Journal Article

Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes: results from the ADVANCE-ON study

Matthews, David R., Zoungas, Sophia, Woodward, Mark, Marre, Michel, Hirakawa, Yoichiro, Harrap, Stephen, Mohammedi, Kamel, Hamet, Pavel, Chalmers, John, Colagiuri, Stephen, Poulter, Neil

2016

Overview

Background Peripheral arterial disease (PAD) is known to be associated with high cardiovascular risk, but the individual impact of PAD presentations on risk of macrovascular and microvascular events has not been reliably compared in patients with type 2 diabetes. We aimed to evaluate the impact of major PAD, and its different presentations, on the 10-year risk of death, major macrovascular events, and major clinical microvascular events in these patients. Methods Participants in the action in diabetes and vascular disease: PreterAx and DiamicroN modified-release controlled evaluation (ADVANCE) trial and the ADVANCE-ON post-trial study were followed for a median of 5.0 (in-trial), 5.4 (post-trial), and 9.9 (overall) years. Major PAD at baseline was subdivided into lower-extremity chronic ulceration or amputation secondary to vascular disease and history of peripheral revascularization by angioplasty or surgery. Results Among 11,140 participants, 516 (4.6 %) had major PAD at baseline: 300 (2.7 %) had lower-extremity ulceration or amputation alone, 190 (1.7 %) had peripheral revascularization alone, and 26 (0.2 %) had both presentations. All-cause mortality, major macrovascular events, and major clinical microvascular events occurred in 2265 (20.3 %), 2166 (19.4 %), and 807 (7.2 %) participants, respectively. Compared to those without PAD, patients with major PAD had increased rates of all-cause mortality (HR 1.35, 95 % CI 1.15–1.60, p = 0.0004), and major macrovascular events (1.47 [1.23–1.75], p < 0.0001), after multiple adjustments for region of origin, cardiovascular risk factors and treatments, peripheral neuropathy markers, and randomized treatments. We have also observed a trend toward an association of baseline PAD with risk of major clinical microvascular events [1.31 (0.96–1.78), p = 0.09]. These associations were comparable for patients with a lower-extremity ulceration or amputation and for those with a history of peripheral revascularization. Furthermore, the risk of retinal photocoagulation or blindness, but not renal events, increased in patients with lower-extremity ulceration or amputation [1.53 (1.01–2.30), p = 0.04]. Conclusions Lower-extremity ulceration or amputation, and peripheral revascularization both increased the risks of death and cardiovascular events, but only lower-extremity ulceration or amputation increased the risk of severe retinopathy in patients with type 2 diabetes. Screening for major PAD and its management remain crucial for cardiovascular prevention in patients with type 2 diabetes (ClinicalTrials.gov number, NCT00949286).

• Publisher: BioMed Central,Springer Nature B.V
• Subject: Aged / Amputation / Angiology / Angioplasty / Cardiology / Diabetes / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - diagnosis / Diabetes Mellitus, Type 2 - drug therapy / Diabetes Mellitus, Type 2 - mortality / Diabetic Angiopathies - diagnosis / Diabetic Angiopathies - etiology / Diabetic Angiopathies - mortality / Diabetic Angiopathies - therapy / Diabetic Retinopathy - etiology / Female / Humans / Hypoglycemic Agents - therapeutic use / Leg Ulcer - etiology / Limb Salvage / Lower Extremity - blood supply / Male / Medicine / Medicine & Public Health / Middle Aged / Original Investigation / Peripheral Arterial Disease - diagnosis / Peripheral Arterial Disease - etiology / Peripheral Arterial Disease - mortality / Peripheral Arterial Disease - therapy / Risk Assessment / Risk Factors / Time Factors / Treatment Outcome / Vascular Surgical Procedures