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Background: Peripheral artery disease (PAD) is the leading cause of non-traumatic lower limb amputation. Microvascular disease (peripheral neuropathy, nephropathy, or retinopathy) increases the risk of lower limb amputation in patients with established PAD.

Purpose: We estimated risk of lower limb amputation associated with microvascular disease and PAD in a Danish cohort.

Methods: We conducted a population-based cohort study of every person living in Western Denmark aged 50-75 years on January 1, 2012 and followed them for 7 years. People with previous lower limb amputation were excluded. People were stratified by the presence of microvascular disease (peripheral neuropathy, nephropathy, or retinopathy) and PAD (peripheral atherosclerosis including intermittent claudication, or previous lower limb revascularization). We estimated the 7-year cumulative incidence and hazard ratio (HR) of lower limb amputation using individuals with neither microvascular disease nor PAD as reference. We also provide a sex-specific analyses and estimated the population attributable fraction of amputation associated with male sex.

Results: We included 933,597 individuals, of whom 16,007 had microvascular disease, 18,400 had PAD, and 1,789 had both microvascular disease and PAD. Patients with either microvascular disease (3.7%) or PAD (3.9%) had similar unadjusted 7-year risks of lower limb amputation (Figure). Microvascular disease (adjusted HR 3.21, 95% CI 2.86-3.59) and PAD (adjusted HR 7.37, 95% CI 6.68-8.14) increased the risk of lower limb amputation separately in adjusted analysis. Individuals with both microvascular disease and PAD had the highest risk of amputation (adjusted HR 11.82, 95% CI 10.11-13.80). While the relative impact of microvascular disease and PAD were similar in men and women, men had increased risk of amputation compared to women, in absolute terms. The population attributable fraction of amputations associated with male sex was 31%.

Conclusion: Microvascular disease and PAD are independently associated with a 3-fold and 7-fold increase of amputation rate, respectively. Combined, microvascular disease and PAD had an additive effect constituting a 12-fold amputation risk. Amputation risk was higher in men than in women, with 3 in 10 lower limb amputations in Western Denmark attributable to male sex.

Microvascular disease, peripheral artery disease, and the risk of lower limb amputation

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Doctor Kevin Kris Warnakula Olesen

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Micro and Macrovascular Interplay in Peripheral Artery Disease

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ESC Congress 2020

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