Effects Of Vitamin D Supplementation And Its Derivatives On Arterial Stiffness:A Meta-Analysis Of Randomized Controlled Trials

Objective:To explore the effect of vitamin D and its derivatives on vascular stiffness.Methods:A separate literature screening of the PubMed,Cochrane Library and EMBASE databases was conducted by 2 reviewers,and all randomized controlled trials with supplements of vitamin D and its derivatives as interventions,with arterial stiffness as outcome measures,were extracted,Data analysis was carried out using Revman5.3,and the outcome measures included arterial pulse wave velocity（pulse wave velocity,PWV）,enhanced exponent（augmentation Index,AI）,and intima-media thickness（intima-media thickness,IMT）,ankle-brachial index（ankle-brachial index,ABI）were counted data,using mean Difference（MD）and 95%ci expression.The I2 test was used to test the heterogeneity of the included study,I²>50%,the stochastic effect model was adopted,and the fixed effect model was adopted in I²<50%.The sensitivity analysis of the included study was carried out by the method of removal of single study,and the funnel map was used to evaluate the included study.Results:1.This analysis included 29 randomized controlled trials.A total of 20 articles introduced the effect of PWV on arterial stiffness,and Vitamin D and its derivatives intervention group were 938 and 851 control subjects.6articles compared the change of PWV,310 in the experimental group and 309in the control group.In the enhancement index AI,a total of 16 studies were included,482 in the experimental group and 481 in the control group.A total of5 studies compared the changes in AI levels.The total number was 398,and the experimental group was 194.Only 3 studies analyzed the effects of Vitamin D and its derivatives on the intima media thickness of the artery.The number of experimental group was 94,while the control group was 98.Only 1 studies have described the effect of vitamin D on ankle brachial index ABI.The control group was 29,and the test group was 26.2.Three different PWV（carotid-radial,carotid-femoral,and carotid-dorsalis-pedis）are analyzed.（I²=0%）,the results showed that the level of PWV in the Vitamin D group was lower than that of the control group.Supplementation of vitamin D could improve arterial stiffness,and tended to protect,but there was no statistical significance（WMD=-0.12,95%CI:-0.31⁰.07,P=0.22）;（WMD=-0.08,95%CI:-0.27⁰.11,P=0.42）;（WMD=-0.14,95%CI:-0.33⁰.04,P=0.13）.The effects of two different vitamin D receptor agonists on PWV were compared.When Vitamin D₂ was adopted as intervention,heterogeneity was greater and the result was not statistically significant（I²=79%,WMD=-0.01,95%CI:-0.18⁰.16,P=0.92）.Sensitivity analysis was carried out by single item study method（I²=0%,WMD=0.07,95%CI:0.01⁰.12,P=0.01）,and the results showed statistical significance.After incorporating the data of Vitamin D₃ for intervention measures,it was shown that the Vitamin D group could promote the improvement of PWV,which was a favorable factor and had statistical significance（I²=32%;WMD=0.06,95%CI:0.01⁰.11,P=0.02）.3.Compared with the Vitamin D group and the control group AI,the heterogeneity was larger.Compared to the control group,Vitamin D could effectively reduce the patient AI and have statistical significance（I²=73%,WMD=-1.63,95%CI:-3.17^-0.1,0.04）.After removing Cora2015 and Dreyer 2014,the homogeneity was satisfactory and the data analysis was statistically significant（I²=27%,WMD=-2.13,95%CI:-3.51^-0.75,P=0.003）.There is a certain heterogeneity in the amount of AI variation.And it does not improve the patient’s AI.（I²=51%,WMD=-0.06,95%CI:-0.80⁰.69,P=0.88）.The weight of Lavienja 2004 and Thomas 2012 was significant.After elimination,heterogeneity could be seen to improve the AI of patients,but there was no statistical significance（I²=0%,WMD=1.5,95%CI:-0.19³.19,P=0.08）.4.Vitamin D supplementation improved the progression of IMT（I²=0%,WMD=-0.06,95%CI=-0.1 to-0.02,P=0.007）.Only 1 studies reported that vitamin D can improve ABI.The baseline data of the control group was1.1±0.13 and there was no significant change after 1.1±0.07.The baseline data of the experimental group were 1.14±0.19,and 1.04±0.15 after follow-up.5.In subgroup analysis of patients with chronic kidney disease,the results showed that the use of vitamin D could improve the progress of PWV but was not statistically significant（WMD=-0.15,95%CI:-0.72⁰.43,P=0.62）.In the subgroup analysis of patients with baseline vitamin D deficiency,the results showed that the use of vitamin D improved the progression of PWV but not statistically significant.（I²=35%,WMD=-0.10,95%CI:-0.38⁰.17,P=0.46）.But it can improve the progress of AI and have statistical significance.（WMD=-1.74,95%CI:-2.23^-1.24,P=<0.00001）.In patients with baseline vitamin D deficiency,the results showed that vitamin D could reduce the PWV level of the three measurement methods,but there was no statistical significance.（WMD=-0.10,95%CI:-0.38⁰.17,P=0.46）.（WMD=-0.26,95%CI:-0.56⁰.04,P=0.09）.（WMD=-0.20,95%CI=-0.50⁰.11,P=0.21）and can improve the progress of AI at the same time without statistical significance（WMD=-1.20,95%CI:-3.26⁰.85,P=0.25）.Conclusion:Supplementation of vitamin D and its derivatives can improve arterial enhancement index and intima-media thickness,and there is no conclusive evidence for arterial pulse wave velocity and ankle-brachial index.Therefore,the effect of supplemental vitamin D and its derivatives on arterial stiffness still requires a larger sample of more closely designed randomized controlled trials and prospective cohort studies to further clarify.