Population-Based Study of the Incidence and Mortality Rate of Acute Aortic Dissection

Abstract

Background: Acute aortic dissection (AAD) has high morbidity and a high fatality rate for a cardiovascular disease. Recent studies suggested that the incidence of AAD is increasing. However, the actual incidence and mortality rates of AAD are not well known. This study investigated the current epidemiology of AAD within the Yatsushiro medical jurisdictional area.

Methods and Results: A population-based review of patients with AAD was performed in a geographically well-defined area. Data were collected retrospectively from January 2011 to December 2020 for a total of 196 patients with AAD (Stanford Type A, n=126 [64.3%]; Stanford Type B, n=70 [35.7%]). The mean patient age was 74.3 years, and 55.6% (109/196) were women. The crude and age-standardized incidence rates of AAD in our medical jurisdictional area were 13.6 and 11.4 per 100,000 inhabitants per year, respectively. The crude and age-standardized 30-day mortality rates of AAD were 4.9 and 4.0 per 100,000 inhabitants per year, respectively. There were upward tendencies for both the incidence and 30-day mortality rate of AAD with age, with both being significantly higher in patients aged ≥85 years (P<0.001).

Conclusions: This population-based study detected a higher incidence of AAD than previous studies, but reported a lower incidence of AAD in men than in women. Increasing age was associated with an increased incidence and mortality rate of AAD.

Acute aortic dissection (ADD) has high morbidity and a high fatality rate for a cardiovascular disease and requires prompt diagnosis and treatment.^1–3 Previous reports have suggested that the number of cases of AAD is increasing.^3–7 This may be due to the improved sensitivity and specificity of diagnoses of AAD using diagnostic modalities such as computed tomography (CT), magnetic resonance imaging, and echocardiography.⁸ However, unlike coronary disease and cerebral artery disease,^9,10 only limited data are available regarding the incidence and outcomes of AAD, and the true incidence of AAD is unknown. Previous studies, often from specialist centers or using retrospective registry data,^1,2,11 may have underestimated the incidence and case fatality rate of AAD by not including deaths that occurred before hospital arrival, which may also have produced bias in the assessment of risk factors and predictors of outcomes.

When treating diseases with associated high morbidity and fatality, such as AAD, it is necessary to shorten the transport time and access advanced medical facilities as quickly as possible. Therefore, it would be clinically meaningful to consider the incidence and mortality rates of AAD with the medical care system in a region with a population composition characteristic of a medical region.

Kumamoto Rosai Hospital is a public hospital with 410 beds that is located in Yatsushiro City in Kumamoto Prefecture, Japan, a medium-sized rural city of approximately 142,000 residents in south Kyushu. Patients diagnosed with AAD within the Yatsushiro medical area are transferred to hospitals with appropriate surgical facilities. During the study period, Kumamoto Rosai Hospital was the only facility providing emergency surgery for cardiac and aortic diseases in our jurisdictional medical area. In this study, we retrospectively studied the incidence of AAD and the early phase mortality of patients with AAD from 2011 to 2020 in a specific patient population in a well-defined geographical area. The purpose of this study was to investigate the current epidemiology of AAD within our jurisdictional medical area.

Methods

Study Population

All patients who were transferred to Kumamoto Rosai Hospital with a diagnosis of AAD within 14 days of onset between January 2011 and December 2020 were enrolled in this study. The diagnosis of aortic dissection was based on imaging findings, findings at surgery, or postmortem examinations, such as autopsy and autopsy imaging (Ai). In this study, AAD included both classic aortic dissection and intramural hematoma. Our selection process and the number of patients selected are shown in Figure 1. During the study period, 272 consecutive patients presenting with aortic dissection were transferred to Kumamoto Rosai Hospital. The onset date and time were ambiguous in 14 patients, who were excluded from the study. Another 2 patients had ADD secondary to trauma and 1 patient had iatrogenic aortic dissection; these patients were also excluded from the study. Of the remaining 255 patients, 59 were transferred beyond our jurisdictional medical area and were excluded from the study. Thus, 196 patients with AAD were included in the analysis.

Figure 1.

Selection process and numbers of patients. Ai, autopsy imaging; AMI, acute myocardial infarction; AoG, aortography; CT, computed tomography.

Diagnosis of AAD

Of the 196 patients included in the study, 145 were diagnosed with CT. Two patients diagnosed with acute myocardial infarction, who underwent coronary artery intervention, were diagnosed by aortography. Forty-nine patients who died prior to the diagnosis of AAD were diagnosed using Ai (Figure 1). During the study period, 686 patients died on arrival at the emergency room of Kumamoto Rosai Hospital. Of these patients, 559 (81.5%) underwent Ai using CT and 5 (0.7%) underwent an autopsy. The families of the remaining 122 patients refused Ai with CT or autopsy. Of the 559 patients who underwent postmortem examinations, 49 (8.8%) had AAD diagnosed by Ai using CT. All CT examinations were analyzed by board-certified radiologists, cardiologists, and cardiovascular surgeons to ensure the accuracy of the diagnosis.

Aortic dissection was anatomically classified according to either the origin of the intimal tear or whether the dissection involved the ascending aorta according to the Stanford system.⁸ According to the Stanford system, all aortic dissections were divided into 2 categories: Type A, which involved the ascending aorta, and Type B, which did not. Malperfusion was defined as radiographic imaging-diagnosed organ blood flow disturbance due to an occlusion of the branch vessel of the aorta related to aortic dissection and clinical features.

Data Collection

Data on all patients with a diagnosis of AAD were obtained from hospital medical records. To assess the impact of age on the incidence and mortality rates of AAD, patients were divided into 4 groups according to age (<65, 65–74, 75–84, and >85 years). Days were divided into eight 3-h periods to evaluate the distribution in AAD occurrence. To assess episodes triggering the onset of AAD, activities occurring during or just before the onset of AAD were divided into 4 groups: physical activity, mental activity, during sleep, and at rest.

Surgical Indications

Patients with Type A AAD with a patent false lumen (communicating type) underwent emergency surgical treatment except when a patient or family refused surgery because the patient was already bedridden due to dementia or paralysis. Of the 196 patients enrolled in this study, 14 presented with Type A AAD but refused surgery. Patients with communicating-type Type A AAD underwent emergency surgical treatment. Patients with a crescent-shaped thrombosed false lumen (non-communicating type) were managed conservatively as long as they were hemodynamically stable. Indications for emergency surgery included severe aortic insufficiency, cardiac tamponade, rupture of the aorta, and/or organ malperfusion, despite the presence of a non-communicating-type of Type A AAD. CT examinations were repeated with contrast medium 1, 3, 7, and 14 days after the onset of ADD for the non-communicating-type. Indications for urgent surgery included an increased diameter of the ascending aorta (>50 mm) or of the thrombosed false lumen (>10 mm) or a communicated thrombosed false lumen with the true lumen (ulcer-like projection) appearing in the ascending aorta.

Patients with Type B AAD without either rupture of the aorta or organ malperfusion were treated conservatively.

Statistical Analysis

Analyses were conducted using SPSS statistical package version 28, including R for SPSS (IBM Corp., Armonk, NY, USA). Direct standardization was used to estimate the annual incidence of AAD. Age- and sex-standardized incidence and mortality rates (per 100,000 inhabitants per year) were calculated according to year, using the Japanese population distribution model in 2015 as a reference. Population data were based on the national population census of 2015 conducted by the Ministry of Internal Affairs and Communications.¹²

Continuous data are presented as the mean±SD or as the median with interquartile range (IQR), as appropriate. Categorical data are expressed as percentages. The significance of group differences in continuous variables was determined using Student’s t-test or the Mann-Whitney U test for parametric and non-parametric values, respectively. The significance of group differences in categorical variables was determined using Fisher’s exact test or the χ² test, as appropriate. A χ² test for goodness of fit was used to determine whether AAD developed uniformly during the day, week, and month. The incidence and mortality rates for the 4 age groups were derived using the Mantel-Haenszel method. The Cochran-Armitage test was used to analyze trends. The association between increasing age and the risk of incidence and mortality rates of AAD were assessed using multivariable binary logistic regression analysis. Statistical significance was set at 2-sided P<0.05.

Results

Patient Characteristics and Variations at the Onset of AAD

Between January 2011 and December 2020, 196 residents in our jurisdictional medical area were diagnosed with AAD. Table 1 shows the clinical characteristics of patients with AAD according to sex and Stanford classification. The distribution of AAD cases according to age and sex is shown in Figure 2A, whereas the distribution of AAD cases according to age and Stanford classification is shown in Figure 2B. The mean age of patients at diagnosis was 74.3±13.2 years (range 28–98 years). Of the 196 patients in this study, 126 (64.3%) presented with Type A AAD. The mean age of patients with Type A AAD was significantly higher than that of patients with Type B AAD (76.4±12.7 vs. 70.5±13.2 years, respectively; P<0.005). Of the 126 patients with Type A AAD, 81 (64.3%) were women. Of the 70 patients with Type B AAD, 42 (60.0%) were men. Hypertension, hyperlipidemia, and a history of smoking were noted in 80.6%, 24.0%, and 24.5% of all patients, respectively (Table 1).

Table 1. Clinical Characteristics of Patients With AAD

	Overall (n=196)	Men (n=87)	Women (n=109)	P value (men vs. women)	Type A AAD (n=126)	Type B AAD (n=70)	P value (Type A vs. Type B)
Age (years)	74.3±13.2	69.7±12.5	77.9±12.6	<0.001	76.4±12.7	70.5±13.2	0.002
Age ≥80 years	82 (41.8)	19 (21.8)	63 (57.8)	<0.001	62 (49.2)	20 (28.6)	0.004
Female sex	109 (55.6)				81 (64.3)	28 (40.0)	<0.001
Clinical presentation
Hypertension	158 (80.6)	65 (74.7)	93 (85.3)	0.06	104 (82.5)	54 (77.1)	0.36
Hyperlipidemia	47 (24.0)	24 (27.6)	23 (21.1)	0.29	31 (24.6)	16 (22.9)	0.78
Diabetes	11 (5.6)	7 (8.0)	4 (3.7)	0.22	5 (4.0)	6 (8.6)	0.18
Marfan syndrome	1 (0.5)	0 (0)	1 (0.9)	0.56	1 (0.8)	0 (0)	0.66
Prior AAD	11 (5.6)	6 (6.9)	5 (4.6)	0.48	7 (5.6)	4 (5.7)	0.59
Prior cardiac surgery	7 (3.6)	5 (5.7)	2 (1.8)	0.25	5 (4.0)	2 (2.9)	0.52
Family history of aortic dissection	16 (8.2)	7 (8.0)	9 (8.3)	0.96	8 (6.3)	8 (11.4)	0.21
Smoking history	48 (24.5)	37 (42.5)	11 (10.1)	<0.001	21 (16.7)	27 (38.6)	<0.001
Current smoker	28 (14.3)	23 (26.4)	5 (4.6)	<0.001	11 (8.7)	17 (24.3)	0.003
Prior smoker	20 (10.4)	14 (16.1)	6 (5.5)	0.015	10 (7.9)	10 (14.3)	0.16
Medication
Steroid	11 (5.6)	2 (2.3)	9 (8.3)	0.07	7 (5.6)	4 (5.7)	0.32
Anticoagulants	12 (6.1)	7 (8.0)	5 (4.6)	0.32	9 (7.1)	3 (4.3)	0.32
Antiplatelet agents	16 (8.2)	5 (5.7)	11 (10.1)	0.27	10 (7.9)	6 (8.6)	0.88

Unless indicated otherwise, data are given as the mean±SD or n (%). AAD, acute aortic dissection.

Figure 2.

(A,B) Distribution of the number of cases of acute aortic dissection by age and sex (A) and classification according to the Stanford type of aortic dissection (B). (C) Monthly distribution of the occurrence of the first symptoms of an episode of aortic dissection. (D) Weekly distribution of the occurrence of the first symptoms of an episode of aortic dissection according to the Stanford classification of the type of aortic dissection.

The monthly and weekly distributions of AAD are shown in Figure 2C,D. The incidence of AAD exhibited a significant monthly variation (P<0.05), with a higher incidence rate in November, December, and January, and a lower rate in July, August, and September. The incidence rate in November (highest) was approximately 3-fold higher than in July and August (lowest). However, there was no significant difference in either sex or Stanford classification (data not shown).

Although the overall distribution of AAD was homogeneous on all days of the week (P=0.97), the incidence of Type A AAD showed small peaks at the beginning of the week (Sunday and Monday) and troughs towards the end of the week (Thursday, Friday, and Saturday).

The circadian distribution of AAD is shown in Figure 3A. The onset of AAD varied significantly (P<0.001), peaking at 06.00–09.00 and 15.00–18.00 hours.

Figure 3.

Distribution of circadian times of the occurrence of the first symptoms of an episode of aortic dissection (A) and according to potential triggers (B).

Presenting Symptoms and Triggering Events

Symptoms at onset and triggering events that occurred during or just before the onset of AAD are presented in Table 2. All patients with AAD presented with an abrupt onset of symptoms, such as sudden severe chest or upper back pain, and syncope. Of the 148 (76.7%) patients with chest or back pain, 94 (48.7%) had radiating pain that spread to the neck or down the back. Among all patients, 66 (34.2%) had syncope. Fifty-seven patients (29.1%) had cardiogenic shock with systolic blood pressure <80 mmHg. Forty-eight patients (24.5%) had cardiac tamponade. Malperfusion was noted in 35 (17.9%) patients. Neurological deficits, heart ischemia, and limb ischemia, including both permanent and temporary deficits, were observed in 9.2%, 5.1%, and 5.1% of patients, respectively (Table 2).

Table 2. Symptoms at Onset and Triggering Events for the Onset of AAD

	Overall (n=196)	Men (n=87)	Women (n=109)	P value (men vs. women)	Type A AAD (n=126)	Type B AAD (n=70)	P value (Type A vs. Type B)
Symptoms at onset
Abrupt onset	196 (100)	87 (100)	109 (100)		126 (100)	70 (100)
Chest or back pain	151 (77.0)	68 (78.2)	83 (76.1)	0.74	85 (67.5)	66 (94.3)	<0.001
Chest pain	106 (54.1)	38 (43.7)	68 (62.4)	0.009	82 (65.1)	24 (34.3)	<0.001
Back pain	115 (59.6)	54 (62.1)	61 (56.0)	0.32	57 (45.2)	58 (82.9)	<0.001
Radiating pain	96 (49.0)	48 (55.2)	48 (44.0)	0.12	52 (41.3)	44 (62.9)	0.004
Syncope	66 (34.2)	26 (30.6)	40 (37.0)	0.32	59 (48.3)	6 (8.7)	<0.001
Cardiogenic shock	57 (29.1)	16 (18.4)	41 (37.6)	0.003	52 (41.3)	5 (7.1)	<0.001
Cardiac tamponade	48 (24.5)	14 (16.1)	34 (31.2)	0.015	45 (35.7)	3 (4.3)	<0.001
Malperfusion	35 (17.9)	13 (14.9)	22 (20.2)	0.62	31 (24.6)	4 (5.7)	<0.001
Brain	16 (8.2)	5 (5.7)	11 (10.1)	0.53	15 (11.9)	1 (1.4)	<0.001
Paraplegia	2 (1.0)	2 (2.3)	0 (0)	0.26	0 (0)	2 (2.9)	<0.001
Coronary	10 (5.1)	3 (3.4)	7 (6.4)	0.62	10 (7.9)	0 (0.0)	0.01
Mesenteric	0 (0.0)	0 (0)	0 (0)		0 (0.0)	0 (0.0)
Renal	4 (2.0)	2 (2.3)	2 (1.8)	0.91	3 (2.4)	1 (1.4)	0.01
Limb	10 (5.1)	5 (5.7)	5 (4.6)	0.87	8 (6.3)	2 (2.9)	0.001
Triggering events for onset			0.11			0.53
Physical activity	152 (77.6)	67 (77.0)	85 (78.0)		101 (80.2)	51 (72.9)
Working or housework	49 (25.0)	19 (21.8)	30 (27.5)		31 (24.6)	18 (25.7)
Eating or drinking	18 (9.2)	6 (6.9)	12 (11.0)		8 (6.3)	10 (14.3)
Defection or urination	18 (9.2)	12 (13.8)	6 (5.5)		12 (9.5)	6 (8.6)
Taking a bath	9 (4.6)	5 (5.7)	4 (3.7)		6 (4.8)	3 (4.3)
Walking	20 (10.2)	7 (8.0)	13 (11.9)		17 (13.5)	3 (4.3)
Driving	7 (3.6)	6 (6.9)	1 (0.9)		5 (4.0)	2 (2.9)
Sporting or exercising	4 (2.0)	3 (3.4)	1 (0.9)		3 (2.4)	1 (1.4)
Getting up	25 (12.8)	9 (10.3)	16 (14.7)		18 (14.3)	7 (10.0)
Brushing teeth	2 (1.0)	0 (0.0)	2 (1.8)		1 (0.8)	1 (1.4)
Emotional stress or excitation	18 (9.2)	11 (12.6)	7 (6.4)		9 (7.1)	9 (12.9)
Talking	8 (4.1)	3 (3.4)	5 (4.6)		6 (4.8)	2 (2.9)
Watching television	7 (3.6)	5 (5.7)	2 (1.8)		2 (1.6)	5 (7.1)
Playing game	3 (1.5)	3 (3.4)	0 (0.0)		1 (0.8)	2 (2.9)
During sleep	21 (10.7)	9 (10.3)	12 (11.0)		13 (10.3)	8 (11.4)
At rest	5 (2.6)	0 (0.0)	5 (4.6)		3 (2.4)	2 (2.9)

Categorical data are presented as n (%). AAD, acute aortic dissection.

Triggering events during or just before the onset of AAD included physical activities (e.g., working, eating, driving, or excising) in 152 (77.6%) patients and emotional stress or excitation (e.g., talking, watching television, or playing games) in 18 (9.2%) patients. AAD occurred during sleep in 21 (10.7%) patients and at rest in 5 (2.6%; Table 2).

The relationship between circadian variation of onset and triggering events of AAD is shown in Figure 3B. AAD occurred predominantly during the daytime. Moreover, 64.3% of episodes occurred between 06.00 and 18.00 hours, although the daytime events were significantly more related to physical or mental activity than the night-time events (92.1% vs. 77.1%, respectively; P<0.005). In contrast, 11 (52.4%) of 21 patients developed AAD while asleep, between midnight and 06.00 hours.

Time From Symptom Onset to Hospital Arrival

The median interval from symptom onset to hospital arrival was 65 min (Table 3). In all, 160 (81.6%) patients were transferred directly to Kumamoto Rosai Hospital, and 135 (68.9%) patients arrived within 2 h after symptom onset. The median interval from symptom onset to arrival directly at Kumamoto Rosai Hospital (50 min) was significantly shorter than for transfer from other primary care facilities (261 min; P<0.001).

Table 3. Interval From Onset to Arrival, Diagnostic Modalities, Surgical Treatment, and Outcomes

	Overall (n=196)	Men (n=87)	Women (n=109)	P value (men vs. women)	Type A AAD (n=126)	Type B AAD (n=70)	P value (Type A vs. Type B)
Median interval from onset to arrival (min)	65.0 [23–2,723]	61.0 [23–2,694]	76.0 [21–3,655]	0.12	61.0 [23–2,762]	71.0 [23–3,514]	0.12
Direct transfer (min)	50 [35–95] (n=160)	46 [34–90] (n=76)	59 [35–110] (n=84)	0.34	48 [27–90] (n=105)	61 [35–121] (n=55)	0.32
Transfer from other hospital (min)	261 [128–700] (n=36)	239 [113–855] (n=11)	307 [147–686] (n=25)	0.57	205 [107–516] (n=21)	395 [245–2,140] (n=15)	0.35
Means of transport to hospital				0.13			0.05
Ambulance	161 (82.1)	75 (86.2)	86 (78.9)		109 (86.5)	52 (74.3)
Helicopter	1 (0.5)	1 (1.1)	0 (0.0)		0 (0.0)	1 (1.4)
Other	34 (17.3)	11 (12.6)	23 (21.3)		17 (13.5)	17 (24.3)
Death prior to diagnosis of AAD	49 (25.0)	22 (25.3)	27 (24.8)	0.93	43 (34.1)	6 (8.6)	<0.001
Certified as cardiac arrest at home	37 (18.9)	18 (20.7)	19 (17.4)		34 (27.0)	3 (4.3)
Cardiac arrest during transport to hospital	5 (2.6)	0 (0.0)	5 (4.6)		4 (3.2)	1 (1.4)
Cardiac arrest after arrival at the ER	7 (3.6)	4 (4.6)	3 (2.8)		5 (4.0)	2 (2.9)
Diagnostic modality
CT	194 (99.0)	87 (100)	107 (98.2)	0.31	124 (98.4)	70 (100)	0.41
Postmortem CT (Ai)	49 (25.0)	22 (25.3)	27 (24.8)		43 (34.1)	6 (8.6)
Aortography/CAG	2 (1.0)	0 (0.0)	2 (1.8)		2 (1.6)	0 (0.0)
Surgical treatment	68 (34.7)	32 (36.8)	36 (33.0)	0.79	58 (46.0)	10 (14.3)	<0.001
Emergency or urgent surgery	56 (28.6)	24 (27.6)	32 (29.4)		55 (43.7)	1 (1.4)
Converted from medical treatment to surgery	12 (6.1)	8 (9.2)	4 (3.7)		3 (2.4)	9 (12.9)
Outcome
30-day fatality
Including death before hospitalization (n=196)	73/196 (37.2)	30/87 (34.5)	43/109 (39.4)	0.48	65/126 (51.6)	8/70 (11.4)	<0.001
Excluding death before hospitalization (n=147)	24/147 (16.3)	8/65 (12.3)	16/82 (19.5)	0.32	22/83 (26.5)	2/64 (3.1)	<0.001
Treatment				0.07			0.29
Emergency or urgent surgery (n=56)	8/56 (14.3)	7/24 (29.2)	1/32 (3.1)		7/55 (12.7)	1/1 (100.0)
Converted from medical treatment to surgery (n=12)	0/12 (0.0)	0/8 (0.0)	0/4 (0.0)		0/3 (0.0)	0/9 (0.0)
Medical treatment (n=79)	15/79 (19.0)	1/33 (3.0)	14/46 (30.4)		14/25 (56.0)	1/54 (1.9)
Discharge home or to other facilitates	123 (62.8)	57 (65.5)	66 (60.6)	0.48	61 (48.4)	62 (88.6)	<0.001

Unless indicated otherwise, data are given as the median [interquartile range] or n (%). Ai, autopsy imaging; CAG, coronary angiography; CT, computed tomography; ER, emergency room.

Death Prior to Diagnosis of AAD

Forty-nine patients died prior to diagnosis of AAD (Figure 1; Table 3). Of these patients, 37 (75.5%) were certified to have had a cardiac arrest episode at home, 5 (10.2%) died upon arrival at hospital, and 7 (14.3%) died after arrival in the emergency room before diagnosis of AAD (Table 3). Although 4 of these 49 patients had a temporary return of spontaneous circulation, none of them could be rescued. The median age of the patients who died prior to diagnosis was significantly higher than that of patients who were hospitalized alive (84.0 vs. 75.0 years, respectively; P<0.001), but there was no significant difference in sex between the 2 groups (P=0.93). A significantly higher rate of death prior to diagnosis of AAD was noted among patients with Type A AAD (P<0.001; Table 3; Supplementary Table).

Management and Outcome

Sixty-eight interventions were performed following AAD during the study period (Table 3). Fifty-six patients, including 1 with Type B AAD, underwent emergency or urgent surgical treatment. The patient with Type B AAD underwent an additional anatomical bypass from the axillary artery to the bifemoral artery for acute limb ischemia.

Of the 126 patients with Type A AAD, 55 (43.7%) underwent emergency or urgent open aortic surgical repairs. Fourteen patients with Type A AAD and a non-communicating-type false lumen were treated conservatively in the acute phase and 3 (21.4%) underwent conversion open aortic surgical repair 30 days after initial presentation. Of the 69 patients left after excluding the 43 patients who died upon arrival at hospital and the 14 patients with Type A AAD who had a severe condition and refused surgical intervention, 58 (79.7%) underwent open aortic surgical repair.

Among patients with Type B AAD, after excluding the 6 patients who died upon arrival at hospital and the 1 patient who underwent emergency surgery, 63 patients underwent conservative treatment, although 9 of these patients underwent open aortic repair or endovascular aortic stenting procedures (5 and 4 patients, respectively).

The outcomes of surgical and medical treatments are listed in Table 3. The overall 30-day fatality rate, including death upon arrival at hospital, was 65 (51.6%) among patients with Type A AAD and 8 (11.4%) among those with Type B AAD. Excluding patients who died before hospitalization, the 30-day fatality rate was 22 (26.5%) among patients with Type A AAD and 2 (3.1%) among those with Type B AAD. Among the 56 of 147 patients who underwent emergency or urgent surgery (excluding those who died before hospitalization), the 30-day fatality rate was 7 (12.7%) among those with Type A AAD and 1 (100%) among those with Type B AAD. In contrast, the 30-day fatality rate for the 79 patients who received medical treatment was 14/25 (56.0%) among those with Type A AAD and 1/54 (1.9%) among those with Type B AAD.

Incidence and Mortality Rates of AAD

The crude incidence rate of AAD was 13.55 per 100,000 inhabitants per year (95% confidence interval [CI] 13.53–13.58 per 100,000 inhabitants per year). The crude incidence rates were similar in men and women (12.82 and 14.20 per 100,000 inhabitants per year, respectively; P=0.48). The crude 30-day mortality rate for AAD was 4.92 per 100,000 inhabitants per year (95% CI 4.90–4.93 per 100,000 inhabitants per year). The crude 30-day mortality rates were similar in men and women (4.22 and 5.52 per 100,000/year, respectively; P=0.27).

The mean annual age-standardized incidence and 30-day mortality rates of AAD were 11.41 (95% CI 9.79–13.03) and 3.97 (95% CI 3.05–4.90) per 100,000 inhabitants per year, respectively. There was no significant difference in the age-standardized incidence rates between men and women (11.46 and 11.43 per 100,000 inhabitants per year, respectively; P=0.53). Conversely, the annual age-standardized 30-day mortality rate was higher in women than in men (4.19 and 3.77 per 100,000 inhabitants per year, respectively; P<0.001).

Figure 4 shows age- and sex-specific population, age-standardized incidence rates, and age-standardized 30-day mortality rates per 100,000 inhabitants per year of AAD in each 4 age groups from 2011 to 2020. In each of the 4 age groups, there was no significant difference in the incidence and 30-day mortality rates of AAD between men and women (P=0.33 and P=0.47, respectively). Overall, there were upward trends in both incidence and 30-day mortality rates of ADD with age, especially for individuals aged ≥85 years (60.56 and 34.99 per 100,000 inhabitants per year, respectively; P<0.001). The population of Yatsushiro was 146,460 in 2011, but decreased to 137,019 in 2020, with an average of 142,389 over the study period.¹³ However, there were no significant changes in annual age-standardized incidence rates and 30-day mortality rates of AAD during the study period (P=0.98 and 0.42, respectively).

Figure 4.

Age- and sex-specific mean annual population and age-standardized incidence and age-standardized 30-day mortality rates per 100,000 inhabitants per year in each of the 4 age groups from 2011 to 2020. CI, confidence interval; OR, odds ratio.

Discussion

The primary objective of the present study was to analyze the current incidence, early fatality, and mortality rates of AAD with the medical care system in our jurisdictional medical area by reporting actual epidemiological information on AAD in a geographically well-defined, medium-sized, rural city. Although recent studies have suggested that the incidence of AAD is increasing,^4–7 the actual incidence and mortality rate of AAD are not well known. Previous studies on AAD have been hospital based or restricted to specialist centers, or have been retrospective studies using registry data.^1,2,11 These studies may have underestimated the incidence and mortality due to incomplete inclusion of deaths before hospital arrival.¹⁴ Howard et al³ reported the incidence of AAD was 6.0 per 100,000 inhabitants per year in their previous Oxfordshire population-based study. However, the ability of that data to capture the cause of death before arrival at hospital may have been limited because of the low rate of postmortem examinations.³ In the present study, we reported an approximately double age-standardized mean annual incidence of AAD (11.4 per 100,000 inhabitants per year). Moreover, in the present study, the rate of Ai or autopsy for patients who were dead on arrival at hospital was 82.2% during the study period. Furthermore, as in previous population-based studies,^3–7,15 we showed that increasing age was significantly associated with an increased incidence of AAD. The increased incidence of AAD in the present study may be attributed to the older mean age of patients and the higher rates of postmortem examinations.

It is presumed that the increased rate of transfer of patients with out-of-hospital cardiac arrest (OHCA) to higher-level emergency medical facilities due to improvements in emergency medical care procedures will also have an effect on the increased incidence of AAD. A recent population-based study in Japan¹⁴ showed a much higher annual incidence of AAD (17.6 per 100,000 inhabitants per year) than that reported in the present study. Although that study was a short-term study (3 years) with patients with similar backgrounds, including age and sex, to those in the present study, the implementation Ai rate in that study was higher than in the present study (96% vs. 81.5%, respectively).¹⁴ The higher Ai rate may have contributed to the difference in results.

In recent years, postmortem CT has become more common as an alternative to conventional autopsies. Tanaka et al¹⁶ reported that among patients with OHCA, 7.0% and 0.4% were diagnosed by postmortem CT with Type A and Type B AAD, respectively. Similarly, Takeuchi et al¹⁷ reported that among patients with OHCA, 7.1% were diagnosed using non-contrast CT as having Type A AAD, and that 7.6% in total were diagnosed as having Type A or Type B AAD. In the present study, the diagnostic rates of AAD using Ai with CT were 7.7% and 1.1% for Type A and Type B AAD, respectively, which is similar to previous reports from Japan.^16,17 The characteristics of previous population-based studies on AAD cited in the present study are summarized in Table 4.

Table 4. Characteristics of Previous Population-Based Studies on Acute Aortic Dissection Cited in This Study

Author (year)	Geographic location	Case ascertainment method	Years of inclusion	Rate per 100,000 inhabitants per year (95% CI)		Mean (±SD) age (years)	% Men
				Incidence	30-day mortality
Howard et al3 (2013)	Oxfordshire, UK	Registry	2002–2014	6.00 (4.58–7.87)	NR	72.0±14.5	59.6
Mészáros et al4 (2000)	Sümeg, Tapolca, and Keszthely, Hungary	Hospital records	1972–1998	2.68 (2.14–3.35)	NR	65.7±13.1	60.7
Olsson et al5 (2006)	Sweden	Administrative codes (ICD-9 and 10)	2002–2014	3.18 (3.09–3.27)	NR	NR	NR
Pacini et al6 (2013)	Emillia-Romagna, Italy	Administrative codes (ICD-9)	2000–2008	4.70 (4.47–4.94)	NR	67.6±13.5	64.4
Landenhed et al7 (2015)	Malmö, Sweden	Administrative codes (ICD-8, 9, and 10)	2002–2014	15.0 (11.7–18.9)	NR	62.3±6.7	65.7
Yamaguchi et al14 (2021)	Nobeoka and Miyazaki, Japan	Hospital records	2016–2018	17.57 (13.69–21.44)	9.87 (6.99–12.76)	75.9±12.9a	53.2
						78.7±9.7b
McClure et al15 (2018)	Ontario, Canada	Administrative codes (ICD-10)	2002–2014	4.60 (4.48–4.72)	NR	66.0±16.7	60.8
Melvinsdottir et al19 (2016)	Iceland	Administrative codes (ICD-9 and 10; SNOMED-CT)	1992–2013	2.53 (2.13–3.00)	NR	66.9±13.6	61.8
Present report	Yatsushiro, Kumamoto, Japan	Hospital records	2011–2020	11.41 (9.79–13.03)	3.97 (3.05–4.90)	74.3±13.2	44.4

^aHospitalized patients. ^bPatients diagnosed by autopsy imaging. CI, confidence interval; ICD, International Classification of Disease; NR, not reported; SNOMED-CT, Systematic Nomenclature of Medicine-Clinical Term.

Despite well-established management of AAD, the early fatality rate of AAD is still high.^8,18 The overall 30-day or in-hospital fatality rate has been estimated to range from 13% to 56%.^3,5,6,19 In particular, Type A AAD remains a highly lethal condition.^3,5,6,8,18 Although the age-standardized mortality rate of aortic dissection is increasing in Japan, in many other countries it is declining.²⁰ In the present study, even though there was no difference in the 30-day fatality rate of AAD between the sexes, the 30-day fatality rate of Type A AAD was significantly higher than that of Type B AAD. Specifically, 43/126 (34.1%) patients with Type A AAD died before diagnosis, with 40 (93.0%) dying within 2 h of symptom onset. Moreover, 47 (37.3%) patients with Type A AAD died within 12 h of AAD onset. These data indicate the need for early diagnosis and time-sensitive treatments.

Forty-nine patients died prior to diagnosis of AAD, of whom 43 (87.8%) had Type A AAD. Type A AAD patients who died prior to diagnosis were older than those who were hospitalized alive, similar to previous reports from Japan.^16,17 However, in contrast with previous reports,^16,17 there were no differences in number of men and women who died prior to diagnosis of AAD.

The actual mortality rate of AAD is not well known. We found that the age-standardized 30-day mortality rate of AAD was 3.97 per 100,000 inhabitants per year. The age-standardized mortality rate of AAD in Japan from 2015 to 2019, calculated based on annual mortality data collected by the Ministry of Health Labour and Welfare Japan,²¹ was 7.96 per 100,000 inhabitants per year (95% CI 7.94–7.97 per 100,000 inhabitants per year). Although the early mortality rate of AAD in the present study was approximately half the calculated age-standardized mortality rate of AAD in Japan, the calculated data appear to include late-phase death, such as ruptured chronic aortic dissection and dissected aortic aneurysms.

In the present study, including cases of cardiopulmonary arrest before AAD diagnosis, predominant features included a higher mean age (74.3 years) and more octogenarians (41.8%) than reported by previous studies in Japan.^2,22,23 Furthermore, in previous studies, women were more frequently (55.6%) affected than men.^{1,3,7,11,14,22–24} The proportion of elderly (age ≥80 years) women in our jurisdictional medical area was 8.2%,¹³ which is higher than the Japanese average (5.8%).²⁵ A recent registry study in Japan also showed an increased incidence rate of AAD in women.² These results may be a consequence of the aging population in Japan and within the relevant medical area of Kumamoto Rosai Hospital.

The onset of AAD showed distinct monthly variations, with a peak in winter and a trough in summer, which is consistent with previous studies.^24,26 A circadian variation in AAD was observed, with a primary morning peak (06.00–09.00 hour) and a secondary peak in the evening (15.00–18.00 hours). This circadian pattern is similar to the onset of acute myocardial infarction and sudden cardiac death.^22–24,27 These variations were also demonstrated in previous studies.^22,24 Blood pressure increases after early morning and reaches a peak at midmorning and in the evening.²⁸ The circadian variation in blood pressure may explain the daily pattern in the onset of AAD.

Kojima et al²³ reported that the onset of AAD was related to physical or mental activity in 226 of 307 (86.6%) cases. Blood pressure is increased by several activities, such as physical exertion or daily stress.²³ We have shown that the onset of AAD was associated with physical activities and emotional stress or excitement, regardless of the time of day.

A shorter duration from symptom onset to hospital arrival was significantly associated with a better survival rate for AAD, whereas the first 24 h after symptom onset was the most important period for improving outcomes.²⁹ The median interval from onset to Japanese high-volume referral centers was 199 min.² In the present study, the median interval was one-third of that reported in previous studies.² Moreover, approximately 70% of patients with AAD were transferred directly to Kumamoto Rosai Hospital within 2 h of symptom onset. These results may reflect the good status of the emergency medical system in our jurisdictional medical area.

Study Limitations

This study has several limitations. First, our study involved analyses of retrospective observational data from a single center in a well-defined geographical area. Second, with the widespread use of CT scanners in Japan, it is possible to diagnose AAD in clinics. Therefore, we cannot rule out the possibility that, after being diagnosed with AAD at another hospital, a patient was then transported to a higher-order emergency hospital with appropriate surgical facilities in another area. Third, due to the low rate of postmortem examinations and the possibility that patients experiencing an OHCA could be transported to other facilities in the same area, our results may underestimate the true incidence of AAD. Therefore, there may be some cases that could not be diagnosed and have not been registered. Moreover, there is no insurance coverage for Ai by CT in Japan, so it is currently difficult to implement Ai by CT for all cases of OHCA.

Conclusions

The present population-based study detected a higher incidence rate for AAD than reported in previous studies, but we found a lower incidence of AAD in men than in women. Increasing age was associated with an increased risk of incident AAD.

Acknowledgments

The authors thank Enago for English language editing a draft of this manuscript.

Sources of Funding

This research was supported by funds to promote the hospital functions of the Japan Organization of Occupational Health and Safety. There was no outside support for this manuscript, including funding for equipment and drugs.

Disclosures

The authors declare that there are no conflicts of interest.

IRB Information

This study was approved by the Institutional Review Board of Kumamoto Rosai Hospital (20200811-11). According to the Personal Information Protection Law and the National Research Ethics Guidelines of Japan, the requirement for informed consent was waived. Patient information was anonymized and deidentified before analysis.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-23-0076

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