Abstract
Aim: To investigate the incidence and in-hospital mortality of acute myocardial infarction (AMI) by conforming to the Universal Definition of Myocardial Infarction (UDMI) in a population-based registry.
Methods: The Shiga Stroke and Heart Attack Registry is a multicenter, population-based registry in the Shiga Prefecture, designed to evaluate the incidence and prognosis of acute cerebro-cardiovascular diseases. We registered patients with AMI as defined by the UDMI, who developed AMI from January 2014 to December 2015 in the Shiga Prefecture. The incidence rate of AMI was calculated and standardized for age by a direct method using the 2015 Japanese population. We also evaluated the in-hospital mortality among hospitalized patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI).
Results: A total of 1,587 patients were diagnosed with AMI, and the age-adjusted incidence rate was 61.9 per 100,000 person-years. The proportions of patients with STEMI, NSTEMI, and type 3 myocardial infarction were 57%, 30%, and 12%, respectively. The incidence rates of AMI increased with age regardless of sex, which was the highest in those 85 years and older, with 389.7 per 100,000 person-years in men and 221.8 per 100,000 person-years in women. Age-adjusted in-hospital mortality among hospitalized patients with STEMI and NSTEMI was 12.3% and 5.8%, respectively.
Conclusions: This population-based registry clarified the age-adjusted incidence rate of AMI under the application of the UDMI, highlighting that in-hospital mortality is still high among patients with STEMI in Japan.
Introduction
Acute myocardial infarction (AMI) is one of the leading causes of death worldwide, including Japan. The recent rapid aging and changes in lifestyle in Japan might have affected the incidence of AMI. In fact, several Japanese population-based registries have reported that the incidence of AMI has gradually increased in the younger population and decreased in the older population, with an age-adjusted incidence of approximately 40 per 100,000 person-years within the last 10 years1-3). In addition, in-hospital mortality in patients with AMI showed an improving trend over time, from approximately 10% in 1990 to 5% in 2015 in Japan1, 2).
The European Society of Cardiology and the American College of Cardiology proposed the Universal Definition of Myocardial Infarction (UDMI) in 2000 4), which was updated to the fourth version in 2018 5). One major difference from the previous definition using the World Health Organization–Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (WHO-MONICA) criteria is that cardiac troponin becomes the preferred biomarker. This means that acute coronary syndrome with elevated cardiac troponin (e.g., unstable angina), which is not classified as myocardial infarction (MI) under WHO-MONICA, is classified as MI under the UDMI, leading to an increase in the number of patients with diagnosed MI6, 7). In contemporary clinical practice, patients with AMI are usually diagnosed by conforming to the UDMI. However, even most of the recent population-based registries reported the incidence of AMI using the definition from the WHO-MONICA criteria1-3). Hence, the results obtained from these registries might not reflect the current clinical situation. Furthermore, no previous population-based studies reported the prevalence or short-term prognosis of patients with ST-elevation MI (STEMI) or non-STEMI (NSTEMI), which were extremely important distinctions in managing patients with AMI.
Aim
In this study, we aimed to investigate the incidence and in-hospital mortality of AMI diagnosed by the UDMI, separately for patients with STEMI and NSTEMI, in a population-based cardiovascular disease registry in Japan.
Materials and Methods
Design of the Shiga Stroke and Heart Attack Registry (SSHR)
The SSHR is an ongoing, multicenter, population-based registry in Shiga Prefecture, Japan. The registry was designed to evaluate the incidence and prognosis of acute cerebro-cardiovascular diseases, including stroke, MI, and aortic disease. Shiga Prefecture consists of approximately 1.4 million people and is ranked almost in the middle of the prefectural population in Japan. The average age of the population in Shiga Prefecture was 44.5 years, which was the third youngest in Japan. In this registry, for the investigation of MI and aortic disease, we constructed a research system among 15 acute care hospitals in the region (Fig.1). The details of each hospital that participated in the SSHR are shown in Supplementary Fig.1. Given the medical system in Shiga Prefecture, most patients with acute cardiovascular diseases are treated at those hospitals. With the approval of the Ministry of Health, Labour and Welfare, we additionally used a death certificate to help identify deaths from acute cerebro-cardiovascular diseases. The SSHR has been approved by the Institutional Review Board of Shiga University of Medical Science (R2011-86).
Data collection was performed based on the prespecified International Classification of Diseases (ICD)-10 codes. The ICD-10 codes were applied to admitted patients or dead patients on the outpatient visit and were listed at each hospital. For patients with AMI, the following ICD-10 codes were applied: I20 for angina pectoris, I21 for AMI, I22 for subsequent MI, I23 for complications following MI, I24 for other acute ischemic heart diseases, I25 for old MI, and I46 for cardiac arrest. Trained investigators reviewed the medical records of all the patients listed at each hospital. Data were extracted from medical records by the investigators using electronic Case Record Forms on a tablet computer. These data were gathered in a central, encrypted database at Shiga University of Medical Science. Variables were checked for accuracy; apparent errors or omissions in the data that required clarification generated queries for resolution.
Definition of AMI and Its Subtypes
We defined AMI according to the fourth UDMI5) and classified it into the following MI types: type 1: MI precipitated by atherosclerotic plaque disruption; type 2: MI because of mismatch between oxygen supply and demand; and type 3: cardiac death suggestive of MI, with death before blood samples for biomarkers could be obtained, or before increases in cardiac biomarkers could be identified. When the troponin level was not available, the WHO-MONICA criteria were applied (i.e., creatine-phosphokinase and/or creatine-phosphokinase-MB fraction at least twice the normal limit)8). For patients who presented with acute coronary syndrome and underwent a prompt coronary revascularization procedure resulting in only a single preprocedural baseline cardiac troponin value that was normal, followed by subsequent postprocedural values that continued to increase, the postprocedural increase should have been attributed to the index event5). Accordingly, for patients who had a normal cardiac troponin value before undergoing revascularization and the postprocedural increase, two cardiologists assessed whether the diagnosis of AMI was reasonable based on the medical records (i.e., not a procedure-related MI). Patients with sudden cardiac death in whom symptom information prior to unconsciousness or cardiac enzyme data or electrocardiogram (ECG) were unavailable were not included in these analyses.
We classified STEMI or NSTEMI according to the ECG findings. ST-elevation was defined as ST-segment elevation in at least two contiguous leads, with V2–3 at least 2.0 mm (0.2 mV) in men aged 40 years and above, at least 2.5 mm (0.25 mV) in men under 40 years, or at least 1.5 mm (0.15 mV) in women of any age, and/or at least 1.0 mm (0.1 mV) in leads other than V2–3 9). In this study, ECG on admission was collected for all patients in their medical records. More than two specialists in cardiology judged the final diagnosis according to the ECG findings. In patients for whom ECG data were not available, MI types were determined based on medical records collected by the trained investigators. Patients with neither ECG data nor sufficient medical records were classified as uncategorized MI.
Definition of Variables
Hypertension, dyslipidemia, and diabetes mellitus were defined based on the use of the respective medications before admission or the description in the medical records. Moreover, for the definition of dyslipidemia, we applied high-density lipoprotein cholesterol levels of ＜40 mg/dL and/or low-density lipoprotein cholesterol levels of ≥ 140 mg/dL. As all blood samples were not taken only during fasting, triglyceride levels were not included. In addition, glycated hemoglobin (HbA1c) of ≥ 6.5% was applied to diabetes mellitus. Other comorbidities were defined based on the medical records. In-hospital death was defined as death from any cause during the index hospitalization.
Study Population
Fig.2 shows the flow of patients enrolled in the study. We registered all patients who developed AMI from January 2014 to December 2015 in Shiga Prefecture. Data were consolidated at Shiga University of Medical Science and evaluated by more than two specialists in cardiology between 2020 and 2021. Of these patients, we then excluded duplicate cases recorded at different hospitals because of transfer and patients living in other prefectures.
We utilized death certificates in 2014 and 2015 to ensure accurate data collection at each hospital. In the death certificates, patients with the following causes of death were included: AMI, recent MI, old MI, MI, acute coronary syndrome, and ischemic heart disease. Of these, we excluded patients with unknown onset time, patients who developed diseases out of the study period, and patients with a presumptive disease name (e.g., suspicion of MI). In addition, we excluded duplicated cases that were enrolled in the SSHR and considered the remaining cases to be death-certificate-only (DCO) cases. We did not include these DCO cases in calculating the incidence rate because it was impossible to determine whether they met the criteria for MI. The flowchart of DCO cases is described in Supplementary Fig. 2.
Statistical Analyses
Categorical data were reported as numbers and percentages, and they were compared using the chi-squared test or Fisher’s exact test. Continuous data were expressed as the mean and standard deviation or median and interquartile range, according to the distribution of the data. Student’s t-test or the Mann–Whitney U test was used for the comparison. The incidence rates of AMI were described by the person-year approach (per 100,000 person-years) using the population in Shiga Prefecture in 2014 and 2015 and were standardized for age by a direct method using the 2015 Japanese population (JP2015) as well as the 2000 World Standard Population (WHO2000)10). We calculated in-hospital mortality among only hospitalized patients with STEMI and NSTEMI (i.e., patients who died in the emergency room were not included). In addition, we evaluated the in-hospital mortality for patients with or without any revascularization therapy. Moreover, each in-hospital mortality was standardized for age by a direct method with the JP2015. All reported p-values were two-sided, and a p-value of ＜0.05 was considered statistically significant. We analyzed all data using SAS software, version 9.4 (SAS Institute, Inc., Cary, NC, USA).
Results
Incidence of AMI
Among 2,443 cases (1,238 in 2014 and 1,205 in 2015) enrolled by a trained investigator, 1,587 cases (768 in 2014 and 819 in 2015) were ultimately analyzed in this study (Fig.2). Of these, 1,334 cases (84%) were diagnosed with AMI under the application of the UDMI (STEMI, 694 [76%]; NSTEMI, 439 [92%]; type 3 MI, 188 [100%]; uncategorized MI, 13 [92%]). Table 1 summarizes the estimated incidence rates of patients with AMI and its subtypes. The crude incidence rate of AMI in Shiga Prefecture was 56.6 per 100,000 person-years, and the age-adjusted incidence rate was 61.9 and 25.7 per 100,000 person-years by the JP2015 and WHO2000, respectively. The proportions of patients with STEMI, NSTEMI, type 3 MI, and uncategorized MI were 57%, 30%, 12%, and 1%, respectively. As shown in Fig.3, men were prone to developing AMI, approximately 2.5 times more than women. The incidence rates of AMI increased with age regardless of sex, which was the highest in those 85 years and older, with 389.7 per 100,000 person-years in men and 221.8 per 100,000 person-years in women. Of the 1,587 cases analyzed in this study, the medical records of patients with a history of previous MI were available in 1,516 cases. Of those, approximately 10% of cases were recurrent cases. Recurrent onset was observed in 8.8% of patients with STEMI, whereas it was observed frequently in 12.5% of patients with NSTEMI (Supplementary Table 1).
Table 1.
Incidence Rates of Patients with AMI and Its Subtypes
|
Overall |
STEMI |
NSTEMI |
Type 3 MI |
Uncategorized MI |
| Age, years |
n＊
|
IR† |
n＊
|
IR† |
n＊
|
IR†
|
n＊
|
IR†
|
n＊
|
IR†
|
| ≤ 34 |
– |
NA |
– |
NA |
– |
NA |
– |
NA |
– |
NA |
| 35–44 |
42 |
10.1 |
26 |
6.3 |
12 |
2.9 |
– |
NA |
– |
NA |
| 45–54 |
148 |
41.8 |
95 |
26.9 |
42 |
11.9 |
10 |
2.8 |
– |
NA |
| 55–64 |
273 |
78.7 |
166 |
47.9 |
93 |
26.8 |
10 |
2.9 |
– |
NA |
| 65–74 |
432 |
121.9 |
262 |
73.9 |
136 |
38.4 |
31 |
8.7 |
– |
NA |
| 75–84 |
419 |
194.8 |
214 |
99.5 |
139 |
64.6 |
62 |
28.8 |
– |
NA |
| ≥ 85 |
269 |
271.9 |
144 |
145.5 |
53 |
53.6 |
71 |
71.8 |
– |
NA |
| Total |
1,587 |
56.6 |
909 |
32.4 |
476 |
17.0 |
188 |
6.7 |
14 |
0.5 |
| Age-adjusted rates‡
|
|
|
|
|
|
|
|
|
|
|
| JP 2015 |
|
61.9 |
|
35.4 |
|
18.6 |
|
7.5 |
|
0.5 |
| WHO 2000 |
|
25.7 |
|
15.2 |
|
7.9 |
|
2.3 |
|
0.3 |
＊–, The actual number was less than 5.
†Incidence rate (IR) was described by the person-year approach (per 100,000 person-years).
‡Age-adjusted incidence rates were standardized for age by a direct method with the 2015 Japanese population (JP 2015) and the 2000 World Standard Population (WHO 2000).
AMI, acute myocardial infarction; IR, incidence rate; MI, myocardial infarction; NA, not applicable; NSTEMI, non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction.
Supplementary Table 1.
Number of Patients with Recurrent or Non-Recurrent AMI
＊
|
Overall |
STEMI |
NSTEMI |
Type 3 MI |
| Age, years |
Recurrence
n†
|
Non-recurrence
n†
|
Recurrence
n†
|
Non-recurrence
n†
|
Recurrence
n†
|
Non-recurrence
n†
|
Recurrence
n†
|
Non-recurrence
n†
|
| ≤ 34 |
– |
– |
– |
– |
– |
– |
– |
– |
| 35–44 |
– |
40 |
– |
25 |
– |
12 |
– |
– |
| 45–54 |
7 |
135 |
7 |
87 |
– |
42 |
– |
5 |
| 55–64 |
24 |
243 |
12 |
152 |
11 |
82 |
– |
6 |
| 65–74 |
43 |
369 |
23 |
237 |
19 |
114 |
– |
15 |
| 75–84 |
43 |
358 |
16 |
195 |
23 |
115 |
– |
46 |
| ≥ 85 |
29 |
220 |
20 |
124 |
6 |
47 |
– |
49 |
| Total |
147 |
1,369 |
79 |
822 |
59 |
413 |
7 |
125 |
| Age-adjusted rates‡
|
|
|
|
|
|
|
|
|
| JP 2015 |
5.8 |
53.4 |
3.1 |
32.0 |
2.3 |
16.1 |
0.3 |
5.0 |
| WHO 2000 |
2.1 |
22.5 |
1.2 |
13.8 |
0.8 |
7.0 |
0.1 |
1.5 |
＊We evaluated a total of 1,516 cases in which the medical record of the history of previous myocardial infarction was available.
†–, The actual number was less than 5.
‡Age-adjusted incidence rates were calculated by the person-year approach (per 100,000 person-years) using the population in Shiga prefecture in 2014 and 2015, and were standardized for age by a direct method with the 2015 Japanese population (JP 2015) as well as the 2000 World Standard Population (WHO 2000).
AMI, acute myocardial infarction; IR, incidence rate; MI, myocardial infarction; NA, not applicable; NSTEMI, non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction.
The baseline characteristics of patients with STEMI or NSTEMI are shown in Table 2. The mean age of patients with both STEMI and NSTEMI was 70 years. Men predominated among both patients with STEMI and NSTEMI, presenting at approximately 70%. As for comorbidities, patients with STEMI were more likely to be current smokers, but less likely to have hypertension, dyslipidemia, and a history of previous MI than those with NSTEMI. On hospital arrival, the number of patients with cardiopulmonary arrest was significantly higher in patients with STEMI (STEMI 9.0% vs. NSTEMI 5.0%; p=0.008). There were 14 deaths in the emergency room (ER) among patients with STEMI. Coronary artery bypass grafting was observed more frequently in patients with NSTEMI (10.7%) than in those with STEMI (3.6%).
Table 2.
Characteristics of Patients with STEMI or NSTEMI
|
Overall N = 1,385 |
STEMI N = 909 |
NSTEMI N = 476 |
P-value＊
|
| Demographics
|
|
|
|
|
| Age, years |
70.3±12.9 |
70.4±13.2 |
70.2±12.3 |
0.799 |
| Men |
983/1,385 (71.0) |
640/909 (70.4) |
343/476 (72.1) |
0.520 |
| Comorbidities
|
|
|
|
|
| Current smoking |
451/1,315 (34.3) |
312/858 (36.4) |
139/457 (30.4) |
0.031 |
| Hypertension |
869/1,376 (63.2) |
544/902 (60.3) |
325/474 (68.6) |
0.003 |
| Diabetes mellitus |
571/1,380 (41.4) |
359/906 (39.6) |
212/474 (44.7) |
0.068 |
| Dyslipidemia |
922/1,380 (66.8) |
582/905 (64.3) |
340/475 (71.6) |
0.006 |
| Previous MI |
138/1,373 (10.1) |
79/901 (8.8) |
59/472 (12.5) |
0.029 |
| Previous PCI |
212/1,367 (15.5) |
112/898 (12.5) |
100/469 (21.3) |
＜0.001 |
| Previous CABG |
13/1,362 (1.0) |
5/894 (0.6) |
8/468 (1.7) |
0.073 |
| Previous ischemic stroke |
130/1,373 (9.5) |
78/900 (8.7) |
52/473 (11.0) |
0.162 |
| Previous intracranial bleeding |
23/1,372 (1.7) |
19/901 (2.1) |
4/471 (0.9) |
0.085 |
| eGFR, mL/min/1.73 m2
|
60.7±25.1 |
60.6±25.0 |
60.8±25.3 |
0.920 |
| Moderate CKD (eGFR 30–59 mL/min/1.73 m2)
|
539/1,381 (39.0) |
363/906 (40.1) |
176/475 (37.1) |
0.276 |
| Severe CKD (eGFR ＜30 mL/min/1.73 m2)
|
138/1,381 (10.0) |
86/906 (9.5) |
52/475 (11.0) |
0.391 |
| Status at hospital arrival
|
|
|
|
|
| CPA |
106/1,385 (7.7) |
82/909 (9.0) |
24/476 (5.0) |
0.008 |
| Death at ER |
14/1,385 (1.0) |
14/909 (1.5) |
0/476 (0.0) |
NA |
| Cardiac enzyme levels†
|
|
|
|
|
| CPK, U/L |
1,145 (452–2,811) |
1,856 (779–3,554) |
519 (222–1,050) |
＜0.001 |
| CK-MB, U/L |
83 (22–224) |
142 (47–306) |
31 (12–75) |
＜0.001 |
| Troponin T or I, ng/mL |
2.0 (0.16–23.1) |
2.3 (0.15–37.9) |
1.1 (0.17–8.7) |
0.004 |
| Treatment
|
|
|
|
＜0.001 |
| PCI |
1,193/1,371 (87.0) |
798/895 (89.2) |
395/476 (83.0) |
|
| CABG |
83/1,371 (6.1) |
32/895 (3.6) |
51/476 (10.7) |
|
| Conservative medication therapy |
95/1,371 (6.9) |
65/895 (7.3) |
30/476 (6.3) |
|
Data are presented as mean±standard deviation or median and interquartile range for continuous variables, or count (%) for categorical variables. CABG, coronary artery bypass graft; CKD, chronic kidney disease; CPA, cardiopulmonary arrest; eGFR, estimated glomerular filtration rate; ER, emergency room; MI, myocardial infarction; NA, not applicable; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.
＊The p-values were calculated between patients with STEMI and those with NSTEMI.
†The maximum values during index hospitalization were presented.
Table 3 summarizes the in-hospital mortality by revascularization therapy among 1,371 admitted patients with STEMI or NSTEMI (not including the 14 patients who died in the ER). Overall, age-adjusted in-hospital mortality was 10.0%, and that in patients with STEMI and NSTEMI was 12.3% and 5.8%, respectively. For the distribution of deceased days after hospitalization, deaths from STEMI tended to occur earlier after admission than those from NSTEMI. Indeed, deaths within the first week after hospitalization accounted for 59.3% and 48.1% of all patients who died because of STEMI and NSTEMI, respectively (Fig.4). Among patients who underwent percutaneous coronary intervention (PCI), age-adjusted in-hospital mortality was 7.2%, and that in patients with STEMI and NSTEMI was 8.5% and 4.4%, respectively. Notably, patients in whom revascularization was not attempted (i.e., conservative medication therapy) were older, especially in those with STEMI (mean age, 84 years), and they had extremely high age-adjusted in-hospital mortality rates in both groups (STEMI, 55.3%; NSTEMI, 23.7%). When comparing in-hospital mortality rates of patients who underwent any revascularization therapy and those in whom revascularization was not attempted, the latter had a significantly higher age-adjusted mortality rate (7.3% vs. 45.5%, respectively; Fig.5).
Table 3.
In-hospital Mortality in Admitted Patients with STEMI or NSTEMI by Revascularization Therapy
|
STEMI＋NSTEMI |
STEMI |
NSTEMI |
P-value＊
|
| Overall
|
N = 1,371 |
N = 895 |
N = 476 |
|
| Age, years |
70.2±12.9 |
70.2±13.2 |
70.2±12.3 |
0.988 |
| In-hospital death, n (%)
|
135 (9.9) |
108 (12.1) |
27 (5.7) |
＜0.001 |
| Age-adjusted in-hospital mortality, % |
10.0 |
12.3 |
5.8 |
|
| PCI
|
N = 1,193 |
N= 798 |
N= 395 |
|
| Age, years |
69.3±12.5 |
69.1±12.7 |
69.6±12.1 |
0.518 |
| In-hospital death, n (%)
|
84 (7.0) |
67 (8.4) |
17 (4.3) |
0.009 |
| Age-adjusted in-hospital mortality, % |
7.2 |
8.5 |
4.4 |
|
| CABG
|
N= 83 |
N= 32 |
N= 51 |
|
| Age, years |
70.3±11.0 |
69.5±11.1 |
70.8±11.0 |
0.587 |
| In-hospital death, n (%)
|
8 (9.6) |
5 (15.6) |
3 (5.9) |
0.250 |
| Age-adjusted in-hospital mortality, % |
9.7 |
16.2 |
5.7 |
|
| Conservative medication therapy
|
N= 95 |
N= 65 |
N= 30 |
|
| Age, years |
81.9±13.6 |
84.2±11.8 |
77.0±16.1 |
0.017 |
| In-hospital death, n (%)
|
43 (45.3) |
36 (55.4) |
7 (23.3) |
0.004 |
| Age-adjusted in-hospital mortality, % |
45.5 |
55.3 |
23.7 |
|
Data are presented as mean±standard deviation for continuous variables or count (%) for categorical variables. Age-adjusted in-hospital mortality rates were estimated by a direct method with the 2015 Japanese population. CABG, coronary artery bypass graft; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.
＊The p-values were calculated between patients with STEMI and those with NSTEMI.
Discussion
In this population-based registry in Shiga Prefecture, Japan, we investigated the incidence and in-hospital mortality of AMI diagnosed by conforming to the UDMI. We found that the age-adjusted incidence rate of AMI was 61.9 per 100,000 person-years, and the incidence of STEMI was almost twice that of NSTEMI. Overall, age-adjusted in-hospital mortality was 10.0%, and for STEMI and NSTEMI, they were 12.3% and 5.8%, respectively. Especially in patients without revascularization therapy, age-adjusted in-hospital mortality was extremely high, presenting at 55.3% and 23.7% in patients with STEMI and NSTEMI, respectively.
There have been several reports on the incidence rates of AMI in Japan, in which the age-adjusted incidence rates per 100,000 person-years were 43.1 in Kumamoto (2011)3), 38.5 in Miyagi (2014)2), and 40.7 in Tokyo (2016)1). In addition, AMI incidence rates per 100,000 person-years from overseas indicated 208 in the United States (2008)11), 251 in Australia (2010)12), 172 in Tanzania (2019)13), 50.7 in Taiwan (2015)14), and 43.2 in Korea (2016)15). It should be noted that the definition of AMI or standard population for age adjustment differs in each study, but Asians tend to be less likely to develop AMI than Westerners or Africans. Our findings showed a numerically higher incidence rate of AMI than these previous population-based registries in Japan. However, these studies mainly applied the WHO-MONICA criteria for the diagnosis of AMI. Indeed, Salomaa et al. have reported that the definition with the use of cardiac troponins identified 83% more definite MIs than the WHO-MONICA criteria6). In addition, Agüero et al. have reported that the application of the UDMI led to an increase in the MI incidence rate by 15% in men and 29% in women, compared with the WHO-MONICA criteria7). Thus, one of the reasons for the higher incidence rate in our study may be attributable to the difference in the diagnosis criteria. Another report from Nobeoka city showed an incidence rate of 66.3 per 100,000 person-years for patients with AMI between 2015 and 2017 under the application of the UDMI16), in which the incidence rate was calculated using the population aged over 30 years as the denominator. Therefore, it may not have implications to directly compare the difference in incidence between previous studies and our study. The incidence of AMI tended to increase from 1990 to 2000 2, 17), and it remained roughly flat or mildly decreased from 2000 to 2014 1-3). To properly evaluate the increase or decrease in the incidence of AMI under the application of the UDMI, further data accumulation will be needed. Notably, patients with sudden death might have a diagnosis related to AMI. Indeed, our study showed a large number of DCO cases (n=725 [n=365 in 2014, n=360 in 2015]). As we cannot conclude that these DCO cases can adequately satisfy the definition of the UDMI, we did not include them in the calculation of the incidence of AMI. However, when we include these DCO cases in the calculation, the age-adjusted incidence rate of AMI increased approximately 1.5-fold, reaching 90.6 per 100,000 person-years (Supplementary Table 2). This indicates that we have provided the incidence rates of patients with AMI in the smallest scenario.
Supplementary Table 2.
Incidence Rates of Patients with AMI Including DCO Cases
|
Overall |
SSHR |
DCO |
| Age (years) |
n＊
|
IR† |
n＊
|
IR†
|
n＊
|
IR†
|
| ≤ 34 |
6 |
0.6 |
– |
NA |
– |
NA |
| 35–44 |
50 |
12.1 |
42 |
10.1 |
8 |
1.9 |
| 45–54 |
178 |
50.3 |
148 |
41.8 |
30 |
8.5 |
| 55–64 |
337 |
97.1 |
273 |
78.7 |
64 |
18.4 |
| 65–74 |
549 |
154.9 |
432 |
121.9 |
117 |
33.0 |
| 75–84 |
646 |
300.3 |
419 |
194.8 |
227 |
105.5 |
| ≥ 85 |
546 |
551.8 |
269 |
271.9 |
277 |
280.0 |
| Total |
2,312 |
82.4 |
1,587 |
56.6 |
725 |
25.9 |
| Age-adjusted rates‡
|
|
|
|
|
|
|
| JP 2015 |
|
90.6 |
|
61.9 |
|
28.7 |
| WHO 2000 |
|
34.6 |
|
25.7 |
|
8.9 |
* –, The actual number was less than 5.
†Incidence rate was described by the person-year approach (per 100,000 person-years).
‡Age-adjusted incidence rates were standardized for age by a direct method with the 2015 Japanese population (JP 2015) and the 2000 World Standard Population (WHO 2000).
AMI, acute myocardial infarction; DCO, death certificate only; IR, incidence rate; NA, not applicable; SSHR, Shiga Stroke and Heart Attack Registry.
Our study showed a higher age-adjusted in-hospital mortality rate of 10.0% than the previous population-based registry of AMI in Japan (approximately 5.0%)1, 2). A recent nationwide real-world database of 20,462 patients in the Japanese Acute Myocardial Infarction Registry (JAMIR), which consisted of 10 representative regional AMI registry groups or institutions in Japan, reported that the overall in-hospital mortality from AMI was 8.3%18). Given that our study population had a higher age than that of the JAMIR (mean age, 68 years), it may be reasonable to understand the higher mortality rate of our study. Indeed, our study showed increased in-hospital mortality with age: 1.7% in those less than 55 years, 5.1% in those 55–74 years, and 18.3% in those 75 years and older. Moreover, we used a death certificate to help identify patients with AMI, which might result in an increased mortality rate. Nevertheless, in-hospital mortality potentially varies by hospital and cannot be compared uniformly19); thus, the interpretation of differences in mortality rate requires caution.
The Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition presented that in-hospital mortality in patients with NSTEMI with elevated CK levels may be equivalent to that in patients with STEMI20). Of the 476 patients with NSTEMI in our study, 250 (53%) had elevated (more than twice the upper limit of normal) CK levels. In addition, the in-hospital mortality rate in patients with NSTEMI with elevated CK levels was 7.6%, which was more than twice as high as in those without elevated CK levels by 3.5%. However, this rate was lower than that in patients with STEMI, highlighting the higher mortality rate of patients with STEMI in our study. Notably, age-adjusted in-hospital mortality among patients without any revascularization therapy was extremely high, at 55.3% in patients with STEMI and 23.7% in those with NSTEMI. An explanation for the high in-hospital mortality rate in these patients may be their advanced age (mean age, 82 years) or their renal dysfunction (mean estimated glomerular filtration rate, 49 mL/min/1.73 m2), or the possibility of poor condition on hospital arrival (i.e., patients consequently were not treated with any revascularization therapy). In addition, the fact that they have not undergone revascularization may be related to their high in-hospital mortality rate. In the JAMIR, revascularization therapy improved short-term prognosis even in those aged over 80 years, and among patients who underwent PCI, in-hospital mortality occurred in 10.2% of those in their 80s and in 17.9% of those in their 90s. These findings were significantly lower than in those who did not undergo PCI (33.3% in the 80s, p＜0.001; 46.3% in the 90s, p＜0.001)18). In the context of a further aging population in the future in Japan, revascularization for much older patients with AMI may be justified in improving in-hospital outcomes.
Our study has some limitations. First, we had no information on patients with AMI who visited hospitals outside Shiga Prefecture. Moreover, even in Shiga Prefecture, we had no data on patients who visited hospitals or clinics that our study did not cover, which might have led to an underestimation of the incidence of AMI. In general, however, it is recommended that patients in whom AMI is suspected, be transported to a hospital that can provide cardiac catheterization therapy21). When calculating the whole number of cardiac catheterization therapeutic procedures in Shiga Prefecture based on the clinical performance data of each hospital, the coverage rate at the hospitals included in our study was achieved at approximately 90%. Moreover, although there is no consensus on DCO% for patients with AMI (DCO% has often been used as a quality measure of a cancer registry, where DCO% of ＜10% is considered acceptable22)), the DCO% of our study was 9.6% when restricted to DCO cases who died in the hospital. Additionally, given the medical system for emergency patients in Shiga Prefecture, most patients with AMI might be included in our study. Second, our study did not include DCO cases in calculating the incidence rates of AMI, which may underestimate their actual incidence rates. However, even in the previous population-based registries that used death certificates to help identify patients with AMI17, 23), DCO cases were not included in the incidence calculation; therefore, the methodology of our study might be valid.
Conclusions
This population-based registry clarified that the age-adjusted incidence rate of AMI defined by the UDMI was 61.9 per 100,000 person-years, which was numerically higher than previous reports using the WHO-MONICA criteria from around the same period in Japan. Furthermore, we found that age-adjusted in-hospital mortality in patients with STEMI remains high, presenting at 12.3%. In particular, patients who did not receive revascularization therapy were older and had an extremely high in-hospital mortality rate. This treatment strategy for very old patients with AMI might be required in a further aging Japanese population.
Acknowledgments and Notice of Grant Support
We thank the SSHR investigators, participating hospitals, and staff for their commitments and outstanding dedication. We also thank Ms. Tomoka Aoki for coordinating the survey at each hospital. We also thank Andrea Baird, MD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.
SSHR is supported by Shiga Prefecture and the Japan Agency for Medical Research and Development (Grant No. 17ek0210090).
Confliat of Interest
The authors declare no conflicts of interest associated with this manuscript.
References
- 1) Yamamoto T, Yoshida N, Takayama M and Tokyo CCUN: Temporal Trends in Acute Myocardial Infarction Incidence and Mortality Between 2006 and 2016 in Tokyo- Report From the Tokyo CCU Network. Circ J, 2019; 83: 1405-1409
- 2) Cui Y, Hao K, Takahashi J, Miyata S, Shindo T, Nishimiya K, Kikuchi Y, Tsuburaya R, Matsumoto Y, Ito K, Sakata Y and Shimokawa H: Age-Specific Trends in the Incidence and In-Hospital Mortality of Acute Myocardial Infarction Over 30 Years in Japan- Report From the Miyagi AMI Registry Study. Circ J, 2017; 81: 520-528
- 3) Kojima S, Matsui K, Ogawa H and Kumamoto Acute Coronary Events Study G: Temporal trends in hospitalization for acute myocardial infarction between 2004 and 2011 in Kumamoto, Japan. Circ J, 2013; 77: 2841-2843
- 4) Antman E, Bassand J-P, Klein W, Ohman M, Lopez Sendon JL, Rydén L, Simoons M and Tendera M: Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction. J Am Coll Cardiol, 2000; 36: 959-969
- 5) Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD and Executive Group on behalf of the Joint European Society of Cardiology /American College of Cardiology /American Heart Association /World Heart Federation Task Force for the Universal Definition of Myocardial I: Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol, 2018; 72: 2231-2264
- 6) Salomaa V, Koukkunen H, Ketonen M, Immonen-Raiha P, Karja-Koskenkari P, Mustonen J, Lehto S, Torppa J, Lehtonen A, Tuomilehto J, Kesaniemi YA and Pyorala K: A new definition for myocardial infarction: what difference does it make? Eur Heart J, 2005; 26: 1719-1725
- 7) Agüero F, Marrugat J, Elosua R, Sala J, Masiá R, Ramos R and Grau M: New myocardial infarction definition affects incidence, mortality, hospitalization rates and prognosis. Eur J Prev Cardiol, 2015; 22: 1272-1280
- 8) Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas AM and Pajak A: Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation, 1994; 90: 583-612
- 9) Kimura K, Kimura T, Ishihara M, Nakagawa Y, Nakao K, Miyauchi K, Sakamoto T, Tsujita K, Hagiwara N, Miyazaki S, Ako J, Arai H, Ishii H, Origuchi H, Shimizu W, Takemura H, Tahara Y, Morino Y, Iino K, Itoh T, Iwanaga Y, Uchida K, Endo H, Kongoji K, Sakamoto K, Shiomi H, Shimohama T, Suzuki A, Takahashi J, Takeuchi I, Tanaka A, Tamura T, Nakashima T, Noguchi T, Fukamachi D, Mizuno T, Yamaguchi J, Yodogawa K, Kosuge M, Kohsaka S, Yoshino H, Yasuda S, Shimokawa H, Hirayama A, Akasaka T, Haze K, Ogawa H, Tsutsui H and Yamazaki T: JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome. Circ J, 2019; 83: 1085-1196
- 10) Ahmad OB, Boschi-Pinto C, Lopez AD, Murray CJL, Lozano R and Inoue M: Age standardization of rates: A new WHO standard. World Health Organization, 2001;
- 11) Yeh RW, Sidney S, Chandra M, Sorel M, Selby JV and Go AS: Population Trends in the Incidence and Outcomes of Acute Myocardial Infarction. N Engl J Med, 2010; 362: 2155-2165
- 12) Wong CX, Sun MT, Lau DH, Brooks AG, Sullivan T, Worthley MI, Roberts-Thomson KC and Sanders P: Nationwide trends in the incidence of acute myocardial infarction in Australia, 1993-2010. Am J Cardiol, 2013; 112: 169-173
- 13) Hertz JT, Madut DB, Rubach MP, William G, Crump JA, Galson SW, Maro VP, Bloomfield GS, Limkakeng AT, Temu G, Thielman NM and Sakita FM: Incidence of Acute Myocardial Infarction in Northern Tanzania: A Modeling Approach Within a Prospective Observational Study. J Am Heart Assoc, 2021; 10:
- 14) Lee CH, Fang CC, Tsai LM, Gan ST, Lin SH and Li YH: Patterns of Acute Myocardial Infarction in Taiwan from 2009 to 2015. Am J Cardiol, 2018; 122: 1996-2004
- 15) Kim RB, Kim HS, Kang DR, Choi JY, Choi N-C, Hwang S and Hwang JY: The Trend in Incidence and Case-fatality of Hospitalized Acute Myocardial Infarction Patients in Korea, 2007 to 2016. J Korean Med Sci, 2019; 34:
- 16) Ogata S, Marume K, Nakai M, Kaichi R, Ishii M, Ikebe S, Mori T, Komaki S, Kusaka H, Toida R, Kurogi K, Iwanaga Y, Yano T, Yamamoto N and Miyamoto Y: Incidence Rate of Acute Coronary Syndrome Including Acute Myocardial Infarction, Unstable Angina, and Sudden Cardiac Death in Nobeoka City for the Super-Aged Society of Japan. Circ J, 2021; 85: 1722-1730
- 17) Rumana N, Kita Y, Turin TC, Murakami Y, Sugihara H, Morita Y, Tomioka N, Okayama A, Nakamura Y, Abbott RD and Ueshima H: Trend of increase in the incidence of acute myocardial infarction in a Japanese population: Takashima AMI Registry, 1990-2001. Am J Epidemiol, 2008; 167: 1358-1364
- 18) Kojima S, Nishihira K, Takegami M, Nakao YM, Honda S, Takahashi J, Takayama M, Shimokawa H, Sumiyoshi T, Ogawa H, Kimura K and Yasuda S: Nationwide real-world database of 20,462 patients enrolled in the Japanese Acute Myocardial Infarction Registry (JAMIR): Impact of emergency coronary intervention in a super-aging population. Int J Cardiol Heart Vasc, 2018; 20: 1-6
- 19) Ando H, Yamaji K, Kohsaka S, Ishii H, Wada H, Yamada S, Sawano M, Inohara T, Numasawa Y, Ikari Y and Amano T: Japanese Nationwide PCI (J-PCI) Registry Annual Report 2019: patient demographics and in-hospital outcomes. Cardiovascular Intervention and Therapeutics, 2022; 37: 243-247
- 20) Ishihara M, Fujino M, Ogawa H, Yasuda S, Noguchi T, Nakao K, Ozaki Y, Kimura K, Suwa S, Fujimoto K, Nakama Y, Morita T, Shimizu W, Saito Y, Tsujita K, Nishimura K, Miyamoto Y and investigators JM: Clinical Presentation, Management and Outcome of Japanese Patients With Acute Myocardial Infarction in the Troponin Era - Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET). Circ J, 2015; 79: 1255-1262
- 21) Kimura K, Kimura T, Ishihara M, Nakagawa Y, Nakao K, Miyauchi K, Sakamoto T, Tsujita K, Hagiwara N, Miyazaki S, Ako J, Arai H, Ishii H, Origuchi H, Shimizu W, Takemura H, Tahara Y, Morino Y, Iino K, Itoh T, Iwanaga Y, Uchida K, Endo H, Kongoji K, Sakamoto K, Shiomi H, Shimohama T, Suzuki A, Takahashi J, Takeuchi I, Tanaka A, Tamura T, Nakashima T, Noguchi T, Fukamachi D, Mizuno T, Yamaguchi J, Yodogawa K, Kosuge M, Kohsaka S, Yoshino H, Yasuda S, Shimokawa H, Hirayama A, Akasaka T, Haze K, Ogawa H, Tsutsui H and Yamazaki T: JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome. Circ J, 2019; 83: 1085-1196
- 22) Pierce Campbell CM, Curado MP, Harlow SD and Soliman AS: Variation of cervical cancer incidence in Latin America and the Caribbean. Rev Panam Salud Publica, 2012; 31: 492-498
- 23) Nakamura M, Tanaka F, Segawa T, Takahashi T, Matsuura Y, Sakai T, Nishiyama O, Niiyama M, Onoda T and Koshiyama M: Temporal Trends in the Incidence and Clinical Features of Acute Myocardial Infarction in a Japanese Rural Area From 2006 to 2014. Circ J, 2017; 81: 1854-1861
