Due to the decreased survival rate, high cost of care, and frequent recurrence of VTE, it is thought to be a critical public health issue.
Although vitamin D is antithrombotic, associations between serum vitamin D status and the risk of venous thromboembolism (VTE) remain inconsistent.
Low vitamin D levels have previously been linked to an increased risk of VTE. However those findings may have been impacted by a potential dose-dependent effect. What's more, a previous meta-analysis that focused on case-control studies revealed no correlation between vitamin D level and VTE, indicating weak evidence on this topic.
To address these concerns, a new meta-analysis has sought to define the relationship between vitamin D level and the risk of VTE, alongside secondary analyses of study designs, the existence of neurological illnesses, and potential effects of vitamin D status.
This analysis included 16 observational studies involving 47,648 individuals, providing strong additional evidence on this topic.
The previous meta-analysis investigated the association of vitamin D status with the risk of VTE by combining odds ratio (OR) and hazard ratio (HR). In contrast, the current analysis assessed the data on OR and HR separately to minimise possible bias. The dose-dependent correlation between vitamin D levels and the risk of VTE was also assessed.
Additionally, this meta-analysis covered studies in various clinical settings so findings could be applied to a spectrum of individuals.
The authors conclude: “This updated meta-analysis of sixteen observational studies enrolling 47,648 individuals revealed a negative relationship between vitamin D status and the risk of VTE. The low heterogeneity (I2 = 31%) and the absence of significant publication bias in the current study highlighted the robustness of the derived evidence.”
Further studies are required to investigate the potential beneficial effect of vitamin D supplementation on the long-term risk of VTE.
Embase, Medaline, Cochrane Library, and Google Scholar databases were pulled to find observational studies exploring links between vitamin D level and the risk of VTE in people. The correlation between vitamin D levels and the risk of VTE was displayed as an OR or HR.
Secondary outcomes included the effects of research design, the existence of neurological disorders, and vitamin D status on the associations.
Pooled revealed a negative relationship between vitamin D levels and the risk of VTE either based on OR (1.74, 95% confidence interval (CI): 1.37 to 2.20, p < 0.00001; I2 = 31%, 14 studies, 16074 individuals) or HR (1.25, 95% CI: 1.07 to 1.46, p = 0.006; I2 = 0%, 3 studies, 37,564 individuals).
This association remained significant in subgroup analyses of the study design and in the presence of neurological diseases. Compared to individuals with normal vitamin D status, an increased risk of VTE was noted in those with vitamin D deficiency (OR = 2.03, 95% CI: 1.33 to 3.11) but not with vitamin D insufficiency.
Mechanism of action
The preservation of calcium and bone homeostasis is a well-known function of vitamin D, a secosteroid hormone. It has been discovered to have pleiotropic extraskeletal effects on the circulatory, nervous, and immunological systems. By its anti-inflammatory and anti-oxidative qualities, vitamin D can also protect vascular endothelial injury.
In addition, vitamin D inhibits the coagulation pathway, which makes it antithrombotic. Hence, a lack of vitamin D may hypothetically result in a prothrombotic state that could aid in the emergence of VTE.
The authors of the meta-analysis noted a number of drawbacks including the use of ‘retrospectively gathered and sparse data’, and the lack of account for the impact of the seasons on 25(OH)D levels.
They add: “Furthermore, extrapolating findings to populations with various ethnic backgrounds may not be justified given the large ethnic diversity in the prevalence of VTE that is known to exist.
“This link was not examined because there was a dearth of pertinent data, despite the gender difference in the prevalence of VTE and vitamin D levels. Additionally, we did not examine additional known blood coagulation-related variables that may affect the development of DVT, such as the existence of current malignancy or coagulopathy.”
“Is Circulating Vitamin D Status Associated with the Risk of Venous Thromboembolism? A Meta-Analysis of Observational Studies”
Authors: Kuo-Chuan Hung, Sheng-Hsiang Yang, Chia-Yu Chang, Li-Kai Wang, Yao-Tsung Lin, Chia-Hung Yu, Min-Hsiang Chuang and Jen-Yin Chen