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Summary: Background: Peripheral artery disease (PAD) impacts 3–12% of patients worldwide and is characterized by endothelial dysfunction and inflammatory pathways which are also common to venous thromboembolism (VTE), but there is a paucity of evidence regarding VTE risk in PAD patients. We investigated whether PAD is an independent risk factor for VTE. Patients and methods: We reviewed medical records of patients undergoing ABI studies at Mayo Clinic from 01/1996-02/2020. We classified patients by ABI (low [1.4]), as well as by specific low ABI subgroup: severely reduced (ABI: 0.00–0.39), moderately reduced (0.40–0.69), mildly reduced (0.70–0.90), and borderline reduced (0.91–0.99). The primary outcome was incident VTE event (acute lower extremity deep vein thrombosis or pulmonary embolism) after ABI measurement. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for age, sex, active smoking, cancer, previous VTE, thrombophilia, anticoagulation, and revascularization. Results: 39,834 unique patients (mean age 66.3±14.3 years, median follow-up 34 months) were identified. 2,305 VTE events occurred in patients without PAD (13.0%), 2,218 in low ABI patients (13.0%), and 751 in elevated ABI patients (14.8%). After risk factor adjustment, VTE risk was modestly increased for PAD overall (HR: 1.12, 95% CI [1.06, 1.18]), including low ABI (HR: 1.11, 95% CI [1.04, 1.18]) and elevated ABI groups (HR: 1.15, 95% CI [1.04, 1.26]), compared to patients without PAD. The greatest VTE risk was in severely low ABI patients (HR: 1.46, 95% CI [1.31, 1.64]). Conclusions: In a large longitudinal cohort, we present strong clinical evidence of PAD, with low and elevated ABI, as an independent VTE risk factor, with the highest risk seen in patients with severely low ABI. Continued research is required to further investigate this relationship and its intersection with functional performance status to optimize VTE risk reduction or anticoagulation strategies in the PAD population.

Peripheral artery disease (PAD) prevalence increases with age, but the relation between age at PAD diagnosis and outcomes is unclear. We investigated the cardiovascular and limb outcomes of patients diagnosed with PAD at different ages. We studied patients with PAD aged ≥18 years who were diagnosed between 1996 and 2020 at Mayo Clinic. Patients were grouped by diagnosis age (50, 50 to 59, 60 to 69, ≥70 years) and ankle brachial index (ABI): low ABI (1.0) or elevated ABI (1.4). Primary outcomes were cardiovascular events (CVEs; myocardial infarction or ischemic stroke) and limb events (LEs; critical limb ischemia or amputation). Competing risk analysis was performed to calculate adjusted hazard ratios. The cohort included 22,073 patients with PAD (low ABI: 77.1%; elevated ABI: 22.9%). CVEs were observed in 8.2% of patients and LEs in 15.6%. The highest CVE risk was observed in patients diagnosed with PAD before age 50 (compared with patients diagnosed after age 70; hazard ratio 2.33 [95% confidence interval 1.95 to 2.78]). CVE risk decreased with older age at diagnosis. Although younger groups demonstrated higher LE risk, there was no clear association with diagnosis age. These patterns of risk were seen both in low and elevated ABI subgroups but in greater magnitude with elevated ABI. Younger patients diagnosed with PAD face increased risk of myocardial infarction and ischemic stroke compared with patients diagnosed at an older age. CVE risk notably exceeds LE risk. In conclusion, younger age at PAD diagnosis may be an important risk factor, which warrants more aggressive interventions focused on CVE prevention.