Dataset Information

Increased platelet activation in sleep apnea subjects with intermittent hypoxemia.

ABSTRACT:

Purpose

Obstructive sleep apnea (OSA) is independently associated with increased risk for stroke and other cardiovascular diseases. Since activated platelets play an important role in cardiovascular disease, the objective of this study was to determine whether platelet reactivity was altered in OSA subjects with intermittent nocturnal hypoxemia.

Methods

Thirty-one subjects, without hypertension or cardiovascular disease and not taking medication, participated in the study. Subjects were stratified based on OSA-related oxygen desaturation index (ODI) recorded during overnight polysomnography. Platelet reactivity to a broad panel of agonists (collagen, thrombin, protease-activated receptor1 hexapeptide, epinephrine, ADP) was measured by monitoring platelet aggregation and ATP secretion. Expression of platelet activation markers CD154 (CD40L) and CD62P (P-selectin) and platelet-monocyte aggregates (PMA) was quantified by flow cytometry.

Results

Epinephrine-induced platelet aggregation was substantially decreased in OSA subjects with significant intermittent hypoxemia (ODI ≥ 15) compared with subjects with milder hypoxemia levels (ODI < 15) (area under curve, p = 0.01). In addition, OSA subjects with ODI ≥ 15 exhibited decreased thrombin-induced platelet aggregation (p = 0.02) and CD40L platelet surface expression (p = 0.05). Platelet responses to the other agonists, CD62P platelet surface expression, and PMA levels were not significantly different between groups. Reduction in platelet responses to epinephrine and thrombin, and decreased CD40L surface marker expression in significant hypoxemic OSA individuals, is consistent with their platelets being in an activated state.

Conclusions

Increased platelet activation was present in otherwise healthy subjects with intermittent nocturnal hypoxemia due to underlying OSA. This prothrombotic milieu in the vasculature is likely a key contributing factor toward development of thrombosis and cardiovascular disease.

Trial registration

NCT00859950.

SUBMITTER: Krieger AC

PROVIDER: S-EPMC7415497 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Obstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, there is very little information about the role of intermittent hypoxemia in LA remodeling in patients with OSAS. In total, 154 patients with sleep-related breathing disorders (SRBD) were prospectively recruited for this study. All enrolled SRBD patients underwent polysomnography and echocardiography. Significant OSAS was defined as an oxygen desaturation index (ODI) of ≥10 per hour. Intermittent hypoxia/reoxygenation (IHR) stimulation was used to test the effect of hypoxia on the viability, reactive oxygen species, apoptosis, and inflammation-associated cytokine expression in the HL-1 cell line. To investigate the effect of patients' exosomes on HIF-1 and inflammation-associated cytokine expression, as well as the relationship between ODI and their expression, exosomes were purified from the plasma of 95 patients with SRBD and incubated in HL-1 cells. The LA size was larger in patients with significant OSAS than in those without. There was a significant association between ODI, lowest SpO2, mean SpO2, and LA size (all p < 0.05) but not between the apnea-hypopnea index and LA size. IHR condition caused increased LDH activity, reactive oxygen species (ROS) levels, and apoptosis in HL-1 cells and decreased cellular viability (all p < 0.05). The expression of HIF-1α, TNF-α, IL-6, and TGF-β increased in the IHR condition compared with the control (all p < 0.05). The expression of HIF-1α, IL-1β, and IL-6 increased in the HL-1 cells incubated with exosomes from those patients with significant OSAS than those without (all p < 0.05). There was a significantly positive correlation between ODI and the expression of HIF-1α, TNF-α, IL-1β, IL-6, and TGF-β; a significantly negative correlation between mean SpO2 and IL-6 and TGF-β; and a significantly negative correlation between the lowest SpO2 and HIF-1α (all p < 0.05). In conclusion, intermittent hypoxemia was strongly associated with LA remodeling, which might be through increased ROS levels, LDH activity, apoptosis, and the expression of HIF-1α and inflammation-associated cytokines.

Project description:Study objectivesTo investigate the effects of different intermittent hypoxemia properties on blood pressure (BP) and short-term blood pressure variability (BPV) in severe obstructive sleep apnea (OSA) patients.MethodsNocturnal BP was continuously monitored by measuring pulse transmit time. Apnea-related systolic BP elevation values were used to reflect BPV. Beat-to-beat R-R interval data were incorporated in polysomnography for heart rate variability analysis. The low-frequency/high-frequency band ratio was used to reflect sympathovagal balance. The rate of pulse oxyhemoglobin saturation (SpO₂) decrease was counted as the change in the percentage of SpO₂ per second after obstructive apnea and expressed as the oxygen desaturation rate (ODR). Patients with severe OSA (n = 102) were divided into 2 groups according to the median ODR: faster ODR (FODR group: ODR > 0.37, n = 50) and slower ODR (ODR ≤ 0.37, n = 52).ResultsComparisons between the 2 groups showed significantly higher systolic BP (SBP) values in the FODR group than in the slower ODR group (awake SBP 149.9 ± 18.3 vs 131.8 ± 15.6 mm Hg; asleep SBP: 149.6 ± 19.9 vs 128.7 ± 15.6 mm Hg; both P < .001), as well as short-term BPV (15.0 ± 4.8 vs 11.6 ± 3.6 mm Hg; P < .001), and the prevalence of hypertension (74.0% vs 26.9%; P < .001). Multiple linear regression analyses revealed that after adjusting for body mass index, functional residual capacity, expiratory reserve volume, and baseline SpO2, ODR, as assessed by ΔSpO₂/Δt, had the strongest association with both BP and short-term BPV. Correlation analysis showed that ODR was positively correlated with the low-frequency/high-frequency band ratio (r = .288, P = .003).ConclusionsODR, as a novel hypoxemia profile, was more closely associated with the elevation of BP and BPV in patients with severe OSA. FODR might be associated with enhanced sympathetic activity.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Characteristics of Obstructive Sleep Apnea Syndrome Related Hypertension and the Effect of Continuous Positive Airway Pressure Treatment on Blood Pressure; URL: https://clinicaltrials.gov/ct2/show/NCT03246022; Identifier: NCT03246022.