Is there an association between Metabolic Syndrome and Peripheral Arterial Disease (PAD)?

From the Guidelines

There is a significant association between Metabolic Syndrome and Peripheral Arterial Disease (PAD), with shared risk factors and underlying mechanisms contributing to the development and progression of both conditions. Metabolic Syndrome, characterized by a cluster of conditions including abdominal obesity, high blood pressure, high blood sugar, and abnormal cholesterol levels, increases the risk of developing PAD. Individuals with Metabolic Syndrome are at higher risk of developing PAD due to shared risk factors such as insulin resistance, inflammation, dyslipidemia, hypertension, and obesity 1.

The link between Metabolic Syndrome and PAD is primarily due to:

• Insulin resistance: A key feature of Metabolic Syndrome that contributes to atherosclerosis and arterial damage
• Inflammation: Both conditions involve chronic low-grade inflammation, which promotes arterial damage and plaque formation
• Dyslipidemia: Abnormal lipid profiles common in Metabolic Syndrome accelerate atherosclerosis in peripheral arteries
• Hypertension: High blood pressure damages arterial walls, increasing the risk of PAD
• Obesity: Excess body fat, especially abdominal fat, promotes inflammation and insulin resistance

To reduce the risk of PAD in individuals with Metabolic Syndrome, management should focus on:

• Weight loss through diet and exercise
• Blood pressure control (target <130/80 mmHg)
• Lipid management (target LDL <100 mg/dL, or <70 mg/dL for very high-risk patients)
• Glycemic control (target HbA1c <7%)
• Smoking cessation Medications may include statins for cholesterol management, antihypertensives like ACE inhibitors or ARBs, and metformin for blood sugar control. Aspirin (75-100 mg daily) may be recommended for cardiovascular protection in high-risk individuals, as suggested by the 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease 1.

Regular screening for PAD in patients with Metabolic Syndrome is crucial, typically involving ankle-brachial index (ABI) measurements. Early detection and management of both conditions can significantly reduce the risk of cardiovascular events and improve overall health outcomes, with a potential average of 6.3 MACE-free years gained in a population of patients observed longitudinally for medical management of PAD 1.

From the Research

Association Between Metabolic Syndrome and Peripheral Arterial Disease (PAD)

• Metabolic syndrome has a strong association with both forms of cardiovascular disease, including coronary artery disease and peripheral vascular disease 2.
• The presence of metabolic syndrome is a predictor of poor prognosis in elderly patients with atherosclerotic cardiovascular disease, and its components have been linked to an increased risk of peripheral arterial disease (PAD) 3, 4.
• Studies have shown that metabolic syndrome is present in over 50% of PAD patients, and its presence is associated with a higher risk of cardiovascular events, including myocardial infarction and stroke 4, 5.

Mechanisms Underlying the Association

• Endothelial dysfunction has been identified as a potential mediator of the association between metabolic syndrome and PAD, but not coronary artery disease 5.
• Low-grade inflammation has also been implicated in the association between metabolic syndrome and both CAD and PAD 5.
• The pathophysiologies of coronary and peripheral artery disease are distinct, with different underlying mechanisms contributing to the development of each condition 5.

Epidemiological Evidence

• A systematic review and meta-analysis found inconsistent evidence on the association between metabolic syndrome and the risk of developing PAD, but suggested that testing for PAD may be recommended in patients with metabolic syndrome due to the high prevalence of risk factors 6.
• Cohort studies have reported varying results, with some finding an association between metabolic syndrome and PAD, while others have found no significant relationship 6.
• The heterogeneity in diagnostic criteria used for metabolic syndrome and PAD may contribute to the inconsistent findings across studies 6.