Atherosclerosis is not merely a degenerative disease of the circulation and vasculature. It receives profound contributions from various inflammatory mechanisms. Early work looking at the white cell count (WCC) as a predictor of vascular events confirmed that WCCs in the high normal range confer a significant risk of future myocardial infarction and stroke. Our own work in critical limb ischaemia also showed the WCC to predict those destined for future amputation. Evidence suggests that for each 1.0 X 109 l-1 cell difference there was an increase in cardiovascular disease risk of 32 % for men and 17 % for women.
The white blood cell may contribute to vascular disease in the patient with claudication through both physical and chemical means. White blood cell (WBC) adhesion and aggregation are increased in these patients and predict those patients with claudication who will subsequently develop critical limb ischaemia (CLI).
WBCs release many cytokines and other inflammatory mediators such as free radicals. These latter are profoundly active chemicals which can be both directly and indirectly prothrombotic and atherogenic. Of particular relevance to the patient with intermittent claudication is reperfusion injury. The generation of superoxide during reperfusion may cause significant vascular injury. Oxidative stress is clearly linked to endothelial cell dysfunction in the patient with intermittent claudication and once again appears to be predictive within the patient group in terms of those patients with intermittent claudication who will subsequently progress to develop CLI.
Thus it has been recognised for some years that the WBC and inflammatory processes are important mediators of the Atherosclerotic process. The oxidative stress generated from the WBC, along with its increased aggregation and adhesion, have the potential to be deleterious in patients with intermittent claudication. Not only is there evidence of increased inflammatory markers in such patients but the higher the levels the more likely the patient is to proceed to critical limb ischaemia. Inflammation appears to be important in atherogenesis in the patient with intermittent claudication. We must focus future studies and evolving therapies in this area.