Vitamin D deficiency, statin-related myopathy and other links with vascular risk

Key words::

• Myopathy
• Statins
• Vascular risk
• Vitamin D

In this issue of Current Medical Research and Opinion, Glueck et al.1 report that supplementation with vitamin D in patients who were vitamin D deficient and also had statin-related myositis–myalgia resulted in considerably more patients able to restart statin treatment. As the authors point out statin-related myopathy is a major cause of lack of adherence (compliance) with statin treatment although these drugs may also have other adverse effects2,3. The authors1 discuss the mechanisms responsible for statin-related myopathy.

The Glueck et al.1 study has limitations as acknowledged by the authors. For example, patients were restarted on different statins and treatment was unblinded. However, their findings are potentially very important as statins are widely prescribed and play a key role in the prevention of vascular events. Good adherence with treatment is therefore clinically relevant2. Indeed, statin discontinuation may increase the risk of vascular events4,5.

This editorial will briefly consider the links between vitamin D and vascular risk. Treatment discontinuation due to statin-induced myopathy is one such link but there are numerous others.

The prevalence of vitamin D deficiency seems to be increasing1,6–8. Obesity may be a cause7 and decreased exposure to sunlight (including the use of sun blocks) may be relevant6. In this context, it is of interest that vitamin D levels were lower in children who spent >4 h/day watching television and videos, or using computers6. Better detection and awareness of this deficiency may also be relevant in clinical practice but would not explain all the epidemiological findings1,6–8.

Vitamin D supplementation seems to be clinically relevant because of links with vascular risk factors9. For example, vitamin D deficiency is associated with an increased risk of insulin resistance, metabolic syndrome and diabetes10–14, at least in some studies15. Interestingly, in obese women a loss of 10% of initial weight after low-calorie diet raised 25-hydroxyvitamin D (25OHD) levels; the increase was mainly associated with improvement of insulin resistance16. This finding agrees with the interpretation that in obesity, both low 25OHD concentration and insulin resistance appear to be dependent on increased body size17, although others showed 25OHD concentration to be independent of adiposity18.

Various links between vitamin D deficiency and dyslipidaemia have been reported in some but not all studies15,19,20. These include possible associations between low vitamin D levels and high triglyceride levels11,21,22, low levels of high density lipoprotein (HDL) cholesterol14,23–25 as well as HDL quality26.

High dose oral vitamin D supplementation did not improve blood pressure (BP) in one study27 but in another one low serum vitamin D levels in US adolescents was associated with hypertension independently of adiposity18. Two systematic reviews/meta-analyses have considered the link between vitamin D and BP28,29. Overall, there is some evidence that vitamin D sufficiency lowers the BP but more research is needed28,29.

As Glueck et al.1 mention, it may also be of interest that some statins (e.g. rosuvastatin and atorvastatin) seem to increase serum 25OHD levels while others (e.g. fluvastatin) do not30,31. There is also evidence showing that atorvastatin is not as effective in patients with vitamin D deficiency compared with patients with higher levels of this vitamin32. The mechanism involved may be interference by ‘vitamin D’ on cholesterol synthesis and potential synergistic action with atorvastatin32.

The work of Glueck et al.1 and others33, underlines the need to extensively investigate the links between vitamin D supplementation and statin-related myopathy as well as the influence of this vitamin on vascular risk. Further research into the mechanism underlying the effect of vitamin D on statin-related myopathy is also needed.

Transparency

Declaration of funding

This editorial was written independently; no company or institution supported it financially. No professional writer was involved.

Declaration of financial/other relationships

Some of the authors have given talks, attended conferences and participated in trials and advisory boards sponsored by various pharmaceutical companies. N.K. has received a grant from the Hellenic Atherosclerosis Society.