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Patients with Asymptomatic, Severe Peripheral Arterial Disease have Worse Outcomes than Patients with Claudication
Kevin Z Chang, Corey A Kalbaugh, Ana Kouri, Mark A Farber, William A Marston, Raghuveer Vallabhaneni
UNC Hospitals, Chapel Hill, NC

Background: Patients are frequently referred to a vascular specialist for evaluation of symptomatic peripheral arterial disease (PAD). However, many patients meeting hemodynamic criteria for severe PAD are asymptomatic, possibly secondary to neuropathy, sedentary lifestyle, or subclinical disease. The aim of our study was to compare the outcomes of patients with asymptomatic, severe PAD to patients with severe PAD and claudication.
Methods: All inpatients and outpatients presenting to our peripheral vascular lab for lower extremity duplex examination between 2008 and 2010 were identified. Patients were categorized by clinical presentation: acute ischemia, asymptomatic, claudication, rest pain, ulceration, and gangrene. For the purposes of this study, only patients with severe hemodynamic evidence of PAD [defined by ankle-brachial index (ABI) <0.5 or toe pressure (TP) <50 mm HG)] without symptoms of acute or critical limb ischemia were included in our cohort. Demographics and comorbidities were compared using chi-square, fishers exact, and t-tests. Long-term outcomes of overall survival, amputation-free survival (AFS), limb salvage, re-vascularization, and progression (or occurrence) of symptoms were examined using Kaplan-Meier Life-Table analysis with log rank testing, as well as multivariable Cox Proportional Hazard models.
Results: Six hundred twelve limbs in 470 patients were identified using our criteria. These patients were separated into 252 patients (with 336 limbs) who had claudication and 220 patients (with 276 limbs) who were asymptomatic. Patients with claudication were more likely to have a history of smoking, hypertension, and hyperlipidemia. Asymptomatic patients were more likely to have cardiovascular disease, chronic kidney disease, dialysis dependence, and a history of limb amputation. Analysis over a mean follow up of 732 +802 days showed longer overall survival, increased limb salvage, and higher AFS in the claudication group compared to the asymptomatic group (p<0.0001). Overall five-year survival was 0.70 in the claudication group and 48% in the asymptomatic group [adjusted HR 1.83 (1.33, 2.51); p<0.0001]. Five-year limb salvage was higher in the claudicant group versus the asymptomatic group [98% vs. 92%, adjusted HR 3.75 (1.09, 12.85), p=0.04]. Five-year AFS was 59% in the claudication group and 30% in the asymptomatic group [adjusted HR 1.91 (1.46, 2.50); p<0.0001]. Patients in the asymptomatic group demonstrated a higher rate of developing symptoms after presentation as compared to the rate of symptom progression in the claudication group. Overall symptom progression at 5 years was 38% among claudicants and 47% among asymptomatic patients [adjusted HR 1.72 (1.14, 2.61); p = 0.001]. Despite the increased rate of symptom progression, the asymptomatic group had a significantly lower rate of vascular intervention.
Conclusions: Patients with asymptomatic, severe PAD had worse overall survival, limb salvage, and AFS when compared to patients who present with severe PAD and claudication. Asymptomatic patients also demonstrate a higher rate of symptom progression when compared to claudicants but have a lower rate of revascularization procedures. Further research is needed to determine specific causes of increased mortality and limb loss in patients with asymptomatic, severe PAD.

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