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

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 effects(2,3). The authors(1) 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 relevant(2). Indeed, statin discontinuation may increase the risk of vascular events(4,5). 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 increasing(1,6-8). Obesity may be a cause(7) and decreased exposure to sunlight (including the use of sun blocks) may be relevant(6). 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 computers(6). Better detection and awareness of this deficiency may also be relevant in clinical practice but would not explain all the epidemiological(1,6-8). Vitamin D supplementation seems to be clinically relevant because of links with vascular risk factors(9). For example, vitamin D deficiency is associated with an increased risk of insulin resistance, metabolic syndrome and diabetes(10-14), at least in some studies(15). 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 resistance(16). This finding agrees with the interpretation that in obesity, both low 25OHD concentration and insulin resistance appear to be dependent on increased body size(17), although others showed 25OHD concentration to be independent of adiposity(18). Various links between vitamin D deficiency and dyslipidaemia have been reported in some but not all studies(15,19,20). These include possible associations between low vitamin D levels and high triglyceride levels 11,21,22, low levels of high density lipoprotein (HDL) cholesterol(14,23-25) as well as HDL quality(26). High dose oral vitamin D supplementation did not improve blood pressure (BP) in one study 27 but in another one low serum vitamin D levels in US adolescents was associated with hypertension independently of adiposity(18). Two systematic reviews/meta-analyses have considered the link between vitamin D and BP(28,29). Overall, there is some evidence that vitamin D sufficiency lowers the BP but more research is needed(28,29). 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 not(30,31). 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 vitamin(32). The mechanism involved may be interference by 'vitamin D' on cholesterol synthesis and potential synergistic action with atorvastatin(32). The work of Glueck et al.(1) and others(33), 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.