Sleep Disorders vs. Systemic Immune-Inflammation Index (SII) in the U.S. Population (2023 Study)

Sleep and inflammation have long been topics of scientific inquiry, with a growing body of evidence underscoring their intricate relationship.

The systemic immune-inflammation index (SII), a novel marker based on leukocyte parameters, has emerged as a significant indicator of systemic inflammation.

A recent study explored the association between sleep-related disorders and SII, revealing intriguing connections that could have profound implications for understanding and managing sleep and inflammatory conditions.

Highlights:

Sleep-Related Disorders & Systemic Inflammation: Sleep problems, symptoms of obstructive sleep apnea (OSA), and daytime sleepiness are positively associated with higher levels of the systemic immune-inflammation index (SII) in adults.
SII as a Novel Inflammatory Marker: SII, calculated based on platelet, neutrophil, and lymphocyte counts, offers a robust measure of systemic immune response and inflammation, surpassing traditional markers like the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).
Implications for Public Health: The strong association between sleep-related disorders and SII highlights the potential of SII as a valuable tool for monitoring systemic inflammation in individuals with sleep disturbances, offering new avenues for research and intervention.
Need for Further Research: Despite the compelling findings, the cross-sectional nature of the study calls for caution in interpretation, underscoring the need for prospective studies to establish causality and further explore the relationship between sleep, SII, and overall health.

Source: BMC Psychiatry (2023)

Sleep & the Systemic Immune-Inflammation Index (Overview)

The relationship between sleep, inflammation, and the Systemic Immune-Inflammation Index (SII) is a compelling area of research that intertwines the domains of sleep science, immunology, and clinical biomarkers.

This intricate relationship highlights how disturbances in sleep can influence systemic inflammation, potentially impacting overall health.

Sleep vs. Inflammation

Sleep is a fundamental physiological process critical for maintaining optimal health and well-being.

It influences various bodily functions, including immune system regulation, metabolic balance, and neurological health.

Disruptions in sleep—whether in duration, quality, or timing—have been associated with an increased risk of developing chronic inflammatory conditions, such as cardiovascular disease, obesity, diabetes, and depression.

Mechanisms Linking Sleep & Inflammation

Cytokine Regulation: Sleep modulates the production and release of cytokines, key inflammatory mediators. Insufficient or disrupted sleep can lead to an imbalance in pro-inflammatory and anti-inflammatory cytokines, skewing towards a pro-inflammatory state.
Immune Cell Activation: During sleep, there are changes in the distribution and function of immune cells, such as neutrophils and lymphocytes. Disturbed sleep patterns can disrupt these changes, leading to altered immune responses and increased inflammation.
Hormonal Pathways: Sleep influences the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system, both of which play crucial roles in immune regulation. Sleep deprivation or disturbances can lead to HPA axis hyperactivity, increasing systemic inflammation.

What is the Systemic Immune-Inflammation Index (SII)?

The SII is a novel inflammatory index that integrates the counts of peripheral blood neutrophils, lymphocytes, and platelets, offering a comprehensive measure of systemic immune response and inflammation.

The calculation of SII is based on the following formula:

$SII = Lymphocyte count Platelet count \times Neutrophil count$

Significance of SII

Comprehensive Inflammatory Marker: SII provides a holistic view of the inflammatory state by combining the roles of platelets, neutrophils, and lymphocytes, each of which plays a distinct role in immune surveillance, response, and inflammation.
Predictive Value: Elevated SII levels have been associated with worse outcomes in various conditions, including cardiovascular diseases, cancer, and psychiatric disorders, highlighting its potential as a prognostic marker.
Sensitivity to Sleep-Related Changes: Given its comprehensive nature, SII appears to be more sensitive to changes related to sleep disturbances compared to traditional inflammatory markers like NLR and PLR.

How the Systemic Immune-Inflammation Index (SII) Works in the Context of Sleep

The relationship between sleep and SII is mediated through systemic inflammation.

Poor sleep quality or insufficient sleep duration can lead to an upregulated inflammatory response, as indicated by increased SII levels.

This elevation in SII may serve as a biomarker for the heightened inflammatory state associated with sleep disturbances, offering insights into the potential mechanisms linking poor sleep to various health risks.

Sleep Disorders & Elevated SII: Individuals with sleep disorders, such as insomnia or obstructive sleep apnea, often exhibit elevated SII levels, reflecting increased systemic inflammation.
Impact of Sleep Quality & Duration: Both short and excessively long sleep durations, as well as poor sleep quality, have been linked to higher SII levels, suggesting a U-shaped relationship between sleep duration, quality, and systemic inflammation.
Potential for Monitoring & Intervention: Monitoring SII levels in individuals with sleep disturbances could offer a valuable tool for assessing the efficacy of interventions aimed at improving sleep quality and reducing systemic inflammation.

Major Findings: Sleep Disorders vs. Systemic Immune-Inflammation Index (SII)

Kaisaierjiang Kadier et al. analyzed the relationship between sleep-related disorders and systemic inflammation, as gauged by the systemic immune-inflammation index (SII) and traditional inflammatory markers (NLR and PLR), in a large and diverse sample – below are the findings.

Sleep Disorders Strongly Linked to SII

The analysis revealed a more pronounced association between sleep-related disorders and the SII compared to traditional inflammatory markers.

Participants reporting sleep problems, symptoms indicative of obstructive sleep apnea (OSA), and those experiencing daytime sleepiness were found to have significantly higher SII levels.

This finding suggests that the SII, which encapsulates the immune response and inflammation via the integration of platelet, neutrophil, and lymphocyte counts, may be a more sensitive marker for detecting systemic inflammation associated with sleep disturbances.

Specific Sleep Disorders Linked to Increased SII

Sleep Problems: Participants who reported sleep problems had a positive association with an elevated SII, with regression coefficients indicating a notable increase in SII levels in this group.
Symptoms of OSA: Similarly, individuals with symptoms suggestive of OSA showed a significant association with higher SII levels, reinforcing the link between sleep-disordered breathing and systemic inflammation.
Daytime Sleepiness: The association between daytime sleepiness and increased SII was particularly striking, suggesting that the consequences of poor sleep quality or quantity extend beyond simple tiredness, potentially exacerbating systemic inflammatory responses.

Comparison with PLR & NLR

Weaker Associations: While the study also assessed traditional inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), these markers showed weaker associations with sleep-related disorders than SII. This distinction underscores the potential of SII as a more comprehensive and sensitive marker of systemic inflammation in the context of sleep disturbances.
Daytime Sleepiness & NLR: An interesting finding was the association between daytime sleepiness and elevated NLR levels, albeit weaker than the association with SII. This highlights a possible specific link between excessive daytime sleepiness and neutrophil-lymphocyte balance, suggesting that sleep quality may directly impact specific components of the immune system.

The Relationship Between Sleep Disorders & Immune-Inflammation (2023 Study)

The study aimed to investigate the relationship between sleep-related disorders and the systemic immune-inflammation index (SII) in a nationally representative sample of nonhospitalized adults in the United States.

It sought to determine whether sleep disturbances such as insufficient sleep duration, sleep problems, high risk of obstructive sleep apnea (OSA), and daytime sleepiness were associated with increased levels of SII, a novel inflammatory marker calculated based on leukocyte subsets.

Methods

Data Source: The study utilized data from the 2005–2008 National Health and Nutrition Examination Survey (NHANES), a large nationwide cross-sectional survey that provides information on the health and nutritional status of noninstitutionalized civilians in the United States.
Participants: Adults aged ≥20 years with available data on complete blood counts, sleep questionnaires, and without history of cancer or pregnancy were included. The final analysis encompassed 8,505 participants.
Sleep-Related Disorders Assessment: Self-reported data on sleep duration, sleep problems, risk of OSA, and daytime sleepiness were obtained from the NHANES Sleep Disorders Questionnaire.
Inflammatory Markers: The primary outcome variable was the systemic immune-inflammation index (SII), calculated using platelet, neutrophil, and lymphocyte counts. Secondary outcomes included traditional inflammatory markers, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).
Statistical Analysis: Multiple linear regression models were used to explore the association between sleep-related disorders and inflammatory markers. Adjustments were made for potential confounders, including demographic, socioeconomic, and health-related factors.

Findings

Association with SII: Sleep-related disorders were significantly associated with higher SII levels. Specifically, participants with sleep problems, symptoms of OSA, and daytime sleepiness showed a positive association with increased SII, even after adjusting for confounders.
Comparison with Traditional Markers: The association between sleep-related disorders and SII was stronger than that observed with traditional inflammatory markers (PLR and NLR).
Daytime Sleepiness and NLR: Among the secondary outcomes, only daytime sleepiness was associated with elevated NLR levels, suggesting a specific link between excessive daytime sleepiness and systemic inflammation.

Limitations

Cross-Sectional Design: The cross-sectional nature of the study limits the ability to infer causality between sleep-related disorders and inflammation.
Self-Reported Sleep Data: The reliance on self-reported measures for sleep-related disorders may introduce reporting bias and does not capture the complexity of sleep patterns as accurately as objective measures like polysomnography.
Single Measurement: Inflammatory markers were assessed based on a single blood test, which may not reflect longitudinal changes in inflammation levels.
Lack of Objective Sleep Measures: The study did not include objective sleep measures such as actigraphy, which could provide a more accurate assessment of sleep patterns and disturbances.
Potential Confounders: Although adjustments were made for a wide range of potential confounders, there may still be unmeasured factors that could influence the relationship between sleep-related disorders and systemic inflammation.

What are the potential implications of the study’s findings?

The study findings, revealing a significant association between sleep-related disorders and elevated levels of the Systemic Immune-Inflammation Index (SII), have broad potential applications and implications in clinical practice, public health policy, and future research.

Clinical Practice

Patient Screening & Monitoring: Clinicians could incorporate SII as a routine screening tool for patients with sleep disorders to identify those at higher risk of systemic inflammation. This would enable early intervention strategies to mitigate the risk of developing inflammation-related diseases.
Tailored Therapeutic Strategies: For patients with elevated SII levels, personalized treatment plans that address both sleep disturbances and underlying inflammatory processes could be more effective. This might include pharmacological interventions, lifestyle modifications, or cognitive-behavioral therapy for sleep disorders.
Prognostic Value: SII could serve as a prognostic marker in patients with existing inflammatory conditions, such as cardiovascular disease or diabetes, where sleep disturbances are known to exacerbate disease progression. Monitoring SII levels could help in predicting disease outcomes and tailoring long-term management plans.

Public Health

Sleep Health Promotion: The study underscores the importance of sleep health as a public health priority. Policies aimed at promoting good sleep hygiene, reducing societal factors that impair sleep (e.g., excessive screen time, work-related stress), and enhancing access to sleep disorder treatments could play a crucial role in mitigating systemic inflammation at the population level.
Educational Campaigns: Public health initiatives could include educational campaigns to raise awareness about the link between sleep, inflammation, and health outcomes. Highlighting the importance of maintaining regular sleep patterns and seeking treatment for sleep disorders could lead to improved health outcomes.
Workplace Health Programs: Employers could implement workplace health programs that encourage practices conducive to good sleep health, such as flexible working hours, stress management programs, and environments that promote physical activity. These programs could help in reducing the burden of sleep-related disorders and associated inflammation among the workforce.

Research

Longitudinal Studies: Future research could focus on longitudinal studies to establish causality between sleep disturbances, changes in SII levels, and the development of inflammatory diseases. This would provide deeper insights into the temporal relationship between sleep health and systemic inflammation.
Interventional Studies: Investigating the effects of interventions aimed at improving sleep quality (e.g., sleep hygiene education, treatment of sleep apnea) on SII levels could offer evidence-based strategies to reduce systemic inflammation.
Mechanistic Studies: Further studies are needed to elucidate the biological mechanisms through which sleep disturbances impact systemic inflammation, as measured by SII. Understanding these pathways could lead to the development of targeted therapies to mitigate inflammation in individuals with sleep disorders.

Conclusion: Sleep vs. Systemic Immune-Inflammation Index

The study highlights a significant link between sleep-related disorders and elevated levels of the Systemic Immune-Inflammation Index (SII), underscoring the intricate relationship between sleep disturbances and systemic inflammation.

By demonstrating that sleep problems, symptoms of obstructive sleep apnea, and daytime sleepiness are associated with higher SII levels, the findings highlight the potential of SII as a comprehensive marker for systemic immune response and inflammation in the context of sleep health.

This association suggests that individuals with sleep disturbances may be at an increased risk for conditions exacerbated by systemic inflammation, emphasizing the importance of integrating sleep health into strategies for disease prevention and management.

The study’s insights offer a foundation for clinical practice to incorporate SII as a screening and monitoring tool, enhancing personalized treatment approaches for patients with sleep disorders.

Moreover, the findings advocate for public health initiatives focused on improving sleep hygiene and addressing sleep disorders as a means to mitigate systemic inflammation.

Additional research should aim to elucidate the mechanisms underlying the sleep-inflammation link and explore intervention strategies to improve sleep quality and reduce inflammation, ultimately enhancing health outcomes.

References

Paper: Analysis of the relationship between sleep-related disorder and systemic immune-inflammation index in the US population (2023)
Authors: Kaisaierjiang Kadier et al.

Sleep Disorders vs. Systemic Immune-Inflammation Index (SII) in the U.S. Population (2023 Study)