Risk factors
Risk factors for PAD are similar to those important in the aetiology of CAD and are the typical risk factors for atherosclerotic disease. These include the traditional risk factors: smoking, dyslipidaemia, diabetes mellitus, and hypertension. For private practice cardiologists three areas are important and are focused upon:
- Extracranial carotid/vertebral artery disease
- Renal artery disease
- LEAD (lower extremity artery disease).
Extracranial carotid/ vertebral artery disease
In general, the risk factors for carotid stenosis are similar to those for LEAD, although smoking, while commonly associated with carotid disease, is not as dominant as it is with LEAD.
In the Western world, ischaemic stroke has a major public health impact as the first cause of long-term disability and the third leading cause of death. Stroke mortality ranges from 10% to 30%, and survivors remain at risk of recurrent neurological and cardiac ischaemic events. The risk of stroke and transient ischaemic attacks (TIAs), defined in most studies as transient neurological deficits usually lasting 1–2 h and no longer than 24 h, increases with age. Major risk factors for stroke include hypertension, hypercholesterolaemia, smoking, diabetes, cerebrovascular disease.
Duplex ultrasound / duplex ultrasonography (DUS) is commonly used as the first step to detect extracranial carotid artery stenosis and to assess its severity. The peak systolic velocity measured in the internal carotid artery is the primary variable used for this purpose; secondary variables include the end diastolic velocity in the internal carotid artery as well as the ratio of peak systolic velocity in the internal carotid artery to that in the common carotid artery.
Although DUS evaluation may be hampered by severe plaque calcifications, tortuous vessels, tandem lesions, and slow turbulent flow in subtotal stenoses, this imaging modality allows for a reliable estimation of the degree of the stenosis as well as for the assessment of plaque morphology in the hands of an experienced investigator.
The advantages of computed tomography angiography (CTA) and magnetic resonance angiography (MRA) include the simultaneous imaging of the aortic arch, the complete common and internal carotid arteries, the intracranial circulation, as well as the brain parenchyma.
MRA is more time-consuming than CTA but does not expose patients to radiation, and the contrast agents used are far less nephrotoxic. CTA offers excellent sensitivity and specificity for the detection of carotid artery stenosis, however the presence of severe plaque calcification may lead to overestimation of the degree of stenosis. In a systematic review and meta-analysis, no major difference was found between DUS, MRA, and CTA for the detection of a significant carotid artery stenosis.
In order to improve the accuracy of the diagnosis, the use of two imaging modalities prior to revascularization is suggested. Digital subtraction angiography (DSA) may be required for diagnostic purposes only in selected cases (e.g. discordant non-invasive imaging results, additional intracranial vascular disease). In patients with severe asymptomatic carotid artery stenosis, imaging of the brain to detect asymptomatic embolic events and a transcranial Doppler for emboli detection, may be considered.
Recommendations for renal disease
Recommendations for diagnostic strategies for renal artery stenosis (RAS)
Medical therapy for renal disease
All patients with atherosclerotic RAS should be treated according to the European Guidelines on Cardiovascular Disease Prevention.
Revascularization for renal disease
There are some new studies that support a more important role for renal revascularization. For example, the ASTRAL (Angioplasty and Stent for Renal Artery Lesions) study.
It is mentioned that ongoing studies such as the CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) trial will provide additional evidence relevant to these recommendations in the near future.
Management of lower extremity artery disease (LEAD)
All patients with LEAD are at increased risk of further CVD events and general secondary prevention is mandatory to improve prognosis.
In LEAD, cigarette smoking has consistently been shown in several epidemiological studies to be an important risk factor and to be dose-dependent.
Diabetes mellitus is the other risk factor especially important in the development of LEAD. This is certainly true for severe disease, notably gangrene and ulceration, but for intermittent claudication the strength of the association with diabetes may be comparable with that for coronary heart disease. The association of diabetes with LEAD is inconsistent on multivariable analysis, which includes other risk factors, but it appears that the duration and severity of diabetes affect the level of risk.
Ankle–brachial (ABI) index is the primary non-invasive test for the diagnosis of LEAD.
In healthy persons, the ABI is 1.0. Usually an ABI 0.90 is used to define LEAD. The actual sensitivity and specificity have been estimated to be 79% and 96% respectively.
For diagnosis in primary care an ABI of 0.8 or the mean of three ABIs of 0.90 had a positive predictive value of ?95%.
An ABI of 1.10 or the mean of three ABIs of 1.00 had a negative predictive value of ?99%. The level of ABI also correlates with LEAD severity, with high risk of amputation when the ABI is 0.50.
An ABI change of 0.15 is generally required to consider worsening of limb perfusion over time, or improving after revascularization.
For its measurement (Figure 2), a 10–12 cm sphygmomanometer cuff placed just above the ankle and a (handheld) Doppler instrument (5–10 MHz), to measure the pressure of the posterior and anterior tibial arteries of each foot, are required.
Usually the highest ankle systolic pressure is divided by the highest brachial systolic pressure, resulting in an ABI per leg.
Recently some papers reported higher sensitivity to detect LEAD if the ABI numerator is the lowest pressure in the arteries of both ankles. Patients with asymptomatic LEAD have no indication for prophylactic revascularization.
The recommendations for patients with intermittent claudication are shown here.
Critical limb ischaemia (CLI) is the most severe clinical manifestation of LEAD, defined as the presence of ischaemic rest pain, and ischaemic lesions or gangrene objectively attributable to arterial occlusive disease. An ankle pressure of 50 mmHg is usually recommended as a diagnostic criterion because it includes most patients for whom rest pain or ischaemic lesions do not improve spontaneously without intervention. For patients with ischaemic lesions or gangrene, CLI is suggested by an ankle pressure of 70 mmHg. Toe pressure of 30 mmHg replaces the ankle pressure criteria in the case of medial calcinosis.
The investigation of the microcirculation (i.e. transcutaneous oxygen pressure) is also helpful in some cases, not only for diagnostic and prognostic purpose, but also sometimes to determine the level of amputation.
CLI is also a marker for generalized,severe atherosclerosis, with a three-fold risk excess of future myocardial infarction, stroke, and vascular death compared with patients with intermittent claudication.
The therapeutic strategies are described in ESC Guidelines on the diagnosis and treatment of peripheral artery diseases chapter 4.5.3
Gaps of evidence
The guidelines acknowledge that solid evidence is still needed in some areas of the management of PAD. See page 111 for the most relevant.