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. 2025 Aug 26;25:631. doi: 10.1186/s12872-025-05055-2

Global burden of peripheral arterial disease and its risk factors, 1990–2021

Mengxia Fu 1, Huan Zhang 2,✉
PMCID: PMC12379400  PMID: 40859165

Abstract

Background

Lower extremity peripheral arterial disease (PAD) is an atherosclerotic condition affecting the peripheral vasculature, resulting in arterial stenosis or occlusion in the lower limbs. The focus is on understanding the epidemiology of this often-overlooked and debilitating disease.

Methods

Data on PAD were retrieved from the GBD 2021. To assess the burden of PAD, we measured prevalence, incidence, disability-adjusted life years (DALYs) and deaths, along with their age-standardized rates (ASRs) per 100,000 person-years.

Results

In 2021, the global incidence of PAD cases was 10.0 million (95% UI: 8.7 to 11.1), with an age-standardized incidence rate (ASIR) of 115.4 per 100,000 person-years (95% UI: 100.0 to 132.7). This decreased by 11.3% (95% UI: -11.2 to -11.4) from 1990 to 2021. The global disability-adjusted life years (DALYs) for PAD in 2021 totaled 1.6 million (95% UI: 1.3 to 2.1), with an age-standardized DALYs rate of 18.6 per 100,000 person-years (95% UI: 15.2 to 24.2), reflecting a reduction of 30.1% (95% UI: -31.8 to -28.3) from 1990. The ASIR increased with age, peaking among female aged 75–79 years, with 1015.8 per 100,000 person-years (95% UI: 686.9 to 1425.0) and male aged 95 + . The age-standardized DALYs rate showed minimal variation when the Sociodemographic Index was below 0.6. However, once the SDI exceeded 0.6, a reversed U-shaped relationship emerged. Behavioral and metabolic risks were identified as significant independent risk factors for PAD. By 2050, the global DALYs due to PAD are projected to reach 3.4 million (95% UI: 2.5 to 4.5), and improvements in these risks could reduce DALY counts by 36.6% (95% UI: -36.7 to -36.3).

Conclusions

The burden of PAD remains heavy in 2021. The disease is disproportionately diagnosed in females and older adults, highlighting the need for increased awareness and targeted interventions in these populations.

Graphical Abstract

graphic file with name 12872_2025_5055_Figa_HTML.jpg

Supplementary Information

The online version contains supplementary material available at 10.1186/s12872-025-05055-2.

Keywords: Peripheral arterial disease, Incidence, Disability-adjusted life years, Risk factor, Prediction

Contributions to the literature

  1. The global burden of lower extremity PAD remains significant, with an age-standardized incidence rate of 115.4 per 100,000 person-years in 2021, disproportionately affecting older adults and females.

  2. Behavioral and metabolic risk factors play a critical role in PAD development, and addressing these modifiable risks could reduce DALYs by 36.6% (95% UI: −36.7 to −36.3) by 2050.

  3. These findings underscore the need for targeted screening, preventive strategies, and tailored interventions to manage PAD, particularly in high-risk populations such as aging individuals and females.

Introduction

Lower extremity peripheral arterial disease (PAD) is an atherosclerotic condition affecting the peripheral vasculature, resulting in arterial stenosis or occlusion in the lower limbs [1]. Despite its significant prevalence and association with adverse clinical outcomes, such as impaired physical function and reduced physical activity [2], PAD remains less studied and less recognized compared to other atherosclerotic diseases, such as myocardial infarction and stroke. This lack of awareness has contributed to underdiagnosis and inadequate treatment of PAD globally [3–6].

Because PAD often leads to lifelong disability, relying solely on cross-sectional prevalence does not capture the full extent of its impact. However, previous systematic review assessing PAD’s global burden have mainly focused on prevalence estimates [7], leaving the global, regional, and national levels of disability resulting from PAD unexamined. While some studies have attempted to estimate the global burden of PAD in 2019 [8–10], they did not include data reflecting the onset of the COVID-19 pandemic or its potential disruptions. In addition, in 2019, 69.4% of global PAD DALYs (1.066 million) were attributed to all estimated risk factors such as smoking, high fasting plasma glucose, high blood pressure, kidney dysfunction, high sodium and lead [8]. It is currently unknown how the convergence of these factors might affect future PAD burden because no recent global PAD burden forecasts have been produced. Characterizing these trends and producing forecasts of estimates into the future, with alternative scenarios based on policy-related interventions, are needed to better understand the nature of PAD, and to inform research and public health priorities for decades to come.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 study offers the latest data for assessing the epidemiological status and trends of 371 diseases and 88 risk factors across 204 countries and territories. The present study extends PAD burden estimates through 2021, thereby capturing the early post-pandemic period and enabling comparison with pre-pandemic trends. Furthermore, this study provides the first global forecast of PAD-related DALYs through 2050 using the IHME Future Health Scenarios framework. We also incorporate stratified analyses by age, sex, and SDI and assess the contribution of key modifiable risk factors at both global and regional levels. These additions offer valuable insights for health policy and resource planning in the coming decades.

Methods

Data source and overview

The Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2021 study generated estimates of deaths, incidence, prevalence, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) for PAD, categorized by age and sex across 204 countries and territories from 1990 to 2021. Data inputs for PAD estimates were derived from a wide range of sources, including population-based surveys (e.g., national health and nutrition surveys using ankle-brachial index), administrative claims and outpatient datasets, hospital discharge records, and vital registration systems. All data were geocoded and integrated via standardized modeling processes. The dataset covered both high-income and low- and middle-income countries across all GBD super-regions. For countries with sparse or incomplete data, statistical models leveraged regional covariates and predictive priors to generate estimates [11]. All data are manually reviewed by the GBD team to ensure accuracy before analysis and summary estimate calculation. The full list of data sources and their geographic coverage can be found in the GBD 2021 data repository and interactive tools provided by the Institute for Health Metrics and Evaluation (IHME, https://www.healthdata.org/).

Case definition of PAD

PAD was defined as an ankle-brachial index (ABI) ≤ 0.90 and included both symptomatic and asymptomatic cases affecting the lower extremities. This case definition aligns with international vascular guidelines and was applied uniformly across studies in GBD 2021.

Joinpoint regression analysis

We employed Joinpoint regression analysis (version 4.9.1.0) to evaluate temporal trends in disease prevalence, incidence, DALYs and mortality. The models incorporated covariates including age group, sex, Socio-demographic Index (SDI) quintile, and GBD super-region to account for demographic and regional variation in trend patterns.

PAD forecasts

Future estimates of PAD burden from 2022 to 2050 were generated using the IHME Future Health Scenarios framework (https://vizhub.healthdata.org/gbd-foresight/), which employs an ensemble forecasting strategy. For the reference scenario, several policy-relevant alternative scenarios were modeled:

  • In the Improved Behavioral and Metabolic Risks scenario, smoking prevalence was assumed to decline to zero, dietary risk factors were reduced, and population-level exposure to high blood pressure, BMI, blood glucose, and LDL cholesterol was substantially lowered in alignment with WHO NCD targets.

  • The Safer Environment scenario modeled significant improvements in air quality (e.g., PM₂.₅ reduction), reduced exposure to extreme temperatures, and improved sanitation, consistent with climate mitigation pathways such as SSP1–1.9.

  • The Improved Childhood Nutrition and Vaccination scenario assumed universal vaccine coverage and elimination of childhood undernutrition (e.g., stunting, vitamin A and iron deficiencies).

  • A Combined Scenario integrated all improvements from the above pathways to simulate the maximal potential benefit.

Detailed methods were described in the supplementary file.

Statistical analysis

To characterize the burden of PAD, we utilized prevalence cases, annual incidence cases, DALYs, deaths, and their corresponding age-standardized rates (ASRs). We calculated percentage changes in ASRs from 1990 to 2021 to evaluate the magnitude and direction of temporal trends. Comparisons were made by sex, age group, and across various SDI levels. The SDI, which assesses social development, is a composite measure that incorporates lag-distributed income per capita, average years of education for individuals aged 15 and older, and fertility rates among females under 25. In the GBD 2021 study, countries and territories were classified into five SDI categories: low, low-middle, middle, high-middle, and high, with SDI values ranging from 0 to 1. To investigate potential linear or non-linear relationships between SDI and ASRs, we employed least squares regression and generalized additive models. All statistical analyses were conducted using R software (version 4.3.0). Group comparisons were performed using t-test, Wilcoxon rank-sum test, chi-square test as appropriate. The full R script and code used for figure generation are available at: https://github.com/Drfumengxia/R-code.

Results

Peripheral arterial disease prevalence, incidence, DALYs and death in global level

In 2021, the worldwide number of PAD cases was 113.7 million (95% UI: 98.5 to 131.2), with an age-standardized prevalence rate (ASPR) of 1326.5 per 100,000 person-years (95% UI: 1153.8 to 1526.5). This decreased 12.3% (95% UI: −12 to −12.6) from 1990 to 2021. However, the global incidence of PAD involved 10.0 million (95% UI: 8.7 to 11.1) cases, with an age-standardized incidence rate (ASIR) of 115.4 per 100,000 person-years (95% UI: 100 to 132.7). This rate had decreased by 11.3% (95% UI: −11.2 to −11.4) between 1990 and 2021. The global disability-adjusted life years (DALYs) for PAD in 2021 was 1.6 million (95% UI: 1.3 to 2.1), with an age-standardized DALYs rate of 18.6 per 100,000 person-years (95% UI: 15.2 to 24.2), which decreased by −30.1% (95% UI: −31.8 to −28.3) between 1990 and 2021. The number of deaths remained at 67.7 thousand (95% UI: 59.9 to 74.3), with an age-standardized mortality rate (ASMR) of 0.8 per 100,000 person-years (95% UI: 0.7–0.9), showing a decrease of 35.9% (95% UI: −36.7 to −35.3) from 1990 to 2021 (Supplementary Table S1).

Peripheral arterial disease prevalence, incidence, DALYs and death in regional level

In 2021, we found that the ASPR and ASIR of PAD was highest in regions with a high SDI, reaching 1828.9 per 100,000 person-years (95% UI: 1608.8 to 2079.2) and 155.0 per 100,000 person-years (95% UI: 135.9 to 176.0), respectively. Geographically, High-income North America had the highest ASPR at 2486.5 per 100,000 person-years (95% UI: 2230.4 to 2766.9) and highest ASIR at 207.2 per 100,000 person-years (95% UI: 184.8 to 231.5), followed by Western Europe (ASPR: 1873.5per 100,000 person-years, 95% UI: 1625.7 to 2169.5; ASIR: 158.1per 100,000 person-years, 95% UI: 136.6 to 182.8) (Supplementary Table S1, Figure S1A, and Fig. 1A). From 1990 to 2021, ASIR trends varied by region. Regions with low-middle SDI and low SDI showed a rise of 6.2% (95% UI: 5.8 to 6.1) and 6.5% (95% UI: 6.2 to 6.3), respectively, while high SDI regions and high-middle SDI regions saw a decrease of 19.3% (95% UI: −20.0 to −18.5) and 5.6% (95% UI: −5.6 to −5.0). Geographically, the North Africa and Middle Eastregion experienced an increase of 17.2% (95% UI: 17 to 17.2), with similar trends in Eastern Europe (9.5%, 95% UI: 9.5 to 10.0) and Western sub-Saharan Africa (9.6%, 95% UI: 9.3 to 9.8). In contrast, High-income Asia Pacific had the largest decline at 32.3% (95% UI: −32.7 to −31.8), followed by Australasia and Western Europe with decreases of 27.6% and 23.8%, respectively (Supplementary Table S1).

Fig. 1.

Fig. 1

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Spatial and age-sex analysis of global peripheral arterial disease burden in 2021. A Age-standardized incidence rates and (B) Age-standardized DALYs rates of PAD global geographical distributions. C Age-standardized incidence rates; (D) Age-standardized DALYs rates of PAD sex- and age-structured analysis

On a global scale, the age-standardized DALYs rate for PAD had decreased overall. The most clear decreases were found in Australasia (−52.6%; 95% UI: −55 to −50.1), Western Europe (−32.8%; 95% UI: −34.4 to −32.3), and Central Latin America (−32.7%; 95% UI: −37.6 to −27.4). In contrast, the highest age-standardized DALYs rate was recorded in Eastern Europe at 54 per 100,000 person-years (95% UI:48.4 to 60.8), Central Europe at 48.7 per 100,000 person-years (95% UI: 43.2 to 55.4), and Southern sub-Saharan Africa at 44.7 per 100,000 person-years (95% UI: 38.7 to 51.7) (Supplementary Table S1, Fig. 1B).

Peripheral arterial disease prevalence, incidence, DALYs and death in national level

As shown in Fig. 1A, the global distribution of PAD burden varies substantially across countries, with particularly high ASIR observed in USA (211.8per 100,000 person-years; 95% UI: 189.7 to 235.8), Denmark (192.8per 100,000 person-years; 95% UI: 165.9 to 224.5), and Canada (169.1per 100,000 person-years; 95% UI: 146.4 to 194.2) (Fig. 1A and Supplementary Table S2). And lower rates in Mongolia (86.1per 100,000 person-years; 95% UI: 74.4 to 100.5), Tajikistan (84.3per 100,000 person-years; 95% UI: 72.8 to 98.3), and Uzbekistan (84.8per 100,000 person-years; 95% UI: 73.2 to 99.7). Between 1990 and 2021, variations in ASIR were observed across different countries. Germany (145.6per 100,000 person-years; 95% UI: 123.7 to 171.3), France (132.4per 100,000 person-years; 95% UI: 112.3 to 156.8), and Italy (125.9per 100,000 person-years; 95% UI: 105.4 to 150.3) showed the highest relative increases in ASIR. Conversely, Japan (75.3per 100,000 person-years; 95% UI: 63.8 to 88.6), South Korea (82.1per 100,000 person-years; 95% UI: 70.5 to 96.3), and Singapore (89.7per 100,000 person-years; 95% UI: 77.4 to 103.9) showed the largest relative decreases in ASIR (Fig. 1A and Supplementary Table S2).

In 2021, specific countries such as Barbados (83.1per 100,000 person-years; 95% UI: 72.3 to 94.3), Cuba (52.4per 100,000 person-years; 95% UI: 45.6 to 59.1), and Ukraine (65.7per 100,000 person-years; 95% UI: 58.6 to 72.7) had comparatively high age-standardized DALYs rates, contrasting with lower figures in parts of Africa, the Middle East, and South Asia, which generally range between 5 and 10 per 100,000 (Fig. 1B and Supplementary Table S2). From 1990 to 2021, the largest age-standardized DALYs rate increases were observed in Georgia (311.3%), Mongolia (136.9%), and Bahrain (103.6%). In contrast, the greatest declines were observed in Norway (−64.7%), Sweden (−60.4%), and Australia (−54.4%). For more information about ASMR, refer to Supplementary Figure S1B and Table S2.

Peripheral arterial disease prevalence, incidence, DALYs and death by age and sex

In 2021, the global prevalence counts of PAD increased with advancing age, reaching their highest levels among older adults aged 70–74 years (6.12 million males, 95% UI: 5 to 7.5; 11.7 million females, 95% UI: 9.4 to 14.4) (Supplementary Figure S1C and Table S3). Beginning at ages 40–44 years, the prevalence of PAD was gradually higher in females than in males. The age group with the highest crude incidence rate for females was 75–79 years (1015.8 per 100,000 females per year; 95% UI: 686.9 to 1425) (Fig. 1C and Supplementary Table S3). The peak counts of DALYs for males occurred at ages 70–74 (0.1 million, 95% UI: 0.1 to 0.2), while for females, the distribution shifted toward older ages, with the highest counts of DALYs seen at ages 80–84 (0.1 million, 95% UI: 0.1 to 0.2) (Fig. 1D and Supplementary Table S3). The largest sex differences in DALYs were noted in the 90–94 and 95 + age groups. Mortality crude rate increased with age, reaching their highest in the 95 + age group (84.7 per 100,000 males per year, 95% UI: 66.1 to 95.2; 108.1 per 100,000 females per year, 95% UI: 77.2 to 124.2) (Figure S1D and Supplementary Table S3), mirroring the trends observed in DALYs. The overall temporal trends of the burden of peripheral arterial disease across sex and age groups are presented in Supplementary Figure S2 and Table S4. These data show a consistently higher mortality crude rate among males, a trend that has remained stable over time, with the exception of individuals aged 80 and older.

Joinpoint analysis of peripheral arterial disease burden by sex and region (1990–2021)

Joinpoint regression analysis revealed that the overall trend in the ASPR of PAD was minor from 1990 to 2021 (AAPC = −0.43%; 95% CI: −0.44 to −0.42; P < 0.001). The ASIR exhibited a global downward trend (AAPC = −0.4%; 95% CI: −0.42 to −0.38; P < 0.001), with the most notable decline during the 1990–1996 period in males (APC = −0.62%; 95% CI: −0.67 to −0.57; P < 0.001). On the contrary, the age standardized rate of DALYs followed an upward trend from 1990 to 1994 (APC = 1.33%; 95% CI: 0.5 to 2.17; P = 0.003), but showed a significant decrease from 2000 to 2007 (APC = −2.44%; 95% CI: −2.85 to −2.03; P < 0.001), with males contributing largely to this change. The trend in ASMR closely mirrored that of the DALYs rate (Fig. 2A and Supplementary Table S5).

Fig. 2.

Fig. 2

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Joinpoint regression analysis of the peripheral arterial disease burden temporal trends, 1990–2021. Trends of age-standardized prevalence rates, incidence rates, DALY rates, and mortality rates by sex globally (A) and for both sexes in the five regions with the highest prevalence rates (High-Income North America, Western Europe, Southern Latin America, Southeast Asia, and East Asia) (B) from 1990 to 2021

An analysis of the regions with the highest global ASIR revealed that East Asia experienced a periodic decline from 2007 to 2019 (APC = −0.31%; 95% CI: −0.34 to −0.29; P < 0.001), while showing increases during other time periods. In contrast, Western Europe displayed a consistent downward trend from 1990 to 2021. High-income North America marked a turning point, with ASIR rising from 2014 to 2021 (APC = 0.51%; 95% CI: 0.31 to 0.73; P < 0.001) (Fig. 2B and Supplementary Table S6).

Association between peripheral arterial disease burden and sociodemographic index

We conducted a correlation analysis to examine the relationship between age-standardized prevalence, incidence, DALY, and death rates in relation to the SDI (Supplementary Figure S3). Our analysis revealed that the age-standardized DALYs rate from PAD showed minimal variation when the SDI was below 0.6. However, as the SDI exceeded 0.6, a reversed U-shaped relationship emerged, peaking at approximately 0.75. Regionally, areas such as Eastern Europe, Southern Sub-Saharan Africa, Caribbean and Tropical Latin America exhibited a higher-than-expected burden relative to their SDI, while regions like High-income Asia Pacific, Central Asia, Andean Latin America, South Asia, and Southeast Asia demonstrated lower burdens than anticipated (Fig. 3A). On a national level in 2021, a linear-shaped trend was observed, with countries like Barbados, Belarus, Hungary, Ukraine and Poland facing significantly higher burdens than expected (Fig. 3B). Furthermore, a J-shaped association between ASIR and SDI was evident for both 1990 and 2021. The relationships between ASMR and age-standardized DALY rates in relation to SDI were also documented in this study (Supplementary Figure S4).

Fig. 3.

Fig. 3

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Age-standardized rates of DALYs for peripheral arterial disease for regions and nations by sociodemographic index. A Age-standardized DALY rates for PAD for 21 Global Burden of Disease regions by SDI, 1990–2021. Each point shows the observed age-standardized DALYs rate for each region from 1990 to 2021. B Age-standardized DALY rates of PAD for 204 countries and territories, by SDI, in 2021. Each point shows the observed age-standardized DALYs rate for each country in 2021. DALYs, disability adjusted life years; SDI, sociodemographic index

Contribution of risk factors to peripheral artery disease-related DALYs

The total number of PAD DALYs globally attributable to all estimated risk factors in 2021 was 1.09 million (95% UI: 0.88 to 1.45) for all ages across both males and females, accounting for 68.75% (95% UI: 69.23 to 71.43) of all PAD DALYs. This figure represented an increase of 78.54% (95% UI: 44.21 to 136.87) since 1990. Among this total, the contribution from males was higher than that from females (Supplementary Table S7). Globally, among the 14 risk factors analyzed, 9 were identified as significant independent risk factors for PAD. These factors include: high fasting plasma glucose (accounting for 36.18% (95% UI: 29.53 to 42.65) of attributable DALYs), kidney dysfunction (28.96%; 95% UI: 20.04 to 37.73), smoking (24.17%; 95% UI: 18.87 to 29.67), high body-mass index (19.24%; 95% UI: 5 to 43.53), high systolic blood pressure (13.12%; 95% UI: 2.68 to 23.73), low physical activity (2.49%; 95% UI: 0.71 to 4.88), diet high in processed meat (2.1%; 95% UI: 0.48 to 4.31), diet high in red meat (1.43%; 95% UI: 0.15 to 3.55), diet low in whole grains (1.37%; 95% UI: 0.32 to 2.74) (Fig. 4A and Supplementary Table S8). From 1990 to 2021, the proportion of PAD DALYs attributed to metabolic risks rose by 8.74% (95% UI: 9.95 to 7.8), primarily due to the increased burden of high BMI and high fasting plasma glucose. Conversely, the share of PAD DALYs linked to behavioral risks decreased by 8.27% (95% UI: −6.88 to −9.68), and those due to dietary risks fell by 2.78% (95% UI: −0.42 to −5.58). These declines were largely driven by reductions in the burden associated with smoking, diets high in processed meat, diet high in red meat, diet low in whole grains, and diet low in fruits (Fig. 4B and Supplementary Table S9). Notable regional differences were observed in the ranking of age-standardized PAD DALYs by risk factors across 21 GBD regions. For example, in most regions, high fasting plasma glucose was the leading contributors to PAD burden. In contrast, in East Asia and Eastern Europe, the burden attributable to smoking was proportionally higher. In the High-income Asia Pacific, kidney dysfunction emerged as a prominent contributor, while in Australasia, high body-mass index played a more dominant role. These regional variations emphasize the importance of tailoring prevention and intervention strategies to the specific epidemiological profiles of each region (Fig. 4C).

Fig. 4.

Fig. 4

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Age-standardized percentage of DALYs due to peripheral artery disease attributed to risk factors in 1990 and 2021. A Most individually significant risk factors for PAD. B Trends in the PAF of PAD DALYs due to risk factors, for both sexes, 1990–2021. C Ranking of age-standardized percentage of PAD DALYs attributable to risk factors by 21 GBD regions, for both sexes, 2021. Data in parentheses are 95% UI; PAF, population attributable fraction; DALYs, disability adjusted life years; GBD, Global Burden of Diseases, Injuries, and Risk Factors Study; UI, uncertainty intervals

Burden forecasts of peripheral artery disease

By 2050, the global DALYs due to PAD is projected to reach 3.39 million (95% UI: 2.45 to 4.53), an increase of 1.79 million (95% UI: 1.15 to 2.43) compared to 1.6 million (95% UI: 1.3 to 2.1) in 2021. As we found that various behavioral and metabolic risks contributed to the DALY burdens for PAD in 2021, we project varying levels of future DALYs burdens across alternative scenarios, both globally and within different regions. On a global scale, the forecasted effects are strongest for the Improved Behavioral and Metabolic Risks scenario, with a 36.64% (95% UI: −36.69 to −36.34) decrease in DALYs counts by 2050 compared to the reference scenario. In 2050, the Safer Environment and Improved Childhood Nutrition and Vaccination scenarios are projected to experience increases of 1.56% (95% UI: 1.4 to 1.58) and 0.03% (95% UI: 0.02 to 0.03), respectively, relative to the reference scenario. Regionally, the largest reductions are forecast for Oceania under the Improved Behavioral and Metabolic Risks scenario (−51.31%, 95% UI: −52.31 to −52.83), followed by North Africa and Middle East (−47.56%, 95% UI: −46.48 to −48.55) and Central Sub-Saharan Africa (47.22%, 95% UI: −49.86 to −45.99). In contrast, Eastern Europe showed the smallest projected reduction in DALYs counts (−17.39%, 95% UI: −18.36 to −16.28), followed by High-income Asia Pacific (−26.69%, 95% UI: −27.25 to −26.36) and East Asia (−29.02%, 95% UI: −30.47 to −28.02) (Fig. 5 and Supplementary Table S10). Results for the impact of the alternative scenarios on age-standardized rate of DALYs are shown on Supplementary Figure S5 and Table S11.

Fig. 5.

Fig. 5

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Global and regional peripheral artery disease to all age DALY counts, for the past and for five future scenarios, 1990–2050. Error bars represent 95% UI; DALYs, disability adjusted life years

The projections of PAD burden to 2050 are further stratified by sex and age groups. Under the Improved Behavioral and Metabolic Risks scenario, the greatest projected reductions in PAD DALY counts by 2050 were observed among younger males in East Asia, with a decrease of −71.98% (95% UI: −86.01 to −60.58), followed by males aged 50–69 years in the Caribbean (−71.21%, 95% UI: −73.61 to −70.57) and the North Africa and Middle East (−70.95%, 95% UI: −72.47 to −69.58). In contrast, the PAD burden among younger individuals (< 50 years) in Western Sub-Saharan Africa showed the least improvement, particularly among females (−6.29%, 95% UI: −20.20 to −3.99) and males (−7.04%, 95% UI: −14.15 to −2.31). Similarly, males aged 70 years and older in Eastern Europe showed minimal decreases (−15.79%, 95% UI: −16.2 to −15.63) (Supplementary Figure S6-S11 and Table S12). These findings highlight considerable regional and demographic disparities in the projected benefits of risk factor control, with younger males in East Asia experiencing greater gains, while younger individuals in Western Sub-Saharan Africa may benefit less without broader systemic improvements. Results for the impact of the Improved Behavioral and Metabolic Risks scenario on DALYs crude rate by age group and sex are shown on Supplementary Figure S12-17 and Table S12.

Discussion

This study provides a comprehensive and up-to-date assessment of the global, regional, and national burden of PAD based on the GBD 2021 database. The main findings are as follows: (i) overall, the age-standardized rates of prevalence, incidence, DALYs, and death have declined noticeably from 1990 to 2021; (ii) females, and the elderly generally experience a higher burden of PAD compared to other demographic groups; and (iii) a considerable burden from PAD persists, particularly in regions with higher sociodemographic levels; (iv) various behavioral and metabolic risks contribute to the DALY burdens for PAD in 2021; (v) the Improved Behavioral and Metabolic Risks scenario is projected to lower the relative DALY counts by 2050 compared to the reference scenario, especially in the lower SDI regions.

Our study revealed significant sex differences in the global burden of PAD (Supplementary Figure S1, S2, and Figs. 1 and 2). Overall, females exhibited higher age-standardized rates of prevalence and incidence from 1990 to 2021 compared to males, while males exhibited higher age-standardized rates of deaths and DALYs than females. Previous research has noted a slightly elevated incidence of PAD in females [12, 13]. While the exact mechanisms behind these sex differences remain unclear, possible contributors such as hormonal influences or immune modulation have been hypothesized [14, 15], but direct mechanistic evidence in PAD populations is currently limited. Further biological and translational research is needed to explore these pathways. Additionally, we observed distinct age-related characteristics in the PAD burden. Notably, we identified the peak in PAD-attributable deaths in individuals over 80 years. Elderly individuals typically face worse overall health and more comorbidities, placing them at a higher risk for mortality [16]. In the future, more targeted prevention and treatment strategies should be developed, taking into account gender differences and the specific needs of the elderly population. Early screening and prevention should be strengthened for female, while treatment strategies should be optimized to address the higher mortality crude rate in male. In particular, for individuals over 80, who bear a heavier PAD burden, a comprehensive management approach is necessary to reduce mortality. Exploring the biological mechanisms behind gender differences will also aid in creating personalized treatment plans.

Atherosclerotic diseases have historically been regarded as conditions primarily affecting wealthier nations, in line with the concept of epidemiological transition [17]. However, the prevalence of vascular disease has been rising sharply in many low- and middle-income countries, partly due to lifestyle and environmental changes driven by development and urbanization [18]. In our study, areas with a high SDI exhibited the highest age-standardized incidence rates (Supplementary Table S1). This likely reflects the combined effects of lifestyle risk factors, metabolic disorders, and health system characteristics. First, physical inactivity is more prevalent in high-income regions due to sedentary occupations, increased car usage, and reduced reliance on active commuting [19, 20]. Recent longitudinal evidence from a population-based cohort of PAD patients suggests that engaging in regular aerobic activity (60 + minutes/week) and resistance training (1–4 sessions/week) is associated with significantly reduced cardiovascular and all-cause mortality among individuals with PAD [21]. This highlights the critical role of physical activity in mitigating PAD-related burden, especially in more developed settings. Second, high consumption of ultra-processed foods (UPFs)-which are rich in sodium, refined sugars, and trans fats-is more common in high-income regions [22]. A study among Brazilian patients with cardiovascular disease found that greater UPF intake was independently associated with higher rates of abdominal obesity, overweight, and PAD, particularly among women [23]. These findings underscore the importance of dietary quality in PAD prevention. Third, obesity, often driven by the above factors, is more common in high-income countries [24]. Elevated BMI contributes to arterial stiffness, endothelial damage, and metabolic syndrome-all of which increase the risk of PAD [25, 26]. In our study, we observed a large proportion of PAD DALYs attributable to high BMI in high-income regions, echoing findings from other GBD analyses (Fig. 4). Fourth, diabetes is a well-known risk factor for PAD and tends to be highly prevalent in high-SDI regions due to aging populations and obesogenic environments [27]. Hyperglycemia accelerates atherosclerotic changes in peripheral arteries and impairs vascular repair mechanisms [28]. The UKPDS and ADVANCE trials have consistently shown well-documented associations between glycemic control and PAD-related outcomes [29, 30]. In addition, this trend may be partly due to a lower prevalence of competing mortality factors, particularly in regions where other conditions that lead to premature death are less common. Furthermore, high SDI regions benefit from advanced healthcare systems, facilitating more frequent health screenings and improved access to medical services, which enhances the detection of PAD cases.

However, we identified a weak correlation between SDI and age-standardized DALYs rate when SDI was below 0.6 (Fig. 3). Above this threshold, a reversed U-shaped relationship emerged, with high-middle SDI regions showing the greatest DALYs burden. This pattern aligns with the relationship between SDI and ASMR (Supplementary Figure S3). The underlying mechanisms for this trend are not fully understood but may involve a combined effect of enhanced diagnostic and treatment capabilities. Policymakers should take socio-economic factors into account when allocating limited healthcare resources to effectively reduce the global burden of PAD.

Apart from population growth and aging [31], several other factors contributing to the rising global burden of PAD, in terms of absolute numbers, are likely linked to the limited effectiveness of current primary vascular disease prevention strategies [32], as well as significant disparities in PAD service availability and access, and the shortage of trained PAD care providers, particularly in low- and middle-SDI countries [33]. While PAD is highly preventable, global trends from 1990 to 2021 show marked increases in DALYs attributable to high BMI and high fasting plasma glucose (Fig. 4). These trends highlight the growing impact of metabolic risk factors on PAD burden. However, during the same period, there was a decrease in the PAF for risks such as smoking, diets high in processed meat, diet high in red meat, diet low in whole grains, and diet low in fruits. This suggests that strategies aimed at reducing exposure to these factors have been effective.

By 2050, global PAD DALYs will stabilize, but in some of the world's poorest regions, the increase in DALYs will remain high. The regions with the highest growth rates in DALYs over the coming decades will mainly be in parts of Sub-Saharan Africa (Fig. 5, Supplementary Figure S5). The significant rise in DALYs in this region may pose a considerable challenge to already overburdened health systems [34, 35]. Policymakers must consider how to sustain the progress in age-standardized disease burden reduction in the face of increased pressure on resources, health systems, and the social environment.

Recent advances in surgical technologies have opened new frontiers in the management of atherosclerotic diseases, including peripheral artery disease. One notable innovation is the integration of the Internet of Things (IoT) in surgical and vascular care. The IoT concept enables real-time monitoring, predictive analytics, and smart intervention strategies through interconnected devices and sensors, thereby improving outcomes in patients with atherosclerotic disorders. IoT-based platforms can assist in postoperative surveillance, early detection of graft failure or restenosis, and individualized rehabilitation plans. These applications may offer novel pathways to reduce disease progression and recurrence in PAD patients, especially in resource-equipped settings [36].

Moreover, emerging evidence has suggested a potential link between cancer and atherosclerotic vascular diseases. Both conditions share common biological mechanisms such as chronic inflammation, oxidative stress, and endothelial dysfunction. Tumor-derived cytokines and systemic pro-inflammatory states may exacerbate vascular damage, while anticancer therapies can induce or accelerate atherosclerotic changes. This bidirectional interaction underscores the importance of integrated care for patients with coexisting cancer and vascular diseases [37].

This study, like other GBD estimation efforts, has several notable limitations. Firstly, the GBD database primarily relies on national and regional reports and publications rather than direct, standardized data collection within each country. A major source of bias arises from the marked heterogeneity in diagnostic capacity across countries—particularly the limited availability of ABI screening and vascular diagnostic tools in low- and middle-income countries (LMICs). These diagnostic gaps are likely to cause substantial under-ascertainment of PAD, especially in asymptomatic or mildly symptomatic individuals. As a result, the true burden of PAD in LMICs may be significantly underestimated, contributing to a systematic bias in global estimates. This under-ascertainment likely distorts the observed SDI gradients, creating an artificial concentration of PAD burden in high-SDI countries where surveillance systems are more robust. Existing reviews emphasize that data from LMICs are “scarce,” [38] reinforcing the concern that PAD is underdetected in these settings. To reduce such structural bias, future burden estimations should incorporate harmonized diagnostic criteria and prioritize active surveillance in underrepresented regions. Second, while country-level correlations between SDI and PAD burden offer policy-relevant insights, these ecological associations cannot be interpreted as individual-level relationships. The inherent risk of ecological fallacy remains significant; for example, individuals living in low-SDI countries do not necessarily have higher or lower personal PAD risk [9, 39]. We did not employ multilevel or hierarchical modeling approaches that would allow for disentangling individual- and population-level effects. Therefore, we strongly caution against drawing individual-level inferences from our findings. Future studies using person-level datasets and appropriate multilevel methods are needed to validate and extend these macro-level associations. Third, while the forecasting results offer valuable insights, it is important to note that long-term projections are inherently uncertain. The models are based on assumptions regarding trends in risk factor exposure, demographic transitions, and policy scenarios. UIs were calculated for all projections and are provided in Supplementary Table S10-S12. However, model calibration and validation rely on historical data trends, which may not capture future policy shifts or unforeseen global events. Therefore, interpretations of these forecasts should be made with appropriate caution. Fourth, it is important to emphasize that the PAFs presented are model-derived estimates, primarily from observational data. These models assume causal relationships and adjust for known confounders; however, residual confounding and bias inherent in observational datasets may remain. Hence, while the PAFs reflect associations, they should not be interpreted as definitive causal effects. Fifth, our analysis was limited by the lack of disaggregated data on ethnicity and rural/urban residence. These dimensions are known to influence PAD risk and healthcare access, but could not be assessed within the constraints of the national-level GBD framework. Future burden studies incorporating within-country sociodemographic heterogeneity would provide a more nuanced understanding of PAD disparities.

Finally, although our study period includes the onset of the COVID-19 pandemic, PAD-specific data reflecting the direct impact of COVID-19 were not incorporated into the GBD 2021 modeling framework. Consequently, we were unable to isolate the pandemic’s effects on PAD burden, which may have introduced bias in estimates for 2020–2021. Emerging evidence suggests multiple mechanisms through which the COVID‑19 pandemic may have influenced PAD burden. First, several studies documented diagnostic and treatment delays: a multicenter cross‑sectional study in China showed that rates of chronic limb‑threatening ischemia increased from 54 to 70% and diabetic foot infections from 29 to 47%, while disease severity scores worsened, indicating care disruptions (2020–2021 vs 2018–2019) [40]. A European systematic review of 132 cardiovascular studies also noted broad declines in acute hospital admissions and delayed treatment initiation during the pandemic [41]. In the U.S., Veterans Affairs hospitals experienced a ~ 42% drop in emergency admissions early in the pandemic, likely delaying PAD‑related acute care [42]. These service disruptions may have resulted in a 3%–6% underestimation of PAD DALYs. Second, post‑COVID vascular risk appears elevated based on cohort data: retrospective studies suggest increased incidence of peripheral arterial occlusive disease and cardiovascular events after SARS‑CoV‑2 infection (hazard ratio ~ 1.4–2.0), persisting over 12 months [43]. This may have contributed an additional 1%–2% to PAD burden. Third, lockdown-related behavioral and metabolic deterioration—evidenced by significant increases in HbA1c (+ 0.3%), BMI (+ 0.6 kg/m2), and marked weight gain, particularly among overweight or diabetic individuals—has likely exacerbated PAD progression [44]; we conservatively estimate this pathway may have contributed approximately 1% additional PAD burden. Fourth, short‑term improvements in air quality—driven by COVID‑19 lockdowns—may have exerted a modest mitigating effect, with early studies linking NO₂ and PM₂.₅ reductions to approximately 0.16–0.91 avoided deaths per 100,000 [45]; however, given the latency in atherosclerotic disease progression, this likely translates to only a 0.5%–1% reduction in PAD burden. Taken together, these pathways suggest that PAD‑related DALYs in 2020–2021 may have been underestimated by approximately 5%–8%, underscoring the importance of explicitly modeling pandemic‑related disruptions and sequelae in future burden assessments.In conclusion, this study offers an updated and comprehensive assessment of the global burden of PAD. The disease remains highly prevalent—particularly among women and older adults—and continues to impose substantial disability worldwide. Strengthening surveillance, targeting high-risk populations, and investigating emerging risk factors will be essential to improving prevention, diagnosis, and management efforts across diverse settings.

Supplementary Information

Supplementary Material 1. (10.7MB, docx)

Acknowledgements

None.

Clinical trial number

Not applicable.

Authors’ contributions

MF: Conceptualization, Methodology, Software, Data acquisition, Data curation, Writing- Original draft preparation, Visualization, Investigation. HZ: Supervision, Writing- Reviewing. All authors read and approved the final manuscript.

Funding

The authors did not receive support from any organization for the submitted work.

Data availability

Data sources and availability can be found on the GBD Sources Tool (https://ghdx.healthdata.org/gbd-2021/sources). The full R script and code used for figure generation are available at: https://github.com/Drfumengxia/R-code.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Material 1. (10.7MB, docx)

Data Availability Statement

Data sources and availability can be found on the GBD Sources Tool (https://ghdx.healthdata.org/gbd-2021/sources). The full R script and code used for figure generation are available at: https://github.com/Drfumengxia/R-code.

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