Peripheral Iron Metabolism is Associated with Leg Movements on Polysomnography but Not with the Severity of Restless Legs Syndrome or Its Impact on Patients

Tiantian Wang; Jiahui Xu; Qinglin Xu; Rui Zhao; Liuqing Pan; Danyan Zhu; Yu Pan; Lehui Chen; Guodong Lou; Xiaoye Xu; Jin Wang; Lisan Zhang

doi:10.2147/NSS.S378970

Peripheral Iron Metabolism is Associated with Leg Movements on Polysomnography but Not with the Severity of Restless Legs Syndrome or Its Impact on Patients

Nat Sci Sleep. 2022 Oct 13:14:1829-1842. doi: 10.2147/NSS.S378970. eCollection 2022.

Authors

Tiantian Wang^{1

2

3}, Jiahui Xu^{2

4}, Qinglin Xu^{2

4}, Rui Zhao⁵, Liuqing Pan², Danyan Zhu³, Yu Pan², Lehui Chen⁶, Guodong Lou^{2

5}, Xiaoye Xu⁷, Jin Wang⁴, Lisan Zhang^{2

4}

Affiliations

¹ Department of Pharmacy, Xiasha Campus, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
² Department of Neurology/Center for Sleep Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
³ Institute of Pharmacology and Toxicology, College of Pharmaceutical Science, Zhejiang University, Hangzhou, People's Republic of China.
⁴ Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
⁵ Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
⁶ Department of Internal Medicine, Hangzhou Wuyunshan Hospital, Hangzhou, People's Republic of China.
⁷ Department of Nursing, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Abstract

Purpose: This study investigated the associations of peripheral iron status with different manifestations of restless legs syndrome (RLS), including leg movements (LMs) on polysomnography (PSG), disease severity, and impact on patients.

Patients and methods: In this cross-sectional study, 108 patients with RLS were enrolled at Sir Run Run Shaw Hospital's Center for Sleep Medicine. Demographic information, disease characteristics, RLS severity, and impact on patients were assessed through a semi-structured questionnaire. Peripheral iron indicators [serum ferritin, iron, and transferrin concentrations; unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC); transferrin saturation (TSAT)] were measured following PSG to assess sleep stages, respiratory events, microarousals and LM parameters. Data from patients with and without ferritin concentration < 50 µg/L were compared in crude analyses, and Spearman correlations of other iron indicators with RLS data were examined. An ordinal logistic regression model was used to adjust for age, sex, body mass index, years of education, age at the time of RLS onset, prior treatment (yes/no), C-reactive protein (CRP)/hemoglobin level, total sleep time and apnea-hypopnea index.

Results: Multivariate analysis showed that periodic LMs during sleep (PLMS) and other LM parameters were significantly associated with a ferritin concentration < 50 µg/L, UIBC, TIBC, and serum transferrin concentration, but not serum iron or TSAT. By contrast, the severity and impact of RLS were not associated with a ferritin concentration < 50 µg/L or other peripheral iron indicators in the multivariate model.

Conclusion: In this study, peripheral iron status was associated mainly with motor components (LMs on PSG) rather than sensory components (severity and impact of RLS) after adequately controlling for potential confounders, such as CRP and hemoglobin levels. Commonly used peripheral iron metabolism indicators may therefore not be ideal biomarkers of RLS severity or impact on patients.

Keywords: impact; leg movements; peripheral iron metabolism; polysomnography; restless legs syndrome; severity.