title: Microvascular and Macrovascular Disease and Risk for Major Peripheral Arterial Disease in Patients With Type 2 Diabetes.
abstract: Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis in type 2 diabetes, but the relationship between other vascular diseases and PAD has been poorly investigated. We examined the impact of previous microvascular and macrovascular disease on the risk of major PAD in patients with type 2 diabetes.
  
  
  
  We analyzed 10,624 patients with type 2 diabetes free from baseline major PAD in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) clinical trial. The primary composite outcome was major PAD defined as PAD-induced death, peripheral revascularization, lower-limb amputation, or chronic ulceration. The secondary end points were the PAD components considered separately.
  
  
  
  Major PAD occurred in 620 (5.8%) participants during 5 years of follow-up. Baseline microvascular and macrovascular disease were both associated with subsequent risk of major PAD after adjustment for age, sex, region of origin, and randomized treatments. However, only microvascular disease remained significantly associated with PAD after further adjustment for established risk factors. The highest risk was observed in participants with a history of macroalbuminuria (hazard ratio 1.91 [95% CI 1.38-2.64], P < 0.0001) and retinal photocoagulation therapy (1.60 [1.11-2.32], P = 0.01). Baseline microvascular disease was also associated with a higher risk of chronic lower-limb ulceration (2.07 [1.56-2.75], P < 0.0001) and amputation (1.59 [1.15-2.22], P = 0.006), whereas baseline macrovascular disease was associated with a higher rate of angioplasty procedures (1.75 [1.13-2.73], P = 0.01).
  
  
  
  Microvascular disease, particularly macroalbuminuria and retinal photocoagulation therapy, strongly predicts major PAD in patients with type 2 diabetes, but macrovascular disease does not.
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Kamel
authors.initials: K
authors.lastname: Mohammedi
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia The George Institute for Global Health, University of Oxford, Oxford, U.K. Department of Epidemiology, Johns Hopkins University, Baltimore, MD.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hirakawa
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia.
authors.forename: Sophia
authors.initials: S
authors.lastname: Zoungas
authors.affiliation: Institute of Cardiovascular Sciences, University College London (UCL) and National Institute of Health Research UCL Hospitals Biomedical Research Centre, London, U.K.
authors.forename: Bryan
authors.initials: B
authors.lastname: Williams
authors.affiliation: The Chinese Hypertension League Institute, Beijing, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Lisheng
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodgers
authors.affiliation: The University of Milan-Bicocca and Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
authors.affiliation: The University of Melbourne and Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Harrap
authors.affiliation: INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Department of Diabetology, Endocrinology and Nutrition, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia chalmers@georgeinstitute.org.au.
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D004338:Drug Combinations; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D005907:Gliclazide / Q000008:administration & dosage; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007190:Indapamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage; D058729:Peripheral Arterial Disease / Q000150:complications*; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D005907:Gliclazide; D006442:Glycated Hemoglobin; D007190:Indapamide; D020913:Perindopril; C494243:indapamide, perindopril drug combination