Worse Prognosis for Patients With Proximal Peripheral Artery Disease

February 24, 2010

February 24, 2010 (Limoges, France) — Individuals with proximal peripheral artery disease (PAD), such as partial or complete obstruction of the large aortoiliac arteries, have a worse prognosis than individuals with more distal PAD, a new study has shown [1]. Individuals with proximal lesions have a significantly greater risk of mortality and cardiovascular disease events, even after adjustment for multiple risk factors and comorbidities, than patients with more distal lesions, report investigators, although they caution against overinterpreting these conclusions.

"The research is really hypothesis generating at this point and needs to be confirmed with other studies," lead investigator Dr Victor Aboyans (Limoges University, France) told heartwire . "We also should really take care not to say that distal peripheral artery disease is not dangerous and not associated with poor prognosis. All we can say is that patients with proximal PAD have a worse situation than those with distal disease, but these [distal] patients are still patients at high risk of mortality and cardiovascular events."

The results of the study are published in the March 2, 2010 issue of the Journal of the American College of Cardiology.

Location, Location, Location

Two smaller studies have suggested that patients with proximal PAD fared worse than patients with more distal disease (including lesions in the femoral and popliteal arteries or those below the knee), although these investigations used noninvasive methods to assess PAD.

In the current study, researchers assessed the general prognosis of 400 PAD patients who underwent angiography on their lower limbs between January 2000 and December 2005. A majority of the patients were male, and the mean age was 68 years old. Those who presented with proximal disease were more likely to smoke, while those with distal PAD, defined as disease distal to the iliac artery, were older and more likely to have diabetes, hypertension, and renal failure.

They found that patients with PAD and aortoiliac disease had significantly reduced cardiovascular-event-free survival than PAD patients with no aortoiliac disease; by contrast, PAD patients with femoral/popliteal or infragenicular arterial disease had no significant differences in event-free survival compared with PAD patients without these specific forms of PAD. In multivariate analysis, after adjustment for several risk factors and comorbidities, proximal PAD was significantly associated with a more than threefold increased risk in adverse cardiovascular outcomes and death compared with distal PAD. By contrast, there was no significant increase in adverse cardiovascular outcomes among patients with femoral/popliteal disease or in those with disease in arteries below the knee.

Association Between Proximal PAD and Prognosis

End point Hazard ratio (95% CI) p (vs distal PAD)
Death, fatal and nonfatal MI or stroke, and coronary and carotid revascularization 3.28 (1.87–5.75) <0.0001
Death 3.18 (1.57–6.46) <0.002

Association Between PAD Localization and Fatal and Nonfatal Cardiovascular Events in Patients With Single-Level Disease

PAD location Hazard ratio (95% CI) p (vs distal PAD)
Aortoiliac 4.70 (1.65–13.31) <0.001
Femoral/popliteal 1.31 (0.52–3.31) NS
Infragenicular Reference --

Aboyans said the results of the study are surprising, and the reason behind the differential prognosis remains unknown. He noted, however, that there are differences in arterial stiffness, with proximal PAD more strongly associated with central arterial stiffness than distal PAD. He said that proximal arteries tend to be richer in elastic fibers, while distal arteries are more muscular. However, other mechanisms still unknown might explain the different prognoses.

He also pointed out that in terms of disease progression, PAD actually tends to be worse in patients with distal disease, partly because there are better treatment options for patients with severe proximal disease, such as revascularization, which is not often not an option in patients with distal PAD. Even if the option is available, long distal bypasses tend to have a worse prognosis than bypasses performed in proximal lesions. As a result, distal PAD patients are at a higher risk of amputation. Aboyans added that patients with distal disease also tend to be older, and while more men than women have peripheral disease, the gender difference is less pronounced in distal PAD than in proximal disease. Finally, he noted that distal PAD patients are more likely to present on dialysis or have chronic kidney diseases.

So, while the current study raises concerns about increased cardiovascular risks of peripheral PAD, this doesn't discount the risks facing people with distal disease.

"The question now is if we have to manage patients with proximal PAD differently," Aboyans told heartwire . "At this stage, we can't say anything, because this study needs to be confirmed by others. Second, patients in our study were hospitalized, so we can't extrapolate our findings to less severe cases, to patients who haven't been hospitalized. We really don't have any data suggesting that if we managed patients with proximal PAD any differently from those with distal PAD that it would change their prognosis."

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