A comprehensive epidemiological analysis utilizing data from the Global Burden of Disease Study 2021 has revealed that lower extremity peripheral artery disease, commonly referred to as LEPAD, experienced substantial increases across the Eastern Mediterranean Region between 1990 and 2021. According to the research findings, the region recorded an age-standardized incidence of 94.7 per 100,000 individuals, with a 95% uncertainty interval ranging from 81.4 to 109.9, and an age-standardized prevalence of 988.4 per 100,000 in 2021. At the same time, the age-standardized disability-adjusted life year rate reached 7.5 per 100,000, while the age-standardized mortality rate stood at 0.2 per 100,000. Over the three-decade evaluation window, age-standardized incidence rose by 17.1%, prevalence expanded by 18.7%, disability-adjusted life years increased by 22.0%, and deaths surged by 81.0%. Absolute measures of disease burden expanded substantially as well, with total regional prevalent cases growing from 1.37 million in 1990 to 4.15 million cases by 2021, and annual fatalities increasing from 121.1 to 523.8 deaths.

Lower extremity peripheral artery disease is characterized pathologically as a progressive atherosclerotic condition in which plaques accumulate in systemic arterial walls, resulting in the progressive narrowing or complete occlusion of peripheral blood flow. As documented by the study authors, the clinical manifestations of this disease exhibit a wide spectrum of severity, varying from completely asymptomatic arterial obstruction to intermittent claudication with severe leg pain during exertion, and progressing toward limb-threatening ischemia that may necessitate urgent surgical revascularization or limb amputation. While global estimates document that peripheral vascular conditions affect roughly 230 million individuals worldwide, previous international evaluations established that age-standardized prevalence, incidence, and death rates had remained relatively stable or experienced slight declines globally between 1990 and 2019. In sharp contrast, the Eastern Mediterranean Region displayed consistent upward trajectories across all age-standardized metrics over the same period, establishing an urgent public health challenge that diverges from broader worldwide trends.

To rigorously evaluate the regional epidemiology of the condition, investigators extracted and analyzed data encompassing 204 countries and territories documented within the Global Burden of Disease 2021 infrastructure. Cases of lower extremity peripheral artery disease were systematically identified using an objective diagnostic threshold defined as an ankle-brachial index less than or equal to 0.9, alongside standardized diagnostic coding mapped to International Classification of Diseases codes from both the ninth and tenth revisions. Primary data inputs synthesized across the regional modeling pipeline incorporated population-based health surveys, household interview instruments, observational clinical studies, vital registration documentation, and published scientific literature. The analytical strategy integrated Cause of Death Ensemble Modeling, which applies Bayesian hierarchical frameworks and linear mixed-effects configurations to capture cause-specific mortality, as well as spatiotemporal Gaussian process regression models and Disease Modeling Meta-Regression version 2.1 to synthesize disparate datasets, address missing information, and generate robust estimates with corresponding 95% uncertainty intervals based on 500 posterior sampling draws.

At the national level, the investigation uncovered notable geographical variation in epidemiological metrics across the countries comprising the Eastern Mediterranean Region. In 2021, the highest age-standardized incidence rates per 100,000 population were observed in Lebanon at 118.7, Iraq at 113.3, and Bahrain at 108.4, whereas the lowest incidence rates were documented in Somalia at 77.4, Djibouti at 77.5, and Pakistan at 89.1. Similarly, age-standardized prevalence reached its regional peaks in Lebanon at 1293.5, Bahrain at 1231.3, and Iraq at 1225.6 per 100,000 people, while Somalia at 710.5, Djibouti at 778.9, and Afghanistan at 892.4 reported the lowest comparative prevalence values. Despite recording lower prevalence, Djibouti reported the highest regional age-standardized death rate at 1.7 per 100,000, followed by Bahrain at 1.4 and the United Arab Emirates at 1.3. Djibouti also led the region in age-standardized disability-adjusted life years at 32.5 per 100,000, followed closely by the United Arab Emirates at 27.1 and Bahrain at 26.4.

Stratified analyses highlighted pronounced demographic disparities across different sex and age categories throughout the Eastern Mediterranean demographic. In 2021, females demonstrated higher overall age-standardized incidence rates than males, recording 112.9 per 100,000 compared to 77.7 per 100,000 among males. Furthermore, over the full thirty-one-year evaluation window, females experienced a dramatic 110.5% surge in age-standardized mortality rates, whereas male mortality rates rose by 65.0%. Across both sexes, the disease burden correlated strongly with advancing age, reaching its maximum values within the oldest population cohorts. The highest incidence rate occurred among individuals aged 95 years and older at 753.8 per 100,000, contrasted with 61.2 per 100,000 among individuals aged 40 to 44 years. In this oldest age bracket of 95 years and above, women exhibited greater vulnerability than men, with female incidence recorded at 758.1 versus 750.4 for men, and female prevalence reaching 16,721.5 per 100,000 compared to 12,375.7 per 100,000 among elderly men.

When examining burden across socioeconomic development tiers using the Socio-demographic Index, which integrates per capita income, average educational attainment, and total fertility rates, distinct relationships emerged. Countries situated in higher Socio-demographic Index quintiles generally exhibited elevated prevalence rates compared to nations in lower quintiles. For example, high-index countries such as the United Arab Emirates and Kuwait documented age-standardized prevalence rates of 1042.7 and 1117.7 per 100,000 individuals, respectively, alongside incidence rates of 93.3 and 98.6. In contrast, lower-index nations including Afghanistan and Yemen reported comparatively lower prevalence rates of 892.4 and 934.4 per 100,000. The study authors explored two distinct mechanisms for this gradient: higher true disease incidence driven by rapid urbanization, sedentary behavior, and metabolic syndrome clustering, versus enhanced diagnostic detection intensity in wealthier states where clinical infrastructure, routine ankle-brachial index screening, electronic health records, and vascular diagnostic laboratories facilitate more comprehensive case ascertainment and clinical coding compared to resource-constrained systems.

The study also comprehensively quantified the specific modifiable risk factors contributing to lower extremity peripheral artery disease burden, showing that age-standardized disability-adjusted life years attributable to all risk factors climbed by 40.7% from 1990 to 2021, reaching 5.7 per 100,000. Among all evaluated risks, high fasting plasma glucose emerged as the leading contributor across the region, accounting for 12,838.9 disability-adjusted life years and 237.7 associated deaths in 2021. Kidney dysfunction represented the second greatest contributor, accounting for 7,777.3 disability-adjusted life years and 152.1 deaths, while tobacco smoking ranked third, responsible for 7,317.4 disability-adjusted life years and 140.5 deaths. While men carried a higher overall risk-attributable burden for smoking-related disability, women experienced greater burdens attributable to high fasting plasma glucose and renal dysfunction, reflecting how metabolic impairment and microvascular damage driven by chronic hyperglycemia and renal disease disproportionately affect female cardiovascular outcomes across the region.

The investigation also evaluated patterns during the initial years of the coronavirus disease pandemic between 2019 and 2021 to determine potential acute disruptions in chronic disease epidemiology. Within this timeframe, statistically significant increases were detected solely in unadjusted all-age incident cases, which grew by 7.4%, and prevalent cases, which rose by 7.2%. In contrast, age-standardized incidence and prevalence rates showed no statistically significant alterations during the pandemic period. The researchers contextualized these observations by noting that widespread healthcare service reallocations, restrictions on elective hospital admissions, and disruptions to outpatient surveillance during emergency periods likely modified diagnostic testing intensity and case ascertainment patterns rather than reflecting fundamental biological shifts in underlying disease incidence, although diagnostic delays may have increased the severity of acute presentations among patients seeking delayed vascular interventions.

To interpret the epidemiological findings within their real-world setting, the authors outlined key structural, geopolitical, and environmental factors that likely contribute to the unique regional trajectory of lower extremity arterial disease. Protracted armed conflicts and sociopolitical instability across multiple Eastern Mediterranean territories have systematically fragmented domestic healthcare delivery, interrupted medication supplies, and displaced large populations, creating severe barriers to continuous management of chronic cardiovascular conditions. These challenges are further compounded by dual-tier healthcare financing systems where out-of-pocket medical expenses disproportionately burden impoverished and rural households. Coupled with high population-level rates of obesity, diabetes mellitus, and tobacco use among rapidly aging demographics, these interwoven systemic stressors provide an explanatory framework for elevated vascular morbidity and mortality across the territory.

The investigators explicitly highlighted several methodological limitations that warrant caution when interpreting regional estimates. Incomplete vital registration coverage, variable diagnostic capabilities, and reliance on self-reported clinical symptoms in lower-income settings introduce potential reporting biases and underestimation of disease burden. Furthermore, inconsistent measurement protocols and variable diagnostic cut-offs for the ankle-brachial index across disparate healthcare facilities complicate cross-country comparability. To mitigate these diagnostic discrepancies in routine clinical practice and strengthen regional surveillance infrastructure, the authors proposed implementing standardized, low-cost ankle-brachial index measurement protocols within primary care networks. Such programs would combine standardized Doppler or oscillometric blood pressure cuffs and bilateral arm and ankle assessments with train-the-trainer clinical modules, integrated electronic health record reporting templates, and systematic clinical audit feedback cycles to ensure consistent case detection and improve epidemiological surveillance across diverse healthcare settings.

Subject of Research: Epidemiology and attributable risk factors of lower extremity peripheral artery disease in the Eastern Mediterranean Region

Article Title: The Growing Burden of Lower Extremity Peripheral Artery Disease and its Attributable Risk Factors in the Eastern Mediterranean Region from 1990 to 2021

Article References: Bastan, M.-M., Shahrokhi Nejad, S., Poormehr, P., & Nejadghaderi, S. A. (2026). The Growing Burden of Lower Extremity Peripheral Artery Disease and its Attributable Risk Factors in the Eastern Mediterranean Region from 1990 to 2021. Artery Research, 32(1), Article 6. https://doi.org/10.1007/s44200-026-00106-1

Image Credits: AI Generated

DOI: 10.1007/s44200-026-00106-1

Keywords: peripheral artery disease, Eastern Mediterranean Region, Global Burden of Disease, vascular disease, atherosclerosis, epidemiology, high fasting plasma glucose, cardiovascular risk, Growing, Burden, Lower, Extremity