INTRODUCTION
Aortic dissection was first described in the necropsy of King George II in 1760. The reported prevalence of aortic dissection after autopsy is as much as 1% to 3% and the annual incidence rate of type A aortic dissection is roughly 3/100,000[1]. Aortic dissection remains a challenging clinical problem and has a reported 5-year survival rate between 55% and 85% in acute cases of type A and type B aortic dissection[2–3] and operative mortality as low as 12%[4]. The mortality rate is approximately 1% per hour initially and 50% by the third day for untreated aortic dissection[5]. Even after release from the hospital, 31% to 66% of deaths are caused by complications associated with aortic dissection[6] in type B cases which had relatively lower risk compared with type A aortic dissection. A 20-year national study showed a significant decrease in in-hospital mortality for type A but not for such a trend was not seen for type B[7–8].In the past, the research and application of the epidemiology of aortic dissection have focused on in-hospital and follow-up mortality. Incidence data have rarely been generated or provided. For this article, the global epidemiology of both type A and type B aortic dissection was reviewed and discussed separately. The incidence data from all 193 countries and 54 regions worldwide and the population structures of 15 selected countries were retrieved. Studies that were included should contain an estimated regional incidence. Results after calibration by postmortem examination were for discussion only rather than drafting. Should discussion of gender differences in aortic dissection should be restricted to physiological men and women. During the study period, we further performed the following data in each country to enrich the potential correlation between clinical features and incidence: the average percentage of male residents (from national statistics), the average percentage of adults over 65 (from national statistics), and hypertension rate. All incidence data were from published articles; other data were collected from the annual reports of national statistical offices. The hypertension rate was from the non-communicable diseases (NCD) Risk Factor Collaboration in 2019[9]. The plot drawing were conducted using R 4.2.1 (https://www.r-project.org/). Package ggplot2, maps, maptools, and dplyr were loaded.
OVERALL INCIDENCE
In Europe, the incidence of type A and type B aortic dissection reported by the Federal Statistical Office of Germany and the emergency department in Berlin was 5.7/100,000 and 5.24/100,000, respectively[10–11]. Mészáros et al reported a 2.9/100,000 incidence of type A and type B in Hungary in 2000[12], whereas the incidence was 4.7/100,000 in Emilia-Romagna, Italy[13]. The Oxford Vascular Study Oxford Vascular Study (OXVASC), a prospective epidemiological study in Oxfordshire, UK, estimated the rate of incident events including any type of aortic dissection at 6/100,000[14]. From their analysis of data from a regional hospital, Tzikas et al estimated that the incidence of type A aortic dissection was 5/100,000 in Greece[15].
For North Europe, Melvinsdottir et al reported a 2.53/100,000 incidence of type A and B aortic dissection based on data from centralized hospital discharge registries, autopsy records, and the Cause of Death Registry in Iceland from 1992 to 2013[16]. Acosta and Gottsäter investigated data of residents of the municipality of Malmo, Sweden in 2000–2004 and 2014–2016, reporting an overall incidence of 3.3/100,000 (2.4/100,000 and 0.9/100,000 for type A and B aortic dissection, respectively)[17]. Another study based on the National Patient Register and the Cause of Death Register in Sweden reported a much higher incidence of 7.2/100,000[18]. In North America, data from Ontario, Canada, showed a prevalence of type A and B for 4.6/100,000[19]. Data from Medicare beneficiaries in the United States in 2010–2011 indicated that the overall hospitalization rate for type A and B aortic dissection was 10/100,000[20].
In Asia, data from China Health Insurance Research supported an estimated 2.8/100,000 incidence of any types of aortic dissection[21]. The detection rate of aortic dissection was roughly 1.2%[22] among those with an abnormally large aortic size (ie, larger than 3.6 cm) in Iran. Japan had a much higher type A and B aortic dissection incidence than other countries, with a prevalence of 17.6/100,000 and 30-day mortality of 74.5% in Miyazak[23] and a prevalence of 10/100,000 in Tokyo[24]. Remarkably, the high incidence was accompanied by a more elaborate investigation and a more comprehensive database of the outside-hospital population and autopsies than other studies. Data from the Nationwide Health Insurance Database of Korea indicated a gradual increase in the incidence of any kinds of aortic dissection and an overall incidence of 3.76/100,000[25].
In Oceania, a survey conducted in New South Wales, Australia estimated the incidence of type A and B aortic dissection aortic dissection at 3.47/100,000[26]. In New Zealand, the incidence of type A and B aortic dissection aortic dissection was 2.8/100,000 in the Midland area but higher than 14/100,000 in Waikato; the difference is likely attributable to the higher incidence of aortic dissection in the Maori population in Waikito[27–28].
Adequate data were often unavailable in African and South American countries. Only Brazil had reported the rate of incidence and prevalence of aortic dissection; the estimated incidence of type A and B aortic dissection aortic dissection was 4.9/100,000 (4.2/100,000 in women and 5.6/100,000 in men)[29].
Importantly, the incidence of aortic dissection cannot be precisely estimated because of pre-hospital death and differing autopsy rates across the world. More than 60% of patients are believed to receive inadequate medical treatment at the time of death[30]. Research in the German region of Berlin and Brandenburg, where autopsy is widely performed, revealed an observably high incidence of type A and B aortic dissection aortic dissection(11.9/100,000)[31]. The overall incidence is shown in Table 1 and depicted as a global incidence map in Figure 1. All researches but data from Greece were included both type A and type B aortic dissections.
Table 1 -
Basic characters of selected studies
| Country |
Authors |
Sample time span (year) |
Type |
Course |
Incidence (per 100,000) |
Male (%) |
Aged over 65 years old (%) |
Hypertension (%) |
| Australia |
Dinh et al[26]
|
2017–2018 |
Type A and B |
Acute |
3.47 |
49.80 |
15.53 |
29.29 |
| Brazil |
Dias et al[29]
|
1998–2007 |
Type A and B |
Acute and chronic |
4.90 |
49.48 |
5.64 |
44.95 |
| Canada |
McClure et al[19]
|
2002–2014 |
Type A and B |
Acute and chronic |
4.60 |
49.59 |
13.86 |
22.08 |
| China |
Xia et al[21]
|
2011 |
Type A and B |
Acute |
2.80 |
51.39 |
8.26 |
27.23 |
| Germany |
Eckstein et al[10]
|
2009 |
Type A and B |
Acute and chronic |
5.70 |
48.99 |
20.30 |
29.65 |
| Greece |
Tzikas et al[15]
|
2018–2019 |
Type A |
Acute |
5.00 |
49.08 |
21.80 |
31.26 |
| Hungary |
Mészáros et al[12]
|
2000 |
Type A and B |
Acute and chronic |
2.90 |
47.58 |
15.10 |
48.04 |
| Iceland |
Melvinsdottir et al[16]
|
1992–2013 |
Type A and B |
Acute |
2.53 |
50.18 |
11.70 |
27.57 |
| Italy |
Pacini et al[13]
|
2000–2008 |
Type A and B |
Acute |
4.70 |
50.14 |
19.33 |
33.72 |
| Japan |
Yamaguchi et al[23]
|
2016–2018 |
Type A and B |
Acute |
17.60 |
48.85 |
27.09 |
31.19 |
| New Zealand |
Xu et al[28]
|
2010–2020 |
Type A and B |
Acute |
2.80 |
49.15 |
14.65 |
30.94 |
| Republic of Korea |
Lee et al[25]
|
2005–2016 |
Type A and B |
Acute and chronic |
3.76 |
50.12 |
10.98 |
26.61 |
| Sweden |
Smedberg et al[18]
|
2002–2016 |
Type A and B |
Acute and chronic |
7.20 |
49.76 |
18.21 |
30.11 |
| United Kingdom |
Howard et al[14]
|
2002–2012 |
Type A and B |
Acute |
6.00 |
49.02 |
16.31 |
26.41 |
| United States of America |
Mody et al[20]
|
2000–2011 |
Type A and B |
Acute and chronic |
10.00 |
49.34 |
12.52 |
31.52 |
;)
Figure 1.: The global incidence geographic distribution of aortic dissection.AD: aortic dissection.
CLINICAL FEATURES AND SERUM MARKERS
The most common clinical feature of acute aortic dissection was pain, although its nature and location varied considerably[32]. The evidence did not support that abnormal body mass index (BMI) was associated with the incidence of aortic dissection; however, BMI was independently associated with higher major in-hospital adverse outcomes in patients regardless of whether they underwent surgery[33]. Uncontrolled hypertension is common in aortic dissection and is believed to be one of the most significant treatable risk factor[34]. In hypertensive patients, the incidence of aortic dissection was 0.5% to 1% in those who suffered systolic blood pressure higher than 180 mmHg or diastolic pressure above 120 mmHg[35] and 7.9% in hypertensive crisis patients[36]. Hibino et al reported that hypertension and elevated systolic blood pressure and diastolic blood pressure were associated with a high risk of aortic dissection. The most distinctive of this study was even blood pressure was in a normal range, the risk of aortic dissection was still positively dose dependent[37]. The abnormal elevation of serum markers such as D-dimer[38] may bolster the diagnosis of aortic dissection, but further evidence for these markers is required. Other studies have found that high white blood cell sensitivity, the triglyceride/high-density lipoprotein cholesterol ratio, and hyperuricemia predict in-hospital mortality[39–41]. The significant differences observed in serum markers require further discussion and were generally more common in older patients compared with younger patients[42].
CLASSIFICATION-BASED DIFFERENCES
Two accepted aortic dissection classifications—Stanford and DeBakey—were reported. Aortic dissection involved the area from the ascending aorta to the aortic arch; even the descending aorta was defined as Stanford type B or DeBakey type III. Stanford type A occurred when the lesion was located in the ascending aorta and includes types I and II of the Debakey classification. DeBakey type II was limited to ascending aorta. The International Registry of Acute Aortic Dissection (IRAD) included 30 centers in 11 countries in North America, Europe, Israel, India, Australia, and Japan. In the IRAD cohort, 90.3% of patients were DeBakey type I aortic dissection, had a younger age, were more often male, and had a higher BMI. DeBakey type II aortic dissection patients were more likely to be female and have a lower rate of preoperative mesenteric and limb ischemia. Type I and II aortic dissections showed similar in-hospital (16.6% and 22.5%, respectively) and 5-year (15.5% and 16.1%, respectively) mortality in the IRAD study, meanwhile type II aortic dissection patients had fewer complications. An earlier study supported similar findings[1]. The outcome of 5-year survival was also similar between type A and B aortic dissection in the OXVASC study; however, type A patients had remarkably higher pre-hospital mortality (100% among pre-hospital deaths) and 30-day mortality (47.4%)[14]. Incidentally, the Stanford classification showed that type A patients were more common and were older adults with more complications and connective tissue disorders compared with type B patients[1,19,43]. In general, the mean age of patients suffering from proximal dissections was approximately 10 years lower than those who had distal dissections[13].
SEX-BASED DIFFERENCES
The incidence of male aortic dissection patients was nearly 61.5% in Australia[26], 56.0% to 65.0% in Canada and the United States[19,20,44], 67.1% in the IRAD study[1], and 67.6% in North Europe[45]. In regions such as Argentina and Spain where Spanish is the official language, the percentages of male patients with aortic dissection in hospitals were similar at approximately 60%, which was lower than in the IRAD study and in North Europe. However, 60.8% to 79.2% of cases in Brazil were male, a range that is generally higher than those reported in the IRAD study[29,46–47]. The OXVASC showed that the average age of female patients in large registered research studies was often approximately 10 years higher (79.3 vs. 67.1 years) when patients suffering from acute aortic dissection were included[14]. Moreover, in their analysis of 5 years of data from a national database in Sweden, Smedberg et al found a decreasing annual incidence of aortic dissection in males from 2002 to 2016 (9.8/100,000 to 8.8/100,000 in male vs. about 5.4/100,1000 in female, P < 0.001 vs. P = 0.105). Women also had higher 30-day mortality than men after acute repair (17% vs. 12%) in the research which might due to higher female mean age in the cohort, bias in referral patterns and improper treatment[18]. In China, male patients were included in studies considerably more often than female patients, with a ratio of greater than 3:1; this compared with ratios of 1.9:1 in IRAD, 1.3:1 in Sweden, and 1.5:1 in the United Kingdom[14,17,48]. Other Asian countries displayed a similar overall trend and female patients were seen in greater numbers. Still, the proportion of female patients hardly account for more than 50% of the whole population of patients, which showed the same trends in Western countries among specific studies[25,49]. On the one hand, the rate of smoking is higher in Chinese males than in females (50% vs. 10%)[50], which may lead to earlier onset. On the other hand, hypertension in young and middle-aged patients is believed to further play a role[51].
Although the majority of patients were male, hypertension, atherosclerosis, diabetes, and connective tissue disease were considerably more important risk factors, especially in the young[42]. Female sex was reported as a risk factor for aortic dissection independent of the ratio of the aneurysm to body size. The loss of female sex hormones may increase collagen deposition and decrease elastin production, thus leading to the impairment of the elastic properties of the aortic wall[52]. Estrogen exerts a protective effect on the aorta primarily by mediating matrix metalloproteinases (MMPs)[53].
In addition, the female sex was a risk factor and was associated with delayed diagnosis because of atypical symptoms[54]. However, whether such pre-hospital disadvantages affected outcomes between males and females remains disputed[55].
AGE-BASED DIFFERENCES
The incidence of aortic dissection has risen sharply in the older adult population and is reported to be 8.6/100,000 in ages 60 to 80 years and 32/100,000 for people aged over 80 years[26]. The average age of 2,137 patients from the German Registry for Acute Aortic Dissection Type A and patients in the German region of Berlin and Brandenburg was 60.5 and 61.4 years, respectively[31,56]. The average age was 66.9 years in Iceland[16], 72 years in the United Kingdom,[14] and 61 years in Sweden[17]. The average age of patients in the United States was approximately 74 to 75 years[20]. Only 19.0% of documented patients in Australia were under 60 years of age[26] and the average age of patients in Canada was roughly 66 to 70 years[19,44]. In North Europe, The Nordic Consortium for Acute Type A Aortic Dissection included 1,159 patients with a mean age of 61.5 years[45].
In Latin America—especially Argentina—many researchers have reported that the mean age of patients undergoing surgery ranged from 52 to 63 years[57]. Another Argentinian multi-center study reported an average age of 58.8 years for aortic dissection patients[43]. The mean age in Brazil was roughly 54.4 years[58]. Burboa-Noriega et al reported a mean age of 54.5 years in Mexico[59].
Studies revealed that the average age of Chinese patients was roughly 10 years lower than that of Western[60] patients. Moreover, patients aged 40 to 60 years were the largest group in Chinese studies, whereas patients aged 60 to 80 years were the largest age group in the IRAD[42] and Latin American studies. This finding was confirmed by multi-center research in China. The average age of patients in the Registry of Aortic Dissection in China (Sino-RAD) was 48.9 years; 89.6% of these patients received surgical treatment[61]. Another study that included 19 centers and 1,812 aortic dissection patients reported an average age of 51.1 years[48]. The other two studies selected reported average patient ages of 51.4 and 48.9 years in Northern China[62–63], where large and sometimes extreme temperature differences are experienced and a “high salt, high oil, high calories” diet is popular. The consequences of these differences are discussed later. The China Health Insurance Research data include patients whose average age was 58.9 years[21]—older than those in the Chinese studies previously mentioned. Data for this study were from 2011; the diagnosis of aortic dissection has since raised patients’ life expectancy and level of health and has led to a younger patient population. A high rate of males (84.49%) and smoking (50.61%) was observed in a study of Chinese patients aged under 45 years. In addition to ethnic factors, potential gene contribution reported by Li et al[64]. High oil and salt diet lifestyle[63], and complications such as hypertension may also contribute to the age profile of Chinese patients[65], especially in the northern area. In addition, the age of Chinese patients was associated with hypertension, which was considerably more common (as high as 26.6% of patients in 2013[66]) and almost certainly further increased with economic development and the aging of the population. Although both China and Japan are Asian countries, the Japan registry of aortic dissection and Miyazaki Prefectural Nobeoka Hospital indicated an older adult population aged between 67.9 and 75.9 years—an average age range higher than in China[23,49]. In Korea, the mean age of 18,565 patients was 67 years[25]. Overall, the age of onset in China was not only lower than that of any country worldwide but was also unique among Asian countries. The difference in age of onset may be attributable to genes or particular lifestyles.
RACE-BASED DIFFERENCES
Studies have reported that operated type A aortic dissection cases in Japan are 27.2 per million persons annually, more than four times higher than in Western countries including the United States and European countries[67]. Acute-type aortic dissection data from Belgian and Japanese centers also showed some variance. The Japanese cohort had significantly more women (48.8% vs. 28.7%), a significantly lower prevalence of hypertension (49.2% vs. 65.8%), and significantly more DeBakey type I dissections (77.2% vs. 48.4%) than the Belgian cohort. However, the age of onset in both cohorts was similar (63.3 vs. 59.3 years)[68]. Unusually, even with higher numbers of acute-type A dissection, the number of annual deaths from circulatory system disease was lower in Japanese women than in Belgian women (38/100,000 vs. 94/100,000). These contradictory findings may be attributable to a more vulnerable vessel wall in Japanese women; some researchers’ findings of low serum cholesterol levels may be linked to the quality of the fragile vessel wall[68].
Chew et al investigated differences in aortic dissection among Chinese, Malay, Indian, and Eurasian patients diagnosed with bicuspid aortic valve (BAV) in Singapore. Findings revealed that the largest mean indexed diameter of the aortic root, which may be associated with aortic dissection, was observed in Chinese patients (34.7%)[69].
Data from the Australian emergency department confirmed the gender balance findings of the IRAD study; however, fewer Caucasians (57.9% vs. 86.4%) and more Asians (17.8% vs. 4.4%) were reported, which may be attributable to higher Asian immigration in Australia compared with that in IRAD study countries[38]. In New Zealand, another major Oceanian country, a considerably earlier onset (ie, by roughly 5 years) of aortic dissection was observed in the Maori (25/100,000) compared with the non-Maori population (14/100,000)[27] in the Waikato area. The same trend was observed in Midland, New Zealand (6.9/100,000 in Maori vs. 2.0/100,000 in non-Maori cohorts) although no statistical differences were observed in 30-day or long-term survival[28].
Bossone et al analyzed data from IRAD and found that Type B acute aortic dissection was more frequent in Black patients (52.4% vs. 39.3%), who were younger (54.6 vs. 64.2 years), more likely to abuse cocaine (12% vs. 1.6%), and more likely to suffer from hypertension (89.7% vs. 73.9%) and diabetes (13.2% vs. 6.4%) compared with non-Black patients. Nevertheless, statistical differences were not observed between in-hospital and 3-year mortality[70]. Sorour et al’s study of 180 patients with acute-type B aortic dissection revealed a considerably younger cohort (58.9 vs. 67.6 years), a more refractory hypertension rate (42.2% vs. 16.4%), poorer compliance to treatment (72.9% vs. 93.3%), and more frequent emergency department usage before onset (57.9% vs. 26.9%) among Black patients, although dissection morphology and clinical outcome were similar[71]. Harris et al found that this phenomenon was dramatically evident among non-White residents in Maryland, USA[72]. Many studies such as those published by Yin et al demonstrate that although Black patients suffer from a higher burden of comorbidities, their perioperative outcomes (odds ratio (OR) = 0.44) and 1-year survival rate (hazard ratio (HR) = 0.65) are better than or at least statistically similar to those of non-Black patients after endovascular surgery[73]. Most of the studies above included the Black population in the United States or Europe. Data on Black patients from Africa were insufficient. Chen et al reported that family history of aortic dissection was a strong risk factor for aortic dissection (risk ratio (RR) = 6.56; 95% confidence interval (CI): 4.92–8.77) and later aortic surgery risk compared with those without family history (HR = 1.40; 95% CI: 1.12–1.76)[74].
PREGNANCY AND SYNDROME FACTORS
Pregnancy was the time during which one or more offspring gestates inside a physiological woman’s womb. The incidence of aortic dissection during pregnancy was approximately 1.45/100,000[75] and the condition appeared in approximately 20% of maternal cardiac deaths[76]. In women under 40 years of age, approximately 50% of aortic dissections occurred during pregnancy and contributed to up to 10% of maternal deaths[77].
Marfan Syndrome (MFS) is a risk factor for aortic dissection and the likelihood to develop aortic dissection at 20 years or younger[78]. In their study of 2,329 patients with MFS from the Taiwan National Health Insurance research database, Chiu et al identified that aortic dissection occurred in roughly 10% of patients at a mean age of 36.6 years[79]. Research based on a regional database in Chinese Taibei further reports that autosomal-dominant polycystic kidney disease, tuberculosis, Sjögren syndrome, and systemic lupus erythematosus are risk factors for aortic dissection[80–83]. Narula et al described aortic dissection tended to occur at an earlier age in the never-pregnant group compared to ever-pregnant women (38 vs. 45 years) but there were no significant differences in aortic dissection prevalence[84].
Aortic dissection is likely associated with syndromes such as MFS, BAV, and Turner syndrome—especially in pregnancy. MFS is believed to be responsible for a maximum of 3% to 7% of aortic dissection cases[85] and Turner syndrome is associated with BAV in 30% of cases[86]. Phenomenon above was further observed in normal patients. Multivariate analysis in a multi-center clinical trial in China showed MFS was a predictive factor for increased in-hospital mortality in patients with aortic dissection and had an odds ratio of 1.76[48]. Duan et al confirmed a 6.4% rate of MFS in a Chinese multi-center study—higher than the 4.5% observed in IRAD[61].
Nevertheless, some earlier studies have not proven a direct correlation between pregnancy and aortic dissection[87]. Much of the adverse opinion surrounding the role pregnancy plays in aortic dissection has been an artifact of selective reporting given that pregnancy and aortic dissection are independent events whereas syndromes appear more likely to affect the condition[88].
SOCIAL AND METEOROLOGICAL FACTORS
International and national geographic differences have not always been based on the environment itself but are often linked to transportation or socioeconomic, educational, or cultural factors. For example, Schachner et al analyzed data on skiing-related aortic dissections in their cardiac surgery clinic. Findings suggested that most affected patients lived at low altitudes and practiced an outdoor sport at unusually high altitudes at cold temperatures, potentially causing peak blood pressure in amateurs[89]. Autumn and winter are globally believed to be associated with an increased incidence of aortic dissection and worsening outcomes[90]. The increased incidence is attributed to higher blood viscosity and vasoconstriction of small vessels, potentially leading to greater arterial sheer force on the aortic wall and a reduction in blood flow in the vasa vasorum[91].
The high risk of aortic dissection in autumn and winter was related to low temperatures and temperature fluctuation over consecutive days. A Chinese multi-center study observed increasing aortic dissection risk with lower temperature cumulated over lag 0 to 1 day when daily mean temperatures were below 24°C; 28°C was associated with the lowest aortic dissection risk[91]. Other research suggests that the average daily temperature declined from 5 to 3 days before acute aortic dissection onset, that female patients were more greatly affected[92–93], and that winter cases accounted for 30% of cases[63]. Data from Brazil supported significant seasonal variation of deaths from aortic dissection, which were highest in winter (χ2 = 321.759, P < 0.0001); the author attributed this finding to increased blood pressure levels, arterial spasm, pulmonary disease exacerbation, and passive smoking in colder weather[94]. The 32.0% and 25.9% incidence of type A aortic dissection in autumn and winter, respectively, in Bosnia and Herzegovina further supports these findings[95]. However, whether low temperature or temperature fluctuation played a key functional role remains unclear, especially during the period before acute aortic dissection onset[91,93]. Research conducted with 1,642 patients from China and the United States indicates that the months in which aortic dissection most commonly occurs are October (10.3%) and February (10.0%), potentially suggesting that temperature fluctuation rather than absolute temperature is more strongly associated with incidence[96]. Data indicating increased mortality in the transitional seasons in Minneapolis, Detroit, and Russia support this view[97–98].
In their analysis of data from 2,120 patients in Wuhan, China, Yu et al found that the lag effect of daily mean temperature on the incidence of aortic dissection was significant within 2 days but lost significance at 1 week[99]. Taheri Shahraiyni et al concluded that meteorological predictors such as temperature or cloudiness together played a more important role in the onset of acute-type A aortic dissection in Berlin than the effect of vorticity and temperature advection by formula inference[100]. In contrast, studies by Majd et al and Repanos et al did not support that atmospheric pressure, air temperature, or the presence of a full moon had any considerable effect on the incidence of aortic dissection[101–102]. Studies about seasonal factors cannot entirely exclude social factors. For example, given that the most important festivals including Christmas and Spring Festival Day occur during the winter period, the temporal distribution of these customs may lead to differing food and alcohol intake and an irregular routine, which lead to chaotic blood pressure peaks.
Pacini et al reported the epidemiology and outcomes of aortic dissection in the hilly, mountainous, and plains areas of Emilia-Romagna, Italy. The incidence in the plains area was substantially higher (20.6/100,000) compared with 4.7/100,000 for hill, 1.8/100,000 for mountain, and the total incidence of 4.7/100,000; however, no differences in survival during follow-up were observed[13].
Whether air pollution causes acute aortic dissection is still under investigation; however, many studies have examined the correlation. Wang et al proved that fine particulate matter (PM) 10 and SO2 produced by automobile exhaust and the active heating system in winter were strong predictors of the incidence of acute aortic dissection in a moderately polluted area[103]. Other studies in China revealed that PM 2.5 is a further risk factor for aortic dissection. Research from Chen et al revealed that a 10 μg/m3 increase in PM 2.5 exposure is associated with a 3.38% increase in aortic dissection hospitalizations in Shanghai, China, and that this relationship is more pronounced among older adults and males[104]. In Southwestern China, Xie et al revealed that the daily air index (OR = 1.006, P = 0.007), PM 2.5 (OR = 1.020, P < 0.001), and SO2 (OR = 1.037, P < 0.001) are independent predictors of the incidence of aortic dissection[105].
In addition, active and passive smoking (HR = 2.39–3.92) is associated with adverse outcomes in aortic dissection[106–107]. The Japan Collaborative Cohort study, which included 34,720 male patients, concluded that patients with an ethanol intake lower than 30 g had a reduced risk of mortality from total aortic disease and aortic dissection compared to never-drinkers[108]. Yamagishi et al proved that people who ate fish more than once or twice weekly had lower mortality from total aortic disease[109].
The onset of aortic dissection is more likely an outcome of social activity or blood pressure variability than an isolated event. The proportion of cases increased in young patients who were exercising before death (5%–7%)[110].
TIME-BASED DIFFERENCES
The likelihood that people suffer from aortic dissection on weekdays and have worse outcomes when visiting the hospital on the weekend is well-established[26], but the day that most affects incidence has not been identified because of differences in customs. Some studies found onset was most frequent on Monday, but Sunday and Wednesday were also considered high risk. Living habits and working systems across countries are important considerations because the exact date is a composite reflection of these factors[96,111].
A meta-analysis by Vitale et al reported an increased risk of acute aortic rupture or dissection between 6:00 am and 12:00 pm[112]. In research in Northern China, the onset of aortic dissection peaked between 1:00 pm and 6:00 pm and especially after 3:00 pm. This finding may be ascribed to the peak in blood pressure in the evening because of social activities and strong liquor, excessive drinking, or active and passive smoking habits on specific occasions[63]. Xia et al reported a notable circadian pattern—2:00 am to 3:00 am, 9:00 am to 10:00 am, and 4:00 pm to 5:00 pm—of aortic dissection onset in Wuhan, China. The author partially attributed this finding to blood pressure variation[113]. Three peaks—9:00 am to 11:00 am, 0:00 am to 3:00 am, and 03:00 pm to 05:00 pm—were also observed in an Argentinian study[43]; peaks once again represented potential social relationships, given that meals are always taken late at night in Buenos Aires.
Overall, the peak time of aortic dissection onset in Asia was commonly the afternoon. Some researchers linked this finding to strong liquor and salty food in the late afternoon or later[63]. However, patients in Italy more commonly experienced onset in the morning, likely due to a blood pressure peak after waking up[111].
OVERALL MORTALITY RATE
Past studies have often focused on the mortality of patients receiving medical attention. The rate of endovascular management for type B aortic dissection had increased from lower than 10% to over 30%, which compared to 92% open procedure with hypothermic circulatory in type A aortic dissection. The overall in-hospital mortality rate of type A aortic dissection was much higher than type B (22.0% vs. 14.0%, respectively), and the former showed a significant decrease in trend[8]. Information on national or regional mortality rates was rare. Abdallah et al analyzed mortality from aortic dissection from the World Health Organization Mortality Database and the Centers for Disease Control WONDER database and assessed the mortality trends in 23 countries between 2000 and 2017. Except for Austria, Czech Republic, Germany, Hungary, Israel, and Japan, countries revealed a death rate from aortic dissection that decreased from 0.06/100,000 to 2.13/100,000 in male patients and from 0.12/100,000 to 1.42/100,000 in female patients[114]. Analysis of data from the Sao Paulo State Data Analysis System in Brazil indicated an estimated 2.43/100,000 death rate due to dissection[94]—a rate higher than the worldwide level.
COST
The median cost in Canada for aortic dissection in hospital was $11,525 and included a higher expense for posthospital service than for aortic aneurysms[44]. The average amount paid per patient in Brazil for elective surgery was roughly $5,406. The mean time from symptom onset to hospital admission was 53.96 hours, which was longer than in developed countries. These delays may contribute to the complication rate and operative mortality[58]. Because of the rapid reform and substantial regional differences in the Chinese healthcare system, databases measuring the accurate cost to the public were not available. Based on an article published in Beijing, China, the cost of surgery is between $20,513 and $34,040 in China based on various operations[115]. The medical costs of patients with type A aortic dissection were higher than those for type B patients, and prices ranged from $9,825 to $51,150. Based on the relatively high requirements of treatment for aortic dissection, spending on operation and transport in underdeveloped countries may be even higher than in developed countries. For example, any patient requiring cardiothoracic surgery in The Republic of Liberia must be transported to nearby countries such as Ghana, Senegal, or Cote D’Ivoire. Air-ambulance helicopters can cost tens of thousands of dollars although 38.6% of Liberians live on less than $1.90 a day[116].
OUT-OF-HOSPITAL TIME
According to the Sino-RAD register in China, although the median time from the onset of symptoms to hospitalization for patients with acute aortic dissection was an acceptable 2 days, only 140 of 1,712 patients visited a cardiovascular department in 8 hours and 763 patients waited for more than 48 hours[61]. Any additional delay is associated with a high probability of the unexpected rupture of the aortic and death. In contrast, the average transportation time for acute aortic dissection patients in Tokyo, Japan from first medical contact to the hospital was only 49 minutes[24].
DRUG ABUSE AND COVID-19
Cocaine use was observed in 1.8% of patients with acute aortic dissection in the IRAD study[117]. Cocaine abuse has been identified as an adverse factor of aortic dissection and was related to earlier onset, the prevalence of hypertensive crises, and higher post-discharge mortality. Amphetamine use was also significantly associated with a higher risk of aortic dissection in young adults[118]. Marijuana taken with other stimulants can increase the heart rate, blood pressure, and systemic sympathetic tone[119]. Nevertheless, Sarmiento et al did not observe short-term mortality differences in groups with or without marijuana abuse[120]. Re-intervention, long-term poor physical condition, and a high rate of complications may affect marijuana users. Cardiovascular patients who visited medical centers during or after the COVID-19 pandemic may typically be older adults who are more likely to be transferred from other hospitals and who have more serious clinical symptoms. Developed countries and relatively complete and systematic health and transportation systems could mitigate the negative impact. Lopez-Marco et al compared approximate acute aortic dissection outcomes before and during the COVID-19 pandemic[121]. Although some data did not support a significant difference before and after the pandemic, the specific number of patients who died during transport or in their domiciles was unknown[122]; more data are required for accurate comparison. Ashur et al demonstrated that in-hospital and 30-day mortality of type A acute aortic dissection increased during the influenza season compared with the non-influenza period (11.0% vs. 5.8% and 9.7% vs. 5.4%, respectively)[123]. Whether differences in virus characteristics, study design, or group selection affected the results remains unclear.
CONCLUSION
Although the incidence of aortic dissection remains relatively stable globally, transportation and key population screening still need considerable improvement, especially in developing countries. We estimated and reviewed risk factors and baseline characteristics related to aortic dissection. We observed a positive correlation between the incidence of aortic dissection and the older adult population; this requires further investigation. Various factors may confound these results because the epidemiological features are considerably complicated. Furthermore, given that some of the data were estimated based on data from only one region and some patients likely die pre-hospital or are not registered as having aortic dissection, these results are useful for reference only. Countries such as Japan included more detailed information in its database, making a comparison of outcomes with other countries difficult. The incidence of the condition in some regions such as Chinese Taibei was not included because data on China were already available. Finally, although the incidence and mortality are totally different in acute or chronic aortic dissection was different, but government or center for disease control and prevention oriented epidemiologic study is almost nonexistent. Most epidemiology studies were based on international classification of diseases (ICD)-9/10 diagnosis code but codes could not distinguish between acute and chronic events, not to mention different classifications. The vast majority of results came from single or multi-center trials and therefore covered a majority subset of acute cases and a small subset of chronic aortic dissections. Public health departments should consider screening target groups and key regions according to the risk factors of incidence and mortality.
AUTHOR CONTRIBUTIONS
WG, JY, and FL conceived the study, designed the method and contributed to the literature searches. JY, JW, PY, and SW investigated the literature and excluded the documents. JY and FL participated in the writing of the paper. WG was the guarantor and pledged that all listed authors meet authorship criteria and no others meeting the criteria were omitted. All authors interpreted the data, read the manuscript, and approved the final version.
CONFLICTS OF INTEREST STATEMENT
The authors declare that they have no conflict of interest with regard to the content of this manuscript.
DATA SHARING STATEMENT
The datasets reviewed during the current study are available in the Pubmed (https://pubmed.ncbi.nlm.nih.gov/), Medline (http://ovidsp.ovid.com/autologin.html), and Embase (www.embase.com) databases. All data reviewed during this study are included in the published article. The figure and table submitted in this paper are original.
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