Forecasting the global burden of peripheral artery disease: implications for wound healing and healthcare systems

Differential burden of peripheral artery disease

Background and purpose: The global burden of peripheral artery disease (PAD) attributable to high fasting plasma glucose (HFG) has not been comprehensively characterized. This study aimed to quantify the global deaths and disability-adjusted life years (DALYs) of PAD attributable to HFG and to project their trends through 2036. Methods: Data on PAD-related deaths and DALYs were obtained from the Global Burden of Disease 2021 Study. Temporal trends were evaluated using estimated annual percentage change (EAPC) and age-period-cohort (APC) models, while future projections were derived from a Bayesian (Bayesian APC) model. Cross-national inequalities were assessed in relation to the sociodemographic index (SDI). All analyses were performed in 2024. Results: Globally, from 1990 to 2021, the overall age-standardized mortality rate (ASMRs) and DALY rate (age-standardized disability rates [ASDRs]) for all-cause PAD decreased by 35.9% and 30.1%, respectively. However, the ASMRs and ASDRs for PAD specifically attributable to HFG increased by 15.3% (95% uncertainty interval [95% UI]: 6.6–24.7) and 20.0% (95% UI: 11.9–29.1). This rise was more pronounced in women, with increases of 15.9% (95% UI: 5.0–26.9) in ASMRs and 21.9% (95% UI: 13.2–31.5) in ASDRs, compared to 12.5% (95% UI: 2.0–24.4) and 17.1% (95% UI: 7.3–27.2) in men, respectively. In 2021, HFG was responsible for 67,744 (95% UI: 59,937–74,257) PAD-related deaths and 1,558,243 (95% UI: 1,266,999–2,045,869) DALYs. Absolute inequality (slope index of inequality) in PAD burden widened over time, with the burden disproportionately concentrated in low- and middle-SDI countries. Projections to 2036 indicate a continued increase in the HFG-attributable PAD burden among women, while a slight decline is projected for men. Conclusions: The global burden of PAD is increasingly driven by HFG, with a disproportionate and growing impact on women and populations in low- and middle-SDI countries. Our findings underscore an urgent need for targeted public health policies that address gender and socioeconomic disparities. Implementing evidence-based interventions focused on glycemic control is critical to mitigating the rising global burden of HFG-attributable PAD.

Type 2 diabetes (T2D) and lower-extremity peripheral artery disease (PAD) are growing global health problems associated with considerable cardiovascular (CV) and limb-related morbidity and mortality, poor quality of life and high healthcare resource use and costs. Diabetes is a well-known risk factor for PAD, and the occurrence of PAD in people with T2D further increases the risk of long-term complications. As the available evidence is primarily focused on the overall PAD population, we undertook a systematic review to describe the burden of comorbid PAD in people with T2D. The MEDLINE, Embase and Cochrane Library databases were searched for studies including people with T2D and comorbid PAD published from 2012 to November 2021, with no restriction on PAD definition, study design or country. Hand searching of conference proceedings, reference lists of included publications and relevant identified reviews and global burden of disease reports complemented the searches. We identified 86 eligible studies, mostly observational and conducted in Asia and Europe, presenting data on the epidemiology (n = 62) and on the clinical (n = 29), humanistic (n = 12) and economic burden (n = 12) of PAD in people with T2D. The most common definition of PAD relied on ankle-brachial index values ≤ 0.9 (alone or with other parameters). Incidence and prevalence varied substantially across studies; nonetheless, four large multinational randomised controlled trials found that 12.5%-22% of people with T2D had comorbid PAD. The presence of PAD in people with T2D was a major cause of lower-limb and CV complications and of all-cause and CV mortality. Overall, PAD was associated with poor quality of life, and with substantial healthcare resource use and costs. To our knowledge, this systematic review provides the most comprehensive overview of the evidence on the burden of PAD in people with T2D to date. In this population, there is an urgent unmet need for disease-modifying agents to improve outcomes.

Global, regional, and national burden of peripheral artery disease: a systematic analysis of prevalence, incidence, deaths, and DALYs with projections for the next 15 years.

SummaryBackgroundPeripheral artery disease is a growing public health problem. We aimed to estimate the global disease burden of peripheral artery disease, its risk factors, and temporospatial trends to inform policy and public measures.MethodsData on peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed.FindingsIn 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99·2–128·4), with a global prevalence of 1·52% (95% UI 1·33–1·72), of which 42·6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14·91% [12·41–17·87] in those aged 80–84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69·4% (64·2–74·3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles.InterpretationThe total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors.FundingBill & Melinda Gates Foundation.

Elderly individuals have a higher burden of peripheral arterial disease (PAD), but currently, there are no global reports on the disease burden of PAD in patients aged 60 and above. This study analyzed data on elderly patients with PAD from 1990 to 2021 using the Global Burden of Disease (GBD) database, focusing on prevalence, mortality, and Disability-Adjusted Life Years (DALYs). We summarized the trends in disease burden across 21 GBD regions and 204 countries and projected the global burden for the next 20 years. Between 1990 and 2021, the prevalence cases of elderly PAD individuals worldwide increased by 105%, from 42,618,313 to 87,523,486. However, the Age-standardized prevalence rate (ASPR) decreased to 8,220.2 cases per 100,000 population (95% UI: 6,717.3-9,995.7), with an Estimated Annual Percentage Change (EAPC) of -0.52 (95% CI: -0.56 to -0.48). Similar trends were observed in mortality and DALYs. In 2021, elderly individuals represented 77% of PAD prevalence cases and 94% of related mortality cases. The ASPR for women was 1.7 times higher than for men, yet women experienced a lower mortality rate and DALY rate, suggesting a heavier overall disease burden. The disease burden increased with the Socio-Demographic Index (SDI), with the fastest growth observed in Low and Low-middle SDI regions. Among the GBD regions, High-Income North America and Western Europe had the highest burden, with the United States bearing the heaviest burden of all 204 countries. High fasting blood glucose was the leading risk factor, contributing 36% of the PAD burden, with population growth being the primary driver of the rising burden. The disease burden is projected to intensify over the next two decades. From 1990 to 2021, the burden of PAD in the elderly has steadily increased, with projections for continued growth over the next two decades. Addressing diabetes and global population trends is essential for guiding effective public health strategies.

Introduction: Lower Extremity Peripheral Arterial Disease (PAD) ranks as the leading cause of incidence among all cardiovascular diseases (CVD) in the United States. Due to a significant lack of data on the overall burden of PAD, this pioneering study investigates the trends of PAD over the past three decades in the US, including the initial two years of the COVID-19 pandemic. Method: We estimated prevalence, incidence, deaths, and disability-adjusted life years (DALYs) due to PAD by age, sex, year and location across the US from 1990-2021 using the global burden of disease 2021 methodology. Results were presented in absolute counts and age-standardized rate (per 100,000 person-years) Results: From 1990 to 2021, the overall prevalence of PAD in the US rose from 8.6 million (95% uncertainty interval: 7.4-10 million) to 14.9 million (13.4-16.6 million). The total percentage change (TPC) in deaths increased by 93% (82%-102%), and DALYs by 87% (79%-96%). Pennsylvania recorded the highest increase in age-standardized incidence rate (ASIR) at 3%, followed by Delaware at 2%. Kansas saw the highest death rate (ASMR) increase at 20%, with Kentucky close behind at 19%. The 65-69 age group had the highest incidence count at 265,188, while the 85-89 age group saw the most deaths at 1,827, and the 70-74 age group recorded the most DALYs at 36,772 in 2021. Males experienced a higher increase in TPC across incidence, deaths, and DALYs compared to females, with figures at 85% vs 56%, 104% vs 85%, and 99% vs 76%, respectively. Conclusion: While deaths due to Peripheral Arterial Disease (PAD) constituted only 1.22% of all cardiovascular-related fatalities in the US in 2021, the growing burden of the disease highlights a critical area for public health focus. Although mortality rates remain relatively low, the high incidence compared to other cardiovascular diseases suggests the need for targeted prevention and early intervention strategies. Strengthening awareness, improving diagnostics, and enhancing treatment accessibility can help mitigate the rising impact of PAD and improve cardiovascular health outcomes nationwide.

The burden of peripheral artery disease (PAD) is increasing in low- and middle-income countries. Existing literature from sub-Saharan Africa is limited and lacks population-representative estimates. We estimated the burden and risk factor profile of PAD for a rural South African population. We used data from 1883 participants from a rural, low-incomecohort of South African adults aged 40 to 69 years with available ankle-brachial index measurements. We defined clinical PAD as ankle-brachial index ≤0.90 or >1.40, and borderline PAD as ankle-brachial index >0.90 and ≤1.00. We compared the distribution of sociodemographic variables, biomarkers, and comorbidities across PAD classifications. To identify associated factors, we calculated unadjusted and age-sex-adjusted prevalence ratios (PRs) with log-binomial models. Overall, 6.6% (95% CI, 5.6-7.7) of the sample met the diagnostic criteria for clinical PAD, while 44.7% (95% CI, 42.4-47.0) met the diagnostic criteria for borderline PAD. Age (PR: 1.9 [95% CI, 1.2-3.1] for ages 50-59 years compared with 40-49 years; PR: 2.5 [95% CI, 1.5-4.0] for ages 60-69 years compared with 40-49 years); diagnosed hypertension (PR: 1.53 [95% CI, 1.08-2.17]); and C-reactive protein (PR: 1.08 [95% CI, 1.03-1.12]) were associated with increased prevalence of clinical PAD. All other examined factors were not significantly associated with clinical PAD. We found high PAD prevalence for younger age groups compared with previous research and a lack of statistical evidence for the influence of traditional risk factors for this rural, low-income population. Future research should focus on identifying the underlying risk factors for PAD in this setting. South African policymakers and clinicians should consider expanded screening for early PAD detection in rural areas.

The global burden of peripheral artery disease

Vascular disease is the leading cause of death worldwide. Predicting the burden of vascular disease and identifying modifiable key risk factors are critical for developing effective prevention strategies. This study aimed to project the global and regional burden of peripheral artery disease (PAD) from 2021 to 2050, with a specific focus on the impact of modifiable key risk factors and the potential benefits of their management. Compared to the 2021 Global Burden of Disease Study (GBD 2021), the number of PAD cases worldwide is projected to increase by 220% by 2050, reaching a staggering 360 million (95% uncertainty interval, 270 to 450). Age-standardized mortality is expected to double, while disability-adjusted life years (DALYs) are forecasted to rise from 19.7 to 33.1 per 100,000. Among individuals aged ≥65 years, PAD prevalence is projected to surge to 21.7% in women and 14.8% in men. Moreover, over 50% of PAD cases are expected to occur in low- and middle-income countries (LMICs). Metabolic diseases are anticipated to be the primary drivers of the rising PAD burden, with diabetes playing a key role in increasing PAD prevalence and severity. By effectively managing metabolic risk factors, age-standardized prevalence could be reduced by 36%, mortality by 17%, and DALYs by 10%. As metabolic risks, particularly diabetes, continue to rise alongside population aging, the global PAD burden is expected to increase substantially, especially in LMICs. Importantly, proactive metabolic risk management strategies have the potential to markedly alleviate the burden of vascular disease and reduce the growing geographic health disparities.

Spinal cord injury leads to increased risk for cardiovascular disease and results in greater risk of death. Subclinical markers of atherosclerosis have been reported in carotid arteries of spinal cord-injured individuals (SCI), but the development of lower extremity peripheral arterial disease (PAD) has not been investigated in this population. The purpose of this study was to determine the effect of spinal cord injury on ankle-brachial index (ABI) and intima-media thickness (IMT) of upper-body and lower-extremity arteries. We hypothesized that the aforementioned measures of lower-extremity PAD would be worsened in SCI compared with controls and that regular participation in endurance exercise would improve these in both groups. To test these hypotheses, ABI and IMT were determined in 105 SCI and compared with 156 able-bodied controls with groups further subdivided into physically active and sedentary. ABIs were significantly lower in SCI versus controls (0.96 ± 0.12 vs. 1.06 ± 0.07, P < 0.001), indicating a greater burden of lower-extremity PAD. Upper-body IMTs were similar for brachial and carotid arteries in controls versus SCI. Lower extremity IMTs revealed similar thicknesses for both superficial femoral and popliteal arteries, but when normalized for artery diameter, individuals with SCI had greater IMT than controls in the superficial femoral (0.094 ± 0.03 vs. 0.073 ± 0.02 mm/mm lumen diameter, P < 0.01) and popliteal (0.117 ± 0.04 vs. 0.091 ± 0.02 mm/mm lumen diameter, P < 0.01) arteries. The ABI and normalized IMT of SCI compared with controls indicate that subclinical measures of lower-extremity PAD are worsened in individuals with SCI. These findings should prompt physicians to consider using the ABI as a screening method to detect lower-extremity PAD in SCI.

Global Burden of Lower Extremity Peripheral Arterial Disease Associated with High Fasting Plasma Glucose: An Analysis of the Global Burden of Disease study 2021.

ObjectivePeripheral arterial disease (PAD) is a common cardiovascular disease that it is an important reason for the decline of patients’ quality of life and the increase of family economic burden. To systematically evaluate the association between environmental lead exposure and peripheral arterial disease (PAD) and to characterize the global distribution of PAD disease burden, while exploring differences among regions with varying socioeconomic development.MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES), the Global Burden of Disease (GBD) database, and genome-wide association studies (GWAS), we employed multivariable logistic regression to examine the link between lead exposure and PAD. Mendelian randomization (MR) was used to infer causality, and we analyzed PAD disease burden trends across countries of differing income levels.ResultsThe burden on PAD patients worldwide shows a downward trend. In high SDI and high middle SDI countries, the burden of PAD gradually decreases, while in low middle SDI and low SDI countries, the burden of PAD gradually decreases. After adjusting for potential confounders, a significant dose-response relationship was observed between blood lead levels and PAD risk (OR = 1.04, 95% CI: 1.00-1.09). This association was more pronounced among males (OR = 1.07, 95% CI: 1.05–1.09), individuals with higher education (OR = 1.24, 95% CI: 1.16–1.32), and patients with hypertension (OR = 1.07, 95% CI: 1.05–1.09). MR analysis supported a causal link between lead exposure and PAD. Global trend analysis indicated that PAD burden is declining in high-income countries but rising in low-income regions, highlighting significant health inequities.ConclusionEnvironmental lead exposure is significantly associated with increased PAD risk, with notable differences in population susceptibility. These findings underscore the necessity of environmental exposure control and tailored prevention strategies to enhance cardiovascular health worldwide.

BackgroundData on burden of peripheral artery disease (PAD) and its attributable risk factors are valuable for policymaking. We aimed to estimate the burden and risk factors for PAD from 1990 to 2019.MethodsWe extracted the data on prevalence, incidence, death, years lived with disability (YLDs), and years of life lost (YLLs) from the Global Burden of Disease Study 2019 to measure PAD burden. Moreover, the attributable burden to PAD risk factors was also estimated.ResultsGlobally, in 2019, 113,443,017 people lived with PAD and 10,504,092 new cases occurred, resulting in 74,063 deaths, 500,893 YLDs, and 1,035,487 YLLs. The absolute numbers of PAD prevalent and incident cases significantly increased between 1990 and 2019, contrasting with the decline trends in age-standardized prevalence and incidence rates. However, no statistically significant changes were detected in the global age-standardized death or YLL rates. The burden of PAD and its temporal trends varied significantly by location, gender, age group, and social-demographic status. Among all potentially modifiable risk factors, age-standardized PAD deaths worldwide were primarily attributable to high fasting plasma glucose, followed by high systolic blood pressure, tobacco, kidney dysfunction, diet high in sodium, and lead exposure.ConclusionPAD remained a serious public health problem worldwide. More strategies aimed at implementing cost-effective interventions and addressing modifiable risk factors should be carried out, especially in regions with high or increasing burden.

Lower extremity peripheral artery disease (PAD) represents a critical global health challenge, with rising burden due to population aging and increasing prevalence of risk factors. While previous Global Burden of Disease (GBD) studies have documented PAD disparities across socioeconomic regions and countries, updated analyses incorporating recent epidemiological transitions and forecasting future trends remain limited. In this study, all overall age-standardized rates (ASRs) specific to the 40+age population. Using GBD 2021 data, we analyzed ASRs of PAD prevalence, incidence, mortality, and disability-adjusted life years (DALYs) across 204 countries from 1990-2021, stratified by Socio-demographic Index (SDI), sex, and age. Bayesian age-period-cohort modeling forecasted trends to 2050. Risk factor attributions were quantified using comparative risk assessment. Globally, the total number of all measures in PAD patients almost doubled from 1990 to 2021, all ASRs showed declines, with significant regional disparities evident across SDI regions. Higher SDI regions demonstrated substantial ASR reductions, while lower-SDI regions exhibited increasing trends. The ASRs for prevalence, mortality and DALY displayed progressive age-dependent increases, and the incidence ASR peaking in the 80-84 age group. Notable sex differences emerged as females had higher prevalence and incidence ASRs whereas males showed higher mortality and DALY ASRs. In low and low-middle SDI regions, ASRs for mortality and DALYs attributable to major risk factors (especially high fasting plasma glucose and kidney dysfunction) continued to rise. Although forecasts indicate further ASR declines through 2050, the overall disease burden is anticipated to remain substantial. The global burden of PAD shows a declining trend but remains at a high level. Significant disparities exist in disease burden and risk factors across different SDI regions. Age and sex also exert distinct influences on the distribution of PAD burden. Targeted prevention and treatment strategies are essential to further reduce this burden and improve patient outcomes.