Peripheral Artery Disease

Many research studies have investigated whether or not hemorheological abnormalities are present in peripheral artery disease (PAD) patients. In an early prospective study of 62 patients with intermittent claudication followed for up to three years, Dormandy et al., observed a significant correlation between the progressive deterioration of peripheral circulatory disturbances and initial blood viscosity levels, as well as the plasma fibrinogen level and the susceptibility of red cell membrane lipids to autoxidation [1].

A second study by the same group reported that blood viscosity was higher in PAD patients with resting pain than in those with intermittent pain. Furthermore, blood viscosity was higher in patients with a claudication distance of less than 91 m than in those less severely disabled (i.e., >91 m) [2]. The researchers suggested that hyperviscosity may be the determining cause of claudication in some PAD patients.

A third study by Dormandy et al., compared 120 patients having intermittent claudication with normal age-matched controls and found blood viscosity was significantly higher among claudicants (p<0.001) with the greatest difference in blood viscosity observed at lowest shears [3]. At high shear rates, patients with blood viscosity above 4.5 cP had mean claudication distance of 126 meters compared to 289 meters for patients with high-shear viscosity below that threshold. Hyperviscosity among claudicants was not attributable to differences in hematocrit but rather to plasma fibrinogen. The researchers sought to examine if the principal cause of circulatory insufficiency in patients with symptoms of intermittent claudication was an abnormally high blood viscosity rather than narrowing of the arteries. They found that many patients with abnormally high blood viscosity have normal arteriograms despite severe symptoms of claudication and suggested the use of the term rheological claudication to describe approximately 25 % of moderate to severe claudicants with hyperviscosity of blood having significantly worse prognoses [3].

Separately, plasma viscosity was shown to be significantly elevated in individuals with intermittent claudication compared with healthy age-matched controls [4]. Plasma viscosity levels in Fontaine IIb and III stage PAD patients correlated with plasma fibrinogen concentrations. Furthermore, the blood filtration rate, a measure of erythrocyte deformability, varied with walking distance and inversely with the stage of disease. In the Edinburgh Artery Study, which followed a random sample of 1,581 men and women 55 to 74 years of age with symptomatic or asymptomatic PAD, blood viscosity (at high shear rate over 300 s-1, p<0.05) and fibrinogen (p<0.01) were independently associated with peripheral arterial narrowing [5]. A positive interaction was found between fibrinogen and smoking in the association with arterial narrowing, and plasma viscosity was also associated with claudication. The risk of claudication for patients in the upper quintile of plasma viscosity was 3.4 times greater than the risk for those in the lowest plasma viscosity quintile. The authors implicated blood rheologic factors in the pathogenesis of lower limb ischemia in the general population. The Edinburgh Artery Study also showed that plasma viscosity is a significant predictor for development of PAD over 17 years of follow-up in a population of subjects free from PAD at baseline [6]. Similarly, a study of 90 PAD patients and 180 controls showed a significant association between the highest tertiles of plasma viscosity and PAD [7]. After adjustment for traditional vascular disease risk factors, the highest tertiles of plasma viscosity remained significantly associated with PAD. The researchers suggested that an alteration of plasma viscosity may modulate predisposition to the disease.

  1. Dormandy J, Hoare E, Khattab A, Arrowsmith D, Dormandy T. Prognostic significance of rheological and biochemical findings in patients with intermittent claudication. Br Med J 1973; 4:581-3.
  2. Dormandy JA,Hoare E, Colley J,ArrowsmithDE, Dormandy TL. Clinical, haemodynamic, rheological, and biochemical findings in 126 patients with intermittent claudication. Br Med J 1973; 4:576-81.
  3. Dormandy JA, Hoare E, Postlethwaite J. Importance of blood viscosity. Rheological claudication. Proc R Soc Med 1974; 67:446-7.
  4. Angelkort B, Spurk P, Habbaba A, Mahder M. Blood flow properties and walking performance in chronic arterial occlusive disease. Angiology 1985; 36:285-92.
  5. Lowe GD, Fowkes FG, Dawes J, Donnan PT, Lennie SE, Housley E. Blood viscosity, fibrinogen, and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburgh Artery Study. Circulation 1993; 87:19150-20.
  6. Tzoulaki I, Murray GD, Lee AJ, Rumley A, Lowe GD, Fowkes FG. Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease: EdinburghArtery Study. Eur Heart J 2007; 28:354-62.
  7. Ricci I, Sofi F, Liotta AA, Fedi S, Macchi C, et al. Alterations of haemorheological parameters in patients with peripheral arterial disease. Clin Hemorheol Microcirc 2013; 55:271-6.