C-Reactive Protein Is Elevated in Heart Failure Patients with Central Sleep Apnea and Cheyne-Stokes Respiration

Abstract

Background: Manifestation of central sleep apnea (CSA) with Cheyne-Stokes respiration is of major prognostic impact in chronic heart failure (CHF). Inflammatory processes have been linked to a progression of cardiovascular diseases, including heart failure. While an association of C-reactive protein (CRP) levels to obstructive sleep apnea has been documented before, there is a lack of information regarding variation of CRP levels in patients with CSA. Objectives: The objective of this study was to investigate a potential association of CRP levels to CSA severity in CHF patients. Methods: High sensitivity CRP levels were analyzed in 966 patients with CHF (BMI 26.3 ± 4.6, New York Heart Association class 2.6 ± 0.5, left ventricular ejection fraction 29.4 ± 7.9%, N-terminal pro-brain natriuretic peptide, NT-proBNP, level 2,209 ± 3,315 pg/ml) without sleep-disordered breathing (SDB; Apnea-Hypopnea Index, AHI, <5/h) or various degrees of CSA, documented by in-hospital cardiorespiratory polygraphy or polysomnography. Results: The CRP concentration in CHF patients was 0.550 ± 0.794 mg/dl in patients without SDB (AHI 0-4/h, n = 403) versus 0.488 ± 0.708 mg/dl in patients with mild CSA (AHI 5-14/h, n = 123, p = n.s.) and 0.660 ± 0.963 mg/dl in patients with moderate CSA (AHI 15-29/h, n = 160, p = n.s.). In patients with severe CSA (AHI ≥30/h, n = 280), significantly higher CRP concentrations were documented (0.893 ± 1.384 mg/dl, p < 0.05). Stepwise regression analysis revealed AHI, NT-proBNP and heart rate to be independently associated with elevated CRP levels. Conclusion: Severe CSA in CHF patients is associated with elevated levels of CRP, a systemic marker of inflammation and cardiovascular risk. This might explain in part the negative prognostic impact of CSA in these patients.

Impacts of Comorbidities on the Association between Arterial Stiffness and Obstructive Sleep Apnea in the Elderly

“…CRP is an important serum biomarker of inflammation that can predict cardiovascular risk in apparently healthy subjects [33] and heart failure patients with central sleep apnea [34]. However, the association between CRP and OSA is controversial [15, 35–37].…”

Brain metabolites in autonomic regulatory insular sites in heart failure

“…HF patients show compromised cerebral perfusion, secondary to low cardiac output, with localized changes in blood flow and axons [9]. Hypoxic/ischemic processes resulting from sleep-disorder breathing, which is commonly reported in HF [26], may also contribute to injury. HF subjects show both obstructive and central (Cheyne-Stokes) sleep apnea.…”

“…HF subjects show both obstructive and central (Cheyne-Stokes) sleep apnea. Apneic events may lead to hypoxic exposure in the brain, and thus, alter brain metabolites; intermittent hypoxic events trigger oxidative and inflammatory injurious mechanisms leading to neural injury [26]. Several limbic sites, including the insular cortices, show injury in obstructive sleep apnea in humans [27], and animal studies simulating intermittent hypoxia also show tissue damage in multiple limbic and cerebellar sites [28].…”

Recent Advances in Biomarker Discovery — from Serum to Imaging-based Biomarkers for a Complex Assessment of Heart Failure Patients

“…16 Another study of 966 patients with CHF showed that severe central sleep apnea (CSA) was associated with high levels of CRP, explaining thus the negative prognostic effect of sleep apnea. 17 pROCalCITONIN Procalcitonin (PCT) represents an inflammatory marker characteristic for early atherosclerosis. A study on 77 patients with ACS showed that an increased PCT in the first 48 h from admission in the hospital may be correlated to higher early and 6-month death rates.…”