Association of Sleep Deprivation and the Risk of Developing Systemic Lupus Erythematosus Among Women

Abstract

Objective: Sleep deprivation has been associated with risk of autoimmune diseases. Using the Nurses' Health Study (NHS) (1986-2016) and NHSII (1989-2017) cohorts, we aimed in the present study to investigate whether sleep deprivation was associated with risk of developing systemic lupus erythematosus (SLE).

Methods: Average sleep duration in a 24-hour period was reported in the NHS (1986-2014) and NHSII (1989-2009). Lifestyle, exposure, and medical information was collected on biennial questionnaires. Adjusted Cox regression analyses modeled associations between cumulative average sleep duration (categorical variables) and incident SLE. Interactions between sleep duration and shiftwork, bodily pain (using the Short Form 36 [SF-36] questionnaire), and depression were examined.

Results: We included 186,072 women with 187 incident SLE cases during 4,246,094 person-years of follow-up. Chronic low sleep duration (≤5 hours/night versus reference >7-8 hours) was associated with increased SLE risk (adjusted hazard ratio [HR_adj ] 2.47 [95% confidence interval (95% CI) 1.29, 4.75]), which persisted after the analysis was lagged (4 years; HR_adj 3.14 [95% CI 1.57, 6.29]) and adjusted for shiftwork, bodily pain, and depression (HR_adj 2.13 [95% CI 1.11, 4.10]). We detected additive interactions between low sleep duration and high bodily pain (SF-36 score <75) with an attributable proportion (AP) of 64% (95% CI 40%, 87%) and an HR for SLE of 2.97 (95% CI 1.86, 4.75) for those with both risk factors compared to those with neither. Similarly, there was an interaction between low sleep duration and depression, with an AP of 68% (95% CI 49%, 88%) and an HR for SLE of 2.82 (95% CI 1.64, 4.85).

Conclusion: Chronic low sleep duration was associated with higher SLE risk, with stronger effects among those with bodily pain and depression, highlighting the potential role of adequate sleep in disease prevention.

Figure 1.. Study schematic illustrating the prospective cohort design for NHSII.

The primary exposure was cumulative average sleep duration and the outcome was SLE onset at least two years after last sleep duration assessment. The primary analysis was conducted so that there was always at least two years between the last sleep duration exposure assessment and the outcome date of SLE diagnosis that occurred in the SLE risk window. The analysis for NHS was similar except for the years of sleep duration assessment (1986–2014). The sensitivity analysis was lagged by another follow-up cycle of two years so that there was at least four years between the last sleep duration exposure assessment and the outcomes dates of SLE diagnosis. NHS, Nurses’ Health Study, NHSII, Nurses’ Health Study II, SD, sleep duration, SLE, systemic lupus erythematosus.