Abstract
(1) Introduction: High sensitivity C-reactive protein (hs-CRP) and CRP are inflammatory biomarkers associated with several inflammatory diseases. In both pediatric and adult individuals with Obstructive Sleep Apnea (OSA) higher hs-CRP and CRP were observed, compared to controls. With the present systematic review, meta-analysis and meta-regression we expand upon previous meta-analyses in four ways: (1) We included 109 studies (96 in adults and 13 in children); (2) we reported subgroup and meta-regression analyses in adults with OSA compared to controls on the serum and plasma levels of hs-CRP; (3) we reported subgroup and meta-regression analyses in adults with OSA compared to controls on the serum and plasma levels of CRP; (4) we reported serum and plasma levels of both hs-CRP and CRP in children with OSA, always compared to controls. (2) Materials and Methods: The PubMed/Medline, Scopus, Cochrane Library, and Web of Science databases were searched to retrieve articles published until 31 May 2020, with no restrictions. The data included basic information involving the first author, publication year, country of study, ethnicity of participants in each study, age, BMI, and AHI of both groups, and mean and standard deviation (SD) of plasma and serum levels of CRP and hs-CRP. (3) Results: A total of 1046 records were retrieved from the databases, and 109 studies were selected for the analysis (96 studies reporting the blood levels of hs-CRP/CRP in adults and 13 studies in children). For adults, 11 studies reported plasma hs-CRP, 44 serum hs-CRP, 9 plasma CRP, and 32 serum CRP levels. For children, 6 studies reported plasma hs-CRP, 4 serum hs-CRP, 1 plasma CRP, and 2 serum CRP levels. Compared to controls, the pooled MD of plasma hs-CRP levels in adults with OSA was 0.11 mg/dL (p < 0.00001). Compared to controls, the pooled MD of serum hs-CRP levels in adults with OSA was 0.09 mg/dL (p < 0.00001). Compared to controls, the pooled MD of plasma CRP levels in adults with OSA was 0.06 mg/dL (p = 0.72). Compared to controls, the pooled MD of serum CRP levels in adults with OSA was 0.36 mg/dL (p < 0.00001). Compared to controls, the pooled MD of plasma hs-CRP, serum hs-CRP, plasma hs-CRP, and serum hs-CRP in children with OSA was 1.17 mg/dL (p = 0.005), 0.18 mg/dL (p = 0.05), 0.08 mg/dL (p = 0.10), and 0.04 mg/dL (p = 0.33), respectively. The meta-regression showed that with a greater apnea-hypapnea index (AHI), serum hs-CRP levels were significantly higher. (4) Conclusions: The results of the present systematic review, meta-analysis and meta-regression showed that compared to healthy controls plasma and serum levels of hs-CRP and serum CRP level were higher in adults with OSA; for children, and compared to controls, just plasma hs-CRP levels in children with OSA were higher.
Highlights
Repeated episodes of partial or complete obstruction of the airways during sleep characterize Obstructive Sleep Apnea (OSA) [1]
110 full text articles were excluded for the following reasons (9 reviews. 4 meta-analyses. 39 articles had no control group or included control group with an Apnea– Hypopnea Index (AHI) > 5 in adults. 3 articles included control group with an AHI > 1 in children. 1 article didn’t show AHI. 4 articles included groups under treatment. 4 articles included overlap data with other studies. 8 articles included OSA participations with other diseases. 17 articles included OSAS. 5 articles included less than 10 cases in one group or both groups. 3 letters to editor. 2 animal studies. 4 included participants with sleep-disordered breathing (SDB). 2 articles didn’t include data. 1 book chapter. 4 articles reported irrelevant data)
The findings of this systematic review, meta-analysis and meta-regression demonstrated that higher plasma and serum levels of hs-C-reactive protein (CRP) and serum levels of CRP in individuals with OSA appeared to be associated with the disease severity
Summary
Repeated episodes of partial or complete obstruction of the airways during sleep characterize Obstructive Sleep Apnea (OSA) [1]. A systematic review in 2017 found that the overall prevalence of OSA ranged from 9 to 38% of the general adult population, from 13 to 33% and 6 to 19% in males and females, respectively, with higher prevalence rates in elderly individuals [5]. OSA is more prevalent in males than females [6], and OSA increases with age in adults [7]. OSA is related to overweight: the prevalence of OSA varies from 60% to 70% in obese people, and reaches more than 90% in individuals with severe obesity [8,9]. OSA may be associated with structural brain alternations [10], and two recent meta-analyses showed that compared to healthy controls inflammation biomarkers such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α (two pro-inflammatory cytokines) were higher in individuals with OSA [11,12]
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