Association of Vitamin D and Incident Statin Induced Myalgia—A Retrospective Cohort Study

Abstract

Background and ObjectivesEvidence is conflicting with regards to the role of vitamin D in statin induced myalgia (SIM). Studies so far have assessed cross-sectional association and were limited by study sample selected predominantly from cardiology clinics. In this retrospective cohort study we assessed the association between vitamin D and SIM and attempted to establish a serum vitamin D cutoff to identify patients at risk for developing SIM.MethodsMedical charts of 5526 consecutive patients from a primary care practice in Scranton, Pennsylvania from 2005–2012 were reviewed. Vitamin D level (25-hydroxy cholecalciferol) at statin initiation was considered “Exposure level”. Vitamin D levels were categorized into quartiles (≤ 10, 11–20, 21–30, >30 ng/ml). SIM was identified by patient report.Results1160 out of 5526 patients were treated with statins. The mean age was 55.9 years. 276 (24%) developed SIM. Unadjusted 7-yr cumulative incidences of SIM for quartiles 1–4 of vitamin D were 32.3, 21.5, 18.3 and 14.6% respectively. The lowest quartile of vitamin D was independently associated with 1.21 times the hazard of the fourth quartile for developing SIM (95% CI: 1.09, 1.33; P-trend = 0.001). Vitamin D cut-off ≤15 ng/ml, showed a positive predictive value, negative predictive value, likelihood ratio (LR) + and LR- of 81, 90, 5.1 and 0.1, respectively for predicting SIM.ConclusionsLow vitamin D level at statin initiation is associated with SIM, levels ≤15 ng/ml have a high predictive accuracy for SIM. Randomized controlled trials are needed to validate our results.

Analysis of vitamin D levels in patients with and without statin-associated myalgia — A systematic review and meta-analysis of 7 studies with 2420 patients

“…In some available studies, low serum concentrations of 25-hydroxyvitamin D (≤ 20 ng/mL) have been associated with myalgia and reduced muscle function [33][34][35][36][37][38][39][40]. Ahmed et al [21] reported that 128 statin-treated patients with myalgia had significantly lower mean serum vit D level than 493 asymptomatic patients (28.6 ± 13.2 vs 34.2 ± 13.8 ng/mL).…”

“…The effect of vit D levels (as well as its supplementation) in patients with statinassociated myalgia was investigated in several studies [21,[33][34][35][36][37][38]. As a part of a cohort study evaluating the relationship between serum vit D levels and myalgia [21], 82 vit D deficient myalgic patients (vit D level: 20.8 ± 7.1 ng/mL) were prescribed 50,000 units of ergocalciferol weekly for 12 weeks.…”

“…Of those, 20 were scrutinized as full texts; 13 studies were considered unsuitable, while 7 [21,[33][34][35][36][37][38] met the inclusion criteria and were included in the analysis (Fig. 1).…”

Vitamin D Deficiency and Cardiovascular Diseases

“…60 Recent studies have reported that vitamin D deficiency is associated with a higher prevalence of myalgia induced by statins. 61 In 2014, Shantha et al 62 performed a retrospective study with 5,526 patients followed by a prospective analysis in which the patients were followed up for 7 years. The patients with measured serum vitamin D levels who started treatment with statins were considered as the exposure group.…”

“…The authors concluded that low levels of vitamin D were associated with myalgia and that a cutoff level of 15 ng/ mL for vitamin D showed a high accuracy in predicting the emergence of myalgia induced by statins. 62 In 2015, Morioka et al 63 performed a study with 5,907 patients to analyze if the level of vitamin D would modify the association between the use of statin and the emergence of musculoskeletal pain. The authors concluded that the group with vitamin D level below 15 ng/mL and using statins presented an approximately two-fold greater chance of developing musculoskeletal pain than patients who also had vitamin D levels below 15 ng/mL but were not treated with statins.…”