The most common clinical presentation of lower extremity arterial disease is intermittent claudication. Current understanding of the pathophysiology of intermittent claudication, as well as its treatment options are limited. The progression of the disease may lead to lower limb amputation, which is devastating for patients' quality of life and is a huge socio-economic burden to society.

Current study allows to determine the acute local metabolomic alterations in the ischaemic limb of the patient with intermittent claudication, and investigate the associations between the metabolomic alterations and the patient's maximal walking distance. This provides potentially valuable insight into the pathophysiology of this disease, and helps lay the groundwork for identifying potential novel targets for instituting more effective therapies for this high-risk population.

Inclusion Criteria:

• LEAD group: Patients with diagnosis of lower extremity arterial disease (Fontaine IIa).
• Control group: Healthy volunteers with no leg symptoms and an ankle-brachial index (ABI) of 1.0-1.4.

Exclusion Criteria:

• Fontaine stages I or IIb-IV
• Exacerbation of limb ischaemia within the preceding 2 weeks;
• strong rest pain of any cause;
• age <18 or >80 years;
• fasting < 6 hours;
• time since last use of tobacco products < 6 hours;
• body mass index ≥ 35 kg/m2
• poor sonographic visibility of femoral artery;
• angina;
• cardiac arrhythmia at the time of presentation;
• presence of cardiac pacemaker;
• myocardial infarction within the preceding 3 months;
• stroke within the preceding 6 months;
• ongoing anticoagulant therapy;
• ongoing dual antiplatelet therapy;
• any revascularization within the preceding 3 month;
• marked heart failure (NYHA III-IV);
• blood pressure ≥ 180/110 mmHg;
• blood pressure <100/70 mmHg;
• clinically significant heart valve disease;
• acute infectious disease;
• active malignancy or chemotherapy or disease-free < 5 years;
• type I diabetes or insulin therapy;
• other clinically significant and untreated endocrine disorders;
• moderate to severe bronchial asthma (GINA 2016);
• severe chronic obstructive pulmonary disease (mMRC grade 3-4);
• acute (KDIGO 2012) or chronic renal disease (eGFR-EPI <30mL/min/1.73 m2);
• acute or chronic liver disease;
• anemia (<110 g/L);
• neuroinflammatory or neurodegenerative disease;
• active rheumatism;
• other diseases and factors that markedly hinder the subject's ability to walk during the treadmill exercise.
• For control group exclusively: history of lower extremity arterial disease / ABI <1.0 or >1.4.

Patients with mild intermittent claudication (Fontaine IIa).