Peripheral Artery Disease (PAD) is a common circulatory condition where arteries, most often in the legs, become narrowed or blocked by plaque buildup (atherosclerosis). While PAD rarely causes sudden death, a diagnosis significantly increases the risk of fatal events over time. The condition indicates that atherosclerosis is widespread throughout the body, raising the probability of severe complications. Mortality associated with PAD is driven by two primary mechanisms: a direct, localized complication in the affected limb, and a systemic risk involving the heart and brain.
The Immediate Threat of Critical Limb Ischemia
Fatal outcomes can begin with the progression of PAD to its most severe form, Critical Limb Ischemia (CLI). CLI signifies a persistent, severe lack of blood flow to the limb, often resulting in pain at rest and the formation of non-healing wounds or ulcers. Without adequate oxygen and nutrients, the tissue dies, leading to gangrene, a direct limb-related complication that can become lethal.
Gangrene allows aggressive infection to enter the bloodstream. This localized infection rapidly escalates into sepsis, a life-threatening complication that damages the body’s organs. Sepsis can lead to septic shock and multi-organ failure, representing the most immediate cause of death for patients with advanced PAD. Approximately 25% of patients diagnosed with CLI die within one year.
Systemic Cardiovascular Mortality Risk
The far more common cause of death for individuals with PAD is associated cardiovascular disease, not the localized limb complication. PAD is a manifestation of systemic atherosclerosis, meaning plaque buildup in the leg arteries is also occurring throughout the entire body. This makes PAD a powerful warning sign that a patient’s coronary and cerebral arteries are at high risk of becoming dangerously narrowed.
The majority of deaths in PAD patients are caused by myocardial infarction (heart attack) or ischemic stroke. These events occur when plaque ruptures in the coronary or carotid arteries, leading to a blood clot that blocks blood flow to the heart muscle or the brain. Patients with PAD have a significantly elevated risk of death from these cardiovascular events compared to the general population. The risk of stroke or heart attack in a PAD patient is considered equivalent to that of a patient already diagnosed with coronary artery disease.
Within five years of a PAD diagnosis, nearly 50% of patients may die, with cardiovascular events being the principal cause. PAD is associated with a three- to six-fold increase in the risk of death from heart attack and cerebrovascular disease. Even in patients with severe CLI, the majority will ultimately die from a cardiac or cerebrovascular event.
Key Risk Factors Elevating Lethality
Certain co-morbidities and lifestyle choices accelerate the atherosclerotic process, significantly increasing the likelihood of fatal outcomes. Smoking is the single strongest risk factor, accelerating plaque buildup and severely damaging arterial walls. Continued tobacco use dramatically increases the risk of PAD progression to CLI and subsequent systemic complications.
Uncontrolled diabetes mellitus is another major contributor to PAD lethality. Diabetes damages small blood vessels and nerves, impairing the immune response and slowing wound healing, which accelerates progression to gangrene and sepsis. Patients with diabetes and PAD have the highest risk of death and major adverse events. Chronic kidney disease, hypertension, and high cholesterol are also strongly associated with higher PAD-related mortality, as they compound systemic arterial damage.
Management to Prevent Fatal Outcomes
Preventing mortality requires a dual-action strategy focused on limb preservation and comprehensive cardiovascular risk reduction. Aggressive medical management is paramount, including high-intensity statins to lower cholesterol and stabilize plaque, which reduces the risk of heart attack and stroke. Antiplatelet agents, such as low-dose aspirin or clopidogrel, are routinely prescribed to reduce the formation of blood clots. For patients not at high risk of bleeding, combination therapy using low-dose aspirin and the anticoagulant rivaroxaban can further reduce the risk of major adverse cardiovascular and limb-related events.
Lifestyle changes are equally important, with smoking cessation being the most impactful action a patient can take to prevent disease progression. Meticulous foot care is crucial for preventing CLI, involving daily checks for injuries and prompt treatment of wounds to avoid infection and sepsis. Structured exercise therapy is also a core component of care, improving blood flow and overall cardiovascular function.
When CLI develops, revascularization procedures, such as angioplasty or surgical bypass, are necessary to restore blood flow to the limb and prevent tissue death. This limb-saving intervention is often performed by a multispecialty care team to optimize outcomes and reduce the patient’s risk of amputation and subsequent sepsis.