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Therapies for improving walking distance in intermittent claudication.

Anne-Mette Hedeager Momsen


This thesis originates from the Surgical Research Unit, Regional Hospital Herning and Department of Vascular surgery, Regional Hospital Viborg. The thesis is based on an overview and two papers.

Background for the thesis
Atherosclerosis-related complications account for the largest group of deaths in the Western world, and atherosclerosis in the arteries of the leg, Peripheral Arterial Disease (PAD) is prevalent in 2/3 >55 years, especially in smokers. PAD (defined by ankle brachial pressure index <0.9) can be asymptomatic, whilst the most common symptom is intermittent claudicatio (IC): exertional calf pain caused by walking that resolves with rest. PAD increases cardiovascular morbidity and death 2-6 times due to the affection of coronary arteries, and patients’ exercise performance is low and detrimental to their quality of life (QoL). Therapy and focus at risk factors is essential, and the options are pharmacological, conservative treatment (exercise and change of life style) or vascular surgery. Earlier studies of pharmacological treatment has shown limited effect, whilst exercise is documented to be effective and has shown an increase in maximal walking distance up to 150% due to development of collaterals. Caffeine has several physiological effects which could increase walking performance: CNS stimulation which reduce rate of perceived exertion, vasodilatation of skeletal muscles possibly effect on muscle endurance and reduced fatigue. To our knowledge there are no studies on caffeine in IC, whereas an increased endurance and decreased experience of exhaustion is shown in healthy elderly.

The first study is a review and meta-analysis of pharmacological management of IC to show effect estimates of improvements of walking distances. Second we carried out two crossover intervention studies to investigate the effect of caffeine on physical capacity in patients with moderate IC. The design of the project was two randomized, double-blind, placebo-controlled crossover studies. In all 88 participated of whom 41 were revascularized after the first crossover study. Participants were tested in two rounds with one week interval between two tests, and the intervention was intake of caffeine (6 mg/kg) or placebo.

Summary of the results
The review shows that pharmacological management yet remains to be defined precisely. Statins showed the highest benefit and because of their dual benefits their importance for patients with IC is re-enforced. Both crossover studies showed that caffeine has potential benefits to improve physical performance: increased walking distance (pain-free and maximal), strength and muscular endurance were significantly improved.

Neither revascularization nor statins cure IC, so exercise is necessary and as increased walking distance is associated with QoL, caffeine can be a mean to improve their training