Article Text

Original research
Factors influencing the incidence and treatment of intracranial aneurysm and subarachnoid hemorrhage: time trends and socioeconomic disparities under an universal healthcare system
1. Won Kyung Lee1,2,
2. Chang Wan Oh3,
3. Heeyoung Lee4,
4. Kun Sei Lee5,
5. Hyeonseon Park6
1. 1 Department of Prevention and Management, Inha University Hospital, Incheon, Republic of Korea
2. 2 School of Medicine, Inha University, Incheon, Republic of Korea
3. 3 Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
4. 4 Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
5. 5 Department of Preventive Medicine, School of Medicine, Konkuk University, Seoul, Republic of Korea
6. 6 Department of Social and Preventive Medicine, School of Medicine, Inha University, Incheon, Republic of Korea
1. Correspondence to Dr. Hyeonseon Park, Department of Neurosurgery, School of Medicine, Inha University, Incheon 22212, Republic of Korea; hspark{at}inha.ac.kr

## Abstract

Background Despite increasing usage of endovascular treatments for intracranial aneurysms, few research studies have been conducted on the incidence of unruptured aneurysm (UA) and subarachnoid hemorrhage (SAH), and could not show a decrease in the incidence of SAH. Moreover, research on socioeconomic disparities with respect to the diagnosis and treatment of UA and SAH is lacking.

Method Trends in the incidences of newly detected UA and SAH and trends in the treatment modalities used were assessed from 2005 to 2015 using the nationwide database of the Korean National Health Insurance Service in South Korea. We also evaluated the influence of demographic characteristics including socioeconomic factors on the incidence and treatment of UA and SAH.

Result The rates of newly detected UA and SAH were 28.3 and 13.7 per 100 000 of the general population, respectively, in 2015. The incidence of UA increased markedly over the 11-year study period, whereas that of SAH decreased slightly. UA patients were more likely to be female, older, employee-insured, and to have high incomes than SAH patients. In 2015, coiling was the most common treatment modality for both UA and SAH patients. Those who were female, employee-insured, or self-employed, with high income were likely to have a higher probability to be treated for UA and SAH.

Conclusion The marked increase in the detection and treatment of UA might have contributed to the decreasing incidence of SAH, though levels of contribution depend on socioeconomic status despite universal medical insurance coverage.

• aneurysm
• subarachnoid
• hemorrhage
• coil
• statistics
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## Introduction

There has been noticeable growth in the volume of endovascular treatment and neurosurgical research since the approval of the US Food and Drug Administration in 1995.1 According to a Nationwide Inpatient Sample in the US, numbers of patients treated surgically or endovascularly for intracranial aneurysms have increased rapidly over the past decade.2 However, most studies have been conducted under controlled circumstances to validate the efficacy of endovascular coiling compared with clipping.1 3 In contrast, the effectiveness of the endovascular treatment was under suspicion because outcome research which evaluates the effect of an intervention as applied to broad populations in real practice is still lacking and cannot suggest that increasing application of preventive treatment for unruptured aneurysm (UA) is related to reducing the incidence of subarachnoid hemorrhage (SAH).1 4

Socioeconomic disparity is an important public health concern from the perspective of health equality.5 Disparity-related research can determine who is deprived of healthcare and the degree of this deprivation.6 For cerebrovascular disease, research has largely concentrated on healthcare disparities for ischemic stroke, while intracranial aneurysms have received little attention despite rapid increases in endovascular treatment.7 8 Previous literature demonstrated that the patients treated for UA were more likely to be insured while those treated for SAH were prone to be self-payers and from poorer neighborhoods in the US.2 However, research suggesting a direct relationship between family or individual income level and the treatment for intracranial aneurysm as well as socioeconomic disparity in a different healthcare setting has been lacking.

Therefore, the aim of this study was to evaluate changes in the incidences of intracranial aneurysm and SAH using nationwide data for the period 2005 to 2015, to explore socioeconomic disparities regarding the diagnosis and treatment of intracranial aneurysms.

## Methods

### Study design and study population

The incidence of UA and SAH was estimated in serial cross-sectional design using the database of the Korean National Health Insurance Service (KNHIS). For the relationship between socioeconomic factors and the diseases, case-control design was used.

We selected all patients newly diagnosed to have an UA or SAH. The assumption of this study was that SAH was caused by the rupture of intracranial aneurysm. UA and SAH were defined using codes of I67.1 and I60, respectively, in the International Classification of Diseases (ICD) version 10. Traumatic SAH (S06.6) was excluded in this study. The eligible patients were those with newly diagnosed UA and SAH at a general hospital. We restricted it to general hospitals because they have facilities and specialists to provide the exact diagnosis and definite care for UA and SAH in Korea. Those with intracranial aneurysm were likely to be diagnosed and treated at a general hospital or transferred to a general hospital after they had been diagnosed at a hospital or clinic. Therefore, the Health Insurance Review and Assessment Service set the target provider as general hospitals for medical claim review and quality assessment of acute stroke care.9

Patients that had been diagnosed to have UA or SAH during the preceding 3 years at any clinic or hospital were excluded to select incident cases which were different from prevalent cases. Study participants were those who were diagnosed as UA or SAH but did not have the past history of UA or SAH in the last 3 years. Those who had a past history of intracranial aneurysm were 34 605 who were excluded from 137 605 patients diagnosed with UA. The excluded patients were 25 066 out of 115 492 patients who were diagnosed with SAH. Among them, the patients who had been diagnosed as UA in the past 3 years constituted only a small proportion (1.2%) of the patients with SAH.

The study population was divided into two groups, i.e., the UA and SAH groups. Those diagnosed as having UA with concomitant SAH were included in the SAH group. This categorization was in line with the  previous literature.2 UA with concomitant SAH might be an incidental finding of multiple aneurysms in the patient with SAH because we excluded those who had a past history of UA. Treatments for UA or SAH consisted of surgical clipping and endovascular coiling. Clipping was defined using procedure code S4640-S4642 in the Korean Classification of Diseases (KCD) procedure codes and coiling was defined using codes M1661, M1662, and M6641.

### Health insurance system and data source

KNHIS is a mandatory program for all residents in South Korea. Medical insurance societies expanded from big companies and public officials to the self-employed in the late twentieth century and then they were integrated into a single national insurer in 2000.10 It still has three categories (employee-insured, self-employed, and medical aid beneficiary) originating from the type of insurance societies before their integration. The contribution of KNHIS is calculated based on an employee’s wage for the employee-insured and the household income and property for the self-employed. Although it covers all the population, it could not be true for all items of healthcare. Generally, the insured pay around 30% of the medical cost related to healthcare benefits. Copayments are applied for all medical procedures and it depends on the level of medical care and admission.

The database of KNHIS from 2002 to 2015 was used for this study. It provides limited open access to the database and almost all inpatient and outpatient medical claim data are available including diagnostic codes, procedure codes, prescriptions, income levels, residential areas, and hospital locations.11 Detail of the information stored in the KNHIS database has been previously described.10 12 The data obtained for the present study was fully anonymized and de-identified, and the study was approved by the Institutional Review Board of Inha University Hospital (2017-04-011).

### Measurements

Demographic information including socioeconomic status was age, sex, residential area, insurance type according to payer, and insurance fee. For the analysis, age was categorized as <50, 50–59, 60–69, 70–79, and ≥80 years. Residential areas were classified using administrative districts. Type of medical insurance was classified by insurance payer, such as employee-insured, self-employed, and medical aid beneficiary. Family income levels, which were directly related to patients’ insurance contributions, were categorized into quintiles excluding medical aid. Comorbidities were evaluated using the Charlson Comorbidity Index (CCI), which classifies comorbidities into 19 underlying disease categories and is used as a marker of the severity of underlying diseases and risk of mortality. In this study, we modified the CCI by deleting cerebrovascular disease as it was the condition being evaluated.13 Weighted sums of CCI scores were categorized as 0, 1–4, and ≥5 for the analysis.

### Statistical analysis

We evaluated the frequencies and incidences of UA and SAH during the 11-year study period. In addition to crude rates, age-standardized rates were estimated to enable adjustment due to changes in the age distribution of the study population. Direct standardization was applied using a standard population of resident population in 2010 with age-specific rates of 5-year groups. Age-standardized incidence rates of the UA and SAH groups were compared with respect to direction and magnitude during the observation period. Annual percent change (APC) and parallelism tests were estimated using the Joinpoint Regression Program version 4.5.0.1 (Statistical Methodology and Applications Branch, Surveillance Research Program, National Cancer Institute).14

We also evaluated whether any shift in treatment modality had occurred for UA and SAH over the study period by calculating proportions of UA and SAH patients treated by clipping and coiling. Supportive treatments (e.g., drainage) were not considered.

The UA and SAH groups were compared with respect to demographic characteristics, including socioeconomic status. Descriptive statistics of the study population are presented and chi-square tests and multiple logistic regressions were performed to determine the significances of intergroup differences. SAS version 9.3 for Windows (SAS Inc, Cary, NC) was used for the analysis, and statistical significance was accepted for P values <0.05.

## Results

During the 2005 to 2015 study period 103 000 and 90 426 patients were newly diagnosed with UA and SAH, respectively. Differences were observed in demographic characteristics including socioeconomic status between the UA and SAH groups (table 1). When compared with the patients diagnosed as SAH, those diagnosed as UA were significantly more likely to be female. The UA group tended to be previously healthy, while the SAH group exhibited underlying diseases. Moreover, the UA group consisted of older people (≥70 years), and the SAH group was more likely to be younger people (<50 years). Those aged ≥50 years constituted 80.3% of the UA group and 67.6% of the SAH group. Employee-insured patients constituted 63% of the UA group and 56.7% of the SAH group. Furthermore, the UA group was likely to have a higher income level than the SAH group. Fourth and fifth quintiles (less deprived) for income level constituted 53.8% of the UA group and 45.1% in the SAH group. In addition, the regional distributions varied between the UA and SAH groups.

Table 1

Socio-demographic characteristics of the study participants

Figure 1 shows age-standardized incidence trends in the UA and SAH groups. The incidence of UA was found to have increased rapidly over the 11-year study period, while that of SAH has decreased slowly. For example, the incidence of UA increased from 6.1 per 100 000 of the general population in 2005 to 28.3 in 2015. Newly diagnosed UA increased from 7.8/100 000 to 37.9/100 000 for females and from 4.3/100 000 to 18.9/100 000 for males. Annual percent change (APC) of UA incidence varied over the study period. For UA, APC was 38.6% (95% CI 30.1 to 47.7) in 2005–2007, 14.7% (95% CI 11.1 to 18.4) in 2007–2011, and 7.8% (95% CI5.7 to 10.0) in 2011–2015. For UA, APC incidences were not significantly different between male and female (P value for parallelism: 0.096). In contrast, the incidence of SAH decreased gradually over the study period (from 20.0/100 000 to 13.7/100 000) and the APC of SAH incidence was −3.93% (95% CI −4.2 to −3.7). Moreover, APC incidences were not significantly different between male and female (P value for parallelism: 0.70).

Figure 1

Trends in the age-standardized incidences of unruptured intracranial aneurysm and subarachnoid hemorrhage (2005–2015).

The result of univariable and multivariable analysis for intergroup incidence comparisons are shown in table 2 and online supplementary Table 1. As shown by the tables, females, the elderly, employee-insured, those with a high income level, and those with a previously healthy status were still more likely to receive a diagnosis of UA after adjusting for covariates. For example, patients in their sixties were more than twice as likely to be diagnosed to have UA as those aged <50. Interestingly, employee-insured patients was more likely to find intracranial aneurysm before rupture than those on medical aid (OR , 1.14; 95% CI 1.09 to 1.18), and those in the highest quintile for income were more likely to be diagnosed with UA (OR , 1.33; 95% CI 1.27 to 1.39) than those on medical aid.

### Supplementary file 2

Table 2

Multivariable analysis of associations between socio-demographic characteristics and the incidences of intracranial aneurysm versus subarachnoid hemorrhage

The proportion of patients treated using an intravascular procedure increased with time, whereas the proportion treated surgically declined (table 3). In 2005, the proportion of the patients treated by coiling accounted for 48% in the UA group and this reached 62% in 2015. In contrast, in 2005, clipping made up 52% of the treatment for UA and this declined to 38% in 2015. In the SAH group changes were more marked. In 2005, coiling consisted of 23% of the patients treated for SAH and this increased to 58.6%, whereas in 2015, 77% were treated by clipping and this reduced to 41.4% in 2015. In the UA group, the proportion of the treated patients by coiling or clipping increased to a peak of 38.4% in 2011 and then decreased to 34.8% in 2015. Whereas in the SAH group, percentages treated by coiling or clipping increased steadily throughout the study period.

Table 3

Treatment modalities used for newly detected unruptured intracranial aneurysm and subarachnoid hemorrhage, 2005–2015

Unadjusted and aOR for the treatment decision of intracranial aneurysm were also calculated (table 4 and online supplementary Table 2). Among all study participants, those with a high income were more likely to be treated by coiling or clipping than those with a low income. Those aged ≥80 were least likely to be treated by coiling or clipping. In the SAH group, OR for treatment increased steadily during the observation period since 2005 and reached 1.92 in 2015, while OR for treatment in the UA group peaked in 2011 (OR , 1.25; 95% CI 1.13 to 1.37) and then decreased slightly. Additionally, univariable and multivariable analysis for the association between sociodemographic characteristics and the treatment modality are suggested in online supplementary Table 3 and 4.

Table 4

Multivariable logistic regression results of associations between socio-demographic characteristics and the treatment decision of unruptured intracranial aneurysm or subarachnoid hemorrhage

## Discussion

In the present study, we evaluated trends in the incidences of newly diagnosed UA and SAH, and factors influencing the incidence and treatment of UA and SAH with respect to socioeconomic disparities over the period 2005 to 2015. Among all study participants the incidence of newly diagnosed UA increased dramatically with time, whereas the incidence of SAH decreased gradually. Furthermore, our data shows that endovascular treatment has become a dominant treatment modality progressively over the study period. Patients with high incomes were more likely to be diagnosed and treated in the state of UA than those with low incomes.

The study shows the incidence of UA increased remarkably over the study period while that of SAH has decreased slightly, which suggests that increased UA detection might be related to the observed decrease in the incidence of SAH. Few reports have been issued on this topic and previously reported trends differ. For example, the incidence of SAH did not exhibit a decrease in Japan from 1990 to 2001, Taiwan from 2000 to 2009, or in the US from 2001 to 2009,4 15 16 and review studies conducted in Europe and Central and South America indicated no significant trend in the incidence of SAH.17 18 However, some authors have suggested the possibility of decreases in the incidence of SAH. In an English study conducted between  1999 and 2010, it was suggested declines in SAH related to hospital admissions and mortality might be due to a possible decrease in the incidence of SAH,19 and in Australia it was reported that the risk of fatal SAH decreased by 2.7% per annum between 2001 and 2009.20

There could be some factors influencing the incidence of newly detected UA and SAH. First, there could be underlying diseases and lifestyle that might be related to the incidence of UA and SAH. Previous research suggested that smoking, drinking alcohol, and hypertension could be risk factors for SAH.21 However, national data could not show a decrease in the risk factors which are consistent with the continuous decline of SAH in Korea. According to the Korea National Health and Nutrition Examination Survey (KNHANES) conducted by Korean CDC,22 those who drink more than once a month increased from 54.6% in 2005 to 60.6% in 2015 (online supplementary figure 1). Binge drinkers also increased from 11.6% to 13.3% during the same period. Moreover, it showed that the age-standardized prevalence of hypertension fluctuated within the range of 24.5% to 28.9%. The percentage of smoker per population fluctuated before 2010 and has declined after then. Furthermore, these risk factors are likely to contribute to the development of intracranial aneurysm. Therefore, the opposite trends between UA and SAH need to be explained by other factors.

### Supplementary file 1

Second, soaring incidence of UA could be caused by an ncrease in the use of CT and MRI. CT examinations increased from 74.7 per 1000 population in 2007 to 174.9 per 1000 population in 2015 according to OECD health data.23 MRI examinations increased from 13.9 per 1000 population to 31.2 per 1000 population during the same period as well.24 South Korea became to be ranked as sixth among 22 OECD countries and fourth among 27 OECD countries in 2015, separately, for the usage of CT and MRI. Therefore, the increased use of diagnostic examinations could extend the detection of UA. This suggestion was in line with other research that an increase in the detected UA could be attributed to the increased use of CT and MRI.4

Third, a decrease in the incidence of SAH might also be attributed to ease of access to preventive treatment for UA, as low procedural costs, high numbers of neurosurgeons, and increased per capita wealth have made treatment for UA more accessible in Korea. For example, GDP per capita increase from $15 931 in 2004 to$25 993 in 2016 and total UA treatment costs were relatively low at $6900 and$9750 for clipping and coiling, respectively, whereas in the US these costs were $32 872 and$31,264, respectively.25 26 In addition, the neurosurgeon to general population in Korea was relatively high at 4.753 neurosurgeon/100 000 people, as compared with 0.340/100 000 in the UK and 1.613/100 000 in the US.27 Therefore, an increased number of the detection and preventive treatment for UA could decrease the incidence of SAH.

For the treatment, those self-employed or employee-insured were more likely to be treated than those on medical aid, and those with a high income were more likely to be treated than those with a low income. These findings indicate insurance type and family income level is a socioeconomic factor that contributes to the treatment of UA and SAH. In Korea, total costs for clipping and coiling were $14 155 and$15 571 per patient, respectively, for SAH in 2003 to 2004.28 Moreover, total hospital costs for clipping and coiling were $6900 and$9750 per patient, respectively, for UA between 2011 and 2014.29 Copayment might be an influencing factor in determining the detection and treatment of UA and SAH despite the universal healthcare system. The previous analyses of US data supported the idea that the treatments of UA and SAH exhibited socioeconomic disparity.2 30 Bekelis et al reported the patients with private insurance and Medicaid were more likely to receive treatment than those on Medicare,30 and Brinjikji et al found self-payers were less likely to be treated for UA.2 However, national inpatient sample data were analyzed in this previous study and income levels were estimated using zip code-assessed mean incomes, and thus, the assumption was made that individual socioeconomic position (SEP) corresponded well with regional SEP, which could have constituted a study limitation.

The difference found between the observed magnitudes of the increase in the incidence of UA and the decrease in the incidence of SAH over the study period could be related to a mismatch between the need and supply for a preventive procedure. One possible explanation is that those at high risk of SAH were less likely to be diagnosed with UA. The known risk factors of SAH are hypertension, smoking, and low socioeconomic standing. Our study showed that those with a high family income level and no comorbidity, who were low risk for SAH, were more likely to be diagnosed to have UA and treated in advance, while the more deprived were prone to be admitted after it ruptured. It concurs with previous reports which showed a negative relation between the CCI and treatment for UA.26 Moreover, others found that low-income patients were more likely not to receive treatment for UA.2 These results suggest that proper preventive treatment should be provided based on rupture risk evaluation regardless of socioeconomic status. It was suggested that certain locations (anterior communicating artery aneurysms and pericallosal artery aneurysms) and larger size was related to the likelihood of rupture.31 Besides, we should focus on the prevention and management of modifiable risk factors such as smoking and hypertension, which was related to growth and rupture of intracranial aneurysm, to reduce the incidence of UA and SAH.

There could be some external factors influencing the treatment of UA and SAH. The proportion of the treated patients by coiling or clipping increased to a peak in 2011 and then decreased gradually in the UA group, while it increased consistently in the SAH group. It might be related to the fact that a Korean version of the guideline for the management of unruptured intracranial aneurysm was published by the Korean Society of Cerebrovascular Surgeons in 2011.32 It could contribute to reducing some excessive prophylactic treatments because it suggested a framework for the treatment decision of UA. Moreover, there are differences in regional economic status and underlying disease which could have an influence on treatment. For instance, gross regional domestic product (GRDP) in South Korea was about $29 018 in 2015. The lowest GRDP was$18 318 in Daegu and the highest was \$34 455 in Jeollanamdo. For hypertension, the prevalence among the persons aged above 30 was 19.3% in 2015. The range was 15.8% of Gwangju to 21.3% of Gangwondo. Additionally, it might be related to hospital factors such as the training experience and preference of neurosurgeons. It was consistent with the previous literature showing that the treatment modality for UA depended on the hospital.33

The strength of the present study is that it utilized nationwide data to evaluate trends in the incidences of newly diagnosed UA and SAH. Furthermore, it suggests relationships exist between family income level and the receipt of treatment received in a country with full healthcare coverage. However, the study also has limitations. A limitation was that this study could not infer a causal relationship because of the study design. It could only suggest the opposite trend of the incidence of UA and SAH with cross-sectional design and some possible explanation. Therefore, other influential factors such as new medication and control of hypertension could not be considered in this study. Moreover, the administrative database used did not contain clinical information, such as details of aneurysm characteristics and the severity of SAH, or details of treatment outcomes, which could have resulted in indication bias and residual confounding. In addition, coding inaccuracies might have made the estimates of incidence invalid. However, we would expect that the codings of subarachnoid hemorrhage in the national claim data were largely reliable34 and we restricted UA and SAH as those admitted at a general hospital to reduce the risk of overestimation. Last, there could be some exceptions to the interchangeable relationship between the rupture of UA and SAH. SAH could be caused by another reason and the rupture of UA could not lead to SAH, although we assumed that SAH was caused by the rupture of UA. For instance, aneurysmal isolated intracerebral hemorrhage could be reported without SAH. However, it might not be influential because there have been only a few case series described as rare and perplexing.35

View Abstract

## Footnotes

• Contributors Study conception and design (CWO, HP, JSL). Statistics (WKL, HL). Manuscript composition (WKL, HP). All authors reviewed the manuscript, provided critical review, and provided final approval of the manuscript to be published.

• Funding This work was supported by the National Research Foundation of Korea (NRF) and Inha University Hospital funded by the Korean government (MSIT) (NRF-2017R1C1B5017736) and Inha University Hospital Research Grant.

• Competing interests None declared.

• Patient consent Not required.

• Ethics approval Institutional Review Board of Inha University Hospital (2017-04-011).

• Provenance and peer review Not commissioned; externally peer reviewed.

• Data sharing statement Limited access was allowed to the database of the Korean National Health Insurance Service, which were used under license for the current study, and so are not publicly available.

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