title: The association of circulating 25-hydroxyvitamin D concentration with peripheral arterial disease: A meta-analysis of observational studies.
abstract: OBJECTIVE
  The association of vitamin D deficiency with cardiovascular disease is controversial. The present meta-analysis was performed to examine if circulating levels of 25-hydroxyvitamin D [25(OH)D] were lower in patients with peripheral artery disease (PAD) when compared to non-PAD controls.
  
  
  METHODS
  A comprehensive database search was conducted in Web of science, Scopus, PubMed, EMBASE and The Cochrane Library to identify observational studies reporting 25(OH)D concentrations in PAD patients and non-PAD participants. Data extraction and study quality assessments were conducted independently. A random-effects model was used to meta-analyse extracted data and generate standardized mean differences (SMDs) in circulating 25(OH)D levels between PAD patients and non-PAD controls. Subgroup analyses were conducted focussing on patients presenting with intermittent claudication (IC) and critical limb ischaemia (CLI).
  
  
  RESULTS
  Six case-control studies assessing 6418 individuals fulfilled the inclusion criteria. Two studies were considered to be of moderate methodological quality and four were considered to be of high quality. A meta-analysis of data from 1217 PAD patients and 5201 non-PAD participants showed that circulating 25(OH)D concentrations were lower in PAD patients compared with non-PAD participants (SMD = -0.32, 95% CI: -0.58, -0.05; P = 0.02). Subgroup analyses showed that 25(OH)D levels were significantly lower among PAD patients with CLI, but not IC, when compared to non-PAD controls (SMD = -1.29, 95% CI: -1.66, -0.91; P < 0.001 and SMD = -0.01, 95% CI: -0.15, 0.13; P=0.88, respectively).
  
  
  CONCLUSIONS
  This meta-analysis suggests that low levels of circulating 25(OH)D are associated with PAD presence, particularly in patients presenting with CLI. These data suggest the possibility that vitamin D insufficiency may contribute to the development of more advanced PAD although this remains to be confirmed.
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Arterial Diseases, College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia.
authors.forename: Vianne
authors.initials: V
authors.lastname: Nsengiyumva
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Arterial Diseases, College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia.
authors.forename: Malindu E
authors.initials: ME
authors.lastname: Fernando
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Arterial Diseases, College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Moxon
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Arterial Diseases, College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia.
authors.forename: Smriti M
authors.initials: SM
authors.lastname: Krishna
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Arterial Diseases, College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia.
authors.forename: Jenna
authors.initials: J
authors.lastname: Pinchbeck
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Arterial Diseases, College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia.
authors.forename: Safraz M
authors.initials: SM
authors.lastname: Omer
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Arterial Diseases, College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia.
authors.forename: Dylan R
authors.initials: DR
authors.lastname: Morris
authors.affiliation: Division of Medicine, Health and Molecular Sciences, James Cook University, Townsville, QLD, Australia.
authors.forename: Rhondda E
authors.initials: RE
authors.lastname: Jones
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Arterial Diseases, College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia.
authors.forename: Corey S
authors.initials: CS
authors.lastname: Moran
authors.affiliation: National Institute of Complementary Medicine (NICM), Western Sydney University, Campbelltown, NSW, 2560, Australia.
authors.forename: Sai W
authors.initials: SW
authors.lastname: Seto
authors.affiliation: The Vascular Biology Unit, Queensland Research Centre for Peripheral Arterial Diseases, College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia; Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, QLD, Australia. Electronic address: jonathan.golledge@jcu.edu.au.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016638:Critical Illness; D015536:Down-Regulation; D006801:Humans; D007511:Ischemia / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D064887:Observational Studies as Topic; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D011379:Prognosis; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: 25-Hydroxyvitamin D; Atherosclerosis; Atherothrombosis; Meta-analysis; Peripheral arterial disease; Vitamin D deficiency