Low vitamin D does not predict statin associated muscle symptoms but is associated with transient increases in muscle damage and pain

Abstract

Background and aims: Low vitamin D (VITD) may contribute to statin-associated muscle symptoms (SAMS). We examined the influence of baseline and change in VITD in patients with verified SAMS.

Methods: SAMS was verified in 120 patients with prior statin muscle complaints using 8-week randomized, double-blind crossover trials of simvastatin (SIMVA) 20 mg/d and placebo. 25 (OH)vitamin D was measured at each phase of the trial.

Results: Forty-three patients (35.8%) experienced muscle pain on SIMVA but not placebo, exhibiting confirmed SAMS. VITD (mean ± standard deviation) prior to SIMVA treatment was not different between patients who did (31.7 ± 12.1 ng/mL, n = 43) or did not (31.6 ± 10.3 ng/mL, n = 77) develop SAMS and did not predict SAMS (p = 0.96). The change in VITD with SIMVA treatment was not different between patients with and without SAMS (0.3 ± 5.9 vs. 0.2 ± 8.3 ng/mL, respectively) and did not predict SAMS (p = 0.96). The proportion of patients classified as VITD deficient (<20 ng/mL) did not differ between patients with (n = 16) and without (n = 10) SAMS (χ2 = 1.45; p = 0.23), nor did the proportion of patients classified as VITD insufficient (<30 ng/mL) (n = 42 vs. 48; χ2 < 0.01 and p = 0.94). Both baseline and on-statin VITD were inversely related to the change in creatine kinase (CK) with statin therapy (p = 0.01 and 0.02, respectively), independent of SAMS (p = 0.36 and 0.35).

Conclusions: Baseline VITD, VITD deficiency/insufficiency and changes in VITD with statin therapy do not predict SAMS in patients with rigorously verified SAMS. However, low VITD may exacerbate statin-induced muscle injury and could contribute to SAMS development with a longer duration of statin treatment.

Trial registration: ClinicalTrials.gov NCT01140308.

Keywords: Muscle symptoms; Statin myalgia; Vitamin D deficiency.

Conflict of interest statement

Conflict of interest

Mrs. Lorson and Dr. White do not have any conflicts of interest or financial disclosures.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Figures

Fig. 1. Seasonal variations in vitamin D

Group means (± standard deviation) of 25 (OH)vitamin D levels post-statin and placebo therapy (A) and as changes with statin and placebo therapy (B), categorized by season.

Fig. 1. Seasonal variations in vitamin D

Group means (± standard deviation) of 25 (OH)vitamin D levels post-statin and placebo therapy (A) and as changes with statin and placebo therapy (B), categorized by season.

Fig. 2. Impact of clinical vitamin D classifications on SAMS

Percent of patients with vitamin D deficiency (vs. did not develop (n=77) confirmed SAMS.

Fig. 3. Creatine kinase levels and vitamin D

Relationship between the chance in creatine kinase with simvastatin treatment and post-simvastatin vitamin D levels, graphed as data points in individual patients with confirmed SAMS (black circles) and without SAMS (white triangles). There was no influence of SAMS so the regression line represents all data in the sample.

Fig. 4. Pain severity and vitamin D

Relationship between the change in pain severity score (PSS) and change in vitamin D with placebo treatment, graphed as data points in individual patients with confirmed SAMS (black circles) and without SAMS (white triangles). There was a significant influence of SAMS (p < 0.01) so regression lines are graphed for each group separately.