Epidemiology of ischemic stroke in China and the United States

Abstract

This study aimed to comprehensively compare the temporal trends, age–period–cohort (APC) effects, and future projections of ischemic stroke burden between China and the United States from 1990 to 2023. This cross-sectional, population-based retrospective study utilized data from the Global Burden of Disease 2023 database (PMID: 41092926). Data on incidence, prevalence, mortality, and disability-adjusted life years (DALYs) for ischemic stroke were extracted for China and the United States from 1990 to 2023, stratified by sex and 19 age groups. Temporal trends were quantified using estimated annual percentage change (EAPC) through log-linear regression and average annual percentage change (AAPC) through joinpoint regression analysis. APC analysis using the intrinsic estimator method was performed to disentangle age, period, and cohort effects. Bayesian APC models with integrated nested Laplace approximation were employed to project disease burden through 2035. From 1990 to 2023, China demonstrated divergent trends with age-standardized incidence increasing by 5.41% (EAPC: 0.06%, 95% CI: −0.09 to 0.22%) and prevalence by 11.96% (EAPC: 0.44%, 95% CI: 0.41–0.46%), while mortality declined by 58.20% (EAPC: −2.68%, 95% CI: −2.84 to −2.51%) and DALYs by 54.99% (EAPC: −2.48%, 95% CI: −2.61 to −2.36%). The United States exhibited declining age-standardized rates across incidence (−27.17%, EAPC: −0.67%, 95% CI: −0.80 to −0.54%), mortality (−40.40%, EAPC: −2.00%, 95% CI: −2.33 to −1.67%), and DALYs (−28.49%, EAPC: −1.36%, 95% CI: −1.60 to −1.12%), with prevalence increasing by 10.93% (EAPC: 0.18%, 95% CI: 0.07–0.30%). Joinpoint analysis revealed heterogeneous patterns with multiple inflection points in both countries. APC analysis demonstrated exponential age effects, U-shaped period effects in China contrasting with declining then increasing patterns in the United States, and consistent cohort-related risk reductions in both nations. Projections to 2035 indicated that despite potential declines in age-standardized rates, absolute disease burden would escalate substantially: China’s incident cases projected to increase from 2656,475 to 4288,943 (61.46% increase), and the United States from 388,155 to 444,961 (14.64% increase). Despite improvements in age-standardized mortality and DALYs, both China and the United States face increases in absolute ischemic stroke burden through 2035 due to population aging, necessitating enhanced prevention strategies and healthcare resource allocation to address this intensifying public health challenge.

1. Introduction

Stroke is a neurological disorder characterized by sudden neurological dysfunction, encompassing primarily ischemic stroke, subarachnoid hemorrhage, and cerebral hemorrhage.^[1] According to the Global Burden of Disease Stroke Working Group study, stroke ranks as the 2nd leading cause of death globally and the 3rd leading cause of death and disability.^[2] Ischemic stroke is the most prevalent form, constituting approximately 65% of all strokes worldwide in 2021.^[3] Despite advancements in treatments, such as thrombolysis and mechanical thrombectomy, patients with ischemic stroke continue to experience a high likelihood of poor functional outcomes or recurrence posttreatment. The high incidence, disability rate, recurrence rate, and substantial economic burden associated with ischemic stroke present a significant threat to global public health. Moreover, stroke incidence exhibits considerable variation across countries, with rates increasing significantly in low- and middle-income countries while declining by 42% in high-income nations.^[4] As the world’s largest developing and developed countries, respectively,^[5] China and the United States serve as quintessential paradigms of these divergent epidemiological trajectories. China faces an escalating stroke burden driven by rapid population aging and lifestyle transitions,^[6] whereas the United States provides established insights into chronic disease management and advanced healthcare delivery.^[7] Comparing these 2 nations offers a unique opportunity to evaluate the effectiveness of different healthcare models and demographic transitions on stroke outcomes. This disparity highlights the urgent need for cross-national comparative studies. Recently, an increasing number of epidemiological studies have investigated the temporal trends of cerebrovascular diseases. Previous analyses have documented the shifting burden of stroke within individual nations, utilizing older iterations of the Global Burden of Disease (GBD) database, such as the GBD 2021 dataset for China^[8] or the GBD 2019 dataset for the United States.^[9] However, the majority of the existing literature is constrained by traditional descriptive epidemiology confined to single countries, often failing to disentangle the complex underlying drivers associated with historical periods and generational cohorts. Furthermore, studies providing long-term, quantitative future projections remain scarce. Ultimately, the current body of research on the effectiveness of healthcare systems across different countries remains limited, impeding collaborative progress in the global prevention and management of ischemic stroke. Consequently, this study utilizes the latest GBD 2023 dataset to conduct the first systematic comparison of the burden of ischemic stroke in China and the United States. Furthermore, this study combines Joinpoint regression to detect hidden temporal inflection points with an age–period–cohort (APC) model utilizing the intrinsic estimator (IE) method to disentangle the independent etiological drivers of aging, historical periods, and generational cohorts. Finally, by employing a Bayesian age–period–cohort (BAPC) model incorporating integrated nested Laplace approximation, we generate robust projections of disease trajectories up to 2035, thereby providing evidence-based healthcare planning for stroke prevention and the long-term allocation of healthcare resources.

2. Materials and methods

2.1. Data source and study design

This retrospective population-based study utilized data from the Global Burden of Disease Study 2023 (GBD 2023) database (https://vizhub.healthdata.org/gbd-results/, PMID: 41092926). The GBD 2023 database provides comprehensive estimates of the burden of 375 diseases and injuries across 204 countries and territories from 1990 to 2023.

Ischemic stroke data were identified using the International Classification of Diseases, 10th Revision (ICD-10) codes: G45 to G46.8, I63 to I63.9, I65 to I66.9, I67.2 to I67.848, and I69.3 to I69.4. The study included 4 primary epidemiological measures: incidence (new cases), prevalence (existing cases), mortality (deaths), and disability-adjusted life years (DALYs). For each measure, we extracted both the absolute number of cases and age-standardized rates per 100,000 population with corresponding 95% uncertainty intervals.

Sex-specific analyses were conducted for males, females, and both sexes combined. Comparative analyses were performed between China and the United States of America to represent contrasting healthcare systems and socioeconomic contexts. This study was conducted in accordance with the principles of the Declaration of Helsinki and followed the Guidelines for Accurate and Transparent Health Estimates Reporting statement.

2.2. Statistical analysis

All statistical analyses were performed using R software (version 4.3.0) with the following packages: tidyverse (version 2.0.0), dplyr (version 1.1.0), ggplot2 (version 3.4.0), ggsci (version 3.0.0), patchwork (version 1.1.2), readxl (version 1.4.0), writexl (version 1.4.0), openxlsx (version 4.2.5), and scales (version 1.2.1).

2.3. Temporal trend analysis

2.3.1. Estimated Annual Percentage Change (EAPC)

The EAPC was calculated to quantify the average annual rate of change in age-standardized rates over the study period. EAPC was derived from a log-linear regression model:

$${\displaystyle y=\alpha +\beta x+\epsilon }$$

where y represents the natural logarithm of the age-standardized rate, x represents the calendar year, and ε represents the error term. The EAPC and its 95% confidence interval (CI) were calculated as: EAPC = 100 × (e^β − 1). A positive EAPC indicated an increasing trend, while a negative EAPC indicated a decreasing trend. The trend was considered statistically significant when the 95% CI of EAPC did not include 0.

2.3.2. Joinpoint regression analysis

Joinpoint regression analysis was performed using the National Cancer Institute’s Joinpoint Regression Program (version 5.0.2) to identify significant changes in temporal trends. The analysis utilized the Grid Search Method to detect up to 5 joinpoints, with a maximum of 5 potential inflection points. The optimal number of joinpoints was determined using the Bayesian Information Criterion and Monte Carlo Permutation tests (P < .05). The natural logarithm transformation model was applied with constant variance assumption.

For age-standardized rates, the annual percent change was calculated for each identified segment between joinpoints, representing the rate of change within each distinct time period. The average annual percent change (AAPC) was computed as a weighted average of the APCs, with weights proportional to the length of each time interval. Both APC and AAPC were reported with 95% CIs, and trends were considered statistically significant when the 95% CI excluded 0 (P < .05).

For age-specific rates and all-ages rates, separate joinpoint regression models were fitted for each age group within each location, sex, and measure combination. The analysis followed the same methodological framework as described above, allowing for the identification of age-specific temporal patterns.

2.4. APC analysis

APC analysis was conducted to disentangle the independent effects of age, time period, and birth cohort on ischemic stroke burden. The IE method was employed to address the collinearity problem inherent in APC models, where age = period − cohort.

Data were organized into 5-year age groups (ranging from 25–29 to 90–94 years) and 5-year calendar periods (1990–1994, 1995–1999, 2000–2004, 2005–2009, 2010–2014, 2015–2019, and 2020–2023). Birth cohorts were derived by subtracting the median age of each age group from the median year of each period, spanning from approximately 1900 to 1998. The analysis was performed using the apc package (version 2.0.0) in R.

The APC model was specified as:

log(Rate_{ijk}) = μ + α_i + β_j + γ_k

where Rate_{ijk} represents the rate for age group i, period j, and cohort k; μ is the intercept; α_i is the age effect; β_j is the period effect; and γ_k is the cohort effect.

Age effects represent the inherent risk associated with biological aging. Period effects capture the influence of historical events, policy changes, or environmental exposures affecting all age groups simultaneously. Cohort effects reflect the cumulative experiences of individuals born in the same time period. Results were presented as rate ratios (RRs) with 95% CIs relative to reference categories (median age group, median period, and median cohort). The model fit was assessed using deviance statistics and the coefficient of determination (R²).

2.5. Forecasting analysis

Future trends in ischemic stroke burden from 2024 to 2035 were projected using BAPC models implemented through the BAPC package (version 0.0.35) in R. The BAPC framework extends traditional APC models by incorporating Bayesian inference with integrated nested Laplace approximation, providing robust uncertainty quantification.

The BAPC model structure incorporated:

• Age effects: modeled using second-order random walk priors to capture smooth age-related variations.

• Period effects: first-order random walk priors to account for temporal trends.

• Cohort effects: first-order random walk priors to represent generational influences.

• Overdispersion parameter: to account for extra Poisson variation in the data.

Model specifications included 5-year age groups (20–24 to ≥95 years) and 5-year periods (1990–1994 through 2020–2023 for historical data, extending to 2030–2034 for projections). The models were fitted separately for each combination of location (China and United States), sex (male, female, and both), and epidemiological measure (incidence, prevalence, deaths, and DALYs).

Predictions were generated for both age-standardized rates per 100,000 population and absolute numbers with 95% credible intervals. The forecasting horizon extended from 2024 to 2035, providing 12-year projections. Model performance was evaluated using deviance information criterion and posterior predictive checks. The forecasts assumed continuation of current trends without accounting for potential future interventions or major epidemiological shifts.

3. Results

3.1. Temporal trends in age-standardized rates of ischemic stroke burden

From 1990 to 2023, China and the United States demonstrated divergent temporal patterns in age-standardized rates of ischemic stroke burden across all epidemiological measures (Table 1, Fig. 1). In China, the age-standardized incidence rate (ASIR) increased modestly from 112.33 per 100,000 population in 1990 to 118.40 per 100,000 in 2023, representing a 5.41% increase, while the prevalence rate rose from 851.25 to 953.08 per 100,000, marking an 11.96% increase. Conversely, the age-standardized mortality rate (ASMR) declined substantially from 94.12 to 39.34 per 100,000 (−58.20%), and the DALY rate decreased from 1783.23 to 802.71 per 100,000 (−54.99%). In contrast, the United States exhibited declining trends across incidence, mortality, and DALYs. The ASIR decreased from 96.17 to 70.04 per 100,000 (−27.17%), mortality rate declined from 29.78 to 17.75 per 100,000 (−40.40%), and DALY rate decreased from 575.17 to 411.32 per 100,000 (−28.49%). Notably, prevalence rates increased in both countries, rising by 10.93% in the United States from 1129.46 to 1252.89 per 100,000.

Table 1.

Temporal trends in age-standardized rates of ischemic stroke burden in China and the United States, 1990 to 2023.

Location	Gender	Indicator	Cases in 1990 (n)	Cases in 2023 (n)	Change in Cases (%)	Age-standardized rate in 1990 (per 100,000)	Age-standardized rate in 2023 (per 100,000)	Change in age-standardized rate (%)	EAPC (95% CI)	AAPC (95% CI)	AAPC P-value
China	Both	Incidence	876,167	2,656,475	203.19	112.33	118.4	5.41	0.06 (−0.09 to 0.22)	0.13 (0.09 to 0.17)	<.001
China	Female	Incidence	389,802	1,066,643	173.64	96.09	91	−5.3	−0.21 (−0.36 to −0.07)	−0.19 (−0.22 to −0.16)	<.001
China	Male	Incidence	486,364	1,589,832	226.88	131.66	148.51	12.8	0.23 (0.07 to 0.39)	0.30 (0.24 to 0.36)	<.001
China	Both	Prevalence	7,436,521	21,229,135	185.47	851.25	953.08	11.96	0.44 (0.41 to 0.46)	0.34 (0.33 to 0.34)	<.001
China	Female	Prevalence	3,478,183	9,165,813	163.52	775.23	801.83	3.43	0.14 (0.11 to 0.16)	0.10 (0.09 to 0.10)	<.001
China	Male	Prevalence	3,958,338	12,063,322	204.76	939.75	1115.83	18.74	0.66 (0.62 to 0.7)	0.52 (0.52 to 0.53)	<.001
China	Both	Deaths	590,439	860,343	45.71	94.12	39.34	−58.2	−2.68 (−2.84 to −2.51)	−2.52 (−2.60 to −2.44)	<.001
China	Female	Deaths	284,203	368,634	29.71	82.96	30.72	−62.97	−3.11 (−3.33 to −2.9)	−2.91 (−2.98 to −2.84)	<.001
China	Male	Deaths	306,236	491,709	60.57	108.43	49.42	−54.42	−2.36 (−2.5 to −2.22)	−2.25 (−2.37 to −2.12)	<.001
China	Both	DALYs	13,378,094	18,090,920	35.23	1783.23	802.71	−54.99	−2.48 (−2.61 to −2.36)	−2.33 (−2.41 to −2.26)	<.001
China	Female	DALYs	6,110,070	7,336,193	20.07	1545.95	615.52	−60.19	−2.94 (−3.1 to −2.78)	−2.71 (−2.78 to −2.66)	<.001
China	Male	DALYs	7,268,024	10,754,727	47.97	2062.32	1009.23	−51.06	−2.17 (−2.28 to −2.05)	−2.08 (−2.17 to −1.99)	<.001
United States of America	Both	Incidence	304,213	388,155	27.59	96.17	70.04	−27.17	−0.67 (−0.8 to −0.54)	−0.94 (−0.97 to −0.91)	<.001
United States of America	Female	Incidence	156,619	180,861	15.48	82.88	59.72	−27.95	−0.75 (−0.87 to −0.63)	−0.97 (−1.00 to −0.94)	<.001
United States of America	Male	Incidence	147,594	207,294	40.45	113.07	81.63	−27.8	−0.63 (−0.78 to −0.49)	−0.97 (−1.00 to −0.94)	<.001
United States of America	Both	Prevalence	3,480,013	6,674,890	91.81	1129.46	1252.89	10.93	0.18 (0.07 to 0.3)	0.34 (0.32 to 0.35)	<.001
United States of America	Female	Prevalence	1,772,390	3,215,234	81.41	1004.65	1143.96	13.87	0.23 (0.06 to 0.4)	0.42 (0.39 to 0.44)	<.001
United States of America	Male	Prevalence	1,707,623	3,459,656	102.6	1292.86	1381.11	6.83	0.1 (0.04 to 0.17)	0.22 (0.20 to 0.24)	<.001
United States of America	Both	Deaths	99,697	118,039	18.4	29.78	17.75	−40.4	−2 (−2.33 to −1.67)	−1.38 (−1.48 to −1.27)	<.001
United States of America	Female	Deaths	62,162	72,264	16.25	27.98	17.73	−36.63	−1.76 (−2.05 to −1.48)	−1.23 (−1.33 to −1.13)	<.001
United States of America	Male	Deaths	37,535	45,774	21.95	31.9	17.19	−46.12	−2.4 (−2.81 to −1.98)	−1.72 (−1.82 to −1.60)	<.001
United States of America	Both	DALYs	1,882,131	2,456,713	30.53	575.17	411.32	−28.49	−1.36 (−1.6 to −1.12)	−0.91 (−0.98 to −0.84)	<.001
United States of America	Female	DALYs	1,069,962	1,342,141	25.44	526.53	395.3	−24.92	−1.19 (−1.38 to −0.99)	−0.77 (−0.83 to −0.71)	<.001
United States of America	Male	DALYs	812,169	1,114,572	37.23	637.52	425.21	−33.3	−1.61 (−1.92 to −1.31)	−1.10 (−1.17 to −1.02)	<.001

ASR = age-standardized rate; CI = confidence interval; DALY = disability-adjusted life year.

Notes: Age-standardized rates per 100,000 population for incidence, prevalence, mortality, and DALYs of ischemic stroke in China and the United States from 1990 to 2023, stratified by sex. The table presents baseline values (1990), endpoint values (2023), absolute change, percentage change, and estimated annual percentage change (EAPC) with 95% confidence intervals. EAPC was calculated using log-linear regression to quantify the average annual rate of change. Positive EAPC values indicate increasing trends, while negative values indicate decreasing trends. Trends were considered statistically significant when the 95% CI of EAPC did not include zero.

Figure 1.

Comparison of age-standardized rates of ischemic stroke burden between China and the United States, 1990 to 2023. Time series plots comparing age-standardized rates per 100,000 population for (A) incidence, (B) prevalence, (C) mortality, and (D) DALYs of ischemic stroke between China (solid lines) and the United States (dashed lines) from 1990 to 2023. Data are shown for both sexes combined, with shaded areas representing 95% uncertainty intervals. DALYs = disability-adjusted life years.

Sex-stratified analyses revealed substantial gender disparities in temporal trends within both countries (Figures S1 and S2, Supplemental Digital Content 1). In China, males experienced a 12.80% increase in ASIR (from 131.66 to 148.51 per 100,000) and an 18.74% increase in prevalence rates (from 939.75 to 1115.83 per 100,000), whereas females demonstrated a 5.30% decrease in incidence rates (from 96.09 to 91.00 per 100,000) but a modest 3.43% increase in prevalence rates (from 775.23 to 801.83 per 100,000). Both sexes in China showed marked reductions in mortality and DALY rates, with females exhibiting greater percentage declines (−62.97% for mortality and −60.19% for DALYs) compared to males (−54.42% for mortality and −51.06% for DALYs). In the United States, both sexes demonstrated comparable reductions in ASIR (−27.95% for females and −27.80% for males), mortality rates (−36.63% for females and −46.12% for males), and DALY rates (−24.92% for females and −33.30% for males). Prevalence rates increased for both sexes in the United States, with a greater percentage increase observed in females (13.87%) compared to males (6.83%). In terms of absolute case numbers, China experienced dramatic increases across all measures, with incident cases rising by 203.19% (from 876,167 to 2656,475), prevalent cases increasing by 185.47% (from 7436,521 to 21,229,135), deaths rising by 45.71% (from 590,439 to 860,343), and DALYs increasing by 35.23% (from 13,378,094 to 18,090,920), whereas the United States demonstrated more moderate increases in incident cases (27.59%), prevalent cases (91.81%), deaths (18.40%), and DALYs (30.53%).

3.2. Joinpoint regression analysis of temporal trends

Joinpoint regression analysis revealed heterogeneous temporal patterns with multiple inflection points in ischemic stroke burden trends for both countries (Table 1, Fig. 2). In China, the AAPC for ASIR was 0.13% (95% CI: 0.09–0.17, P < .001), with 6 distinct phases identified: an initial increase from 1990 to 1994 (APC: 1.75%, 95% CI: 1.34–2.38), followed by stabilization from 1994 to 2000 (APC: 0.13%, 95% CI: −0.49 to 0.40, P = .423), a subsequent rise from 2000 to 2010 (APC: 1.01%, 95% CI: 0.90–1.19), a sharp decline from 2010 to 2015 (APC: −2.89%, 95% CI: −3.13 to −2.69), an increase from 2015 to 2019 (APC: 1.33%, 95% CI: 0.94–1.78), and a recent decline from 2019 to 2023 (APC: −1.06%, 95% CI: −1.53 to −0.62). The prevalence rates demonstrated consistent upward trends with an AAPC of 0.34% (95% CI: 0.33–0.34, P < .001), though a recent downturn emerged from 2020 to 2023 (APC: −0.41%, 95% CI: −0.48 to −0.34). For mortality and DALYs in China, significant declining trends were observed with AAPCs of −2.52% (95% CI: −2.60 to −2.44, P < .001) and −2.33% (95% CI: −2.41 to −2.26, P < .001), respectively. Notably, both measures exhibited accelerated declines from 2017 to 2020 (mortality APC: −9.90%, 95% CI: −10.82 to −8.86; DALYs APC: −7.71%, 95% CI: −8.60 to −6.42), followed by stabilization from 2020 to 2023 (mortality APC: 0.90%, 95% CI: −0.23 to 2.05, P = .110; DALYs APC: 0.49%, 95% CI: −0.62 to 1.95, P = .264).

Figure 2.

Joinpoint regression analysis of age-standardized ischemic stroke rates in China and the United States, 1990 to 2023. Joinpoint regression results showing (A) incidence, (B) prevalence, (C) mortality, and (D) DALYs of ischemic stroke for both sexes combined in China and the United States from 1990 to 2023. Each panel displays age-standardized rates per 100,000 population on a logarithmic scale with identified joinpoints (marked by circles) representing significant changes in temporal trends. Solid line segments indicate periods of statistically significant trends, with annual percent change values and 95% confidence intervals annotated for each segment. Vertical dashed lines denote joinpoint years. The analysis identifies distinct phases of trend changes, revealing heterogeneous temporal patterns within the study period. Average annual percent change (AAPC) for the entire period is provided for each country and measure. APC = annual percent change; AAPC = average annual percent change, DALYs = disability-adjusted life years.

In the United States, ASIR showed a consistent declining trend with an AAPC of −0.94% (95% CI: −0.97 to −0.91, P < .001), characterized by a steep initial decline from 1990 to 1994 (APC: −3.97%, 95% CI: −4.19 to −3.74), a moderate decrease from 1994 to 1999 (APC: −0.81%, 95% CI: −1.10 to −0.61), a transient increase from 1999 to 2005 (APC: 0.74%, 95% CI: 0.60–0.92), a sharp decline from 2005 to 2010 (APC: −2.80%, 95% CI: −2.93 to −2.67), stabilization from 2010 to 2020 (APC: 0.40%, 95% CI: 0.33–0.48), and a recent decline from 2020 to 2023 (APC: −1.70%, 95% CI: −2.00 to −1.23). Prevalence rates exhibited an AAPC of 0.34% (95% CI: 0.32–0.35, P < .001), with notable phases including rapid increases from 1995 to 2000 (APC: 1.61%, 95% CI: 1.47–1.85), a prolonged decline from 2005 to 2019 (APC: −0.41%, 95% CI: −0.45 to −0.38), and a recent upturn from 2019 to 2023 (APC: 0.84%, 95% CI: 0.64–1.00). Mortality rates declined with an AAPC of − 1.38% (95% CI: −1.48 to −1.27, P < .001), driven primarily by a steep decrease from 1999 to 2011 (APC: −4.35%, 95% CI: −4.87 to −4.01), followed by an increase from 2011 to 2023 (APC: 1.15%, 95% CI: 0.80–1.59). DALYs demonstrated an AAPC of −0.91% (95% CI: −0.98 to −0.84, P < .001), with a marked decline from 1998 to 2011 (APC: −2.94%, 95% CI: −3.19 to −2.75) and a subsequent rise from 2011 to 2023 (APC: 0.90%, 95% CI: 0.69–1.17). Sex-stratified joinpoint analyses revealed distinct patterns between males and females in both countries (Figures S3 and S4, Supplemental Digital Content 2). In China, males exhibited a higher AAPC for incidence (0.30%, 95% CI: 0.24–0.36) compared to females (−0.19%, 95% CI: −0.22 to −0.16), while females demonstrated greater declines in mortality (AAPC: −2.91%, 95% CI: −2.98 to −2.84) and DALYs (AAPC: −2.71%, 95% CI: −2.78 to −2.66) than males (mortality AAPC: −2.25%, 95% CI: −2.37 to −2.12; DALYs AAPC: −2.08%, 95% CI: −2.17 to −1.99). In the United States, both sexes exhibited comparable declining trends in incidence (females AAPC: −0.97%, 95% CI: −1.00 to −0.94; males AAPC: −0.97%, 95% CI: −1.00 to −0.94), while males showed steeper declines in mortality (AAPC: −1.72%, 95% CI: −1.82 to −1.60) and DALYs (AAPC: −1.10%, 95% CI: −1.17 to −1.02) compared to females (mortality AAPC: −1.23%, 95% CI: −1.33 to −1.13; DALYs AAPC: −0.77%, 95% CI: −0.83 to −0.71).

3.3. Age-specific trends in ischemic stroke burden

Age-stratified analyses demonstrated distinct patterns across the lifespan, with marked differences between China and the United States in both temporal trends and absolute burden (Table 2, Fig. 3). As vividly illustrated by the spatiotemporal heatmaps (Fig. 3), the burden of ischemic stroke strongly positively correlated with age in both nations, with the darkest red regions (highest rates) concentrated in the oldest age groups. In China, incidence rates among younger age groups (<40 years) exhibited predominantly increasing trends, with the most pronounced increases observed in the 30–34 year age group (rate change: 29.54%, AAPC: 0.72%, 95% CI: 0.62–0.80, P < .001) and 35–39 year age group (rate change: 32.62%, AAPC: 0.74%, 95% CI: 0.68–0.80, P < .001). Conversely, middle-aged and older adults demonstrated heterogeneous patterns, with the 55–59 year age group showing stable rates (rate change: 0.71%, AAPC: −0.01%, 95% CI: −0.06 to 0.04, P = .547) and the ≥75 year age groups showing modest increases (75–79 years: rate change 10.54%, AAPC: 0.26%, 95% CI: 0.20–0.30, P < .001). In the United States, incidence rates declined across most age groups ≥50 years, with the steepest declines in the 60–64 year age group (rate change: −32.01%, AAPC: −1.15%, 95% CI: −1.20 to −1.11, P < .001) and 65–69 year age group (rate change: −36.78%, AAPC: −1.37%, 95% CI: −1.40 to −1.33, P < .001), while younger age groups (30–44 years) showed increasing trends (35–39 years: rate change 26.99%, AAPC: 0.73%, 95% CI: 0.71–0.76, P < .001).

Table 2.

Age-specific trends in ischemic stroke burden in China and the United States, 1990 to 2023.

Location	Gender	Indicator	Age group	Cases in 1990 (n)	Cases in 2023 (n)	Change in cases (%)	Rate in 1990 (per 100,000)	Rate in 2023 (per 100,000)	Change in rate (%)	EAPC (95% CI)	AAPC (95% CI)	AAPC P-value
China	Both	Incidence	5 to 9	7126	5738	-19.48	6.82	5.67	−16.78	−0.62 (−0.78 to −0.47)	−0.56 (−0.60 to −0.51)	<.001
China	Both	Incidence	10 to 14	6317	5373	−14.94	6.16	6.05	−1.72	−0.14 (−0.27 to −0.02)	−0.10 (−0.13 to −0.07)	<.001
China	Both	Incidence	15 to 19	8041	5538	−31.14	6.33	6.87	8.56	0.01 (−0.1 to 0.11)	0.21 (0.14 to 0.26)	<.001
China	Both	Incidence	20 to 24	9542	6046	−36.64	7.21	8.54	18.54	0.23 (0.12 to 0.34)	0.47 (0.39 to 0.54)	<.001
China	Both	Incidence	25 to 29	9708	8578	−11.65	8.81	11	24.81	0.47 (0.37 to 0.57)	0.62 (0.52 to 0.70)	<.001
China	Both	Incidence	30 to 34	10,985	17,273	57.24	12.41	16.08	29.54	0.58 (0.48 to 0.68)	0.72 (0.62 to 0.80)	<.001
China	Both	Incidence	35 to 39	16,341	27,981	71.23	17.85	23.67	32.62	0.58 (0.46 to 0.7)	0.74 (0.68 to 0.80)	<.001
China	Both	Incidence	40 to 44	21,331	36,382	70.56	31.7	40	26.19	0.48 (0.33 to 0.63)	0.68 (0.63 to 0.74)	<.001
China	Both	Incidence	45 to 49	27,960	65,322	133.63	54.02	65.49	21.23	0.44 (0.26 to 0.62)	0.55 (0.49 to 0.62)	<.001
China	Both	Incidence	50 to 54	53,353	142,288	166.69	111.53	120.18	7.76	0.13 (−0.02 to 0.28)	0.19 (0.14 to 0.24)	<.001
China	Both	Incidence	55 to 59	88,195	241,402	173.71	202.76	204.19	0.71	−0.08 (−0.2 to 0.05)	−0.01 (−0.06 to 0.04)	.547
China	Both	Incidence	60 to 64	119,961	269,620	124.76	338.37	331.11	−2.15	−0.19 (−0.32 to −0.07)	−0.11 (−0.16 to −0.06)	<.001
China	Both	Incidence	65 to 69	141,731	379,287	167.61	517.05	497.02	−3.88	−0.28 (−0.41 to −0.15)	−0.18 (−0.24 to −0.12)	<.001
China	Both	Incidence	70 to 74	134,794	444,988	230.13	714.08	728.83	2.07	−0.02 (−0.19 to 0.15)	0.02 (−0.04 to 0.08)	.407
China	Both	Incidence	75 to 79	106,194	377,921	255.88	929.34	1027.31	10.54	0.33 (0.11 to 0.55)	0.26 (0.20 to 0.30)	<.001
China	Both	Incidence	80 to 84	66,212	298,042	350.13	1185.71	1326.73	11.89	0.34 (0.13 to 0.55)	0.29 (0.25 to 0.33)	<.001
China	Both	Incidence	85 to 89	29,866	205,060	586.6	1496.24	1644.14	9.88	0.19 (0.02 to 0.37)	0.27 (0.24 to 0.30)	<.001
China	Both	Incidence	90 to 94	6824	88,378	1195.1	1812.14	1951.61	7.7	0.08 (−0.06 to 0.23)	0.21 (0.20 to 0.23)	<.001
China	Both	Incidence	95 plus	1364	27,591	1923.22	2082.68	2222.23	6.7	−0.05 (−0.19 to 0.09)	0.18 (0.16 to 0.20)	<.001
China	Both	Prevalence	5 to 9	66,783	44,871	−32.81	63.87	44.35	−30.56	−1.28 (−1.38 to −1.19)	−1.13 (−1.16 to −1.10)	<.001
China	Both	Prevalence	10 to 14	99,933	65,798	−34.16	97.44	74.12	−23.93	−0.97 (−1.05 to −0.9)	−0.85 (−0.86 to −0.83)	<.001
China	Both	Prevalence	15 to 19	165,883	86,308	−47.97	130.62	107.13	−17.98	−0.73 (−0.8 to −0.65)	−0.61 (−0.63 to −0.60)	<.001
China	Both	Prevalence	20 to 24	220,412	101,442	−53.98	166.51	143.37	−13.9	−0.55 (−0.6 to −0.5)	−0.45 (−0.46 to −0.44)	<.001
China	Both	Prevalence	25 to 29	231,276	146,201	−36.78	209.92	187.46	−10.7	−0.37 (−0.4 to −0.34)	−0.34 (−0.35 to −0.34)	<.001
China	Both	Prevalence	30 to 34	234,002	269,891	15.34	264.41	251.25	−4.98	−0.15 (−0.18 to −0.13)	−0.15 (−0.16 to −0.15)	<.001
China	Both	Prevalence	35 to 39	309,408	406,281	31.31	337.91	343.67	1.7	0.04 (0.03 to 0.06)	0.05 (0.05 to 0.06)	<.001
China	Both	Prevalence	40 to 44	301,289	436,242	44.79	447.76	479.67	7.13	0.23 (0.2 to 0.25)	0.22 (0.21 to 0.22)	<.001
China	Both	Prevalence	45 to 49	334,096	717,296	114.7	645.51	719.13	11.4	0.39 (0.35 to 0.43)	0.33 (0.33 to 0.34)	<.001
China	Both	Prevalence	50 to 54	473,236	1,316,958	178.29	989.24	1112.32	12.44	0.48 (0.43 to 0.53)	0.36 (0.35 to 0.37)	<.001
China	Both	Prevalence	55 to 59	696,547	2,117,992	204.07	1601.32	1791.53	11.88	0.48 (0.44 to 0.53)	0.34 (0.33 to 0.34)	<.001
China	Both	Prevalence	60 to 64	893,165	2,298,153	157.3	2519.36	2822.3	12.02	0.46 (0.43 to 0.49)	0.34 (0.33 to 0.35)	<.001
China	Both	Prevalence	65 to 69	1,063,330	3,266,407	207.19	3879.15	4280.28	10.34	0.36 (0.34 to 0.38)	0.30 (0.29 to 0.30)	<.001
China	Both	Prevalence	70 to 74	1,021,479	3,638,928	256.24	5411.34	5960.08	10.14	0.35 (0.33 to 0.37)	0.29 (0.28 to 0.29)	<.001
China	Both	Prevalence	75 to 79	752,759	2,779,503	269.24	6587.63	7555.55	14.69	0.53 (0.5 to 0.56)	0.41 (0.40 to 0.42)	<.001
China	Both	Prevalence	80 to 84	392,833	1,946,182	395.42	7034.78	8663.38	23.15	0.81 (0.76 to 0.87)	0.63 (0.61 to 0.64)	<.001
China	Both	Prevalence	85 to 89	128,356	1,100,885	757.68	6430.46	8826.72	37.26	1.21 (1.13 to 1.29)	0.96 (0.95 to 0.97)	<.001
China	Both	Prevalence	90 to 94	21,326	381,879	1690.68	5663.19	8432.87	48.91	1.53 (1.43 to 1.64)	1.21 (1.20 to 1.22)	<.001
China	Both	Prevalence	95 plus	3313	97,595	2845.4	5060.33	7860.45	55.33	1.66 (1.55 to 1.78)	1.34 (1.32 to 1.35)	<.001
China	Both	Deaths	5 to 9	94	19	−79.85	0.09	0.02	−79.18	−4.52 (−5.22 to −3.81)	−4.73 (−4.98 to −4.54)	<.001
China	Both	Deaths	10 to 14	76	22	−70.83	0.07	0.02	−66.3	−3.11 (−3.61 to −2.6)	−3.33 (−3.49 to −3.21)	<.001
China	Both	Deaths	15 to 19	372	68	-81.85	0.29	0.08	-71.39	-3.59 (-3.74 to −3.43)	-3.66 (-3.75 to −3.55)	<.001
China	Both	Deaths	20 to 24	691	86	-87.55	0.52	0.12	-76.71	-4.65 (-4.95 to −4.35)	-4.12 (-4.22 to −4.03)	<.001
China	Both	Deaths	25 to 29	747	168	-77.57	0.68	0.21	-68.31	-3.84 (-4.19 to −3.49)	-3.39 (-3.48 to −3.30)	<.001
China	Both	Deaths	30 to 34	1079	481	−55.38	1.22	0.45	−63.24	−3.27 (−3.55 to −3)	−3.00 (−3.09 to −2.93)	<.001
China	Both	Deaths	35 to 39	1991	1110	−44.25	2.17	0.94	−56.82	−2.8 (−3.03 to −2.57)	−2.46 (−2.54 to −2.38)	<.001
China	Both	Deaths	40 to 44	3476	2095	−39.74	5.17	2.3	−55.42	−2.82 (−3.09 to −2.55)	−2.33 (−2.45 to −2.20)	<.001
China	Both	Deaths	45 to 49	6583	5237	−20.44	12.72	5.25	−58.72	−2.86 (−3.06 to −2.65)	−2.68 (−2.75 to −2.61)	<.001
China	Both	Deaths	50 to 54	14,505	13,033	−10.14	30.32	11.01	−63.69	−3.05 (−3.21 to −2.89)	−3.02 (−3.09 to −2.95)	<.001
China	Both	Deaths	55 to 59	28,107	23,564	−16.16	64.62	19.93	−69.15	−3.63 (−3.83 to −3.43)	−3.31 (−3.47 to −3.12)	<.001
China	Both	Deaths	60 to 64	54,680	39,906	−27.02	154.24	49.01	−68.23	−3.6 (−3.79 to −3.42)	−3.42 (−3.50 to −3.35)	<.001
China	Both	Deaths	65 to 69	83,198	76,693	−7.82	303.52	100.5	−66.89	−3.47 (−3.7 to −3.24)	−3.30 (−3.40 to −3.21)	<.001
China	Both	Deaths	70 to 74	121,746	123,992	1.85	644.95	203.08	−68.51	−3.62 (−3.78 to −3.45)	−3.48 (−3.64 to −3.28)	<.001
China	Both	Deaths	75 to 79	119,294	147,142	23.34	1043.98	399.98	−61.69	−3 (−3.17 to −2.84)	−2.85 (−2.98 to −2.71)	<.001
China	Both	Deaths	80 to 84	94,307	174,326	84.85	1688.83	776.01	−54.05	−2.42 (−2.65 to −2.19)	−2.38 (−2.46 to −2.31)	<.001
China	Both	Deaths	85 to 89	45,454	150,689	231.52	2277.19	1208.2	−46.94	−1.78 (−1.99 to −1.57)	−1.65 (−1.84 to −1.43)	<.001
China	Both	Deaths	90 to 94	11,712	77,237	559.44	3110.29	1705.59	−45.16	−1.73 (−1.93 to −1.53)	−1.71 (−1.87 to −1.49)	<.001
China	Both	Deaths	95 plus	2010	24,457	1116.75	3069.67	1969.78	-35.83	−1.33 (−1.53 to −1.12)	−1.44 (−1.55 to −1.33)	<.001
China	Both	DALYs	5 to 9	20,263	10,076	−50.27	19.38	9.96	−48.61	−2.12 (−2.32 to −1.91)	−2.02 (−2.10 to −1.97)	<.001
China	Both	DALYs	10 to 14	24,388	14,136	−42.04	23.78	15.92	−33.03	−1.31 (−1.43 to −1.18)	−1.25 (−1.28 to −1.21)	<.001
China	Both	DALYs	15 to 19	57,543	21,040	−63.44	45.31	26.12	−42.36	−1.7 (−1.79 to −1.62)	−1.65 (−1.69 to −1.61)	<.001
China	Both	DALYs	20 to 24	87,522	24,681	−71.8	66.12	34.88	−47.24	−2.14 (−2.27 to −2.01)	−1.85 (−1.89 to −1.81)	<.001
China	Both	DALYs	25 to 29	90,041	37,709	−58.12	81.73	48.35	−40.84	−1.78 (−1.92 to −1.63)	−1.55 (−1.60 to −1.52)	<.001
China	Both	DALYs	30 to 34	105,660	78,085	−26.1	119.39	72.69	−39.11	−1.67 (−1.78 to −1.55)	−1.53 (−1.58 to −1.48)	<.001
China	Both	DALYs	35 to 39	162,009	133,407	−17.65	176.93	112.85	−36.22	−1.54 (−1.67 to −1.42)	−1.33 (−1.37 to −1.29)	<.001
China	Both	DALYs	40 to 44	220,764	178,935	−18.95	328.09	196.75	−40.03	−1.83 (−2.02 to −1.64)	−1.54 (−1.62 to −1.46)	<.001
China	Both	DALYs	45 to 49	341,399	350,417	2.64	659.62	351.31	−46.74	−2.05 (−2.19 to −1.91)	−1.91 (−1.97 to −1.87)	<.001
China	Both	DALYs	50 to 54	636,195	729,158	14.61	1329.89	615.86	−53.69	−2.31 (−2.42 to −2.19)	−2.30 (−2.36 to −2.25)	<.001
China	Both	DALYs	55 to 59	1,067,787	1,173,304	9.88	2454.78	992.45	−59.57	−2.8 (−2.96 to −2.64)	−2.56 (−2.67 to −2.44)	<.001
China	Both	DALYs	60 to 64	1,744,231	1,580,782	−9.37	4919.98	1941.32	−60.54	−2.94 (−3.09 to −2.78)	−2.79 (−2.86 to −2.73)	<.001
China	Both	DALYs	65 to 69	2,223,629	2,463,367	10.78	8112.06	3227.98	−60.21	−2.89 (−3.07 to −2.71)	−2.76 (−2.86 to −2.68)	<.001
China	Both	DALYs	70 to 74	2,631,709	3,166,183	20.31	13,941.61	5185.79	−62.8	−3.12 (−3.25 to −2.99)	−3.02 (−3.16 to −2.86)	<.001
China	Both	DALYs	75 to 79	2,061,548	2,885,469	39.97	18,041.25	7843.6	−56.52	−2.63 (−2.76 to −2.5)	−2.51 (−2.62 to −2.39)	<.001
China	Both	DALYs	80 to 84	1,265,160	2,557,964	102.18	22,656.23	11,386.72	−49.74	−2.14 (−2.34 to −1.95)	−2.11 (−2.18 to −2.05)	<.001
China	Both	DALYs	85 to 89	481,978	1,718,072	256.46	24,146.48	13,775.22	−42.95	−1.56 (−1.75 to −1.37)	−1.46 (−1.63 to −1.27)	<.001
China	Both	DALYs	90 to 94	105,787	747,406	606.52	28,092.15	16,504.63	−41.25	−1.51 (−1.7 to −1.33)	−1.52 (−1.67 to −1.32)	<.001
China	Both	DALYs	95 plus	17,064	217,111	1172.35	26,059.92	17,486.52	−32.9	−1.19 (−1.39 to −0.99)	−1.32 (−1.42 to −1.20)	<.001
United States of America	Both	Incidence	5 to 9	1506	1647	9.35	8.12	8.15	0.43	0.21 (0.02 to 0.39)	0.03 (0.00 to 0.06)	.044
United States of America	Both	Incidence	10 to 14	1056	1418	34.35	5.99	6.74	12.54	0.47 (0.23 to 0.72)	0.39 (0.36 to 0.42)	<.001
United States of America	Both	Incidence	15 to 19	1225	1515	23.64	6.75	6.86	1.73	−0.15 (−0.36 to 0.07)	0.03 (0.00 to 0.06)	.045
United States of America	Both	Incidence	20 to 24	1787	1950	9.17	9.11	8.98	−1.44	−0.34 (−0.49 to −0.19)	−0.05 (−0.07 to −0.03)	<.001
United States of America	Both	Incidence	25 to 29	2845	2865	0.72	13.08	13.04	−0.31	−0.27 (−0.36 to −0.18)	−0.02 (−0.04 to −0.01)	.013
United States of America	Both	Incidence	30 to 34	4259	5077	19.21	19.07	21.51	12.8	0.26 (0.16 to 0.36)	0.37 (0.36 to 0.39)	<.001
United States of America	Both	Incidence	35 to 39	5517	7760	40.66	27.08	34.39	26.99	0.76 (0.6 to 0.92)	0.73 (0.71 to 0.76)	<.001
United States of America	Both	Incidence	40 to 44	7537	10,537	39.81	41.71	48.09	15.28	0.52 (0.38 to 0.65)	0.44 (0.41 to 0.46)	<.001
United States of America	Both	Incidence	45 to 49	8846	12,501	41.31	63.2	62.98	−0.35	0.08 (−0.03 to 0.19)	0.01 (−0.02 to 0.04)	.410
United States of America	Both	Incidence	50 to 54	11,711	18,021	53.88	102.08	86.78	−15	−0.28 (−0.42 to −0.15)	−0.47 (−0.52 to −0.42)	<.001
United States of America	Both	Incidence	55 to 59	16,605	24,666	48.55	157.99	119.24	−24.53	−0.53 (−0.7 to −0.35)	−0.82 (−0.88 to −0.76)	<.001
United States of America	Both	Incidence	60 to 64	25,985	35,336	35.99	243.86	165.8	−32.01	−0.76 (−0.95 to −0.56)	−1.15 (−1.20 to −1.11)	<.001
United States of America	Both	Incidence	65 to 69	36,168	43,594	20.53	358.89	226.89	−36.78	−0.92 (−1.12 to −0.72)	−1.37 (−1.40 to −1.33)	<.001
United States of America	Both	Incidence	70 to 74	43,005	52,648	22.42	531.8	339.31	−36.2	−0.88 (−1.05 to −0.71)	−1.33 (−1.37 to −1.30)	<.001
United States of America	Both	Incidence	75 to 79	46,462	56,970	22.62	757.66	502.16	−33.72	−0.79 (−0.94 to −0.64)	−1.22 (−1.26 to −1.18)	<.001
United States of America	Both	Incidence	80 to 84	40,585	47,707	17.55	1030.74	687.24	−33.33	−0.88 (−1.01 to −0.75)	−1.20 (−1.23 to −1.17)	<.001
United States of America	Both	Incidence	85 to 89	27,918	34,333	22.98	1371.53	900.43	−34.35	−1.06 (−1.2 to −0.93)	−1.25 (−1.28 to −1.22)	<.001
United States of America	Both	Incidence	90 to 94	12,398	19,062	53.76	1712.21	1107.56	−35.31	−1.19 (−1.35 to −1.04)	−1.30 (−1.33 to −1.27)	<.001
United States of America	Both	Incidence	95 plus	4600	8228	78.87	2061.87	1308.91	−36.52	−1.3 (−1.48 to −1.13)	−1.36 (−1.39 to −1.32)	<.001
United States of America	Both	Prevalence	5 to 9	26,214	22,613	−13.74	141.24	111.91	−20.77	−0.78 (−1.03 to −0.52)	−0.68 (−0.73 to −0.64)	<.001
United States of America	Both	Prevalence	10 to 14	32,903	35,602	8.2	186.82	169.32	−9.37	−0.29 (−0.55 to −0.04)	−0.25 (−0.29 to −0.21)	<.001
United States of America	Both	Prevalence	15 to 19	41,534	48,921	17.79	228.68	221.62	−3.09	−0.08 (−0.32 to 0.16)	−0.05 (−0.09 to −0.01)	.026
United States of America	Both	Prevalence	20 to 24	53,703	60,114	11.94	273.75	276.65	1.06	0.03 (−0.19 to 0.26)	0.08 (0.04 to 0.12)	<.001
United States of America	Both	Prevalence	25 to 29	73,358	77,963	6.28	337.33	354.82	5.18	0.15 (−0.05 to 0.36)	0.20 (0.16 to 0.24)	<.001
United States of America	Both	Prevalence	30 to 34	95,822	112,197	17.09	429.08	475.4	10.79	0.33 (0.15 to 0.51)	0.36 (0.33 to 0.40)	<.001
United States of America	Both	Prevalence	35 to 39	115,040	154,405	34.22	564.61	684.16	21.17	0.64 (0.49 to 0.78)	0.63 (0.59 to 0.66)	<.001
United States of America	Both	Prevalence	40 to 44	137,103	218,970	59.71	758.83	999.27	31.69	0.91 (0.8 to 1.03)	0.88 (0.85 to 0.91)	<.001
United States of America	Both	Prevalence	45 to 49	146,871	284,365	93.61	1049.23	1432.58	36.54	1 (0.9 to 1.1)	0.98 (0.95 to 1.00)	<.001
United States of America	Both	Prevalence	50 to 54	168,554	415,286	146.38	1469.3	1999.73	36.1	0.93 (0.83 to 1.03)	0.96 (0.94 to 0.99)	<.001
United States of America	Both	Prevalence	55 to 59	221,889	566,587	155.35	2111.17	2738.88	29.73	0.69 (0.57 to 0.81)	0.82 (0.80 to 0.85)	<.001
United States of America	Both	Prevalence	60 to 64	320,567	777,274	142.47	3008.48	3647.17	21.23	0.41 (0.27 to 0.55)	0.61 (0.58 to 0.63)	<.001
United States of America	Both	Prevalence	65 to 69	426,728	897,281	110.27	4234.33	4670.15	10.29	0.09 (−0.06 to 0.23)	0.31 (0.30 to 0.33)	<.001
United States of America	Both	Prevalence	70 to 74	466,514	902,915	93.55	5768.95	5819.15	0.87	−0.2 (−0.33 to −0.07)	0.04 (0.02 to 0.06)	<.001
United States of America	Both	Prevalence	75 to 79	459,313	814,381	77.3	7490.09	7178.41	−4.16	−0.37 (−0.49 to −0.25)	−0.12 (−0.14 to −0.11)	<.001
United States of America	Both	Prevalence	80 to 84	359,577	601,945	67.4	9132.29	8671.34	−5.05	−0.4 (−0.52 to −0.29)	−0.15 (−0.17 to −0.14)	<.001
United States of America	Both	Prevalence	85 to 89	213,048	392,194	84.09	10,466.62	10,285.74	−1.73	−0.28 (−0.38 to −0.17)	−0.05 (−0.07 to −0.04)	<.001
United States of America	Both	Prevalence	90 to 94	82,386	202,814	146.18	11,378.22	11,783.86	3.57	−0.08 (−0.17 to 0.01)	0.11 (0.10 to 0.12)	<.001
United States of America	Both	Prevalence	95 plus	26,640	81,632	206.42	11,941.4	12,986.54	8.75	0.12 (0.04 to 0.2)	0.26 (0.24 to 0.27)	<.001
United States of America	Both	Deaths	5 to 9	9	3	−64.66	0.05	0.02	−67.54	−3.73 (−4.31 to −3.16)	−3.11 (−3.41 to −2.73)	<.001
United States of America	Both	Deaths	10 to 14	7	3	−54.3	0.04	0.02	−61.72	−3.8 (−4.44 to −3.15)	−2.70 (−2.94 to −2.41)	<.001
United States of America	Both	Deaths	15 to 19	14	7	−49.55	0.08	0.03	−58.5	−2.94 (−3.35 to −2.53)	−2.55 (−2.90 to −2.19)	<.001
United States of America	Both	Deaths	20 to 24	23	13	−42.86	0.12	0.06	−48.41	−1.85 (−2.31 to −1.39)	−2.03 (−2.30 to −1.80)	<.001
United States of America	Both	Deaths	25 to 29	35	25	−28.88	0.16	0.11	−29.61	−0.83 (−1.37 to −0.29)	−0.80 (−1.19 to −0.54)	.008
United States of America	Both	Deaths	30 to 34	64	58	−9.25	0.28	0.24	−14.13	−0.38 (−0.96 to 0.21)	−0.35 (−0.54 to −0.13)	.003
United States of America	Both	Deaths	35 to 39	102	101	−1.31	0.5	0.45	−10.9	−0.64 (−1.35 to 0.07)	−0.13 (−0.33 to 0.07)	.195
United States of America	Both	Deaths	40 to 44	160	193	20.86	0.89	0.88	−0.35	−0.57 (−1.29 to 0.15)	0.17 (0.00 to 0.34)	.048
United States of America	Both	Deaths	45 to 49	294	358	22.01	2.1	1.81	−13.96	−0.89 (−1.66 to −0.12)	−0.31 (−0.51 to −0.08)	.010
United States of America	Both	Deaths	50 to 54	465	661	42.05	4.05	3.18	−21.53	−1.08 (−1.92 to −0.23)	−0.51 (−0.70 to −0.33)	<.001
United States of America	Both	Deaths	55 to 59	803	1182	47.22	7.64	5.71	−25.2	−1.35 (−2.34 to −0.34)	−0.68 (−0.87 to −0.49)	<.001
United States of America	Both	Deaths	60 to 64	2584	3216	24.46	24.25	15.09	−37.77	−2.13 (−2.94 to −1.31)	−1.35 (−1.52 to −1.15)	<.001
United States of America	Both	Deaths	65 to 69	4586	4670	1.83	45.51	24.31	−46.59	−2.71 (−3.44 to −1.97)	−1.66 (−1.78 to −1.53)	<.001
United States of America	Both	Deaths	70 to 74	10,277	9590	−6.68	127.09	61.81	−51.37	−2.84 (−3.33 to −2.34)	−2.05 (−2.17 to −1.90)	<.001
United States of America	Both	Deaths	75 to 79	15,558	13,386	−13.96	253.7	117.99	−53.49	−2.86 (−3.29 to −2.43)	−2.11 (−2.22 to −1.98)	<.001
United States of America	Both	Deaths	80 to 84	22,474	21,505	−4.31	570.79	309.8	−45.72	−2.27 (−2.57 to −1.96)	−1.66 (−1.76 to −1.54)	<.001
United States of America	Both	Deaths	85 to 89	21,647	25,071	15.82	1063.47	657.52	−38.17	−1.87 (−2.16 to −1.58)	−1.28 (−1.40 to −1.15)	<.001
United States of America	Both	Deaths	90 to 94	13,945	23,129	65.86	1925.96	1343.85	−30.22	−1.42 (−1.64 to −1.19)	−1.03 (−1.10 to −0.97)	<.001
United States of America	Both	Deaths	95 plus	6533	14,845	127.23	2928.36	2361.62	−19.35	−0.85 (−1.06 to −0.64)	−0.56 (−0.63 to −0.51)	<.001
United States of America	Both	DALYs	5 to 9	4211	3295	−21.75	22.69	16.3	−28.13	−1.05 (−1.24 to −0.86)	−0.94 (−1.00 to −0.89)	<.001
United States of America	Both	DALYs	10 to 14	4866	4977	2.27	27.63	23.67	−14.33	−0.48 (−0.69 to −0.28)	−0.42 (−0.46 to −0.38)	<.001
United States of America	Both	DALYs	15 to 19	6406	6893	7.61	35.27	31.23	−11.46	−0.35 (−0.54 to −0.16)	−0.32 (−0.38 to −0.26)	<.001
United States of America	Both	DALYs	20 to 24	8558	8787	2.68	43.62	40.44	−7.3	−0.2 (−0.36 to −0.04)	−0.18 (−0.24 to −0.12)	<.001
United States of America	Both	DALYs	25 to 29	11,854	11,816	−0.32	54.51	53.77	−1.35	0.02 (−0.12 to 0.16)	0.03 (−0.03 to 0.08)	.310
United States of America	Both	DALYs	30 to 34	16,331	18,246	11.73	73.13	77.31	5.72	0.23 (0.14 to 0.32)	0.20 (0.16 to 0.25)	<.001
United States of America	Both	DALYs	35 to 39	20,415	25,597	25.38	100.2	113.42	13.2	0.4 (0.34 to 0.46)	0.41 (0.37 to 0.46)	<.001
United States of America	Both	DALYs	40 to 44	25,344	37,607	48.39	140.27	171.62	22.35	0.58 (0.5 to 0.67)	0.66 (0.60 to 0.70)	<.001
United States of America	Both	DALYs	45 to 49	31,155	51,248	64.49	222.57	258.18	16	0.42 (0.27 to 0.57)	0.52 (0.45 to 0.58)	<.001
United States of America	Both	DALYs	50 to 54	38,801	77,048	98.57	338.23	371.01	9.69	0.23 (0.03 to 0.43)	0.38 (0.33 to 0.44)	<.001
United States of America	Both	DALYs	55 to 59	54,924	110,598	101.36	522.58	534.63	2.31	−0.08 (−0.34 to 0.19)	0.16 (0.11 to 0.22)	<.001
United States of America	Both	DALYs	60 to 64	115,332	189,870	64.63	1082.37	890.92	−17.69	−0.94 (−1.29 to −0.59)	−0.46 (−0.52 to −0.39)	<.001
United States of America	Both	DALYs	65 to 69	165,581	224,243	35.43	1643.02	1167.13	−28.96	−1.48 (−1.83 to −1.13)	−0.93 (−0.99 to −0.86)	<.001
United States of America	Both	DALYs	70 to 74	268,198	309,229	15.3	3316.56	1992.93	−39.91	−2.01 (−2.32 to −1.69)	−1.46 (−1.54 to −1.38)	<.001
United States of America	Both	DALYs	75 to 79	315,785	330,197	4.56	5149.56	2910.54	−43.48	−2.17 (−2.47 to −1.86)	−1.58 (−1.65 to −1.50)	<.001
United States of America	Both	DALYs	80 to 84	338,083	361,430	6.91	8586.4	5206.59	−39.36	−1.9 (−2.15 to −1.65)	−1.38 (−1.46 to −1.29)	<.001
United States of America	Both	DALYs	85 to 89	250,694	312,348	24.59	12,316.06	8191.69	−33.49	−1.63 (−1.88 to −1.38)	−1.11 (−1.20 to −1.00)	<.001
United States of America	Both	DALYs	90 to 94	135,147	234,908	73.82	18,664.92	13,648.59	−26.88	−1.26 (−1.46 to −1.06)	−0.90 (−0.96 to −0.85)	<.001
United States of America	Both	DALYs	95 plus	58,287	135,439	132.36	26,127.29	21,546.59	−17.53	−0.78 (−0.97 to −0.58)	−0.50 (−0.56 to −0.45)	<.001

Abbreviations: DALY, disability-adjusted life year; CI, confidence interval.

Notes: Age-specific rates per 100,000 population for incidence, prevalence, mortality, and DALYs of ischemic stroke across 19 age groups (<5 to ≥ 95 years) in China and the United States from 1990 to 2023, stratified by sex. For each age group, measure, and sex combination, the table presents baseline values (1990), endpoint values (2023), absolute change, percentage change, and estimated annual percentage change (EAPC) with 95% confidence intervals. This comprehensive age-stratified analysis reveals distinct age-specific temporal patterns in ischemic stroke burden between the 2 countries.

Figure 3.

Spatiotemporal heatmaps of age-specific rates for ischemic stroke burden in China and the United States, 1990 to 2023. The heatmaps display the age-specific rates (per 100,000 population) for (A) incidence, (B) prevalence, (C) mortality, and (D) DALYs of ischemic stroke across different age groups in China and the United States from 1990 to 2023. The x-axis represents the calendar year, and the y-axis represents the age groups. The color gradient indicates the magnitude of the rates, with darker red/orange colors representing higher rates and lighter yellow colors representing lower rates. This visualization illustrates the dynamic shift of disease burden across age groups over the past 3 decades. DALYs = disability-adjusted life years.

Prevalence rates in China increased across all age groups ≥30 years, with the most substantial increases in the oldest age categories (≥95 years: rate change 55.33%, AAPC: 1.34%, 95% CI: 1.32–1.35, P < .001; 90–94 years: rate change 48.91%, AAPC: 1.21%, 95% CI: 1.20–1.22, P < .001; 85–89 years: rate change 37.26%, AAPC: 0.96%, 95% CI: 0.95–0.97, P < .001), while younger age groups (<30 years) demonstrated declining trends. In the United States, prevalence rates increased across age groups 25–64 years, with peak increases in the 40–49 year age range (40–44 years: rate change 31.69%, AAPC: 0.88%, 95% CI: 0.85–0.91, P < .001; 45–49 years: rate change 36.54%, AAPC: 0.98%, 95% CI: 0.95–1.00, P < .001), while age groups ≥75 years showed declining rates (75–79 years: rate change −4.16%, AAPC: −0.12%, 95% CI: −0.14 to −0.11, P < .001). Mortality rates declined substantially across all age groups in both countries, though the magnitude of decline varied by age. In China, the steepest declines occurred in younger age groups (20–24 years: rate change −76.71%, AAPC: −4.12%, 95% CI: −4.22 to −4.03, P < .001; 25–29 years: rate change −68.31%, AAPC: −3.39%, 95% CI: −3.48 to −3.30, P < .001), with progressively smaller declines in older age groups (≥95 years: rate change −35.83%, AAPC: −1.44%, 95% CI: −1.55 to −1.33, P < .001). Similarly, in the United States, younger age groups experienced greater proportional reductions (60–64 years: rate change −37.77%, AAPC: −1.35%, 95% CI: −1.52 to −1.15, P < .001; 65–69 years: rate change −46.59%, AAPC: −1.66%, 95% CI: −1.78 to −1.53, P < .001) compared to the oldest age groups (≥95 years: rate change −19.35%, AAPC: −0.56%, 95% CI: −0.63 to −0.51, P < .001). DALY rates followed similar patterns to mortality across age groups in both countries. In terms of absolute case numbers (Figures S5 and S10, Supplemental Digital Content 3), China experienced dramatic increases across most age groups, particularly among older adults (≥75 years), reflecting both population aging and changing disease patterns, whereas the United States demonstrated more modest increases or stable absolute numbers in most age categories, with substantial increases primarily observed in the 40–64 year age range. Crucially, when stratifying these spatiotemporal trends by sex (Figures S6–S9, Supplemental Digital Content 4), a striking disparity was observed in the Chinese population. The heatmaps visually confirm that Chinese males bear a substantially heavier and more rapidly intensifying age-specific burden across all metrics (incidence, prevalence, mortality, and DALYs) compared to Chinese females. This male-predominant escalation is evident across almost all adult age groups, underscoring the profound impact of sex-specific risk factors, which warrants further etiological investigation.

3.4. APC effects on ischemic stroke burden

To disentangle the independent contributions of age, time period, and birth cohort, APC analyses were performed for both countries across all epidemiological measures (Fig. 4, Figure S11, Supplemental Digital Content 5). In China, age effects demonstrated exponential increases in risk across all measures, with incidence showing RRs rising from 0.06 (95% CI: 0.06–0.07) for the 15–19 year age group to 7.36 (95% CI: 7.28–7.44) for the ≥95 year age group, and mortality rates escalating from RR 0.03 (95% CI: 0.03–0.03) for 15–19 years to RR 13.10 (95% CI: 12.80–13.39) for 95–99 years, relative to the reference age group of 60–64 years. Period effects revealed U-shaped patterns for incidence and prevalence, with nadir RRs occurring during 2004 to 2008 (incidence RR: 0.91, 95% CI: 0.91–0.91; prevalence RR: 0.98, 95% CI: 0.98–0.99) followed by upward trends through 2019–2023 (incidence RR: 1.22, 95% CI: 1.21–1.22; prevalence RR: 1.24, 95% CI: 1.23–1.24). Mortality and DALYs demonstrated declining period effects from 1994–1998 (mortality RR: 0.83, 95% CI: 0.82–0.84) to 2004 to 2008 (mortality RR: 0.91, 95% CI: 0.91–0.92), followed by increases to 2019 to 2023 (mortality RR: 1.21, 95% CI: 1.20–1.22). Cohort effects exhibited consistent monotonic declines across successive birth cohorts for all measures, with incidence RRs decreasing from 2.67 (95% CI: 2.65–2.69) for the 1899 to 1903 cohort to 0.26 (95% CI: 0.26–0.27) for the 2004 to 2008 cohort, and mortality RRs declining from 6.57 (95% CI: 6.14–7.04) to 0.10 (95% CI: 0.07–0.13) across the same cohorts, indicating progressively lower intrinsic risk among more recently born generations.

Figure 4.

Age–period–cohort (APC) analysis of ischemic stroke burden in China, 1990 to 2023. APC decomposition of (A) incidence, (B) prevalence, (C) mortality, and (D) DALYs of ischemic stroke in China from 1990 to 2023.

In the United States, age effects similarly demonstrated exponential increases, with incidence RRs ranging from 0.13 (95% CI: 0.13–0.13) for 15 to 19 years to 4.70 (95% CI: 4.65–4.75) for 95 to 99 years, and mortality RRs spanning from 0.03 (95% CI: 0.02–0.04) to 15.07 (95% CI: 14.22–15.96) across the same age range. Period effects for incidence displayed continuous declines from 1994 to 1998 (RR: 0.78, 95% CI: 0.78–0.79) through 2004 to 2008 (RR: 0.99, 95% CI: 0.99–0.99), followed by increases to 2019 to 2023 (RR: 1.26, 95% CI: 1.26–1.27). Prevalence period effects showed initial increases from 1994 to 1998 (RR: 1.09, 95% CI: 1.09–1.09) peaking in 1999 to 2003 (RR: 1.13, 95% CI: 1.13–1.13), then declining to 2014 to 2018 (RR: 0.88, 95% CI: 0.88–0.88) before rising in 2019 to 2023 (RR: 0.90, 95% CI: 0.90–0.90). Mortality and DALY period effects demonstrated marked declines from 1994 to 1998 through 2009 to 2013, followed by recent upward trends. Cohort effects revealed substantial declines for incidence from the 1899 to 1903 cohort (RR: 3.78, 95% CI: 3.68–3.88) to the 2004 to 2008 cohort (RR: 0.33, 95% CI: 0.32–0.35), with similar patterns for mortality (1899–1903 cohort RR: 6.13, 95% CI: 5.65–6.64; 2004–2008 cohort RR: 0.15, 95% CI: 0.12–0.18). Comparative analyses between China and the United States revealed that while both countries exhibited similar age and cohort effect patterns, period effects diverged substantially, with China showing more recent deterioration in mortality and DALY trends beginning from the 2009 to 2013 period, whereas the United States demonstrated earlier improvements followed by recent stabilization or modest increases.

3.5. Projected trends in ischemic stroke burden to 2035

BAPC projections extending to 2035, under the assumption that current trends continue without major policy changes or unforeseen events, suggested contrasting trajectories between China and the United States, with potential implications for future disease burden (Figures 5 and 6, Figures S12 and S13, Supplemental Digital Content 6). In China, the model estimated that ASIR would increase modestly from 118.40 per 100,000 in 2023 to 140.35 per 100,000 in 2035 for both sexes combined, representing an estimated 18.53% increase, with males (185.41 per 100,000) demonstrating higher projected rates than females (90.61 per 100,000) (Fig. 5A). Age-standardized prevalence rates (ASPR) showed a modest upward trend from 953.08 to 982.35 per 100,000 (3.07% increase) (Fig. 5B), while mortality rates remained relatively stable, declining from 39.34 to 36.39 per 100,000 (−7.50% decrease) (Fig. 5C), and DALY rates decreased from 802.71 to 726.05 per 100,000 (−9.55% decrease) (Fig. 5D). However, if current demographic and epidemiological trends persist, the absolute burden was projected to escalate substantially across all measures (Figure S12, Supplemental Digital Content 6). Despite declining ASMR, the absolute number of deaths was projected to increase dramatically from 860,343 in 2023 to 1187,385 in 2035, representing a 38.02% increase (Figure S12C, Supplemental Digital Content 6). Incident cases were projected to rise from 2656,475 to 4288,943 (61.46% increase) (Figure S12A, Supplemental Digital Content 6), prevalent cases to increase from 21,229,135 to 29,407,969 (38.53% increase) (Figure S12B, Supplemental Digital Content 6), and DALYs to grow from 18,090,920 to 22,893,218 (26.55% increase) (Figure S12D, Supplemental Digital Content 6). Sex-stratified projections indicated that males would bear a disproportionately higher burden, with male-to-female ratios projected at 2.05 for incidence rates, 1.53 for prevalence rates, and 1.71 for DALY rates by 2035.

Figure 5.

Projections of age-standardized ischemic stroke rates in China, 2024 to 2035. Bayesian age–period–cohort (BAPC) model projections of age-standardized rates per 100,000 population for (A) incidence, (B) prevalence, (C) mortality, and (D) DALYs of ischemic stroke in China from 1990 to 2035. Historical data (1990–2023) are displayed as solid lines, while projected estimates (2024–2035) are shown as solid lines with points. Shaded ribbons represent 95% credible intervals for the forecasts. DALYs = disability-adjusted life years.

Figure 6.

Projections of age-standardized ischemic stroke rates in the United States, 2024 to 2035. Bayesian age–period–cohort (BAPC) model projections of age-standardized rates per 100,000 population for (A) incidence, (B) prevalence, (C) mortality, and (D) DALYs of ischemic stroke in the United States from 1990 to 2035. Following the same visualization framework as Figure 5, historical data (1990–2023) are shown as solid lines, and projections (2024–2035) are displayed as solid lines with points. Shaded ribbons represent 95% credible intervals. DALYs = disability-adjusted life years.

In the United States, ASIR was projected to decline from 70.04 per 100,000 in 2023 to 63.75 per 100,000 in 2035 (−8.98% decrease) (Fig. 6A), while prevalence rates showed an upward trend from 1252.89 to 1454.89 per 100,000 (16.12% increase) (Fig. 6B). ASMR demonstrated a modest increase from 17.75 to 18.36 per 100,000 (3.44% increase) (Fig. 6C), and DALY rates rose from 411.32 to 459.79 per 100,000 (11.78% increase) (Fig. 6D). Critically, despite declining or stabilizing age-standardized rates for incidence, absolute case numbers were projected to increase substantially due to population aging and growth (Figure S13, Supplemental Digital Content 7). Incident cases were projected to rise from 388,155 to 444,961 (14.64% increase) (Figure S13A, Supplemental Digital Content 7), prevalent cases to increase from 6674,890 to 9441,012 (41.44% increase) (Figure S13B, Supplemental Digital Content 7), deaths to rise from 118,039 to 185,873 (57.47% increase) (Figure S13C, Supplemental Digital Content 7), and DALYs to grow from 2456,713 to 3639,368 (48.14% increase) (Figure S13D, Supplemental Digital Content 7). Comparative projections revealed that while the United States was expected to experience more favorable trends in ASIR, both nations faced substantial increases in absolute disease burden, with China experiencing more pronounced increases due to its larger population base and more rapid demographic aging. By 2035, China was projected to account for 4288,943 incident cases compared to 444,961 in the United States (9.6-fold difference), and 29,407,969 prevalent cases versus 9441,012 (3.1-fold difference). These model-based projections suggest that, conditional on the continuation of current trends, despite improvements in age-standardized rates, the absolute burden of ischemic stroke may intensify substantially in both countries, underscoring the need for enhanced prevention strategies, healthcare resource allocation, and public health interventions to address this potential challenge.

4. Discussion

This study provides a comprehensive assessment of the incidence, prevalence, mortality, and DALYs associated with ischemic stroke in China and the United States over the past 30 years, along with projections for the next decade. We examined disparities in ischemic stroke burden across different age groups and genders in China and the United States. The findings indicate that from 1990 to 2023, China witnessed a significant decline in ASMR and DALYs, whereas ASIR and prevalence showed an upward trend. Conversely, the United States exhibited decreases in all age-standardized rate indicators. Furthermore, substantial differences in disease burden distribution by gender and age were observed between the 2 nations. The APC model revealed that despite a reduction in the intrinsic risk among younger generations, population aging is becoming the dominant driver of disease burden in both countries. Projections for the next decade indicate a substantial increase in the burden of ischemic stroke in both nations, particularly in China. Consequently, ischemic stroke poses unprecedented challenges to public health systems, necessitating more robust public health strategies.

Specifically, between 1990 and 2023, China achieved remarkable success in terms of ASMR and DALYs for ischemic stroke. However, this progress contrasts with the rising ASIR and ASPR, indicating that the population affected by ischemic stroke is expanding, which is consistent with previous findings.^[8] This diverging trend could potentially reflect the expansion of disease screening and changing diagnostic practices,^[8] as well as shifts in health behaviors accompanying economic development.^[9] In sharp contrast, although the prevalence rate in the United States has increased, there are favorable trends in ASIR, mortality rates, and DALY rates, which is consistent with previous findings.^[10] This suggests that stroke survivors in the United States are living longer, and greater attention should be paid to the long-term care and management of complications in this population. The prevalence of ischemic stroke in China is higher than that in the United States, reflecting the need to further improve the prevention and control of risk factors, such as hypertension, environmental particulate matter pollution, and high LDL cholesterol levels. In the future, efforts should shift from being primarily focused on treatment to prioritizing prevention and management, enhancing tiered diagnosis and treatment as well as community rehabilitation, and improving follow-up systems.^[11]

This unequal distribution underscores the urgency to conduct cross-national comparative studies. However, current research evidence on the effectiveness of healthcare systems across different countries remains limited, and this lack of evidence has, to some extent, hindered collaborative progress in the global prevention and management of ischemic stroke.^[12] Women demonstrated a more substantial decline in mortality and DALY rates (−62.97% for mortality and −60.19% for DALYs), exhibiting better outcomes than men. This may be attributed to women’s heightened health awareness. Women have been reported to be generally more receptive to health-related information and more likely to modify unhealthy lifestyles. In the United States, improvements in incidence rates were relatively balanced between genders, with men showing greater reductions in mortality rates. This suggests that implementing prevention and control measures tailored to gender differences could be beneficial for reducing the burden of ischemic stroke. Furthermore, the substantial sex disparity in the ischemic stroke burden in China, where men experience a disproportionately higher incidence and prevalence than women, warrants particular attention. This phenomenon strongly correlates with the profoundly gendered patterns of tobacco consumption in the country. Recent nationally representative epidemiological data reveal that while smoking prevalence among Chinese women remains extremely low (approximately 2%), over 50% of adult men are current smokers, accounting for almost all tobacco consumption nationwide.^[13] Notably, despite a gradual decline in overall smoking rates, there has been an alarming upward trend among young men residing in rural areas (born after 1990), whose smoking prevalence surged from 40.2% in 2010 to over 52% in 2018.^[13] Given that smoking is a potent and modifiable risk factor for cerebrovascular events, this persistent and high exposure among Chinese males – coupled with the rising rates among rural youth – likely serves as a major contributing factor to the escalating ischemic stroke burden in this demographic. Consequently, to effectively mitigate the future threat of ischemic stroke, it is imperative to implement targeted, rigorous tobacco control strategies specifically tailored to male populations and rural communities. Simultaneously, as the world transitions toward aging societies, we observe that the peak prevalence rates in both countries occur among the elderly. Moreover, China’s elderly population exhibits the most rapid growth in absolute case numbers, highlighting the critical role of population aging as an “amplifier” of disease burden. Furthermore, a particularly alarming trend is the rising incidence rates among younger age groups in both countries (defined as 30–39 years old in China and 30–44 years old in the United States). This reveals a global challenge regarding stroke onset at younger ages. Beyond the accumulation of metabolic risk factors during youth, air pollution and longer working hours are also considered emerging risk factors.^[14] Both countries should advance cardiovascular risk factor screening and lifestyle interventions in younger populations.

The APC model analysis indicated that across all indicators in both countries, risk increased exponentially with age. Aging is the strongest nonmodifiable risk factor for ischemic stroke.^[15] Elderly patients have higher mortality rates and poorer functional outcomes,^[16] reflecting irreversible biological processes, such as vascular aging^[17] and cumulative atherosclerosis.^[18] The age effect analysis revealed a significant finding: after controlling for age structure, the relative risk of mortality across all age groups in the United States was consistently higher than that in China, indicating poorer outcomes for age-matched patients in the United States. Studies suggest this disparity might be influenced by variations in healthcare access and underlying socioeconomic determinants.^[19] Period effects revealed distinct public health trajectories between the 2 countries, with China exhibiting a U-shaped pattern. Around 2004 to 2008, China experienced the lowest incidence and prevalence risks for ischemic stroke (RR: 0.91), accompanied by sustained declines in mortality and DALYs. This trend coincided with rapid economic growth and may partially reflect the initial benefits of strengthened public health initiatives during that period. However, all indicators rebounded after 2009 to 2013, with the incidence risk surging to RR 1.22 by 2019 to 2023. This indicates that, compared to the baseline period, the current risk of ischemic stroke among Chinese residents has increased by over 20%. It is plausible that the negative impacts of risk factors such as the rising prevalence of metabolic diseases,^[20] air pollution,^[21] and shifts in dietary patterns^[22] may have begun to offset the earlier gains. In contrast, the United States experienced a sustained decline in period risks for ischemic stroke mortality and DALYs during the earlier period from 1990 to 2010. This earlier phenomenon has often been attributed in the literature to the proactive management of risk factors,^[23] advances in acute treatment technologies (such as tissue plasminogen activator),^[24] and the implementation of broader public health initiatives.^[18] However, this downward trend stalled and reversed after 2010, which may be associated with factors such as the rapid accumulation of metabolic risk factors among younger cohorts^[25,26] and population aging.^[27] This suggests diminishing marginal benefits from early effective interventions, while responses to new challenges have yet to reverse the overall trend. Regarding cohort effects, both countries observed progressively lower intrinsic risk among more recently born generations, indicating overall declines in incidence and mortality rates across later birth cohorts. This confirms that feasible long-term primary prevention strategies yield cumulative intergenerational protective effects. Across all age cohorts, ischemic stroke incidence, mortality, and DALYs showed consistent downward trends. Notably, the recent decline in ischemic stroke DALYs in the United States has shown signs of stagnation or even reversal. This aligns with findings from U.S. ischemic stroke healthcare cost assessments; as patient survival increases, the healthcare burden of ischemic stroke may increase.^[28] In summary, both countries exhibit similar age and cohort effects but divergent period effects. For China, while reaping the dividends of cohort effects, it must immediately curb the prevalence of risk factors through enhanced primary prevention to sustain long-term health gains. For the United States, despite observing the benefits of past public health investments, there is an urgent need for innovative prevention strategies focused on younger populations and health inequities to reverse recent adverse trends.

This study projected the disease burden over the next decade using BAPC models. These conditional forecasts suggest that, if prevailing trends continue, by 2035 ischemic stroke may pose a persistent and significant public health threat to both China and the United States. China may face dual pressures, namely, rising ASIR and absolute case numbers, which would necessitate strengthened primary prevention to reduce population-level risk while expanding healthcare provision. The United States must prioritize long-term care for stroke survivors to mitigate the risk of surging ASPR and DALYs. Finally, our model-based estimates suggest that demographic forces may offset declines in age-standardized rates. Under the assumption of status quo continuation, the projections indicate potentially substantial increases in absolute ischemic stroke cases, deaths, and DALYs in both countries, particularly among men. Given China’s larger population base, its growth will be especially rapid. Therefore, facing this impending crisis, both nations should shift from primarily treatment-oriented approaches to strengthening primary prevention and poststroke rehabilitation as key priorities, while developing targeted interventions for high-risk groups, such as males.

5. Strength and limitations

This study represents the first systematic comparison of differences in the burden of ischemic stroke between China and the United States, revealing the heterogeneity of disease characteristics and highlighting the impact of macro-level factors, such as aging and population growth, on disease burden. It provides epidemiological evidence to inform the development of strategies tailored to the specific circumstances of both nations. Furthermore, utilizing GBD data from 1990 to 2023, we observed long-term trend changes in ischemic stroke. Finally, by analyzing the characteristics of ischemic stroke burden in both nations, this study facilitates proactive planning for healthcare resources and prevention measures, thereby optimizing resource allocation.

Several limitations should be acknowledged. First, the reliability of GBD estimates depends on the quality and availability of underlying data sources, including national vital registration systems, hospital discharge records, disease registries, and survey data. The completeness and diagnostic accuracy of these sources vary substantially between China and the United States. China’s vital registration system has historically had incomplete coverage, particularly in rural areas, and variations in diagnostic coding practices may lead to misclassification between ischemic and hemorrhagic stroke subtypes. Although the GBD modeling framework employs sophisticated statistical methods, including spatiotemporal Gaussian process regression and ensemble modeling, to address data gaps and inconsistencies, these modeled estimates inevitably carry greater uncertainty in data-sparse regions. The 95% uncertainty intervals reported in GBD estimates reflect sampling and modeling uncertainty but may not fully capture systematic biases arising from differential data quality between the 2 countries.^[29] Consequently, cross-national comparisons should be interpreted with caution, as apparent differences in disease burden may partly reflect disparities in data infrastructure rather than true epidemiological variation. Second, several methodological limitations related to the APC and BAPC models should be acknowledged. The APC model using the IE method, while providing a mathematically unique solution to the APC identification problem, relies on the assumption that the true effects can be adequately represented by a linear combination of age, period, and cohort parameters. This approach may not fully capture nonlinear interactions among these 3 dimensions. Furthermore, the use of 5-year grouping intervals for age and period may obscure finer-grained temporal variations. The BAPC forecasting model assumes that historical trends in age, period, and cohort effects will continue into the future and does not account for potential future policy changes, technological breakthroughs in stroke prevention or treatment, major shifts in risk factor prevalence, or unforeseen events such as pandemics. Therefore, the projections should be interpreted as conditional model-based forecasts representing 1 plausible trajectory under the assumption of status quo continuation, rather than definitive predictions. Additionally, the study lacked granular data on ischemic stroke subtypes or specific risk factor characteristics, limiting our capacity for more targeted etiological interpretations. Moreover, the GBD database does not provide demographic stratifications differentiating urban and rural residency. Consequently, we were unable to conduct a subgroup analysis comparing the stroke burden between urban and rural populations, despite the well-documented disparities in risk factors such as the escalating smoking rates among young rural Chinese males. Finally, the absence of other population-specific analyses, such as those examining young-to-middle-aged individuals with ischemic stroke in both countries, provides avenues for future research.

6. Conclusion

Overall, this study provides a comprehensive analysis and projection of the burden and trends of ischemic stroke in China and the United States. While China has achieved notable success in reducing ASMR and DALYs over the past 30 years, further efforts are required to curb its rising incidence rates. Conversely, although the United States has implemented primary prevention measures effectively, it still faces a significant issue with the large number of stroke survivors. Over the next decade, accelerating population aging may gradually offset the benefits of declining age-standardized rates, leading to a substantial increase in the absolute burden of ischemic stroke in both countries. These findings indicate that both nations must proactively address the growing disease burden. While the elderly constitute the primary high-risk population in both countries, the trend of ischemic stroke burden shifting toward younger age groups also warrants attention. Therefore, beyond prioritizing healthy aging initiatives, both nations must rationally allocate healthcare resources. China should focus on promoting metabolic risk management and healthy lifestyle behaviors to curb rising incidence rates, whereas the United States should enhance supportive care systems for stroke survivors to ensure access to sustained rehabilitation services. Such interventions hold promise for effectively reducing the absolute burden of ischemic stroke in both countries.

Acknowledgments

We thank the Institute for Health Metrics and Evaluation (IHME) for providing open access and the individuals who contributed to the 2023 Global Burden of Disease Study.

Author contributions

Conceptualization: Xue Ren.

Data curation: Xue Ren.

Formal analysis: Xue Ren.

Investigation: Xue Ren.

Methodology: Xue Ren.

Project administration: Jiening Wang.

Software: Xue Ren.

Supervision: Zixuan Lu, Jiaohua Chen.

Validation: Xue Ren.

Visualization: Xue Ren, Jiening Wang.

Writing – original draft: Xue Ren.

Writing – review & editing: Xue Ren