230 Million People Have PAD — Here's What the Latest Science Reveals
A sweeping 2025 review reframes peripheral artery disease as a global crisis demanding urgent, multidisciplinary action.
Summary
Peripheral artery disease (PAD) affects roughly 230 million people worldwide and is driven by atherosclerosis, aging, smoking, diabetes, hypertension, and dyslipidemia. This 2025 Nature Reviews Disease Primers comprehensive review covers PAD's epidemiology, diagnosis, risk stratification, and management. Patients face elevated risks of major cardiovascular events, limb loss, and severely reduced walking capacity. Treatment guidelines emphasize antithrombotic, lipid-lowering, glucose-lowering, and antihypertensive therapies combined with structured exercise programs. Revascularization is reserved for limb-threatening ischemia or refractory functional impairment. The authors stress that a multidisciplinary vascular team is essential for individualized care and call for greater research focus on reducing health disparities and improving guideline-directed therapy implementation.
Detailed Summary
Peripheral artery disease (PAD) is one of the most prevalent yet underrecognized cardiovascular conditions globally, silently impairing quality of life and dramatically increasing the risk of heart attack, stroke, and limb amputation. Despite affecting an estimated 230 million people worldwide, PAD frequently goes undiagnosed until significant damage has occurred — making this 2025 comprehensive review in Nature Reviews Disease Primers especially timely.
The review systematically covers PAD's core pathophysiology: arterial blockage in the lower extremities caused primarily by atherosclerosis and thrombosis. Major risk factors include smoking, type 2 diabetes, hypertension, and dyslipidemia — all conditions increasingly prevalent in aging populations. The rising global burden of PAD is therefore expected to continue growing as demographics shift.
Diagnosis relies on clinical assessment, imaging, and risk stratification tools. The ankle-brachial index (ABI) remains a cornerstone screening measure. Once identified, patients should receive guideline-directed medical therapy (GDMT) encompassing antiplatelet or anticoagulant agents, statins, glucose-lowering drugs, and antihypertensives. Structured exercise therapy is highlighted as critical not only for improving walking performance but also for reducing cardiovascular and limb-related events.
For patients with limb-threatening ischemia — whether acute or chronic — or those who fail to improve with conservative management, revascularization procedures are recommended. The complexity of these decisions underscores the need for coordinated, multidisciplinary vascular care teams.
The authors identify significant gaps: persistent health disparities in PAD diagnosis and treatment, incomplete implementation of GDMT in real-world settings, and insufficient evidence on optimizing exercise regimens. Future research priorities include targeted strategies to close these gaps and improve patient quality of life. As a primer, this review provides clinicians and researchers a definitive updated framework for understanding and managing PAD.
Key Findings
- PAD affects approximately 230 million people globally, with prevalence rising due to aging and cardiovascular risk factors.
- Patients with PAD face significantly elevated risks of major cardiovascular events, limb loss, and impaired walking ability.
- Guideline-directed medical therapy — including antithrombotics, statins, and antihypertensives — is the cornerstone of PAD management.
- Structured exercise therapy improves both functional capacity and cardiovascular outcomes in PAD patients.
- Revascularization is indicated for limb-threatening ischemia or severe functional impairment unresponsive to conservative care.
Methodology
This is a comprehensive narrative review published as part of the Nature Reviews Disease Primers series, synthesizing current epidemiological, pathophysiological, diagnostic, and therapeutic evidence on PAD. It was authored by a multinational panel of vascular medicine experts from Europe and North America. As a primer, it does not report original experimental data but distills the existing evidence base into clinical and research guidance.
Study Limitations
As a review based only on the abstract, specific data points, meta-analytic findings, or novel recommendations beyond current guidelines cannot be confirmed. The review is narrative rather than systematic or meta-analytic, which may introduce selection bias in evidence synthesis. Conflict of interest disclosures from multiple authors with pharmaceutical ties warrant consideration when interpreting emphasis on pharmacological therapies.
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