The association of circulating 25-hydroxyvitamin D concentration with peripheral arterial disease: A meta-analysis of observational studies

• Conflicting evidence exists on the association of vitamin D deficiency with cardiovascular disease.
• This meta-analysis showed that patients with PAD have lower circulating 25(OH)D than non-PAD controls.
• Sub-group analysis showed that this negative association was limited to patients presenting with critical limb ischaemia.
• Whether vitamin D deficiency plays a causal role in the development of severe PAD warrants further investigation.

Background and aimsThe 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.MethodsA 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).ResultsSix 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).ConclusionsThis 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.