The association of circulating 25-hydroxyvitamin D concentration with peripheral arterial disease: A meta-analysis of observational studies.
BACKGROUND AND AIMS
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.
['Nsengiyumva|Vianne|V|', 'Fernando|Malindu E|ME|', 'Moxon|Joseph V|JV|', 'Krishna|Smriti M|SM|', 'Pinchbeck|Jenna|J|', 'Omer|Safraz M|SM|', 'Morris|Dylan R|DR|', 'Jones|Rhondda E|RE|', 'Moran|Corey S|CS|', 'Seto|Sai W|SW|', 'Golledge|Jonathan|J|']
D015415:Biomarkers D016022:Case-Control Studies D016009:Chi-Square Distribution D016638:Critical Illness D015536:Down-Regulation D006801:Humans D007511:Ischemia D064887:Observational Studies as Topic D058729:Peripheral Arterial Disease D011379:Prognosis D012307:Risk Factors D014807:Vitamin D D014808:Vitamin D Deficiency
25-Hydroxyvitamin D Peripheral arterial disease Meta-analysis Vitamin D deficiency Atherosclerosis Atherothrombosis