Elsevier

Atherosclerosis

Volume 238, Issue 1, January 2015, Pages 77-82
Atherosclerosis

Vitamin D status modifies the association between statin use and musculoskeletal pain: A population based study

https://doi.org/10.1016/j.atherosclerosis.2014.11.012Get rights and content

Highlights

  • We examined the effect of vitamin D on statin-associated musculoskeletal pain.

  • Statin users with low vitamin D were more likely to report musculoskeletal pain.

  • Statin users with 25OHD ≥15 ng/mL had no increased risk for musculoskeletal pain.

  • Vitamin D status appears to modify the effect of statins on musculoskeletal pain.

Abstract

Background: Past studies examining the effect of vitamin D on statin myalgia have been variable; however, these studies were done in limited samples not representative of the general population. We aimed to evaluate whether vitamin D status modifies the association between statin use and musculoskeletal pain in a sample representative of the general population. Methods: We conducted a cross-sectional study using the National Health and Nutrition Examination Survey 2001–2004. Musculoskeletal symptoms and statin use were self-reported. Vitamin D status was assessed using serum 25 hydroxyvitamin D (25[OH]D), categorized as <15 ng/mL or ≥15 ng/mL. To evaluate if vitamin D status modifies the association between statin use and prevalent musculoskeletal pain, we performed multivariable-adjusted logistic regression models stratified by 25(OH)D status. Results: Among 5907 participants ≥40 years old, mean serum 25(OH)D was 23.6 ng/mL (95% CI, 22.9–24.3). In stratified multivariable-adjusted logistic regression models, individuals with 25(OH)D <15 ng/mL, using a statin had a significantly higher odds of musculoskeletal pain compared to those not using a statin (adjusted odds ratio [aOR], 1.90; 95% CI, 1.18–3.05). Among those with 25(OH)D ≥15 ng/mL, we found no significant association between statin use and musculoskeletal pain (aOR, 0.91; 95% CI, 0.71–1.16). Conclusion: Among adults ≥ 40 years old with 25(OH)D <15 ng/mL, statin users had nearly 2 times greater odds of reporting musculoskeletal pain compared to non-statin users. Our findings support the hypothesis that vitamin D deficiency modifies the risk of musculoskeletal symptoms experienced with statin use.

Introduction

Statin use is associated with a higher risk for musculoskeletal pain [1]. Vitamin D status has been proposed to modify the effect of statin use on musculoskeletal pain, with deficient vitamin D increasing the risk of statin-associated musculoskeletal symptoms [2]. However, prior studies have included statin-users only, and have yielded mixed results [2], [3], [4], [5], [6]. Therefore, it remains uncertain whether vitamin D deficiency modifies the effect of statin use by increasing the risk of musculoskeletal pain beyond that associated with statin use or vitamin D deficiency alone, or, alternatively, whether any association exists after adjustment for important confounders. We aimed to examine the effect of vitamin D on the relationship between statin use and musculoskeletal pain in the general population.

Section snippets

Methods

For this cross-sectional study we analyzed data from the National Health and Nutrition Examination Survey (NHANES), an ongoing, cross-sectional survey that uses a complex, stratified, multistage, probability-cluster design to select a representative sample of the civilian, non-institutionalized US population. All participants gave written informed consent. Public use data files were obtained from the NHANES website, and our analyses of these de-identified data were approved for exemption by the

Results

Among 5907 participants ≥40 years, 1057 participants, representing 19.6 million individuals, reported statin use. The distribution of serum 25(OH)D for participants is depicted in Fig. 1. The mean serum 25(OH)D for the overall study population (23.6 ng/mL; 95% confidence interval [CI], 22.9–24.3) did not differ from the mean serum 25(OH)D among statin users (23.4 ng/mL; 95% CI, 22.3–24.4). Table 1 shows that participants with 25(OH)D <15 ng/mL, compared to those with higher levels of vitamin D,

Discussion

In this cross-sectional study of 5907 individuals, we found that vitamin D deficiency modified the effect of statin on musculoskeletal pain among adults ≥40 years. Specifically, individuals with 25(OH)D <15 ng/mL who were using a statin had a nearly 2 times greater odds of musculoskeletal pain within the past month compared to those with 25(OH)D <15 ng/mL who did not use a statin. In contrast, among adults who had serum 25(OH)D ≥15 ng/mL, use of statins was not associated with musculoskeletal

Conclusion

In this cross-sectional nationally-representative study of 5907 individuals, we found that among adults ≥40 years with vitamin D deficiency (25(OH)D<15 ng/mL), use of a statin was associated with a nearly 2 times greater odds of reporting musculoskeletal pain compared to non-statin users. However, among individuals with vitamin D levels ≥15 ng/mL, no association between statin use and musculoskeletal pain was observed. Our findings support the hypothesis that vitamin D deficiency modifies the

Funding sources

Dr. Buettner was supported by K23 Career Development Award (K23AR055664). Dr. Bertisch was supported by K23 Career Development Award (K23AT005104). This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources) and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102 and financial contributions from Harvard University and its affiliated academic

Disclosures

The authors' affiliated organizations and funding sources had no involvement in the study design; collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the article for publication. Dr. Buettner and Beth Israel Deaconess Medical Center have applied for a patent for the combination of statin and vitamin D as a prophylactic treatment in migraine. All other authors have no indicated no financial conflicts of interests.

References (15)

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