Trends in Subtypes of and Risk Factors for Stroke in Tianjin, China, 2005-2020

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Trends in Subtypes of and Risk Factors for Stroke in Tianjin, China, 2005-2020

https://doi.org/10.21203/rs.3.rs-4750570/v1

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Objective

A more detailed understanding of stroke is essential for the implementation of effective prevention strategies and mitigation of the disease burden. The aim of our study was to examine the temporal trends in age- and sex-specific risk factors for stroke subtypes in Tianjin.

Methods

We retrospectively analyzed stroke data from 2005 to 2020. The trend in the proportion of people hospitalized and age- and sex-specific risk factors were evaluated using linear regression analysis.

Results

Overall, the proportion of AIS (acute ischemic stroke, AIS) showed an upward trend from 64% in 2005 to 80% in 2020, while ICH (intracerebral hemorrhage, ICH) and SAH (subaraclmoid hemorrhage, SAH) showed a downward trend from 26.7% and 15.05% in 2005 to 9.2% and 5.03% in 2020, respectively (p < 0.001). The average age of onset of AIS showed a downward trend from 63.45 years in 2005 to 62.99 years in 2020 (p < 0.001). The trend change was mainly attributed to male patients, the average age of whom decreased from 61.96 in 2005 to 61.49 years in 2020 (p = 0.02). Based on age correlation analysis, people with a cumulative incidence of AIS tended to be younger. Stroke combined with both hypertension and diabetes showed an upward trend for different stroke subtypes, especially AIS and ICH.

Conclusions

In 2005–2020, the average age of onset of stroke in Tianjin, China, was younger. There was a trend toward a younger age, a greater proportion of young people with incident cases and male sex and a trend toward increased common risk factors for stroke. This is of great public health importance because additional interventions for common risk factors are necessary to prevent stroke, particularly in certain populations.

Stroke

Temporal trends

Subtypes

Sex specific

Risk factor

Stroke is a leading cause of mortality and long-term disability, especially in low-income and middle-income countries ¹. The Global Burden of Disease Study (GBD) 2017 estimated that deaths caused by stroke in China reached approximately 2 million in 2017, and stroke became the leading cause of years of life lost ^{2 3}. The knowledge and implementation of effective prevention strategies is therefore essential to mitigate the disease burden of stroke in China.

With striking improvement in prevention strategies and specialist stroke care, China has experienced a transition in the epidemiology of stroke. There is a marked increase in stroke prevalence and incidence, decreased incidence of recurrent stroke within one year, and a generally stable mortality rate compared with the values reported in the past ^1–6. Stroke in China is characterized by predominance among females, more cases of ischemic than hemorrhagic stroke, more cases in low-income than high-income areas, more cases in rural than urban areas, a higher rate in the north and lower rate in the south, and a greater prevalence in the central region ^{1 2 7}.

Stroke incidence has a very strong age gradient, with an exponential growth curve as the individual ages, and most strokes occur in older cohorts. Hence, even a moderate decrease in the age-adjusted stroke incidence for elderly people could potentially disguise a considerable increase in stroke incidence among younger individuals. The increase in these risk factors, in addition to China’s rapidly growing elderly population, forebodes a worsening of the stroke epidemic in China. It is important to understand whether risk factor patterns are similar among those experiencing an acute stroke, and it is critically important for timely policy-making for stroke prevention and control in China to recognize and understand the epidemiological trends during a period of economic transition.

According to the Health Status Report of Tianjin Residents (2017–2020), there has been a marked increase in stroke incidence in Tianjin, a city in North China. However, the age- and sex-specific trends and the main risk factors for stroke subtypes remain unclear. The aim of our study was to examine the temporal trends in the proportion of stroke subtypes, age- and sex-specific risk factors and the main common risk factors based on medical institution data from 2005 to 2020 in Tianjin, a city in northern China.

Data Sources and Study Sample

We used data from Tianjin Huanhu Hospital, a tertiary hospital specializing in encephalopathy in which the number of stroke patients diagnosed and treated accounts for more than half of the city and can basically reflect the epidemic level of cerebrovascular disease in the whole city to a certain extent. All acute stroke inpatients were included from 2005 to 2020 and verified by study physicians. This study was approved by the Tianjin Huanhu Hospital Ethics Committee.

In our study, stroke subtypes were established by a combination of the judgment of a neurologist or physician using neuroimaging (including CT and MRI) according to the WHO criteria ⁸. Considering that most TIA (transient ischemic attack, TIA) patients are mainly treated as outpatients, patients with a history of only TIA were excluded. Patients with multiple hospitalizations were evaluated according to the number of hospitalizations. There were three main subtypes of stroke in our study. The following International Classification of Diseases, 10th edition (ICD-10) diagnosis codes were used for case ascertainment: I63 (acute ischemic stroke, AIS), I61 (intracerebral hemorrhage, ICH), and I60 (subarachnoid hemorrhage, SAH). For each hospitalization, only the principal diagnosis code was used to identify events, which were then assigned to 1 of 3 mutually exclusive categories: AIS, ICH and SAH. The risk factors associated with stroke in our study were mainly hypertension, diabetes, dyslipidemia and atrial fibrillation (AF), and the following secondary ICD-10 diagnosis codes were used for case ascertainment: I10, I2, E11, and I48.

Data Analyses

The trends of stroke subtypes were analyzed from 2005 to 2020. Age was classified into six groups according to patients’ age at stroke onset or visit: <40, 40–50, 50–60, 60–70, 70–80 and ≥ 80 years. The average age of onset of stroke was calculated using the weighted arithmetic average. The temporal trend analysis of the proportion of hospitalized people, age- and sex-specific and common risk factors were calculated using linear regression analysis, and P < 0.05 was used to indicate statistical significance.

Trends in the proportions of stroke subtypes from 2005 to 2020

Overall, the proportion of AIS inpatients showed an upward trend from 64% in 2005 to 80% in 2020, while the proportions of ICH and SAH showed a downward trend from 26.7% and 15.05% in 2005 to 9.2% and 5.03% in 2020, respectively (p < 0.001) (Table 1, Suppl Figs. 1). In additional analyses, we evaluated possible sex differences and found that the proportion of AIS and ICH in males was higher than that in females and showed an upward trend from 64.35% and 64.54% in 2005 to 69.24% and 68.02% in 2020, respectively (p < 0.001), while a downward trend was shown in SAH from 44.47% in 2005 to 41.29% in 2020 (p < 0.001) (Table 2, Suppl Figs. 2).

Trends in the average age of onset of stroke subtypes from 2005 to 2020

The average age of onset of AIS showed a downward trend from 63.45 in 2005 to 62.99 years in 2020 (p < 0.001). The change in the trend was mainly attributed to male patients, whose average age decreased from 61.96 in 2005 to 61.49 years in 2020 (p = 0.02), while there was no significant change for females, whose average age of onset was 66.34 years in 2020 (p = 0.49). However, the average age of onset of SAH showed an upward trend from 52.61 in 2005 to 55.01 years in 2020 (p < 0.001). The average age of onset showed an upward trend among males and females from 49.5 and 50.19 in 2005 to 55.10 and 58.4 years in 2020, respectively (p = 0.003), while there was no significant change in the trend of age of onset for ICH (p = 0.32) (Table 3).

For different stroke subtypes, the average age of onset was lower for males than for females, and this difference showed an upward trend only for AIS but not for ICH or SAH (p = 0.03, p = 0.06 and p = 0.67, respectively). In 2020, the differences in the average age of onset between males and females with AIS, ICH and SAH were 4.85, 6.18 and 8.21 years, respectively (Suppl Table 4).

Trends in the proportions of stroke subtypes by age from 2005 to 2020

Based on age correlation analysis, people with a cumulative incidence of AIS tended to be younger. The change in the trend was mainly attributed to the 60–70 and 70–80 age groups, in which the incidence increased from 27.98–37.59% and decreased from 27.29% in 2005 to 19.5% in 2020, respectively (p < 0.001) (Table 4.1 and Figs. 3). In a sex-specific analysis, the proportion of AIS gradually decreased with age in male patients. Among them, the proportions of those aged 50–60 and 60–70 years increased significantly (p = 0.009 and p < 0.001, respectively) (Table 4.2).

There was no significant change in ICH. However, the proportion of ICH in the under 40 age group showed an upward trend from 7.54% in 2005 to 9.79% in 2020 (Table 5 and Figs. 4). In a sex-specific analysis, the proportion of ICH gradually decreased with age in male patients. Among them, the proportion of male patients aged under 40 and 60–70 years increased significantly (p = 0.009 and p < 0.001, respectively) (Table 5.1).

Similarly, the cumulative incidence of SAH showed an aging trend. The trend change was mainly attributed to the 40–50, 50–60 and 60–70 age groups, in which the incidence decreased from 25.24% and 33.65% in 2005 to 18.86% and 26.56% in 2020 and increased from 17.31% in 2005 to 31.25% in 2020, respectively (p < 0.001, p = 0.04 and p < 0.001, respectively) (Table 6 and Figs. 5). In a sex-specific analysis, the proportion of SAH gradually decreased with age in male patients. Among male patients, the proportion aged under 40, 40–50 and 60–70 years increased significantly (p = 0.04, p < 0.001 and p < 0.001, respectively) (Table 6.1).

Analysis of the trend of common risk factors in stroke subtypes

Considering that SAH patients with diabetes, dyslipidemia and atrial fibrillation are rare, the trend of those risk factors in SAH was not included in the analysis.

Stroke combined with hypertension

Both all stroke and different stroke subtypes combined with hypertension showed an upward trend (p < 0.001). The proportion of stroke subtypes complicated with hypertension was the highest for ICH, followed by AIS, and this upward trend became stable after 2012. In a sex-specific analysis, there were more male patients with AIS and ICH complicated with hypertension than female patients, 68.18% and 69.16%, respectively, in 2020, while there were fewer male patients than female patients with SAH, 36.48%, in 2020. The proportion of male patients with AIS complicated with hypertension was slightly greater (P < 0.01) (Table 7 and Figs. 6A and B).

Stroke combined with diabetes

Both all stroke and different stroke subtypes combined with diabetes showed an upward trend (p < 0.001). The proportion of stroke subtypes complicated with diabetes was the highest for AIS, followed by ICH. In a sex-specific analysis, the proportions of male patients with AIS and ICH complicated with diabetes were higher than those of female patients, 66.41% and 66.1% in 2020, respectively, and there was no significant change in the sex proportion. The proportion of male patients with cerebral infarction complicated with hypertension was slightly greater (P < 0.01) (Table 7 and Figs. 6C and D).

Stroke combined with AF

AF is mainly a risk factor for AIS, and there was no significant change in the trend of AIS combined with AF, but in a sex-specific analysis, there was an upward trend for males, and the proportion was slightly greater than that of females, which was 60.35% in 2020. ICH combined with AF showed an upward trend (p < 0.001), but there was no significant change in the sex proportion (p = 0.13) (Table 7 and Figs. 6E and F).Discussion

Stroke causes a notable health burden worldwide. It is the leading cause of death and DALYs in China (1.79 million deaths, 38.6 million DALYs in 2016) ^{9 10}. Timely stroke prevention and control in China are critically important to recognize and understand the epidemiological trends during a period of economic transition. In contrast to the downward trend in most regions worldwide, the incidence of stroke is increasing in China and is leading to an alarming burden for the national health care system ⁵. The analysis of the proportion of stroke subtypes, age- and sex-specific and main common risk factors showed temporal trends in Tianjin.

In our study, partly similar to the Health Status Report of Tianjin Residents (2018–2020) and the China Stroke Statistics 2019, we observed that the proportion of AIS in all stroke hospitalizations showed an upward trend, accounting for approximately 80% in 2020, while ICH and SAH accounted for approximately 15% and 5%, respectively. This proportion is slightly lower than that of all Tianjin residents, who reported a 90.22% proportion of AIS in 2020 and 81.9% in 2018 ¹¹. All the patients in our study were hospitalized with acute stroke, which may partly explain the slightly lower proportion. The increase in the proportion of AIS is also an important feature of the epidemiological transition of stroke in China. The sex differences in stroke subtypes are also of interest. It is well established that both AIS and ICH are more common in males than in females, but SAH is more common in females ^{11 12}.

Despite a rapidly aging society, in contrast to the upward trend in the average age of onset of total stroke from 1984 to 2004, we observed that the average age of onset of AIS was younger, and the trend change was mainly attributed to male individuals. For different stroke subtypes, the average age of onset was lower in males than in females, and the sex and age differences

showed an upward trend in patients with AIS and ICH ^{6 13}. Furthermore, in the age-specific analysis, we found that the age of onset of the cumulative incidence of AIS showed a downward trend, which was mainly attributed to the 60–70 age group and increased from 27.98–37.59% during the 15 years. In the sex-specific analysis, the proportion of AIS gradually decreased with age in male patients, and the proportion of patients aged 50–60 and 60–70 years increased significantly. Similar to the study by George, M., et al., while there was no significant change in the trend of age of onset of ICH in our study, the proportion of ICH patients under 40 years of age showed an upward trend ¹⁴. Additionally, in a sex-specific analysis, the proportion of ICH gradually decreased with age in male patients. In other words, the trend of younger age groups can also be interpreted as an increase in the incidence of younger age groups ¹⁵. However, there is still a need to note the trends related to male sex in the younger age group. Based on this, we understand that there has been a considerable change over time, characterized as a shift in stroke towards younger individuals from 2005 to 2020. This also suggests that we need to pay much more attention to stroke prevention in males.

Hypertension, dyslipidemia, diabetes, smoking, alcohol consumption, air pollution, diets low in fruits and vegetables, and high sodium intake are the most common and modifiable risk factors for stroke in China. Identifying risk factors is important for stroke prevention. Hypertension is the most important modifiable risk factor for stroke ¹¹. Lifestyle habits in China are changing as the country experiences a demographic transition, resulting in rising rates of stroke risk factors ¹⁶. Although improvements in patient awareness and the treatment and control of hypertension are encouraging, the proportion of people with hypertension is still unacceptable. Similarly, diabetes (prevalence of 11%) is relatively common and poorly controlled in China ¹¹. We also examined common risk factors for stroke. We found that stroke combined with both hypertension and diabetes showed an upward trend for different stroke subtypes, especially AIS and ICH. Additionally, of the studied common risk factors, hypertension and diabetes appeared to be the most important contributors. There were also sex differences. We found that there were more male patients with AIS and ICH complicated with hypertension than female patients, while there were fewer male patients with SAH than female patients. However, similar to the proportion of people hospitalized for AIS, the proportion of male patients with AIS complicated with hypertension was slightly greater. This may be a warning for the management of hypertension. AF is mainly a risk factor for AIS, and there was no significant change in the trend of AIS combined with AF, but in a sex-specific analysis, there was an upward trend for males; despite similar results from China Stroke Statistics 2019, the proportion was slightly greater than that for females ¹⁶. Awareness, treatment, and control of common risk factors are particularly important in hypertension, diabetes and especially among males.

This study has several strengths in that the data allowed the reporting of trends periodically over 15 years. The reported comorbidities and risk factors were documented in medical records using ICD-10 codes. However, this study also has some limitations. First, the data we used from a tertiary hospital specializing in encephalopathy in Tianjin do not comprise all cases in the entire population of the study area, and the exact incidence of different stroke subtypes was not known. Additionally, a more detailed classification of ischemic stroke into large-vessel, cardioembolic and lacunar stroke types was not available. Moreover, we could not account for other risk factors that may have affected stroke incidence, such as alcohol intake, dietary patterns, and air pollutants.

In 2005–2020, the average age of onset of stroke in Tianjin, China, was younger. There was a trend toward a younger age, incidence at a younger age of onset and male sex and a trend toward increased common risk factors for stroke. This is of great public health importance because additional interventions for common risk factors are necessary to prevent stroke, particularly in certain populations.

Consent for publication

Not applicable.

Competing interests

The authors have no conflicts of interest to declare.

Ethics declarations

The study was approved by the Committee for Medical Research Ethics at Tianjin Huanhu Hospital (ID: 2023 − 157). Informed consent was waived by our Institutional Review Board because of the retrospective nature of our study.This study was designed and conducted in accordance with the Declaration of Helsinki.

Author details

Tianjin Dementia Institute, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases.

Tianjin Huanhu Hospital, No.6 Jizhao Road, Jinnan District, Tianjin 300350, China.

Hao Wu^†, Shuai Liu, Yong Ji*

Cangzhou People’s Hospital, No.7 Qingchi North Road, Xinhua District, Cangzhou Hebei Province, 061000, China.

Meimei Zuo†

Funding

This work was supported by the National Natural Science Foundation of China [grant number 82171182], Tianjin Health Research Project [grant number TJWJ2023QN060] and Tianjin Municipal Education Commission Research projects[grant number 2023KJ060].

Author Contribution

Yong Ji designed the study. Hao Wu and Meimei Zuo performed the data analysis and wrote the manuscript. Shuai Liu contributed to the revision of the manuscript.

Acknowledgement

We thank all participants for their time and contributions to this study. We also thank the Tianjin Key Medical Discipline (Specialty) Construction Project [grant number TJYXZDXK-052B]

Zhou W, Chen R, Hopkins A, et al. Association between socioeconomic status and incident stroke in China. J Epidemiol Commun Health. 2020;74(6):519–26. 10.1136/jech-2019-213515. [published Online First: 2020/04/29].
Liu TGMJLMXTY. Rapid transitions in the epidemiology of stroke and its risk factors in China from 2002 to 2013. Neurology. 2017;89(1):53–61. 10.1212/WNL.0000000000004056.
Xu J, Zhang X, Jin A, et al. Trends and Risk Factors Associated With Stroke Recurrence in China, 2007–2018. JAMA Netw open. 2022;5(6):e2216341. 10.1001/jamanetworkopen.2022.16341. [published Online First: 2022/06/16].
Liu M, Wu B, Wang W-Z, et al. Stroke in China: epidemiology, prevention, and management strategies. Lancet Neurol. 2007;6(5):456–64. 10.1016/s1474-4422(07)70004-2.
Lin X, Wang H, Rong X, et al. Exploring stroke risk and prevention in China: insights from an outlier. Aging. 2021;13(11):15659–73. 10.18632/aging.203096.
Xue X, Jiang G, Li W et al. [Epidemiological characteristics of hemorrhagic stroke among residents in Tianjin from 1999 to 2018]. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 2021;42(8):1460-65. 10.3760/cma.j.cn112338-20201028-01288
Wang Y, Peng Q, Guo J, et al. Age-Period-Cohort Analysis of Type-Specific Stroke Morbidity and Mortality in China. Circulation journal: official J Japanese Circulation Soc. 2020;84(4):662–69. 10.1253/circj.CJ-19-0803.
Feigin V, Norrving B, Sudlow CLM et al. Updated Criteria for Population-Based Stroke and Transient Ischemic Attack Incidence Studies for the 21st Century. Stroke 2018;49(9):2248-55. 10.1161/STROKEAHA.118.022161
Collaborators GS. Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019(18(5)) 10.1016/S1474-4422(19)30034-1 [published Online First: 458].
Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019;394(10204):1145–58. 10.1016/s0140-6736(19)30427-1.
Wang YJ, Li ZX, Gu HQ, et al. China Stroke Statistics 2019: A Report From the National Center for Healthcare Quality Management in Neurological Diseases, China National Clinical Research Center for Neurological Diseases, the Chinese Stroke Association, National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations. Stroke vascular Neurol. 2020;5(3):211–39. 10.1136/svn-2020-000457. [published Online First: 2020/08/23].
Ma Q, Li R, Wang L, et al. Temporal trend and attributable risk factors of stroke burden in China, 1990–2019: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2021;6(12):e897–906. 10.1016/s2468-2667(21)00228-0.
Zhao D, Liu J, Wang W, et al. Epidemiological transition of stroke in China: twenty-one-year observational study from the Sino-MONICA-Beijing Project. Stroke. 2008;39(6):1668–74. 10.1161/STROKEAHA.107.502807.
George M, Tong X, Bowman B. Prevalence of Cardiovascular Risk Factors and Strokes in Younger Adults. JAMA Neurol. 2017;74(6):695–703. 10.1001/jamaneurol.2017.0020.
Kleindorfer BKJKKACMD. Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology. 2012;79(17):1781–87. 10.1212/WNL.0b013e318270401d.
Zhou M, Wang H, Zhu J, et al. Cause-specific mortality for 240 causes in China during 1990–2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet. 2016;387(10015):251–72. 10.1016/s0140-6736(15)00551-6.

Tables 1 to 7 are available in the Supplementary Files section.

No competing interests reported.

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You are reading this latest preprint version

Trends in Subtypes of and Risk Factors for Stroke in Tianjin, China, 2005-2020

Status:

Version 1

Abstract

Objective

Methods

Results

Conclusions

Figures

INTRODUCTION

METHODS

Data Sources and Study Sample

Data Analyses

Results

Trends in the proportions of stroke subtypes from 2005 to 2020

Trends in the average age of onset of stroke subtypes from 2005 to 2020

Trends in the proportions of stroke subtypes by age from 2005 to 2020

Analysis of the trend of common risk factors in stroke subtypes

Stroke combined with hypertension

Stroke combined with diabetes

Stroke combined with AF

Conclusions

Declarations

Consent for publication

Ethics declarations

Author details

Funding

Author Contribution

Acknowledgement

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1