 2016. During this period, the number of hospitalizations increased by 14.4% in Zagreb and by 41.5% in Croatia.

Translation of the results obtained by current treatment of ACS to the outcomes recorded in clinical routine has been evident in many countries (6, 8-10), and confirmed by the present study analyzing data on routine mortality and morbidity statistics. During the 2001-2016 period, the number of deaths from AMI decreased both in Zagreb and in Croatia. As the number of deaths from IHD showed no substantial decline, it was concluded that deaths due to IHD entities other than AMI were on an increase in both Zagreb and Croatia during the study period.

A declining trend in ASDR from AMI has already been reported in the 1979-2001 period for Zagreb (11) and in the 1998-2008 period for Croatia (12), now substantiated again by the results of the present study. In Zagreb, the ASDR from AMI decreased steadily, to be lower by 55.6% and 58.1% in active population in 2016 as compared with 2001. During this period, the respective ASDR declined by 35.6% and 39.5% in Croatia. In the 2009-2016 period, the rate of hospital treatment for AMI increased by 14.4% in Zagreb and 41.5% in Croatia. This increase in the number of hospitalizations could be greatly ascribed to the establishment of new interventional cardiology centers, which resulted in numerous patient transfers, as well as to better diagnostics.

The reasons for reduction in ASDR from AMI during the 2001-2016 period are complex; however, they certainly include higher treatment quality, improved availability of cardiologic care, better diagnostics, as well as measures of primary and secondary prevention. Many factors are known to play a major role in AMI outcome, e.g., time elapsed from initial symptoms to medical attention, extent of changes in coronary circulation, efficient management of cardiovascular risk factors and comorbidities, mode of healthcare organization, and proportion of healthcare costs in gross domestic product. (7, 13-15)

Since 1999, the actions promoting health and disease prevention have been intensified, contributing to public awareness and knowledge of healthy lifestyle, possibilities of disease prevention, as well as early recognition of AMI symptoms and need of urgent intervention (16). Establishment of the Croatian Network of Interventional Treatment of AMI, implementation of the evidence based efficacious treatment, and efficient AMI management by the Emergency Medicine Service (EMS) staff are the main contributors to the reduced AMI mortality in Croatia. In Zagreb, the average waiting time to EMS team intervention for AMI, i.e. 1^st degree emergency intervention, is 8 minutes. (17) According to the latest Eurostat statistical data, in 2015, the availability of angiographic devices in Croatia was highest across all European countries, i.e. 1.6/100,000 population. (18) In 2016, Eurostat reports the rates of transluminal coronary angioplasty and aortocoronary shunting in Croatia to among highest in Europe (354/100,000 and 106/100,000, respectively). (19) About 43% of the Croatian healthcare resources are located in Zagreb (20), thus it is no wonder that four high-volume centers performing PCI in AMI patients 24 h a day/seven days a week are located within 8 km of the Zagreb downtown. In addition, urgent PCI for AMI has been performed at another 10 interventional centers, some of them located up to 100 km from county hospitals. Availability of new-generation stents and drug-eluting balloons required for optimal efficacy and safety of interventional cardiology has also been upgraded. (21, 22) At the same time, the quality of prescribing and outpatient use of cardiovascular drugs has been improved (23), confirming the results from randomized studies and guidelines to have been implemented in daily clinical routine.

In conclusion, analysis of data on mortality and in-hospital morbidity in Zagreb and Croatia during the 2001-2016 period revealed the number of deaths due to AMI to have continuously decreased. During the study period, the ASDRs from AMI were reduced by more than one-third all over Croatia and by more than half in Zagreb. However, the number of deaths due to the IHD group of syndromes showed no substantial decline from 2001 to 2016, suggesting that deaths due to other IHD group entities were on an increase in both Zagreb and Croatia; accordingly, more attention should be paid to those other IHD entities.