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

Atherosclerosis. 2017 Jan;256:100-104. doi: 10.1016/j.atherosclerosis.2016.11.011. Epub 2016 Nov 12.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / blood
  • Creatine Kinase / blood
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Male
  • Middle Aged
  • Myalgia / blood
  • Myalgia / chemically induced*
  • Myalgia / diagnosis
  • Risk Assessment
  • Risk Factors
  • Simvastatin / adverse effects*
  • Time Factors
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / diagnosis

Substances

  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Vitamin D
  • 25-hydroxyvitamin D
  • Simvastatin
  • Creatine Kinase

Associated data

  • ClinicalTrials.gov/NCT01140308