Bayer Pharma AG

Essence of this article

Coronary artery disease (CAD) and peripheral arterial disease (PAD) often coexist, and the latter is a marker of systemic atherosclerosis. Most patients with PAD also have concomitant CAD, and a large burden of morbidity and mortality in patients with PAD is related to myocardial infarction, ischaemic stroke and cardiovascular death. A better understanding of the underlying pathophysiological association between CAD and PAD will lead to the development of safer and more effective therapeutic options that could benefit the clinical management of patients with one or both of these diseases.

About coronary and peripheral artery disease


Peripheral arterial disease (PAD) is a progressive atherosclerotic condition that causes stenosis and occlusion of non-cerebral and non-coronary arteries,418 including those found in the extra-cranial carotid circulation, mesenteric circulation, renal circulation and the upper and lower extremities.419

Based on epidemiological projections, 27 million people in Europe and North America (16% of the population aged ≥55 years) have PAD: an estimated 10.5 million cases are symptomatic, but the majority, 16.5 million patients, have asymptomatic PAD.420

Patients with PAD can experience an array of symptoms such as pain in the muscles of the leg while walking (intermittent claudication), pain at rest, ischaemic ulcerations and gangrene.419 Complications of PAD may result in critical limb ischaemia leading to amputation and an increased risk of death.419 Although some patients follow a gradual progression from asymptomatic PAD to intermittent claudication and then critical limb ischaemia, this is the exception rather than the rule. More than half of patients undergoing major amputation for critical limb ischaemia have experienced no symptoms of ischaemia in the 6 months prior to surgery.418 The major risk factors for PAD have been determined from large epidemiological studies and are consistent with the risk factors for cerebrovascular disease and ischaemic heart disease including, but not limited to, advanced age, smoking, diabetes, hypertension and hyperlipidemia.421, 422 Because of the high prevalence of asymptomatic disease and because only a small percentage of PAD patients present with classic claudication, PAD is frequently underdiagnosed and thus undertreated.423

PAD and progression of coronary artery disease

Patients with PAD frequently have concomitant coronary artery disease (CAD) and display a higher risk for myocardial infarction, stroke, death due to cardiovascular events or all-cause mortality compared with patients without CAD424-427

  • Approximately 55% of patients with severe lower-extremity PAD requiring surgery have significant CAD (at least one coronary artery with significant narrowing)428
  • All-cause mortality for combined lower-extremity PAD and CAD is approximately twice as high as that resulting from either of the individual conditions429
  • The 1-year risk of cardiovascular death, myocardial infarction, stroke or hospitalization for atherothrombotic events of patients with concomitant lower-extremity PAD and CAD was higher (23.1%) than for those with CAD or PAD alone (13–17%)429

The clinical importance of PAD is reflected by the fact that patients with PAD and/or CAD harbour more extensive and calcified coronary atherosclerosis, constrictive vascular remodelling and accelerated disease progression (Figure 1).430 Future therapeutic options that modulate one or more of these clinical factors could lead to effective reductions in cardiovascular risk.

Figure 1. Clinical presentation, natural history and outcomes in patients with atherosclerotic PAD.423
CV, cardiovascular; MI, myocardial infarction; PAD, peripheral arterial disease.

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