Epidemiological aspects of peripheral arterial disease

Peripheral arterial disease (PAD) is defined as atherosclerosis in the arteries distal to the aortic bifurcation, with or without symptoms in the legs. It is diagnosed by ankle brachial pressure index (ABI) measurements and symptoms, and a confirmed diagnosis is associated with an increased cardiovascular (CV) mortality reaching the same levels as in patients with symptomatic coronary disease. The overall aim of this study was to describe PAD epidemiology and its consequences from a societal perspective with special focus on sex differences.

Eight-thousand subjects, aged 60-90 years, were selected at random and invited to participate in a survey performed in 2004. Of those 63% participated and had their ABI measured and they also completed questionnaires covering medical history, current medication, PAD symptoms and walking ability. A subset of subjects with intermittent claudication (IC) at inclusion was followed up 2008 with the same procedures. A walking test and duplex scanning of leg arteries, echocardiography and an interview were added to gain further insight of disease specifics. Survey data and published studies were finally used to estimate cost-effectiveness of CV risk prevention with drugs in subclinical PAD.

PAD prevalence was 18% and varied with stage of disease, geographic region and patients' sex. Women dominated when diagnosis was based on ABI only, but for diagnosis of IC, it was more frequent among men. The prevalence of critical limb ischemia was around one percent. Risk factor profiles differed among PAD stages and sexes. Men, for example, reported having diabetes mellitus and stroke more often than women, who in turn reported hypertension more frequently. Smoking for 10 years was associated with having PAD in women, but for men this relationship occurred first after 30 years of smoking. Women also reported use of less CV preventive medication. Women with IC had a lower walking speed and more joint problems than men, and in the follow up cohort most IC disease specifics were similar. Another difference was that women reported atypical symptoms more often than men. The cost-effectiveness modelling revealed that of the evaluated drugs, ACE-inhibitors (ACE-i), statins, aspirin and clopidogrel, there were differences. ACE-i displayed the largest reduction of CV events leading to the highest mean gain in quality-adjusted life-years compared with the other treatments. It was far below willingness to pay thresholds. Aspirin treatment did not appear to be cost-effective due to low rate of event reduction.

In conclusion, the studies performed in this thesis points out that PAD is common among elderly, and especially so in women. Risk factors occurring simultaneously with PAD are the known ones and many subjects with this disease have only PAD and do not report smoking habits. A majority is not medicating to reduce their high CV disease risk. Diagnosis of IC is a particular problem for epidemiological studies, and the prevalence of this PAD stage may therefore be underestimated in women. ACE-i may be the drug of choice for early prevention of CV risk in PAD and the benefits of aspirin may be overrated.

List of scientific papers

I. Sigvant B, Wiberg-Hedman K, Bergqvist D, Rolandsson O, Andersson B, Persson E, Wahlberg E (2007). A population-based study of peripheral arterial disease prevalence with special focus on critical limb ischemia and sex differences. J Vasc Surg. 45(6): 1185-91
https://pubmed.ncbi.nlm.nih.gov/17543683

II. Sigvant B, Wiberg-Hedman K, Bergqvist D, Rolandsson O, Wahlberg E (2009). Risk factor profiles and use of cardiovascular drug prevention in women and men with peripheral arterial disease. Eur J Cardiovasc Prev Rehabil. 16(1): 39-46
https://pubmed.ncbi.nlm.nih.gov/19237996

III. Sigvant B, Lundin F, Nilsson B, Bergqvist D, Wahlberg E (2009). Intermittent claudication is the same disease in women and men but differs in presentation. [Submitted]

IV. Sigvant B, Henriksson M, Lundin F, Wahlberg E (2009). Asymptomatic peripheral arterial disease: Is pharmacological prevention of cardiovascular risk cost-effective? [Submitted]