Why are patients with known disease in one arterial bed at risk of atherothrombotic events in another?

Coronary artery disease (CAD), peripheral artery disease (PAD) and cerebrovascular/carotid artery disease share a common underlying pathophysiology, atherosclerosis,1,2 as well as overlapping risk factors (including dyslipidemia, hypertension, diabetes mellitus and smoking).3 Atherosclerotic plaques may therefore develop in multiple arterial beds at the same time, which means a diagnosis of disease in one bed may be a symptom of widespread atherosclerosis4 – in fact, patients with PAD are more likely to experience an ischaemic event in the heart or brain in the first five years after presentation than in the peripheral arteries.5 The likelihood of patients experiencing atherosclerotic disease in multiple arterial beds is highlighted by data from the prospective REACH registry, which enrolled approximately 68,000 patients with symptomatic cardiovascular (CV) disease or risk factors for atherothrombotic events.6 In this population, approximately 25% of patients with CAD and 62% of patients with PAD had documented disease in at least one additional bed.4 This is clinically significant because polyvascular disease (symptomatic disease affecting two or more arterial beds) is associated with a particularly high risk of major CV events, and the prognosis worsens as the number of affected arterial beds increases.4,7,8 In REACH, the risk of major adverse CV events in patients with polyvascular disease was almost double that observed in those with disease in a single arterial bed at 1 year and 3 years follow-up.4,7 Similar findings were also reported in the CRUSADE registry, where all-cause mortality rates at 3 years increased from 33% in patients with CAD alone, to 59% in patients with disease in all three arterial beds.8

polyvascular disease in the reach registry
Patients with polyvascular disease in the REACH registry.4
A large proportion of patients in the REACH registry had polyvascular disease.

While the degree of overlap between CAD, PAD and cerebrovascular disease reported in registries such as REACH is striking, it is likely to underestimate the true incidence of polyvascular disease because these diseases are frequently undiagnosed. In the IPSILON study, general practitioners used the ankle–brachial index (ABI) to assess peripheral stenosis in 1340 patients with CAD and no known PAD.9 PAD was identified in 27% of these patients; 16% had no symptoms of PAD. Taken together with registry data on known polyvascular disease, these data demonstrate that a patient with documented arterial disease in one bed is at risk of an ischaemic event in any arterial bed – even if no additional symptoms are present.


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