Burden of lower extremity peripheral arterial disease in the Western Pacific region, 1990–2021: a comparative analysis

Abstract

Background:

Lower extremity peripheral arterial disease (PAD) significantly impairs limb function, yet research is limited. This study utilized data from the Global Burden of Disease (GBD) study to analyze the epidemiological trends of PAD in the Western Pacific region.

Methods:

This study analyzed PAD burden among individuals aged ≥40 in four representative countries during 1990–2021, using the GBD 2021 dataset, including prevalence, incidence, and disability-adjusted life years (DALYs). The sociodemographic index (SDI) was used to quantify developmental status. Joinpoint regression analysis was employed to assess temporal trends. The Bayesian age–period–cohort model was utilized to predict incidence through 2041.

Results:

In 2021, the Philippines had the highest incidence, prevalence, and DALY rates, followed by China and Japan. The affected population in the Philippines was younger than in other countries, indicating a uniquely severe burden. China had the highest number of new cases, with 2 447 372 in 2021. Women had a higher disease burden. Incidence, prevalence, and DALY rates all peaked in older age groups. From 1990 to 2021, the PAD burden in China and the Philippines showed an upward trend, whereas that in Japan and South Korea showed a downward trend. Future projections indicate that China will experience an increase in disease burden.

Conclusion:

PAD imposes a substantial burden in the Western Pacific region. Middle-SDI regions should address its socioeconomic impacts and strengthen prevention strategies, while high-SDI regions should focus on disease control in the elderly. PAD serves as an indicator of arterial health. Preventing PAD may block more fatal cardiovascular events.

Introduction

Non-communicable diseases (NCDs) are the leading causes of morbidity and mortality worldwide^[1,2^]. The burden of NCDs is rapidly increasing due to population aging and greater exposure to chronic disease risk factors, such as smoking, alcohol consumption, hypertension, diabetes, obesity, and hypercholesterolemia. A quarter of global deaths from NCDs occur in the Western Pacific region^[3^]. Assessing the current burden of major NCDs at the global or regional level may help inform effective and cost-efficient response strategies. Despite its clinical significance, peripheral arterial disease (PAD) has been overlooked in epidemiological research compared to other atherosclerotic diseases. It is the third most prevalent atherosclerotic vascular disease after coronary heart disease and stroke^[1^]. Its pathological hallmark is the narrowing or occlusion of the arterial lumen in the lower limbs^[4^]. Clinical manifestations include intermittent claudication, leg pain, and pain at rest^[5^], with severe cases potentially leading to limb ischemia and necrosis^[6,7^]. Although PAD primarily affects the elderly, epidemiological data indicate a trend toward a younger age of onset^[2^].

The Western Pacific region faces multiple public health challenges, including population aging, rising cardiovascular risk factors, lifestyle changes with socioeconomic development, and the uneven distribution of medical resources^[8^]. PAD has affected a large number of groups in this region over the past three decades. Accurate epidemiological data are critical for early medical intervention and are of practical significance for disease prevention, optimizing resource allocation, and guiding public health priorities.

Although previous studies have partially explored the prevalence and characteristics of PAD at global or regional levels, these investigations have been limited by fragmented content and outdated data. To address these limitations, this study leverages the latest GBD 2021 data. The study systematically analyzes the age–sex–time distribution patterns and, for the first time, predicts the future disease burden of PAD. Moreover, using age-standardized indicators, this study is the first to quantitatively assess regional disparities in the PAD disease burden across the Western Pacific region.

This study focuses on China, Japan, South Korea, and the Philippines, which represent diverse economic, social, and healthcare contexts in the Western Pacific region. We analyzed the prevalence, incidence, and DALYs of PAD from 1990 to 2021. The use of age-standardized rates (ASRs) ensured fair cross-country comparisons. Joinpoint regression was employed to identify temporal trends, and the Bayesian age–period–cohort (BAPC) model was used to project the burden up to the year 2041.

In accordance with the TITAN 2025 guidelines regarding transparency in the use of artificial intelligence tools in scientific work, we confirm compliance with all ethical and technical reporting standards^[9^].

Methods

Overview of the study

Publicly available data from GBD 2021 were used for secondary analysis. GBD 2021 is a large-scale global collaborative research initiative that quantifies the burden and distribution of major diseases, injuries, and risk factors worldwide. Its data were collected from multiple sources, including vital registration systems, censuses, household surveys, disease-specific registries, and health service contact data. Detailed information on all data sources is available online through the GBD 2021 Source Tool on the IHME website (https://ghdx.healthdata.org/gbd-2021/sources). After data collection, DisMod-MR 2.1, a standardized statistical modeling tool, was used to assess and adjust for potential biases in each dataset. GBD 2021 provides estimates for 371 diseases and injuries and 88 risk factors across 204 countries and territories, stratified by year (1990–2021), age (birth to ≥ 95 years), and sex (male, female, both). It offers annual data at the global, regional, and national levels from 1990 to 2021. For this study, PAD data from China, South Korea, Japan, and the Philippines for 1990–2021 were extracted. The data were adjusted for country-specific factors, such as differences in healthcare infrastructure and diagnostic practices, to more accurately reflect the true disease burden in each country.

Sociodemographic index (SDI) is a composite indicator of the development status of a country or region and is used to analyze the relationship between health and socioeconomic development. It is derived from fertility rates among people <25 years of age, mean educational attainment for those aged ≥15, and income per capita. Values range from 0 to 1, with higher values indicating higher development. Based on SDI, 204 countries and territories are divided into five tiers: low, low-middle, middle, high-middle, and high sociodemographic development. Japan and South Korea are classified as high, whereas China and the Philippines are classified as middle.

Data sources

The prevalence, incidence, and DALYs of PAD in China, South Korea, Japan, and the Philippines, along with 95% uncertainty intervals (UIs), are available from GBD 2021 (https://vizhub.healthdata.org/gbd-results/).

HIGHLIGHTS

• High Burden in Lower Sociodemographic Index Countries: The Philippines and China exhibited the highest age-standardized incidence, prevalence, and DALY rates for lower extremity peripheral arterial disease (PAD), with the Philippines bearing the heaviest burden among the four countries studied.

• Significant Gender and Age Disparities: Across all four countries, women consistently showed a higher burden of PAD than men, and the elderly (80 + years) were the most affected age group, highlighting important demographic risk patterns.

• Divergent Temporal Trends: From 1990 to 2021, Japan and South Korea experienced significant declines in PAD burden, while China and the Philippines showed increasing trends, reflecting the influence of socioeconomic and healthcare system differences.

• Future Projections Reveal Ongoing Challenges: Bayesian projections indicate that China will see a slight rise in PAD incidence by 2041, while Japan and South Korea will continue to decline, and the Philippines will remain stable, underscoring the need for targeted public health strategies.

Burden description

This study uses incidence, prevalence, and DALYs to describe the burden of PAD. Incidence measures new cases, prevalence measures the affected population at a given time, and DALYs sum years of life lost (YLLs) due to premature death and years lived with disability (YLDs). YLLs are calculated by multiplying deaths by standard life expectancy, and YLDs by multiplying age–sex–region–year-specific prevalence by the corresponding disability weights.

Estimates are reported as 95% UIs, taken at the 2.5th and 97.5th percentiles from 100 uncertainty samples.

Age-standardized rates (ASR) (per 100 000 population) were calculated using the GBD standard population to eliminate the influence of differing age structures.

Joinpoint regression analysis

The Joinpoint regression model uses multiple linear statistical models to analyze time trends of disease burden^[10^]. This model takes trend data and fits the simplest joinpoint model allowed by the data. The model starts with the minimum number of connection points, tests whether more are statistically significant, and adds them to the model up to the maximum number. Tests of significance were performed using the Monte Carlo permutation method. Joinpoint models capture trend turning points and quantify changes at each stage.

This study used the Joinpoint regression model to analyze temporal trends in the incidence, prevalence, and DALYs of PAD in China, Japan, South Korea, and the Philippines (1990–2021), calculating the annual percent change (APC) and average annual percent change (AAPC) with 95% UIs. APC represents the annual rate of change for a specific period, while AAPC reflects the overall average across the study period. The statistical significance of trends was determined by whether the 95% UI excluded zero: entirely above zero indicates a significant upward trend; entirely below zero indicates a downward trend; and including zero indicates a non-significant trend. A P-value < 0.05 was considered statistically significant.

BAPC analysis

A BAPC model was used to predict the future incidence of PAD. In this study, 1990–2021 incidence data from the four countries were used to predict the incidence of PAD through 2041. The BAPC model is an extension of the traditional age–period–cohort model, addressing identification challenges and providing flexible parameter estimation with a better quantification of uncertainty. It constrains parameters with prior distributions and uses posterior inference to quantify the uncertainty of the effects.

All analyses and visualizations were performed in R 4.5.1.

Results

Burden of PAD in China, Japan, South Korea, and the Philippines in 2021

In China, there were 2 447 372 incident PAD cases (95% UI: 2 109 991–2 854 291), 28 474 886 prevalent cases (95% UI: 24 446 553–33 220 180), and 171 757 DALYs (95% UI: 99 158–301 528). ASRs for incidence, prevalence, and DALYs were 112.66 (95% UI: 97.75–130.73), 1331.13 (95% UI: 1147.49–1544.17), and 8.36 (95% UI: 4.87–14.33), respectively (Table 1; Supplementary Digital Content Table 1, available at: http://links.lww.com/MS9/B290).

Table 1.

Burden of lower extremity peripheral arterial disease among China, Japan, South Korea, and Philippines in 2021.

Location	Sex	Age-standardized prevalence rate	Age-standardized incidence rate	Age-standardized DALYs rate
China	Both	1331.13(1147.49–1544.17)	112.66(97.75–130.73)	8.36(4.87–14.33)
	Female	1854.94(1596.94–2148.61)	155.62(134.88–180.26)	10.35(5.52–19.06)
	Male	747.8(641.62–868.51)	67.49(58.71–78.53)	6.06(4.14–9.10)
Japan	Both	1309.38(1135.62–1515.95)	113.02(97.48–130.17)	9.66(7.00–14.13)
	Female	1863.96(1615.40–2154.20)	157.38(135.73–181.69)	10.27(6.73–16.47)
	Male	659.73(567.25–771.91)	63.52(54.85–73.71)	8.74(7.24–11.23)
Korea	Both	1132.29(989.94–1314.26)	100.88(86.62–116.11)	7.94(5.55–11.89)
	Female	1463.98(1268.87–1704.65)	127.35(109.86–146.90)	7.29(4.36–11.94)
	Male	718.91(619.69–840.11)	69.55(59.99–81.07)	9.04(6.82–11.95)
Philippines	Both	1398.11(1209.27–1619.81)	123.84(106.98–144.23)	11.82(7.55–19.42)
	Female	1800.44(1560.57–2085.88)	158.72(137.07–184.48)	12.25(6.86–22.30)
	Male	890.20(768.22–1036.26)	82.63(71.73–96.43)	10.97(8.01–15.56)

DALYs, disability-adjusted life years.

In Japan, there were 376 222 incident PAD cases (95% UI: 323 285–432 518), 4 885 245 prevalent cases (95% UI: 4 233 083–5 631 107), and 45 590 DALYs (95% UI: 33 650–63 004). ASRs for incidence, prevalence, and DALYs were 113.02 (95% UI: 97.48–130.17), 1309.38 (95% UI: 1135.62–1515.95), and 9.66 (95% UI: 7.00–14.13), respectively (Table 1; Supplementary Digital Content Table 1, available at: http://links.lww.com/MS9/B290).

In South Korea, there were 95 649 incident PAD cases (95% UI: 82 020–110 495), 1 070 954 prevalent cases (95% UI: 935 686–1 245 048), and 7482 DALYs (95% UI: 5182–11 324), respectively. ASRs for incidence, prevalence, and DALYs were 100.88 (95% UI: 86.62–116.11), 1132.29 (95% UI: 989.94–1314.26), and 7.94 (95% UI: 5.55–11.89), respectively (Table 1; Supplementary Digital Content Table 1, available at: http://links.lww.com/MS9/B290).

In the Philippines, there were 104 168 incident PAD cases (95% UI: 89 923–121 956), 1095,304 prevalent cases (95% UI: 940 456–1 279 930), and 8635 DALYs (95% UI: 5679–13 901). ASRs for incidence, prevalence, and DALYs were 123.84 (95% UI: 106.98–144.23), 1398.11 (95% UI: 1209.27–1619.81), and 11.82 (95% UI: 7.55–19.42), respectively (Table 1; Supplementary Digital Content Table 1, available at: http://links.lww.com/MS9/B290).

Among age groups, the Philippines and Japan exhibited the highest incidence in the 75–79 age group, at 817.39 (95% UI: 544.45–1152.27) and 880.10 (95% UI: 591.12–1243.70), respectively. South Korea and China had the highest incidence in the ≥ 80 age group, at 845.30 (95% UI: 625.91–1093.14) and 704.91 (95% UI: 522.57–910.88), respectively. Across all countries, the highest prevalence and DALYs were observed in the ≥ 80 age group. Women consistently bore a heavier PAD burden (Figs 1–4).

Figure 2.

Burden of PAD regarding sex and age in Japan in 2021. (A) In 2021, the prevalence rate (line chart) and number of cases (bar chart) of PAD in different age and sex groups in Japan. (B) In 2021, the incidence rate (line chart) and number of cases (bar chart) of PAD in different age and sex groups in Japan. (C) In 2021, the DALYs rate (line chart) and number of cases (bar chart) of PAD in different age and sex groups in Japan.

Figure 3.

Burden of PAD regarding sex and age in South Korea in 2021. (A) In 2021, the prevalence rate (line chart) and number of cases (bar chart) of PAD in different age and sex groups in South Korea. (B) In 2021, the incidence rate (line chart) and number of cases (bar chart) of PAD in different age and sex groups in South Korea. (C) In 2021, the DALYs rate (line chart) and number of cases (bar chart) of PAD in different age and sex groups in South Korea.

Figure 1.

Burden of PAD regarding sex and age in China in 2021. (A) In 2021, the prevalence rate (line chart) and number of cases (bar chart) of PAD in different age and sex groups in China. (B) In 2021, the incidence rate (line chart) and number of cases (bar chart) of PAD in different age and sex groups in China. (C) In 2021, the DALYs rate (line chart) and number of cases (bar chart) of PAD in different age and sex groups in China.

Figure 4.

Burden of PAD regarding sex and age in the Philippines in 2021. (A) In 2021, the prevalence rate (Line chart) and number of cases (Bar chart) of PAD in different age and sex groups in the Philippines. (B) In 2021, the incidence rate (Line chart) and number of cases (Bar chart) of PAD in different age and sex groups in the Philippines. (C) In 2021, the DALYs rate (line chart) and number of cases (bar chart) of PAD in different age and sex groups in the Philippines.

Trends of PAD in China, Japan, South Korea, and the Philippines from 1990 to 2021

Between 1990 and 2021, PAD burden trends varied among the four countries. China and the Philippines experienced increases, whereas Japan and South Korea showed continuous declines.

In the Philippines, AAPCs for age-standardized DALY, prevalence, and incidence rates were 0.22 (95% UI: 0.21–0.24), 0.09 (95% UI: 0.08–0.09), and 0.01 (95% UI: 0.01–0.02), respectively. In China, although the disability rate due to PAD decreased, the AAPC for the age-standardized DALY rate was −0.24 (95% UI: −0.26 to −0.23); however, ASRs for prevalence and incidence showed an upward trend, with AAPCs of 0.20 (95% UI: 0.19–0.21) and 0.08 (95% UI: 0.08–0.09), respectively. Japan and South Korea saw significant declines. In Japan, AAPCs for DALYs, prevalence, and incidence were −0.96 (95% UI: −1.04 to −0.87), −1.34 (95% UI: −1.35 to −1.33), and −1.26 (95% UI: −1.29 to −1.22), respectively. In South Korea, the corresponding AAPCs were −1.47 (95% UI: −1.50 to −1.45), −1.09 (95% UI: −1.10 to −1.07), and −1.14 (95% UI: −1.18 to −1.11), respectively (Fig. 5).

Figure 5.

APC among four countries from 1990 to 2021. (A) The APC of age-standardized prevalence rates in four countries. (B) The APC of age-standardized incidence rates in four countries. (C) The APC of age-standardized DALY rates in four countries.

Forecast of PAD Burden in China, Japan, South Korea, and the Philippines from 2022 to 2041

In China, the PAD burden is expected to increase slightly in the future. The ASR of PAD in China is projected to be 112.70 (95% UI: 111.67–113.73) in 2022 and 114.10 (95% UI: 92.49–137.11) in 2041. Among these, females represent the primary affected group, with age-standardized incidence rates of 155.88 (95% UI: 154.00–157.75) in 2022 and 161.61 (95% UI: 118.41–208.48) in 2041. In contrast, the incidence among Chinese males shows a downward trend, decreasing from 67.30 (95% UI: 66.24–68.33) in 2022 to 63.52 (95% UI: 47.04–79.89) in 2041 (Supplementary Digital Content Figure 1, available at: http://links.lww.com/MS9/B290).

Japan and South Korea are projected to experience a significant decline in future PAD burden. Japan’s ASR is estimated to be 111.21 (95% UI: 103.86–118.52) in 2022 and 89.63 (95% UI: 36.19–160.93) in 2041 (Supplementary Digital Content Figure 2, available at: http://links.lww.com/MS9/B290). South Korea’s ASR is projected to decrease from 99.34 (95% UI: 93.02–105.66) in 2022 to 79.95 (95% UI: 34.52–141.51) in 2041 (Supplementary Digital Content Figure 3, available at: http://links.lww.com/MS9/B290).

In the Philippines, the PAD burden is expected to remain stable. The ASR is forecasted to be 123.72 (95% UI: 122.68–124.81) in 2022 and 122.00 (95% UI: 102.15–143.30) in 2041 Supplementary Digital Content Figure 4, available at: http://links.lww.com/MS9/B290).

Discussion

This study aimed to describe and analyze the burden of PAD in China, Japan, South Korea, and the Philippines, revealing differences in trends, age, and gender across regions with varying economic and cultural backgrounds in the Western Pacific. The incidence and prevalence of PAD in China have slightly increased, while Japan and South Korea have experienced significant declines in PAD burden. Although the Philippines has relatively stable trends in both incidence and prevalence, there has been a notable increase in disability burden. Compared with the other three countries, the PAD-affected population in the Philippines is younger, and disability is more concentrated among younger individuals. Across all countries, women bear a higher PAD burden than men.

PAD has now become a major global health challenge, affecting over 230 million adults globally^[11^]. PAD serves as a warning sign for cardiovascular diseases, sharing major risk factors such as hypertension, smoking, diabetes, and hyperlipidemia^[1,3,5,6^]. Patients with PAD have increased risks of myocardial infarction, ischemic stroke, and cardiovascular death^[3^]. Some patients also face a potential risk of lower limb amputation^[12^], leading to impairments in motor function, mental health disorders, reduced social participation, and increased medical and economic burdens^[13^]. However, existing research exhibits limitations, including a lack of incidence trend data and insufficient evidence on regional disparities.

The incidence of PAD in Japan and South Korea showed a downward trend, and the overall disease burden was lower than that in China and the Philippines. This may be attributed to the countries’ high SDI, well-established healthcare systems, strong public health awareness, and effective management of vascular risk factors. Additionally, surgical interventions and rehabilitation for PAD are more advanced in these countries. Japan’s low-salt diet and relatively low smoking rate play a role in reducing the onset of and disability associated with vascular diseases^[14,15^]. Compared with high-income regions in Europe and North America, PAD in Japan and South Korea is more concentrated among the elderly. In high-income areas of Europe and North America, cases are primarily found among individuals aged 55 and above^[1^], whereas in Japan and South Korea, the affected populations are mainly those aged ≥70 and ≥60, respectively. This difference may be related to the higher degree of population aging in these two countries (Japan: 28.9% aged ≥ 65 years^[3^]; South Korea: 16.5% aged ≥ 65 years^[3^]). Given these epidemiological characteristics, Japan and South Korea should prioritize elderly populations in PAD management strategies. The declining PAD burden in Japan and South Korea parallels substantial reductions in age-standardized mortality from ischemic heart disease and stroke observed in GBD studies^[16,17^]. This concordance reinforces PAD’s role as a sentinel marker for systemic atherosclerotic burden, suggesting that improvements in managing vascular risk factors in these high SDI countries have translated into broad-based cardiovascular benefits.

China and the Philippines, classified as middle-SDI countries, face a relatively heavier PAD burden. In recent years, China has seen a significant increase in both the prevalence and incidence of PAD^[18^], partly due to an aging population (≥ 65 years: 13.8%)^[3^]. However, during the study period, the overall burden of PAD showed a declining trend. This may be related to improved disease management capabilities and increased survival rates, which may have led to a reduction in disability rates. Additionally, enhanced accessibility to healthcare has played a positive role. By lowering drug prices and implementing a rural cooperative medical scheme^[19^], basic medical needs for low-income groups have been met. Furthermore, increased awareness has further reduced the disability burden. Among the four countries included in this study, the Philippines had the most severe PAD burden. Prior studies indicate that adults in low- and middle-income regions have higher PAD risk^[20–22^]. Insufficient PAD prevention investment and uneven medical resource distribution are key factors. High-quality hospitals are overly concentrated in major cities (e.g., Eastern China, Manila), while remote areas (e.g., Western China, Mindanao) lack facilities and doctors. Inadequate investment in PAD prevention and control directly contributes to the increase in PAD risk factors. In 2021, the prevalence of type 2 diabetes in China increased by 61.60% compared to 1990^[23^]. Growth in China’s hypertension prevalence accelerated significantly after 2004, rising from 0.29% to 2.45% per year^[24^]. The rates of overweight and obesity have also shown a continuous upward trend^[25^]. Furthermore, existing studies have shown an overall negative correlation between the density of the health workforce and vascular disease mortality and DALYs, indicating that increasing the human resources for vascular health should be a key priority^[3,26,27^]. The continuously worsening risk factors for non-communicable diseases also pose a serious threat to vascular health in both countries. For instance, China has a relatively high smoking rate^[28^]. Increased opportunities for both active smoking and exposure to secondhand smoke may be one of the main reasons for the growing PAD burden. Tobacco control, health promotion programs, risk factor management, and early referral to specialized services are critical measures to reduce vascular disease incidence^[12^].

The PAD burden in the Philippines increased from 1990 to 2021 but is projected to stabilize through 2041. Factors such as enhanced public health awareness^[29,30^], healthcare system improvements (e.g., strengthened primary care^[31,32^]), tobacco control^[33^], and a relatively young population may have slowed PAD risk accumulation. Nevertheless, these findings should not be interpreted as an alleviation of the future PAD burden in the Philippines. On the contrary, this indicates that the country will continue to face significant disease pressure in the future. Even without considering population aging, the risk of PAD among the younger generation of Filipinos is unlikely to decline.

Early exposure to risk factors (e.g., smoking, obesity) and insufficient public health response may be reasonable explanations for the higher PAD prevalence among individuals in the Philippines aged < 55 years^[1^]. Despite progress in tobacco control, adult smoking remains high (28.3%)^[33^]. More than one in ten adolescents currently smoke, and 58.6% of adolescents have been exposed to secondhand smoke in public places^[34^]. The harms of smoking are relatively delayed. Most smokers start during adolescence, and if smoking continues into adulthood, it markedly increases the risk of early-onset cardiovascular diseases^[35,36^]. High-sugar diets and limited PAD awareness in younger populations exacerbate the risk. A study of diabetic patients in Luzon, Philippines, showed that only about one-third were aware of their condition^[37^]. A nationwide survey in the Philippines revealed that 83.4% of adults had never heard of PAD^[38^].

Differences in diagnostic criteria affect PAD incidence and prevalence. The ankle-brachial index (ABI) (ABI ≤ 0.90) is the first-line method for diagnosing PAD^[4,39^]. However, this criterion may overestimate prevalence in women^[40^] and underestimate it in patients with diabetes or chronic kidney disease^[41^]. The toe-brachial index (TBI ≤ 0.70) can supplement ABI in patients with vascular calcification^[11^]. However, some low-income countries still rely solely on ABI, which can easily lead to underdiagnosis^[12^]. Symptom assessment methods may also influence PAD prevalence. Questionnaires screening for intermittent claudication could show varying sensitivity due to cognitive and cultural differences. Disparities in screening coverage are even more pronounced. Furthermore, PAD screening is more common in economically developed countries, whereas economically disadvantaged regions rely on late-stage symptom-based diagnoses, resulting in a large number of unrecorded asymptomatic PAD cases.

Gender differences in PAD burden across the four countries are notable, with women generally experiencing a higher disease burden. This disparity is first rooted in biological factors. The primary risk factors for PAD differ between sexes: smoking is the leading risk factor for men, whereas hypertension and diabetes are predominant in women^[42^]. Loss of estrogen protection after menopause raises the risk of disease in women^[43^]. Clinical manifestations also vary by gender^[44,45^]. Women are more likely to present with asymptomatic or atypical symptoms^[4,46^], leading to under-diagnosis or misdiagnosis. Second, studies have confirmed that due to physiological differences such as height, the average ABI in healthy women is lower than in men^[40^]. Using a uniform diagnostic threshold (ABI ≤ 0.90) exhibits methodological bias, which may lead to an overestimation of PAD prevalence in women. This is a non-negligible confounding factor when interpreting epidemiological data. Moreover, sociodemographic factors also play an important role, especially in countries like China, Japan, and South Korea, which are experiencing severe population aging. Women’s longer life expectancy results in a higher proportion in the older population. Since PAD prevalence increases with age, population aging itself expands the base of affected women. Meanwhile, PAD patients often die from concurrent cardiovascular events, in which mortality is higher in men^[47–50^]. These factors give female PAD patients longer cumulative survival time, presenting a “survival advantage” that further widens the gender gap in the affected population. In summary, the gender difference in PAD prevalence is both a real epidemiological phenomenon and one that is amplified by the limitations of current diagnostic methods. This disparity reflects the genuine vulnerability of women due to specific risk factors (e.g., hypertension, diabetes), aging burden, and unique pathophysiological mechanisms, as well as the shortcomings of existing screening tools and standards in cross-gender application. Prevention strategies should be gender-specific, focusing on smoking control in men and blood pressure and glucose management in women. Future research should establish more precise diagnostic criteria incorporating gender and height and improve data quality to correct estimation biases. Regardless of the exact magnitude of the difference, there is an urgent need to strengthen screening, diagnosis, and evidence-based management for women.

This study utilized reliable data from the GBD 2021 to report on the prevalence, incidence, and DALYs of PAD in two high-SDI countries (Japan and South Korea) and two middle-SDI countries (China and the Philippines) in the Western Pacific region. Additionally, we projected the incidence of PAD in these four countries up to the year 2041. However, this study had several limitations. First, the GBD study has inconsistencies in national data reporting and modeling assumptions. The data from different countries vary significantly in terms of quality, coverage, and standards; low-income and conflict-affected regions exhibit substantial gaps. Furthermore, differences in disease classification and diagnostic capabilities across countries have led to large disparities in reporting rates for the same health conditions. The GBD employs statistical models to fill data gaps and achieve global comparability, but the assumptions underlying these models may smooth over local realities. Especially in data-scarce regions, the results rely more on extrapolation than on actual measurements. Therefore, GBD estimates are model-based scientific inferences, and their UIs cannot fully account for the systematic biases inherent in the models themselves. Although the analytical processes and methodologies of GBD have improved continuously, the quality and collection of raw data remain major limiting factors. Therefore, this study did not analyze countries in the Western Pacific region with low sociodemographic development levels. Second, only a small number of patients die directly from PAD; most deaths are due to myocardial infarction, stroke, or sepsis. Consequently, the true burden of PAD may be underestimated. Third, the 95% UI for 2041 is very wide. Given that long-term forecasts are highly uncertain, over-interpretation of the point estimates should be avoided.

Overall, PAD burden varies across countries with different SDI levels in the Western Pacific region. High SDI countries show declining trends, whereas middle SDI countries remain heavily affected. PAD is expected to be an obstacle to future development in middle SDI countries. The PAD burden also exhibits complex trends related to age, gender, and time, with a particularly high burden among elderly individuals. Addressing PAD risk factors may reduce PAD incidence and the broader vascular disease burden.

Ethical approval

Only publicly available aggregated data from the Global Burden of Disease (GBD) study database were used, with no access to individually identifiable information. Therefore, ethical approval was not required for this study.

Consent

This study did not recruit human participants for the study. The authors did not have access to any personally identifiable information during the entire research process. Informed consent was not required.

Sources of funding

We did not receive any funding; therefore, we had no sponsors for this research.

Author contributions

D.Z., J.C.: Conceptualization, investigation. All authors were involved in project administration, validation, visualization, writing – original draft, and writing – review and editing. All authors have read and approved the final manuscript.

Conflicts of interest disclosure

The authors declare no conflicts of interest.

Research registration unique identifying number (UIN)

This study involves research on human health data, with a focus on the quantitative analysis of diseases. This study did not involve human subjects. Therefore, research registration was not applicable.

Guarantor

Jun Chen.

Peer and provenance statement

Not commissioned; externally peer-reviewed.

Data availability statement

Available freely.

Assistance with the study

None.

Presentation

The preprint of this article, 10.1101/2025.09.07.25335289, has been posted on medRxiv: https://medrxiv.org/cgi/content/short/2025.09.07.25335289v1