Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes

Results from the ADVANCE-ON study

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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).

Original languageEnglish
Article number129
JournalCardiovascular Diabetology
Volume15
Issue number1
DOIs
Publication statusPublished - Sep 2 2016
Externally publishedYes

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Peripheral Arterial Disease
Type 2 Diabetes Mellitus
Amputation
Lower Extremity
perindopril drug combination indapamide
Gliclazide
Peripheral Vascular Diseases
Mortality
Light Coagulation
Peripheral Nervous System Diseases
Blindness
Disease Management
Vascular Diseases
Angioplasty
Kidney
Therapeutics

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Cite this

Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes : Results from the ADVANCE-ON study. / Mohammedi, Kamel; Woodward, Mark; Hirakawa, Yoichiro; Zoungas, Sophia; Colagiuri, Stephen; Hamet, Pavel; Harrap, Stephen; Poulter, Neil; Matthews, David R.; Marre, Michel; Chalmers, John.

In: Cardiovascular Diabetology, Vol. 15, No. 1, 129, 02.09.2016.

Research output: Contribution to journalArticle

Mohammedi, K, Woodward, M, Hirakawa, Y, Zoungas, S, Colagiuri, S, Hamet, P, Harrap, S, Poulter, N, Matthews, DR, Marre, M & Chalmers, J 2016, 'Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes: Results from the ADVANCE-ON study', Cardiovascular Diabetology, vol. 15, no. 1, 129. https://doi.org/10.1186/s12933-016-0446-x
Mohammedi, Kamel ; Woodward, Mark ; Hirakawa, Yoichiro ; Zoungas, Sophia ; Colagiuri, Stephen ; Hamet, Pavel ; Harrap, Stephen ; Poulter, Neil ; Matthews, David R. ; Marre, Michel ; Chalmers, John. / Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes : Results from the ADVANCE-ON study. In: Cardiovascular Diabetology. 2016 ; Vol. 15, No. 1.
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abstract = "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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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

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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