Peripheral Artery Disease (PAD) is a common circulatory disorder where narrowed arteries reduce blood flow, typically to the lower extremities. This condition is caused by atherosclerosis, a process where fatty plaque builds up inside the artery walls. Understanding the causes of PAD is important because it is a multifactorial disease, meaning that biological inheritance and acquired lifestyle factors work together to determine an individual’s overall risk. PAD is not purely hereditary, but genetic predisposition plays a significant role in increasing susceptibility to the condition.
Understanding Peripheral Artery Disease
Peripheral Artery Disease is primarily a manifestation of systemic atherosclerosis in the non-coronary arteries, most often those supplying the legs and feet. This buildup of plaque within the artery walls narrows the vessel lumen, which restricts the amount of oxygen-rich blood that can reach the muscles and tissues in the limbs. The resulting lack of sufficient blood flow, or ischemia, is what causes the symptoms of the condition.
The most recognizable symptom of PAD is a painful muscle ache or cramp in the calves, thighs, or buttocks that occurs during physical activity like walking and consistently resolves with a few minutes of rest; this is known as intermittent claudication. Many individuals experience no symptoms at all, or only atypical complaints such as leg fatigue, weakness, or aching. In more severe disease stages, reduced blood flow can lead to non-healing wounds, ulcers, loss of hair on the legs, and a persistent, burning pain in the feet even at rest.
The Influence of Family History and Genetics
While PAD is not inherited in a simple Mendelian pattern, there is a strong heritable component. Having a first-degree relative, such as a parent or sibling, with PAD or other atherosclerotic cardiovascular diseases like heart disease or stroke increases a person’s chances of developing the condition. Studies examining twins and families have suggested that genetic effects may account for a significant portion of the variability in PAD risk.
The genetic predisposition to PAD is polygenic, meaning that multiple genes contribute small effects that accumulate to increase overall susceptibility. These genetic variants influence several biological pathways involved in the development of atherosclerosis. For instance, certain genes affect lipid metabolism, altering how the body processes cholesterol and other fats that form the arterial plaque. Other implicated genes regulate chronic inflammation, which is a key driver in the progression of artery wall damage.
Genetic variants also exist that impact vascular function and the risk of thrombosis, or blood clot formation, which can acutely block a narrowed artery. An example is the Factor V Leiden mutation, which increases the tendency for blood clotting and has been linked to an elevated risk of PAD. Additionally, some individuals inherit a tendency for common risk factors like high blood pressure or diabetes, which indirectly raises their PAD risk. Research continues to identify specific locations on chromosomes, such as the 9p21 locus, consistently associated with a higher risk for multiple forms of atherosclerotic vascular disease, including PAD.
Major Non-Hereditary Risk Factors
Acquired health conditions and lifestyle choices account for a substantial portion of the overall risk, independent of genetic factors. Smoking is considered the single most significant non-hereditary risk factor for PAD, with some systematic reviews suggesting it is responsible for up to half of all cases. The chemicals in tobacco smoke directly damage the lining of the blood vessels, accelerating the process of plaque buildup and reducing blood flow.
Type 2 diabetes is another powerful acquired risk factor, as consistently high blood sugar levels damage the blood vessels and nerves in the extremities. People with diabetes are at a significantly increased risk of developing PAD and experiencing more severe complications. Similarly, uncontrolled hypertension, or high blood pressure, puts constant strain on the artery walls, promoting injury and the subsequent deposit of atherosclerotic plaque.
Dyslipidemia, characterized by unhealthy levels of cholesterol and triglycerides, contributes directly to the formation of plaque inside the arteries, restricting circulation. Other factors that compound risk include increasing age, physical inactivity, and obesity, which is itself linked to many of the other primary risk factors.
Screening and Prevention Strategies
Understanding the interplay between genetic predisposition and acquired risk factors provides a clear path for prevention and management. For all individuals, and especially those with a family history, primary prevention focuses on modifying the risk factors that are within one’s control. This includes complete cessation of smoking, which is the most impactful step a person can take to lower their risk.
Managing co-existing medical conditions is a form of secondary prevention that involves using guideline-directed medical therapy. This often includes medications to control blood pressure, reduce unhealthy cholesterol levels, and manage blood glucose in people with diabetes. Regular physical activity, such as a structured walking program, is also a highly effective non-pharmacological treatment that can improve walking distance and overall function in those with PAD.
Screening for PAD is performed using the Ankle-Brachial Index (ABI), a simple, non-invasive test that compares the blood pressure measured at the ankle to the pressure measured at the arm. An ABI value below 0.90 is used to define the presence of PAD. Screening is recommended for individuals over the age of 65, or for those over 50 who have a history of smoking or diabetes, as early detection allows for risk factor modification before symptoms become severe.