In our present study, we found patients with SVD were correlated with the deficiency of 25(OH)D. We also found that there was a significant interaction between vitamin D status and hypertension in patients with SVD.
SVD is a common cause of stroke and worsens all stroke outcomes. SVD is associated with vascular risk factors such as hypertension. As a neurosteroid, vitamin D may play a vital role in preventing vascular injury through the mechanisms of lowering blood pressure, inhibiting the renin-angiotensin-aldosterone system, and inhibiting atherogenesis [6]. Accumulating evidences have also supported the hypothesis that lower 25(OH)D level was associated with increased risk of ischemic stroke, higher mortality and poor functional outcome in different races or ethnicities [11-22], and higher level of vitamin D was linked with a decreased risk of cerebrovascular disease [23]. These findings were also substantiated from meta-analysis [24]. However, as for the SVD, the relationship between vitamin D status and SVD has been still uncertain [25]. Recently, some cross-sectional studies proved that 25(OH)D was inversely associated with lacunes, WMHs and deep CMBs [7]. The findings from India also revealed that deficient levels of vitamin D were associated with 2.2-fold increase in odds of VaD due to SVD [8]. As for the total burden of SVD, lower levels of 25(OH)D was associated with greater total SVD burden seen on MRI in ischemic stroke [9]. However, the above studies had limited representation of the individuals from China. In our study, we further confirmed patients with SVD were correlated with the deficiency of 25(OH)D. Our study was in line with the former studies in different race such as in in Nepalese population or India [11, 26-30].
Hypertension is considered as an important, preventable risk factor for cardiovascular and stroke. There is a growing body of evidences about the association between vitamin D and hypertension in different ethnicities. In Asian Indian population, an inverse association was found between 25(OH)D and risk of ischemic stroke, which indicated that management of hypertension and treatment of severe vitamin D deficiency particularly in hypertensive subjects could be helpful to prevent stroke effectively [31]. Another observational studies also supported a relationship between 25(OH)D, a higher blood pressure and ischemic stroke [32]. Our results are consistent with the former studies [8, 31], with the evidence that presence of hypertension may amply aggravate the risk of SVD with low vitamin D levels [33]. Our findings also seem to be in some accordance with the evidence of cardiovascular disease from our research team, with the results that presence of hypertension may modify the association of vitamin D deficiency with severity of coronary stenosis [34]. As known, both hypertension and vitamin D deficiency are controllable and treatable parameters, thus, monitoring and management of vitamin D and hypertension may reduce the risk of SVD in China. Random clinical trials should also focus on supplementation of vitamin D in subjects with vitamin D deficiency and particularly those with a history of hypertension.
However, the mechanism of deficiency of vitamin D and the developing of SVD is not fully understood. It has been reported that vitamin D may also play a role in neuroprotection, perhaps through detoxification pathways, stimulation of neurotrophic factors, inhibition of inducible nitric oxide synthase, antioxidation/anti-inflammatory, neuronal calcium regulation, enhanced nerve conduction, as well as antithrombotic properties [35]. Serum vitamin D levels were inversely associated with the levels of interleukin-6 and C reactive protein, suggesting a potential anti-inflammatory role for vitamin D in stroke [36, 37]. It is also plausible that vitamin D supplementation could be a beneficial intervention for the prevention and treatment of stroke. Contributing mechanisms have been linked to the association of vitamin D deficiency with the presence of hypertension and atherosclerosis, however, the conclusions are still conflicting and data from large, randomized clinical trials are needed to clarify these speculations[38].
Our study also had some limitations. Firstly, this study was designed as a cross-sectional study from two centers in north of China, however, we could not prove a causal relationship between 25(OH)D and SVD. Studies with a larger numbers from multiple centers in China are needed urgently to further confirm our findings. Secondly, the multiple other factors such as nutrition status, physical activity, additional vitamin D supplementation, the levels of serum calcium, phosphorus and parathyroid hormone, health education, social status, levels of inflammatory markers, seasonal categories (such as summer or winter), vitamin D receptor gene polymorphism were not available in our study [8, 31, 39]. However, these factors were also of utmost importance, and we could not adjust multivariable analysis for these variables. Thirdly, we did not classify SVD into different types according to neuroimaging such as lacunes, WMHs, CMBs or brain atrophy [7, 40]. It has been reported that the severity of SVD could be assessed by total SVD burden (0 to 4) [9]. Further studies are required to confirm this association and explore the association among different subtypes of SVD on neuroimaging [7, 13]. Fourthly, there were some different categories according to levels of vitamin D (stratified into 2 or 3 or 5 categories) in different studies [31, 41], such as deficiency (<25nmol/L or <20ng/mL), insufficiency (25–50nmol/L or 20–30ng/mL), sufficiency (≥50nmol/L or ≥ 30ng/mL) [37, 42, 43]. In spite of these limitations, to the best of our knowledge, this is the first study to report a link between vitamin D status and hypertension associated with SVD in Chinese population. However, our findings also need to be validated in a larger study in other regions in China.