Epidemiology and future trend predictions of ischemic stroke based on the global burden of disease study 1990–2021

Global level

In 2021, 69.9 million (Supplementary Data 1) prevalent cases of ischemic stroke (IS) were published globally, with an age-standardized point prevalence of 819.5 per 100,000, a decrease of 3.5% compared with 1990 (Fig. 1 and Supplementary Data 1). And 7.8 million (Supplementary Data 1) incident cases of ischemic stroke (IS) were reported globally, concerning an age-standardized point incidence of 92.4 per 100,000, a decrease of 15.8% since 1990. IS added up to 3.6 million (Supplementary Data 1) deaths in 2021, with an age-standardized rate of 44.2, a decrease of 39.6% from 1990. In 2021, the case numbers of DALYs for IS globally was 70.4 million (Supplementary Data 1), with a standardized rate of 837.4 DALYs per 100,000, a 34.9% decrease from 1990.

Regional level (V体育ios版)

Figure S1–S4 show the 2021 age-standardized prevalence, incidence, mortality, and DALYs of ischemic stroke across 21 GBD regions, stratified by sex. In 2021, Southern Sub-Saharan Africa (1122), Western Sub-Saharan Africa (1046), and East Asia (1018) had the highest age-standardized point prevalences for IS (per 100,000), while South Asia (497.7), Andean Latin America (515.1) and Central Latin America (552.6) had the lowest (Fig. S1 and Supplementary Data 1). In 2021, Eastern Europe (142.6), East Asia (134.8), and Central Asia (132.9) had the highest age-standardized incidences for IS (per 100,000), whereas the lowest rate occurred in Andean Latin America (46.3), Central Latin America (52), and Australasia (52.8) (Fig. S2 and Supplementary Data 1). In 2021, Eastern Europe (91), North Africa and the Middle East (73.7), and Central Asia (71) had the highest age-standardized death rates for IS (per 100,000), however, Australasia (14.1), High-income Asia Pacific (15.8), and Western Europe (16.7) had the lowest (Fig. S3 and Supplementary Data 1). In 2021, Eastern Europe (1601.2), Central Asia (1356.1), and North Africa and the Middle East (1329.4) had the highest age-standardized DALY rates for IS (per 100,000), but Australasia (249.5), Western Europe (297.7), and Andean Latin America (320.1) had the lowest (Fig. S4 and Supplementary Data 1). Figure S1–S4 demonstrate the age-standardized point prevalence, incidence, death, and DALY rates of IS, respectively, by sex in 2021 for all regions in the Global Burden of Disease study.

Figure S5–S8 show Percentage change in age-standardized prevalence (S5), incidence (S6), death rates (S7), and DALYs (S8) of ischemic stroke (1990–2021) across 21 GBD regions, by sex. The biggest increase in the age-standardized point prevalence of IS, from 1990 to 2021, was found in East Asia (31.5%), which is the only region where ASPR has grown. The biggest decreases in the ASPR of IS were discovered in Tropical Latin America (−28.7%), Southern Latin America (−25.5%), and High-income Asia Pacific (−24.7%) (Fig. S5 and Supplementary Data 1). The biggest increase in the age-standardized incidence of IS, from 1990 to 2021, was found in East Asia (33%). There was no significant change in terms of the ASIR of Southeast Asia. The biggest decreases in the ASIR of IS were discovered in High-income Asia Pacific (−46.6%), Western Europe (−45.1%), and Tropical Latin America (−44.3%) (Fig. S6 and Supplementary Data 1). During the same period, all regions apart from Southern Sub-Saharan Africa (27.5%) showed a decrease in the age-standardized death rates from IS, with the largest decreases in High-income Asia Pacific (−74.9%), Western Europe (−73.4%), and Australasia (−69.2%) (Fig. S7 and Supplementary Data 1). The age-standardized DALY rates decreased in all regions in addition to Southern Sub-Saharan Africa (17.1%) from 1990 to 2021, with the largest decreases in Western Europe (−69.1%), High-income Asia Pacific (−68%), Australasia (−65.1%), and Tropical Latin America (−62%) (Fig. S8 and Supplementary Data 1). Figure S5–S8 demonstrate the percentage change, from 1990 to 2021, in age-standardized point prevalence, incidence, death, and DALY rates for IS by sex, respectively.

The number of prevalent cases of IS increased from 34.7 million in 1990 to 69.9 million in 2021. East Asia, Western Europe, and South Asia had the largest numbers of prevalent cases in 1990, whereas East Asia, South Asia, and Southeast Asia had the largest cases in 2021(Supplementary Data 1). The number of incident cases of IS increased from 4.2 million in 1990 to 7.8 million in 2021. East Asia, Western Europe, and South Asia had the largest number of incident cases in 1990, whereas East Asia, South Asia, and Southeast Asia had the largest cases in 2021(Supplementary Data 1). The number of death cases due to IS increased from 2.3 million in 1990 to 3.6 million in 2021. East Asia, Eastern Europe, and Western Europe had the largest numbers of death cases in 1990, whereas East Asia, South Asia and Southeast Asia had the largest cases in 2021 (Supplementary Data 1). The number of DALYs caused by IS increased from 3.6 million in 1990 to 5.5 million in 2021. East Asia, Eastern Europe, and Western Europe had the largest numbers of DALYs in 1990, whereas East Asia, South Asia, and Southeast Asia had the largest cases in 2021 (Supplementary Data 1).

National level

Figure S9–S11 present the 2021 age-standardized incidence (S9), mortality (S10), and DALYs (S11) of ischemic stroke per 100,000 population across countries. In 2021, the national ASPR of IS ranged from 312.3 to 1603.9 cases per 100,000. In 2021, Ghana (1603.9), Sao Tome and Principe (1422.2), Nauru (1369.0), Madagascar (1365.6), and Botswana (1339.1) had the highest ASPR for IS (per 100,000), whereas Cyprus (312.3), Malta (383.7), Ireland (392.9), Luxembourg (408.8), Portugal (411.6) had the lowest (Fig. 1 and Supplementary Data 3). In 2021, the national ASIR of IS ranged from 38.9 to 214.4 cases per 100,000. In 2021, North Macedonia (214.4), Bulgaria (168.9), Botswana (163.1), Kazakhstan (154.8), Serbia (153.3) had the highest ASIR for IS (per 100,000), whereas Malta (38.9), Puerto Rico (39.2), Ireland (39.6), Luxembourg (41.1), Cyprus (41.8) had the lowest (Fig. S9 and Supplementary Data 4). The national age-standardized death rates for IS in 2021 varied from 7.0 to 216.9 deaths per 100,000. The highest rates were seen in North Macedonia (216.9), Bulgaria (147.6), and Egypt (139.8), whereas the lowest rates were found in Singapore (7.0), Puerto Rico (9.3), and Israel (10.8) (Fig. S10 and Supplementary Data 5). In 2021, the national age-standardized DALY rate of IS ranged from 180.9 to 3037.4 patients per 100,000. The highest rates were seen in North Macedonia (3037.4), Egypt (2462.6), and Bulgaria (2383.6), whereas the lowest rates were in Puerto Rico (180.9), Switzerland (202.3), and Singapore (205.8) (Fig. 11 and Supplementary Data 6).

The percentage change in the ASPR, from 1990 to 2021, differed obviously between countries, with China (34.2%), Turkmenistan (22.4%), Egypt (21.6%), and Lesotho (20.4%) having the largest increases. On the contrary, Portugal (−58.3%), Singapore (−51.6%), and the Republic of Korea (−49.6%) had the largest decreases (Supplementary Data 3). In the same period, Lesotho (40.6%), China (35.7%), and the Philippines (26.8%) had the largest increases in the ASIR. Inversely, the largest decreases were seen in Portugal (−70.3%), Singapore (−65%), and the Republic of Korea (−63.9%) (Supplementary Data 4). Over the same period, Montenegro (65%), Lesotho (55.8%), and Indonesia (36.8%) had the largest increases in the age-standardized death rate, whereas the largest decreases were found in Singapore (−87.6%), Luxembourg (−83.2%), and Portugal (−83%) (Supplementary Data 5). Lesotho (58.9%), Montenegro (40.4%), and Zimbabwe (39.7%) had the largest increases in age-standardized DALY rate of IS from 1990 to 2021. Constantly, the largest decreases during the research period were found in Portugal (−82.7%), Singapore (−81.9%), and Luxembourg (−81.4%) (Supplementary Data 6).

"VSports app下载" Age and sex patterns

Figure. S12–S22 detail the 2021 global ischemic stroke burden by age and sex, covering prevalence (S12–S13), incidence (S14–S16), mortality (S17–S19), and DALYs (S20–S22), including rates, counts, and uncertainty intervals. In 2021, the global prevalence rate of IS in men increased up to 75–79 years and then decreased with advancing age up to 90–94 years and increased again. The global point prevalence of IS in females increased with age and peaked in the oldest age group (≥95 years old). Before the age of 45–49, the prevalence was higher in women than in men, and after that age, the prevalence was higher in men than in women. The number of prevalent cases in males was highest in the 65–69 age group and then decreased with increasing age. However, the number of prevalent cases in females was highest in the 70–74 age group and then decreased with increasing age (Fig. 2, Fig. S12, Fig. S13, and Supplementary Data 2). In 2021, the global incidence of IS in both males and females increased with age and peaked in the oldest age group (≥95 years old). The number of incident cases in males was highest in the 70–74 age group and then decreased with increasing age. The number of incident cases in females was highest in the 70–74 age group. There are more incident cases in women than men in the age group of less than 34 years, more incident cases in men than women in the age group of 40–79 years, and again more incident cases in women than men in the age group of 80 years (Fig. S14, Fig. S15, and Fig. S16). In 2021, the global IS death rate in men increased up to 90–94 years and then decreased with advancing age. However, the global death rate of IS in females increased with age and peaked in the oldest age group (≥95 years old). In the 55–94 age group, the death rate is higher for males than for females. The number of deaths was highest in the 80–84 age groups, for both sexes, after which the numbers decreased with increasing age. In the age group over 80, the number of deaths is higher among women, and in the age group between 30 and 80, the number of deaths is higher among men (Fig. S17, Fig. S18, and Fig. S19). In men, the global DALY rate of IS increased up to age 90–94 years and then decreased with advancing age, whereas, for women, the DALY rate increased up to the oldest age group (≥95 years). This rate was higher in men between 45 and 94 years old. Also, the number of DALYs peaked in the 70–74 age groups in males but peaked in the 80–84 age groups in females (Fig. S20, Fig. S21, and Fig. S22).

Association with the sociodemographic index

Figure S23–S27 analyze ischemic stroke DALYs, comparing observed vs. expected burden by SDI (S23) and attributing DALYs percentages to top 12 risk factors (e.g., hypertension, diet) across GBD regions (S24–S25) and age groups (S26–S27). At the regional level, we found the association between the sociodemographic index and the age-standardized DALY rate of IS started relatively flat, with a small peak up to a sociodemographic index of about 0.7, and then declined rapidly, from 1990 to 2021. Eastern Europe, Central Europe, North Africa, and Middle East, and Western Sub-Saharan Africa had higher than expected DALY rates, based on their sociodemographic index, from 1990 to 2021. In contrast, Eastern Sub-Saharan Africa, South Asia, and Oceania, central Latin America, Andean Latin America, Caribbean, southern Latin America, High-income North America, Western Europe, and Australasia had lower-than-expected burdens from 1990 to 2021 (Fig. S23).

At the country level, in 2021, the burden of IS rose gently with increasing socioeconomic development until the sociodemographic index reached about 0.35, then slowly declined until the sociodemographic index reached about 0.68, then it reached a small peak again up to a sociodemographic index of about 0.75, but then decreased. Countries and territories such as North Macedonia, China, Bulgaria, Serbia, Latvia, Egypt, and Yemen had much higher than expected burdens, whereas Singapore, Spain, the United States, Ethiopia, and South Sudan had much lower than expected burdens (Fig. 3 and Supplementary Data 3).

In terms of the number of prevalent cases in 2021, the five regions stratified by SDI level ranked from highest to lowest were Middle SDI (22,230,670.7), High-middle SDI (17,110,640.3), High SDI (15,864,865.5), Low-middle SDI (10,234,283.1), and Low SDI (4,447,699.2) region (Supplementary Data 1). In terms of ASPR in 2021, the regions ranked from highest to lowest in sequence were High-middle SDI (893.3 per 100,000 population), Middle SDI (838.4), High SDI (813.9), Low SDI (755.7), and Low-middle SDI (669.3) region (Supplementary Data 1). In terms of the percentage change in ASPR from 1990 to 2021, the region with the largest decline in ASPR was the High SDI (−12.8%) region (Supplementary Data 1). The only region where ASPR has increased was the Middle SDI (9.5%) region (Supplementary Data 1).

In terms of the number of incident cases in 2021, the five regions stratified by SDI level ranked from highest to lowest were Middle SDI (2,648,524.6), High-middle SDI (2,243,339.9), High SDI (1,351,912.5), Low-middle SDI (1,120,427.2), and Low SDI region (433,298.4) (Supplementary Data 1). In terms of ASIR in 2021, the regions ranked from highest to lowest in sequence were High-middle SDI (116 per 100,000 population), Middle SDI (103), Low SDI (82.2), Low-middle SDI (80.7), and High SDI (66.1) region (Supplementary Data 1). In terms of the percentage change in ASIR from 1990 to 2021, he region with the largest decline in ASPR was the High SDI region (−37.4%). The only region where ASIR has increased was the Middle SDI region (6.2%) (Supplementary Data 1).

In terms of the number of death cases in 2021, the five regions stratified by SDI level ranked from highest to lowest were Middle SDI (1171548.3), High-middle SDI (1,151,654.6), Low-middle SDI (581,649.1), High SDI (507,950.1), and Low SDI (174,655.2) region (Supplementary Data 1). In terms of ASDR in 2021, the regions ranked from highest to lowest in sequence were High-middle SDI (59.7 per 100,000 population), Middle SDI (51.6), Low-middle SDI (50.9), Low SDI (49.4), High SDI (19.4) region (Supplementary Data 1). In terms of the percentage change in ASDR from 1990 to 2021, the regions in order of decline ranked from highest to lowest were High SDI (−63.9%), High-middle SDI (−46.7%), Middle SDI (−22.4%), Low-middle SDI (−13.7%), and Low SDI (−13.5%) region (Supplementary Data 1).

In terms of the number of age-standardized DALYs in 2021, the five regions stratified by SDI level ranked from highest to lowest were Middle SDI (23,896,856.7), High-middle SDI (21,054,343.3), Low-middle SDI (12,300,861.9), High SDI (8,975,176.2), and Low SDI (4,059,454.6) region (Supplementary Data 1). In terms of age-standardized DALY rate in 2021, the regions ranked from highest to lowest in sequence were High-middle SDI (1076.5 per 100,000 population), Middle SDI (960.7), Low-middle SDI region (942.3), Low SDI (914.3), and High SDI region (395.6) (Supplementary Data 1). In terms of the percentage change in age-standardized DALY rate from 1990 to 2021, he regions in order of decline ranked from highest to lowest were High SDI(−56.8%), High-middle SDI(−42.9%), Middle SDI(−21.4%), Low SDI(−14.9%), and Low-middle SDI(−13.9%) region(Supplementary Data 1).

"VSports注册入口" Association with the standard World Bank classification of economies

In 2021, the lowest age-standardized DALYs were observed in high-income countries (385.13 per 100,000 population, [95% UI, 343.71 to 422.68]) and the highest in low-income countries(1053.94 per 100,000 population, [95% UI, 902.08 to 1254.22]). Similarly, the lowest ASDR was found in high-income countries (19.81 [95% UI, 16.78 to 21.39]), and the high ASDR was found in low-income countries(55.1 [95% UI, 46.79 to 66.7]) and lower-middle-income countries(56.46 [95% UI, 50.69 to 61.91]) and upper-middle-income countries(56.39 [95% UI, 49.02 to 62.9]). The lowest ASIR were found in high-income countries (63.13 [95% UI, 56.04 to 70.56]), and the high ASIR were found in in low- income countries(104.96 [95% UI, 91.98 to 118.07]) and lower-middle-income countries(84.06 [95% UI, 72.86 to 95.63]) and upper-middle-income countries(118.35 [95% UI, 99.56 to 137.76]). The lowest ASPR was found in lower-middle-income countries (694.04 [95% UI, 635.91 to 750.41]), and the highest ASPR was found in low-income countries(936.37 [95% UI, 888.99 to 980.65]).

To summarize, while more economically developed countries had the lowest burden of IS(measured in age-standardized DALYs, ASDR, and ASIR). (Supplementary Data 2).

"V体育官网" Risk factors

The proportion of DALYs on account of IS attributable to individual risk factors differed across the Global Burden of Disease regions. The proportion of DALYs on account of IS attributable to individual risk factors by region and sex is shown in Fig. 4, Fig. S24, and Fig. S25. The proportion of DALYs due to IS that were attributable to dietary risks, tobacco, alcohol use, and other environmental risks was higher in men. Inversely, high body mass index, kidney dysfunction, and low physical activity were higher in women (Fig. 4 and Supplementary Data 4). Globally, high systolic blood pressure (58.0%), high LDL cholesterol (29.4%), air pollution (25.8%), dietary risks (18.3%), high fasting plasma glucose (17.6%), and tobacco (15.1%) had the highest contributions to DALYs on account of IS (Fig. S24 and Fig. S25). Among the five regions divided according to SDI, the proportion of air pollution in low SDI (47.4%) and low-middle SDI (38%) countries is relatively high, indicating that air pollution is a particular concern. In countries with high SDI, the proportion of air pollution was only about 11.1%. High-income North American countries had the lowest proportion of air pollution among all regions, at only 3.1%. However, the proportion of high fasting plasma glucose in high-income North American countries was higher than in other regions. The proportion of alcohol use in Western Europe and Australasia was higher than in other regions. The proportion of high body-mass index was higher in high SDI countries High-income North America as well as North Africa and the Middle East. In the 25–44 age group, hyperlipidemia is the most important risk factor (Fig. S26). For people over 45 years of age, high blood pressure is the most important risk factor for IS (Fig. S26). The influence of dietary factors on IS decreases gradually with the increase in age (Fig. S26). The proportion of air pollution for young people is higher than that for old people (Fig. S26). The proportion of tobacco use in patients aged 30–60 years is of great significance (Fig. S26). The proportion of High fasting plasma glucose among people aged 75–79 was higher than that of other age groups (Fig. S26). The proportion of High body mass index among people aged 35–39 was higher than that of other age groups (Fig. S27). The proportion of low physical activity among people aged 35–39 was higher than that of other age groups (Fig. S27). The proportion of other environmental risks among people aged 65–69 was higher than that of other age groups (Fig. S27). An interesting observation can be made that alcohol has a protective effect on the development of IS in people aged 15–19 years (Fig. S27). We speculate that this may be due to the protective effect of moderate alcohol consumption against IS and that confounding factors such as other social characteristics of adolescents who drink alcohol in this age group, such as being socially active, enjoying sports, and having discretionary money, may also be responsible. The proportion of alcohol use among people aged 50–59 was higher than that of other age groups (7.2%). The proportions of nonoptimal temperature were higher in the two extreme age groups of 95 years (7.2%) and older and younger than 5 years (4.8%). Nonoptimal temperature is a critical risk factor for adolescents under the age of 20 (Fig. S27). Kidney dysfunction is an important risk factor for the age group of 95 years (12.4%) and older (Fig. S27). Because these risk factors coexist with each other, the PAF does not add up to.

The estimated annual percentage change (EAPC) of IS

From 1990 to 2021, the EAPCs of global level in the ASPR, ASIR, ASDR, and ASR of DALY were −0.18(95% CI: −0.21, −0.16), −0.67(95% CI: −0.76, −0.58), −1.83 (95% CI: −1.92, −1.74) and −1.59 (95% CI: −1.68, −1.5), respectively, which presented a decrease in the GBD 2021 on account of IS (Supplementary Data 7). The EAPC of ASPR, in East Asia, the only region where EAPC increased, was 0.95 (95% CI: 0.89, 1). The largest decline in the EAPC of ASPR was in Tropical Latin America, which was −1.24 (95% CI: −1.3, −1.18). The EAPC of ASPR, in the Middle SDI region, was 0.27 (95% CI: 0.24, 0.3), which has increased. The EAPC of ASIR, in East Asia, the only region where EAPC increased, was 0.86 (95% CI: 0.8, 0.92). The largest decline in the EAPC of ASIR was in Western Europe, which was −2.12 (95% CI: −2.21, −2.03). The EAPC of ASIR, in the Middle SDI region, was 0.12 (95% CI: 0.07, 0.16), which has increased. However, the EAPC of ASIR, in High-income Asia Pacific, was −2.53 (95% CI: −2.73, −2.33), which has decreased maximally. Except for Southern Sub-Saharan Africa, whose EAPC was 0.94 (95% CI: 0.47,1.42), the EAPCs of ASDR in different regions have all decreased. In the high-income Asia Pacific and High SDI region, the EAPCs of ASDR have deceased maximally, were −4.76(95% CI: −4.91, −4.6) and −3.58(95% CI: −3.71, −3.44) respectively. Except for Southern Sub-Saharan Africa, whose EAPC was 0.64 (95% CI: 0.22, 1.06), the EAPCs of age-standardized DLAY rates in different regions have all decreased. In high-income Asia Pacific and High SDI regions, the EAPCs of age-standardized DLAY rate have deceased maximally, were −3.99 (95% CI: −4.14, −3.83) and −2.98 (95% CI: −3.11, −2.85), respectively. More detailed information is in Supplementary Data 7.

Frontier analysis of IS burden

Figure S28–S36 project future ischemic stroke burden, including SDI-DALYs trends (S28) and 2036 age-standardized prevalence, incidence, mortality, and DALYs cases by SDI level for males (S29–S32) and females (S33–S36). To estimate the effective difference between each country and region and the border, the 2021 DALYs and SDI were put to use (Fig. 5, Fig. S28, Supplementary Data 8 and Supplementary Data 5). The top five countries or regions with the largest effective difference from their frontier included North Macedonia, Egypt, Bulgaria, Iraq, and Serbia.

Given the position in the development spectrum, the top five countries or regions with the lowest DALY rates had the lowest effective differences, including Somalia, Puerto Rico, Ethiopia, El Salvador, and Israel (Supplementary Data 8).

The solid black line represents the frontier, and the dots represent the countries and regions. The blue dots indicate the upward trend, while the red dots indicate the opposite.

Among countries with different SDI levels, countries that have played a leading role in the prevention and control of IS include Germany, Monaco, Lithuania, the Republic of Korea, Taiwan (Province of China), Nepal, Uganda, South Sudan, Ethiopia, and Somalia. These countries at the forefront of prevention and control management are role models for the world to follow.

Prediction analysis of IS burden (V体育官网入口)

The prevalence rate, incidence rate, death rate, and DALYs rate will change variously along with time and in different regions. To precisely determine the true epidemiology of IS in different countries worldwide, it is indispensable for us to conduct higher-quality epidemiological research. According to the BAPC model, the future prevalence of IS in the world will increase and will be expected to reach 912.4 per 100,000 population for males, and 873.5 per 100,000 population for females, respectively. The future incidence of IS in the world will increase and will be expected to reach 109.3 per 100,000 population for males and 91.4 per 100,000 population for females in 2036. The future death rate of IS in the world will decease and will be expected to reach 43.6 per 100,000 population for males, and 31 per 100,000 population for females, in 2036. The future DALYs rate of IS in the world will decrease and will be expected to reach 881.4 per 100,000 population for males, and 665.8 per 100,000 population for females, respectively, in 2036(Fig. S29–S36). The ARIMA model was used to predict the same outcomes (incidence, prevalence, mortality, and DALYs) from 2021 to 2036, and the results were compared to the projections from the BAPC model. Both models produced consistent trends, suggesting robustness in the long-term predictions. (Fig. 6 and Supplementary Data 6)

"VSports" Principal findings

In this research, based on data from the Global Burden of Disease 2021 study, we have provided up-to-date information on the prevalence, incidence, death, and DALY cases of IS from 1990 to 2021, together with the age-standardized rates across 204 countries and territories. Globally, IS accounted for 69.9 million prevalent cases, 7.8 million incident cases, 3.6 million deaths, and 70.4 million DALYs in 2021. Although the age-standardized point prevalence, deaths, and DALY rates due to IS have decreased over the past three decades, the absolute counts are increasing, which could be a result of population growth, as well as population aging and a rise in life expectancy.

Strengths and limitations

In contrast to previous studies that only analyzed changes in stroke prevalence according to GBD 2019, we comprehensively evaluated the entire spectrum of population-level ischemic stroke dynamics, including incidence, prevalence, mortality, and DALYs. At the same time, we focus on a pathological subtype of stroke, ischemic stroke, to further explore the epidemiological trend of IS and its risk factors, and make future predictions. Because of the large heterogeneity between diseases, digging deeper into a disease is conducive to precise treatment and developing preventive strategies.

For areas with sparse data, we use data from data-rich areas to simulate and estimate, but the calculation model ultimately has an inherent error range, which cannot fully reflect the actual disease burden. However, this limitation is an unavoidable limitation for research based on the GBD database, which requires further refinement and improvement of the GBD database, as well as strengthening the recording and management of medical data in areas with scarce data. On the other hand, another study based on GBD2019 assessed the overall burden of all kinds of stroke and the population attributable fraction (PAF) of DALYs associated with 19 risk factors by sex, age group, and World Bank country income level⁹. We focused on ischemic stroke, the most common disease in stroke. In order to avoid excessive stratification of risk factors resulting in too small a proportion of each factor and too coarse stratification to accurately measure risk factors, we selected 12 leading risk factors (Level 3), and calculated population attributable fractions (PAFs) of DALYs by age, region and gender. Compared with the GBD2019 study on risk factors, we have adopted different data visualization methods for the study of risk factors, but our study has comprehensively covered different regions, ages, and genders. We also categorize risk factors, such as metabolic factors, behavioral factors, and environmental factors. We can also visualize the age-standardized percentage of IS DALYs attributable to all risk factors in males and female, the number of DALYs attributable to all risk factors combined, all ages, both sexes, and Global ischaemic stroke-related DALYs attributable to risk factors in 1990 and 2021, and so on. In addition, our research can be refined into the distribution of each risk factor in different countries and displayed on a world map.

A study based on GBD 2019 reported that the ASIR and ASDR of IS and ASR of DALYs due to IS decreased from 1990 to 2019 in high SDI regions. The ASIR of IS remained stable from 1990 to 2015 in middle SDIs, and then continuously increased from 2015 to 2019. However, the ASIR and ASDR of IS and ASR of DALYs due to IS had steadily and markedly decreased in high SDI and high-middle SDI regions since 1995, whereas the burden of ischemic stroke remained unchanged in low-middle and low SDI regions from 1990 to 2019²³. In our study, the EAPC of prevalence and Incidence in Middle SDI region were 0.27 and 0.12 from 1990 to 2021². The findings suggest that moderate SDI countries face rising morbidity and prevalence after 2015, and reflect the impact of new socio-economic development modalities on health and general health. The survival rate of ischemic stroke patients in low and middle-income countries is worse than that of patients in high-income countries, which may lead to an underestimation of the burden of ischemic stroke in low and middle-income countries.

Studies have shown that in areas with higher SDI, the proportion of IS in the elderly is higher and the proportion in the young is lower, which is related to population aging and low fertility²⁴.

In 2019, the worldwide ASIR of IS in females was slightly higher than that in males, while the ASDR of IS and the ASR of DALYs due to IS in females were lower than those in males. The higher risk in women among older patients may be related to women’s higher life expectancy²⁵. Previous studies have estimated that at least half of all strokes could be prevented through changes to lifestyle factors. The government should reduce the abuse of tobacco and alcohol through legislation and taxes on tobacco and alcohol, improve health care conditions, combat air pollution, and improve inequalities in health care, education, and employment². The strength of our study is the use of the latest data from the GBD2021 up-to-date database and the revision of the original burden of disease estimates based on new data and improved methodologies. The quality and accuracy of GBD data in some underdeveloped areas cannot be guaranteed when estimating etiological-specific mortality and nonfatal burden. Research organizations and social groups should increase capital and manpower input to build a complete disease registration system and death information system in underdeveloped areas.

In 2019, adult young women had a higher age-standardized incidence of ischemic stroke than men, while age-standardized mortality and DALY rates were lower than men. This can be due to factors such as patent foramen ovale, migraines, preeclampsia, high blood pressure during pregnancy, oral hormonal contraceptives, and more²⁶. In our study, it was also observed that estrogen has a protective effect against IS in people aged 40 to 50 years, and the incidence of IS in women younger than 40 years is higher than that in men, which is probably due to the above reasons.

It is essential for implementing effective individual-level changes and primary and secondary prevention measures to develop guidelines specifically for the best and timely identification and management of stroke in different populations. To the best of our knowledge, this is the first research to estimate the latest epidemiological patterns of and risk factors for ischemic stroke at the global, regional, and national levels by sex, age, and SDI and to conduct the future trend forecast and frontier analysis. Compared with Ding’s research, we also provided the leading risk factors for the disease burden for young adults in different SDI regions, which has important public health significance for the prevention of ischemic stroke in this age group².

Our study comprehensively listed the distribution of risk factors in different ages, genders, and regions according to the contribution of risk factors, instead of selecting some risk factors according to common sense or experience to study their effects. The results of our risk factor study are conducive for regions and countries to take targeted primary prevention measures on their circumstances. In addition, the distribution of risk factors changes dynamically with the development of the social economy, which is time-sensitive. Therefore, we should objectively and accurately assess the importance of risk factors rather than relying on experience to determine which risk factors are most important. The development of imaging techniques has also improved the detection of IS, which has increased the incidence compared to the past²⁷.

GBD imputable burden estimation has implemented more explicit bias correction and improved risk exposure estimation than previous studies, but the availability and quality of raw data remain its existing limitations. In addition, we need to design rigorous prospective clinical trials to verify the true biological effects and dose-response relationships of various risk factors²⁷.

Compared with developed countries, the decrease in stroke mortality among people aged 0–19 years from 1990 to 2013 was lower in developing countries, especially among newborns aged 0–27 days, which may reflect the higher incidence of undiagnosed stroke in developing countries due to limited imaging resources, lower visit rates, and poor health facilities. With significant increases in life expectancy in low- and middle-income countries, noncommunicable diseases are replacing infectious diseases as the leading causes of disability and death. A 2010 literature review recommended that the GBD include VTE in its measurement for a specific cause of death²⁸. For the construction and improvement of the GBD database, we suggest that the types of ischemic stroke diseases and pathological types of various tumors can be refined in the future, such as the classification of the ischemic stroke into the large atherosclerotic ischemic stroke, cardiogenic embolic stroke, small-vessel occlusive stroke, etc., and the classification of breast cancer into triple-negative breast cancer. Her-2 overexpressed breast cancer, hormone receptor-positive breast cancer, etc., the nervous system tumors were refined into glioma, craniopharyngioma, ependymoma, meningioma, etc. Because there is great heterogeneity in risk factors, prognosis, prevention, and treatment for different pathological types of diseases, the improvement of the database is conducive to accurate prevention and treatment. The common pathology of ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE) is thrombosis. Studies have shown that the occurrence of venous thromboembolism is positively correlated with age^28,29. Previous studies have found that age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology. This study explained at a mechanistic level the increase in the incidence of IS observed with age in our study. Clinical trials have shown that estrogen, represented by 17β-estradiol, can reduce brain damage in ischemic stroke by modulating the response of immune cells³⁰. This mechanism explained the conclusion found in our study that the mortality rate and the number of deaths of male IS patients are higher than that of females, and for middle-aged IS patients, the incidence rate and the number of incident cases of female are lower than that of male, which is conducive to guiding global researchers to develop alternative treatment drugs³¹. A population-based cohort study involving 27,204 individuals ≥60 years old in Southern Catalonia, Spain, which collected all cases of hospitalization from ischemic stroke (confirmed by neuro-imaging) from 01/12/2008 until 30/11/2011, reported that the mean incidence rate reached 453 cases per 100,000 person-years. Besides, Maximum rates appeared among individuals with a history of prior stroke (2926 per 100,000), atrial fibrillation (1815 per 100,000), coronary artery disease (1104 per 100,000), nursing-home residence (1014 per 100,000), and advanced age ≥80 years (1006 per 100,000). Age, history of prior stroke, history of coronary artery disease, atrial fibrillation, diabetes mellitus, and smoking emerged independently associated with an increased risk of ischemic stroke. According to the elderly population, the corresponding stratification factors should be adopted, especially the nursing care of the elderly in the nursing home and the prevention of cerebral infarction³².

In our study, we found that high systolic blood pressure, high LDL cholesterol, and high fasting plasma glucose are the most important risk factors for IS in elderly patients, and the management of comorbidities of chronic senile diseases as well as the early detection and standardized treatment of hypertension, diabetes, and hyperlipidemia are the key to solving the occurrence of cerebral infarction in elderly patients and improving their prognosis.

A study reported the prevalence of an estimated glomerular filtration rate (GFR) determined by the Modification of Diet in Renal Disease equation less than 60 mL/min/1.73 m(2) was investigated in older persons in an academic nursing home with either hypertension, diabetes mellitus, coronary artery disease (CAD), peripheral arterial disease (PAD), ischemic stroke, or congestive heart failure (CHF). The results of the study revealed older persons with hypertension, diabetes mellitus, CAD, PAD, ischemic stroke, or CHF have a high prevalence of moderate or severe renal insufficiency and should be treated optimally to reduce the increased risk of cardiovascular events and mortality in this high-risk population³³. This supported our findings that renal dysfunction IS also an important risk factor for IS in the elderly population. This suggested that the occurrence of renal dysfunction and IS may be mutually causal. Improving the outcome of diseases requires the joint efforts of multiple disciplines and the improvement of the comprehensive treatment level of community doctors and nursing home doctors for elderly diseases. Air pollution has a serious impact on stroke DALYS in people of all ages. The intensification of global industrialization and urbanization, the dramatic increase in the number of cars, the destruction and felling of forests and trees, the increase of reinforced concrete buildings, the reduction of green areas, the burning of large amounts of oil and coal, and the imperfect air control have all led to the deterioration of air quality in recent years. Health management departments should strengthen cooperation with environmental protection departments, expand the area of green plants, use environmentally friendly energy, and strengthen the research and development of industrial toxic and harmful gas treatment and waste gas cleaning equipment. People should wear masks that filter air when they go out. The world should work together to reduce the global burden of IS at its source. High body mass index and low physical activity have become an important disease risk factor in young and middle-aged people aged 30–50 years. This age group is at the age of starting a family and becoming the breadwinner of the family. The increasing pressure of social competition, the extension of working hours and work intensity, and the lack of awareness of long-term health management are all reasons for this situation. Managers should strengthen education among young people, enhance the awareness of physical exercise among young and middle-aged people, regularly hold public physical exercise activities with full participation, improve basic physical exercise facilities, and strengthen regular physical examinations of young people.

Overview and case definition

The Global Burden of Disease 2021 study estimated the burden(e.g., incidence, death, and prevalence, DALYs) of 371 diseases and injuries and 88 risk factors from 1990 to 2021 in seven super-regions, 21 regions, 204 countries and territories(including 21 countries with subnational locations), and 811 subnational locations^1,10. Detailed descriptions of the methodologies, reported fatal estimates, and reported nonfatal estimates are publicly available at https://vizhub.healthdata.org/gbd-compare/ 192 and https://ghdx.healthdata.org/gbd-results-tool.

Details of the GBD 2021 eligibility criteria, the literature search strategy, and data extraction are described in the Supplementary Methods section of the Supplementary Information. In the GBD 2021 dataset, ischemic stroke is defined according to the clinical criteria of the World Health Organization (WHO) as an episode of neurological dysfunction due to focal cerebral, spinal, or retinal infarction^1,7,9,10. The different categories of ischemic stroke in the GBD 2021dataset are classified based on the International Classification of Diseases (ICD)−9 codes 433–435.9, 437.0–437.2, and 437.4–437.9, as well as the ICD-10 codes G45–G46.8, I63–I63.9, I65–I66.9, I67.2–I67.848, and I69.3–I69.41^1,7,9. Because this study was based on data from a public database and did not involve confidential information about human participants, the Ethics Committee of the Chinese People’s Liberation Army General Hospital deemed no ethical review was required.

Calculation model (VSports app下载)

The GBD 2021 employed standardized tools to model processed data, estimating epidemiological and burden parameters based on age, sex, location, and year. The three primary models used are the Cause of Death Ensemble Modeling (CODEm) framework, the DisMod-MR 2.1 (disease-model Bayesian meta-regression) tool, and spatiotemporal Gaussian process regression (ST-GPR)⁵². The comparative risk assessment framework of the GBD was applied to estimate the burden attributable to various risk factors. The theoretical minimum risk exposure level (TMREL) is defined as the level of exposure that minimizes risk across the population, serving as a counterfactual for comparisons. The attributable burden is the difference between the currently observed burden and the burden that would be observed if exposure levels were equal to the TMREL⁵³.

VSports最新版本 - The sociodemographic index (SDI)

The Sociodemographic Index (SDI) is a composite indicator reflecting a country’s development level based on lag-distributed income per capita, average educational attainment for individuals over 15 years, and the total fertility rate for those under 25 years⁶. The SDI ranges from 0 (minimal development) to 1 (maximal development)^53,54. Based on SDI values, the 204 countries and regions were categorized into five groups: high-SDI, medium-high-SDI, medium-SDI, medium-low-SDI, and low-SDI regions⁵⁴.

World Bank Income Group Classification

Countries were classified by economic development according to the standard World Bank classification of economies (high-, upper-middle-, lower-middle-, and low-income countries)⁵⁵.

Estimated annual percentage changes (EAPC)

We calculated the Estimated Annual Percentage Changes (EAPCs) in age-standardized rates of ischemic stroke to describe trends over specific time intervals. These EAPCs were determined using the regression model: Y = α + βX + ε, where Y represents the natural logarithm of the age-standardized rate, X is the calendar year, and ε is the error term⁸. Here, β represents the trend in the age-standardized rate. The natural logarithm of an age-standardized rate is assumed to be linear over time, with EAPC calculated as 100 × (exp(β) – 1). The 95% confidence interval (CI) of an EAPC is derived from this linear model². If both the EAPC and the lower limit of its 95% CI are positive, the age-standardized rate is increasing; if both the EAPC and the upper limit of its 95% CI are negative, the rate is decreasing. Otherwise, the rate is considered stable².

To examine the relationship between the ischemic stroke burden and SDI, we used data from 1990 to 2021 to conduct a frontier analysis based on age-standardized death rates (ASDR) and SDI, aiming to understand potential improvements in ischemic stroke DALYs that might be achieved in different countries or regions^56,57.

Bayesian Age-Period-Cohort (BAPC)

In this study, we utilized a Bayesian age-period-cohort (BAPC) model with integrated nested Laplace approximations to project future trends in ischemic stroke burden. Previous research indicates that the BAPC model offers superior coverage and precision compared to alternative prediction methods^58–61.

"V体育安卓版" Autoregressive Integrated Moving Average (ARIMA) model

To further validate the projections obtained using the Bayesian Age-Period-Cohort (BAPC) model, we employed the Autoregressive Integrated Moving Average (ARIMA) model, a widely used time series forecasting method. ARIMA was applied to the data from 1990 to 2021 to assess the consistency and reliability of the predicted trends for ischemic stroke incidence, prevalence, mortality, and DALYs. The ARIMA model was selected due to its capacity to model temporal dependencies and trends without requiring complex assumptions about underlying causal mechanisms⁶².

V体育2025版 - Statistic analysis

All charts were made by R software (version 4.3.2) (R Foundation for Statistical Computing, Vienna, Austria). P Values less than 0.05 were considered statistically significant.

Reporting summary

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

Peer review information (V体育ios版)

Communications Medicine thanks Michael Brainin, Charles D A Wolfe, and the other anonymous, reviewer(s) for their contribution to the peer review of this work. [A peer review file is available].