TY - JOUR
T1 - Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes
T2 - Results from the ADVANCE-ON study
AU - Mohammedi, Kamel
AU - Woodward, Mark
AU - Hirakawa, Yoichiro
AU - Zoungas, Sophia
AU - Colagiuri, Stephen
AU - Hamet, Pavel
AU - Harrap, Stephen
AU - Poulter, Neil
AU - Matthews, David R.
AU - Marre, Michel
AU - Chalmers, John
N1 - Funding Information:
Dr. Kamel Mohammedi was supported by grants from the Société Francophone du Diabète (SFD) and the Association Diabète Risque Vasculaire (ADRV).
Funding Information:
Dr. Kamel Mohammedi reports personal fees from Novo-Nordisk, outside the submitted work; Prof. Marc Woodward reports personal fees from Amgen, outside the submitted work; Prof. Pavel Hamet reports grants from Servier, during the conduct of the study; other from Servier, outside the submitted work; Prof. Stephen Harrap reports grants from National Health and Medical Research Council of Australia, grants from The George Institute for Global Health, during the conduct of the study; other from Servier, outside the submitted work; Prof. Neil Poulter reports grants from The George Institute, grants from British Heart Foundation/Diabetes UK/The George Institute, during the conduct of the study; grants from The George Institute, grants from BHF/DUK/The George Institute, outside the submitted work; Prof. Michel Marre reports grants and personal fees from Novo Nordisk, grants and personal fees from Sanofi, grants and personal fees from Eli Lilly, personal fees from Servier, grants and personal fees from Merck Sharp and Dohme, personal fees from Abbott, grants and personal fees from Novartis, personal fees from Astra Zeneca, outside the submitted work; and Prof. John Chalmers reports grants from National Health and Medical Research Council of Australia, grants and personal fees from Servier, outside the submitted work. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/9/2
Y1 - 2016/9/2
N2 - 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).
AB - 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).
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U2 - 10.1186/s12933-016-0446-x
DO - 10.1186/s12933-016-0446-x
M3 - Article
C2 - 27590190
AN - SCOPUS:84984972641
VL - 15
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
SN - 1475-2840
IS - 1
M1 - 129
ER -