Vascular Disease Management

Abstract

Peripheral arterial disease (PAD) represents a continuum of arterial obstructive syndromes that for the lower extremity ranges from the asymptomatic to limb loss. The overall prevalence of PAD has been estimated to be as high as 20% of the general population. However, the overall prevalence of critical limb ischemia (CLI) is sparse in the general population, whereas the progression of arterial obstructive disease to CLI is highly variable in the published literature. CLI represents the ultimate progression of arterial obstructive disease that may culminate in limb loss. In this manuscript we discuss the prevalence of CLI in the general population and further evaluate the likelihood of progression to a state of CLI from non-critical disease states in the lower extremities.

VASCULAR DISEASE MANAGEMENT 2010;7:E182–E184

Introduction

Peripheral arterial disease (PAD) represents a continuum of disease entities that range from asymptomatic PAD, stable symptomatic intermittent claudication, critical limb ischemia (CLI), acute limb ischemia and amputation. CLI is defined as PAD causing resting lower-extremity pain or having threatened or frank tissue loss,1,2 and is classified as Rutherford-Becker Class 4–6 or Fontaine Class III and IV.2 CLI is a disabling disease and represents the end of the spectrum of PAD prior to tissue and limb loss. Other definitions for CLI have been suggested to include absolute pressures of ankle pressure < 50–70 mmHg, or toe pressure < 30–50 mmHg, or reduced TCPO2 < 30–50 mmHg.¹⁰ Here we review the epidemiologic and clinical syndrome of CLI and its progression from non-limb-threatening PAD.

Prevalence of CLI

The prevalence of CLI in the general population is scarce and difficult to assess, while the incidence of progression of PAD to CLI is widely variable in the published literature. The largest published population study, known as the HUNT 2 study, involved a questionnaire completed by 20,291 Norwegian men and women (9,640 men and 10,651 women) in Nord-Trondelag County between 1995 and 1997 and included all residents between ages 20–69 years.⁸ CLI was defined as a toe, foot or ankle ulcer that failed to heal or a persistent pain in the forefoot in the supine position that improves with standing. The prevalence of CLI in this population was 0.24% (0.26% for men and 0.24% for women). The age-adjusted prevalence of CLI increased with age (0.14% in those aged 40–49 years, 0.26% in those aged 50–59 years, and 0.39% for those aged 60–69 years). Smoking conferred a 2.3 times increased risk of CLI compared to subjects who never smoked, while diabetes mellitus conferred a 4.4 times increased risk of developing CLI compared to the general population. Subjects with older age, angina pectoris, elevated total cholesterol, elevated serum triglyceride and higher body mass index were independently associated with an increased risk of developing CLI compared with the general population. The prevalence of CLI was estimated to be 2,500 per million inhabitants. This prevalence, however, may be higher in the elderly population (age > 70 years). The prevalence of CLI in this population might have been confounded by including ulcers with non-atherosclerosis etiology such as venous ulcers which can cause pain and take a long time to heal.

In another European cross-sectional study, 5,080 Swedish subjects between the ages of 60 and 90 years were examined and completed questionnaires to determine the prevalence of PAD and CLI.⁹ PAD was defined as an ankle-brachial index (ABI) < 0.9, and an ankle pressure of < 70 mmHg (severe ischemia [SI]) was a surrogate for CLI. The prevalence of PAD was 18%, asymptomatic PAD was 11%, IC was 7% and CLI (SI) was 1.2%. If a resting lower-extremity pain and ankle pressure < 70 mmHg were used, then the prevalence of CLI was lower at 0.5%. Patients with ulcers or non-healing wounds were not included in the definition of CLI. It was interesting to note that women had a higher prevalence of ABI < 70 mmHg (SI) compared to men (1.5% vs. 0.8 %; p = 0.008). When resting pain was included, the prevalence was 0.6 in women versus 0.1 in men. While the prevalence of PAD continued to increase with increasing age, the prevalence of SI also increased with age and reached a peak in the 80–84 year-old age group, and declined in the 85–90 year-old age group. The prevalence was lowest, at 0.3%, in the 60–64 year-old age group, and increased steadily to reach a peak of 3.3% in the 80–84 year-old group. This trend, however, could be biased because the lowest rate of responders to the questionnaire was in the 88–90 year-old age group, leading to a lower rate of events in this group. The Swedish study showed regional variation, an increased female prevalence, and greater age in the prevalence of PAD and CLI. The authors estimated that in 1999, the number of American > 60 years of age with CLI (based on a definition of ankle pressure < 7 0mmHg) and a prevalence of CLI to be 1% per 500,000 individuals. However, this estimate may not be accurate, unless the U.S. mirrors the Swedish regional and population trends exactly.