Relationship between plasma fibrinogen level and obstructive sleep apnea

Open Access
01.12.2024
Research

Erschienen in:

Verfasst von: Reda Abd El-Razek; Tarek Elnahriry; Abdullah Hashish; Osama Shehab
Erschienen in: The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Ausgabe 1/2024

Abstract

Background

Obstructive sleep apnea (OSA), which causes recurring hypoxemia owing to upper airway closure, is one of the most frequent sleep disorders. OSA patients are more prone to suffer cardiovascular disease (CVD) and stroke. One primary mechanism connecting OSA with cardiovascular problems is the prothrombotic state. Our goal in this research is to confirm the relationship between plasma fibrinogen levels and OSA.

Results

A case–control study involved 20 adults, non-obese participants who had been recently diagnosed with OSA, had never been treated for OSA before, and did not have any other preexisting conditions, and 20 controls underwent measurement of plasma fibrinogen levels following whole night polysomnography. The patient's plasma fibrinogen levels were substantially more significant than the controls' (399.8 ± 54.7 versus 309.8 ± 26.7 mg/dL, respectively), with a p-value of less than 0.001. Plasma fibrinogen levels in moderate and severe OSA (383.6 ± 20.6 mg/dL and 454.4 ± 25.6 mg/dL, respectively) were significantly higher than in controls (309.8 ± 26.7 mg/dL) (p < 0.001 and p < 0.001) and mild OSA patients (335 ± 27.8 mg/dL) (p = 0.013 and p < 0.001). Plasma fibrinogen levels were not significantly different between the controls and patients with mild OSA (p = 0.219). Apnea–hypopnea index, arousal index, and oxygen desaturation index showed positive correlations with plasma fibrinogen (r = 0.953, 0.888, and 0.894, p = < 0.001, < 0.001, and < 0.001, respectively). The total sleep time, sleep efficiency, N3%, REM%, and lowest oxygen saturation showed negative correlations (r = − 0.860, − 0.877, − 0.611, − 0.844, and − 0.745, p = < 0.001, < 0.001, < 0.001, and < 0.001, respectively).

Conclusion

Elevated levels of plasma fibrinogen in individuals with moderate-to-severe OSA may be attributed to sleep apnea and these increased levels could serve as a significant risk factor that establishes a connection between OSA and pathology of the cardiovascular and cerebrovascular systems. These results could significantly affect OSA diagnosis, therapy monitoring, and outcome.

Hinweise
Abkürzungen

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Arousal index

AHI

Apnea–hypopnea index

BMI

Body mass index

CPAP

Continuous positive airway pressure

CRP

C-reactive protein

CVD

Cardiovascular diseases

EDS

Excessive daytime sleepiness

ESS

Epworth Sleepiness Scale

non-REM

Non-rapid eye movement

mg/dL

Milligrams per deciliter

ODI

Oxygen desaturation index

OSA

Obstructive sleep apnea

PSG

Polysomnography

REM

Rapid eye movement

SaO₂

Oxygen saturation

Background

Obstructive sleep apnea (OSA), which causes recurring hypoxemia owing to upper airway closure, is one of the most frequent sleep disorders. Between 14 and 49% of middle-aged males have OSA [1]. Recent studies show that OSA patients are more prone to cardiovascular disease (CVD) and stroke [2]. One primary mechanism connecting OSA with cardiovascular problems is the prothrombotic state. Hypercoagulability may develop in OSA patients due to abnormalities in hemostasis brought on by recurrent episodes of hypoxia during the night and disturbed sleep [3].

The liver is responsible for producing fibrinogen, one of the plasma proteins. Because it is an acute-phase protein, fibrinogen levels rise in inflammatory and infectious diseases as it is extremely important in blood clotting. Both the inflammatory phase of atherogenesis and the occurrence of coronary artery disease due to thrombus are associated with high fibrinogen levels [4]. According to a meta-analysis, fibrinogen levels were substantially linked to heart attacks and strokes [5]. The risk of major CVD almost doubles for every 100 mg/dL increase in fibrinogen levels [6].

Multiple studies have examined OSA patients' blood fibrinogen levels. The reason OSA patients had elevated fibrinogen levels is unknown, and various studies reported conflicting results. Our goal in doing this research is to confirm the relationship between plasma fibrinogen levels and OSA-related measures, such as the oxygen desaturation index (ODI), minimal oxygen saturation (SaO₂), arousal index (AI), and apnea–hypopnea index (AHI).

Methods

This case–control research included 20 adult patients at least 18 years old, regardless of gender, and who were not obese and had a body mass index (BMI) below 30 kg/m² [7] with clinical suspicion of OSA transferred to the sleep lab. Patients with anatomical features in the upper airway that obstruct airflow during sleep such as nasal obstruction due to polyps, stenosis, or septal deviation, patients with retroglossal blockage from macroglossia, and patients with retropalatal obstruction from an elongated palate, tonsil, uvula, or adenoid hypertrophy were included [8‐10]. Patients who are smokers, alcoholics, with other diseases such as acute or chronic cardiovascular, hypertension, diabetes mellitus, renal disease, hepatic disease, inflammatory or hyperfibrinogenemia inducing disease using any medications or had been treated for OSA were excluded. We recruited 20 healthy controls matched with patients regarding age, sex, and BMI. The ethical committee of the faculty of medicine approved the study, and informed consent forms were filled out by each participant.

All individuals who met the study's requirements underwent a comprehensive history taken from each participant, a thorough physical and neurological examination, and routine laboratory testing, which included C-reactive protein (CRP), screening for vasculitis, renal and liver function tests, lipid profile, fasting, postprandial blood sugar, hemoglobin A1C, and erythrocyte sedimentation rate were executed.

Epworth Sleepiness Scale (ESS) Arabic version was utilized for clinical estimation of OSA [11]. The total score range was 0–24. A score greater than ten was used as an indication of excessive daytime sleepiness (EDS) [12].

A whole night diagnostic polysomnography (PSG) study was conducted between 10:00 p.m. and 6:00 a.m. The E-Series EEG/PSG device, developed by Compumedics Limited in 2004 in Australia, was used by a sleep technologist to conduct the PSG exam, which includes the following: a thermal device designed to measure nasal–oral airflow and nasal pressure; a snoring sensor; respiratory effort assessed using abdominal and chest belts; electromyography (EMG) performed on the anterior muscles of the right and left tibia; electroencephalography (EEG) with two derivations in the front, two in the center, and two in the occipital regions; and electrooculography (EOG) performed on the right and left eye. Clinical neurophysiologists used the American Academy of Sleep Medicine-established principles to manually stage sleep and rate events [13]. The total sleep time, sleep onset, sleep efficiency, awakenings number, sleep stages and latency, AHI, AI, ODI, minimal SaO₂, SaO₂ during rapid eye movement (REM), and non-rapid eye movement (non-REM) sleep were recorded.

For at least 10 s, a 90% decrease in airflow was considered an apnea, while a 30% decrease in airflow for at least 10 s and a SaO₂ drop of 3% or more, or the presence of arousal was considered a hypopnea [13]. The apnea–hyperpnea index (AHI), which was computed as the count of apneas and hypopneas per hour of sleep. Mild, moderate, and severe OSA were classified using thresholds of ≥ 5 to 15, ≥ 15 to 30, and ≥ 30 of AHI, respectively [14].

Measurement of plasma fibrinogen level: 2 ml of venous blood was taken from patients following a whole night of PSG, between 6:00 to 7:00 a.m. in the early morning, using sterile tubes kept under rigorous aseptic conditions. The blood was then centrifuged to separate the plasma. We used fibrinogen reagents (BioMed-FIBRINOGEN, EGYCHEM LAB Technology, Badr City, Egypt) and the clotting method of Clauss to quantitatively determine fibrinogen in plasma that had been stored at -80°C.

The latex agglutination test was applied to measure the CRP, which looks for visible agglutination immediately after removing the slide from the rotator using (CRP Latex test kit, Immuno-Diagnostics, USA, Ref-310-100-31). The average result was less than 6 mg/L.

Statistical analysis

Version 20.0 of the IBM SPSS software program was utilized to analyze the data entered into the computer (16 June 2016; Redwood City, New York: IBM Corporation). To depict categorical data, percentages, and numbers were utilized. Two groups were compared using the Chi-square test. In cases where the predicted cell counts for more than 20% of the cells were less than five, the Monte Carlo adjustment test was also employed.

Using the Shapiro–Wilk test, the normality of the continuous data was confirmed. The range (minimum and maximum), mean, standard deviation, and median represent quantitative data. In the context of contrasting two groups using normally distributed quantitative variables, the Student’s t-test was utilized. The one-way ANOVA test was utilized to compare the four evaluated groups. For pairwise comparisons, the post hoc test (Tukey) was employed. When comparing groups using non-normally distributed quantitative variables, the Mann–Whitney test was utilized. When comparing groups using other non-normally distributed quantitative variables, the Kruskal–Wallis test was applied. Then, the post hoc test (Dunn's for multiple comparisons test) was implemented for pairwise comparisons. At the 5% level, the findings were deemed statistically significant.

Results

This study had 40 participants—20 OSA cases and 20 controls. The ages of the controls were between 19 and 50 years old (mean = 36.55 ± 9.34), and the cases were between 22 and 53 years old (mean = 35.9 ± 9.36). In the case group, there were nine (45%) male subjects and eleven (50%) female subjects; in the control group, there were 10 (50%) male subjects and 10 (50%) female individuals. For patients, the mean BMI was 23.05 ± 1.5, while for controls it was 22.1 ± 1.7. Age, gender, and BMI variations between the two groups were statistically insignificant. (p = 0.819, 0.752, and 0.827, respectively). The ESS ranged from 11 to 18 in patients with a mean of 13.6 ± 2, which was statistically substantially higher than the ESS range of 0–8 in controls with a mean of 4.2 ± 2.2 (p < 0.001) (Table 1).

Table 1

Demographic and clinical data among the participants

	Patient (n = 20)	Control (n = 20)	Test of Sig	p
Gender
Male	9 (45%)	10 (50%)	χ² = 0.100	0.752
Female	11 (55%)	10 (50%)	χ² = 0.100	0.752
Age (years)
Mean ± SD	35.9 ± 9.36	36.55 ± 9.34	U = 183.000	0.827
Median (Min.–Max.)	35 (22–53)	37 (19–50)	U = 183.000	0.827
BMI (kg/m²)
Mean ± SD	23.05 ± 1.5	22.1 ± 1.7	t = 0.230	0.819
Median (Min.–Max.)	24 (20–25)	22 (19–25)	t = 0.230	0.819
Epworth Sleepiness Scale
Normal (score ≤ 10)	0(0%)	20 (100%)	χ² = 40.0*	< 0.001*
Abnormal (score > 10)	20 (100%)	0(0%)	χ² = 40.0*	< 0.001*
Mean ± SD	13.6 ± 2	4.2 ± 2.2	t = 14.240*	< 0.001*
Median (Min.–Max.)	14 (11–18)	4.5 (0–8)	t = 14.240*	< 0.001*

Chi-square test (χ²); standard deviation (SD); p: p value; BMI: body mass index; Student’s t-test (t); *: statistically significant at p ≤ 0.05; Mann–Whitney test (U); Min.–Max.: minimum–maximum

The total sleep time, sleep onset, the efficiency of sleep, N3%, and the percentage of REM sleep were all significantly lower in the patients than in the controls (347.7 ± 62.7, 9.7 ± 6.2, 77.1 ± 9.6, 11.5 ± 7.2, and 14.3 ± 5.1 versus 403.8 ± 35.8, 19.9 ± 12.9, 88.7 ± 3.9, 23.4 ± 6.5, and 21.2 ± 3.9. p-value 0.002, for each). In contrast to the controls, the patients had significantly greater values of the arousal index (AI), latency to N3, and REM latency (21.5 ± 6.9, 101.5 ± 27.5, and 144.1 ± 19.7 Versus 4.5 ± 2.9, 66 ± 14, and 100 ± 10.9, respectively) (Table 2).

Table 2

Sleep structure and sleep stages among the participants

Total sleep time (min)	Patient (n = 20)	Control (n = 20)	Test of Sig.	p
Total sleep time (min)	Mean ± SD Median (Min.–Max.)	Mean ± SD Median (Min.–Max.)	Test of Sig.	p
	347.7 ± 62.7	403.8 ± 35.8	t = 3.474*	0.002*
	333 (252–456)	399 (330–474)	t = 3.474*	0.002*
Sleep onset (min)	9.7 ± 6.2	19.9 ± 12.9	U = 102.000*	0.007*
	6.9 (3.8–22)	19.8 (4.2–42)	U = 102.000*	0.007*
Sleep efficiency (%)	77.1 ± 9.6	88.7 ± 3.9	t = 5.008*	< 0.001*
	76.5 (61–92)	88.6 (81.8–94.5)	t = 5.008*	< 0.001*
Arousal index	21.5 ± 6.9	4.5 ± 2.9	U = 0.000*	< 0.001*
	24.3 (10.2–30.8)	3.5 (1–9)	U = 0.000*	< 0.001*
N1 latency (min)	9.7 ± 6.2	19.9 ± 12.9	U = 102.000*	0.007*
	6.9 (3.8–22)	19.8 (4.2–42)	U = 102.000*	0.007*
N1%	16 ± 4.9	8.9 ± 4	t = 4.988*	< 0.001*
	16.5 (8.9–25.3)	8.8 (2.6–16)	t = 4.988*	< 0.001*
N2 latency (min)	27.3 ± 8.8	39.7 ± 13.8	t = 3.402*	0.002*
	24.3 (15.5–43)	37.3 (20.5–65.5)	t = 3.402*	0.002*
N2%	58.2 ± 7.2	46.5 ± 9.2	t = 4.467*	< 0.001*
	60.3 (43.3–69.3)	46.3 (18–57)	t = 4.467*	< 0.001*
N3 latency (min)	101.5 ± 27.5	66 ± 14	t = 5.156*	< 0.001*
	100.4 (55.6–165)	66.2 (35–94)	t = 5.156*	< 0.001*
N3%	11.5 ± 7.2	23.4 ± 6.5	t = 5.499*	< 0.001*
	10.2 (1.3–27.7)	24.4 (12.5–36.5)	t = 5.499*	< 0.001*
REM latency (min)	144.1 ± 19.7	100 ± 10.9	t = 8.754*	< 0.001*
	143 (92.3–182)	98.8 (83.5–123.5)	t = 8.754*	< 0.001*
REM%	14.3 ± 5.1	21.2 ± 3.9	t = 4.805*	< 0.001*
	14.3 (5.1–22.6)	20.1 (16.4–34.3)	t = 4.805*	< 0.001*
Non-REM %	85.7 ± 5.1	78.8 ± 3.9	t = 4.805*	< 0.001*
	85.7 (77.4–94.9)	79.9 (65.7–83.6)	t = 4.805*	< 0.001*

REM rapid eye movement, SD standard deviation, Non-REM non-rapid eye movement, p: p value, TST total sleep time, Student’s t-test (t); *: statistically significant at p ≤ 0.05; Mann–Whitney test (U); AHI: apnea–hypopnea index; N1: stage 1 of non-REM; N2: stage 2 of non-REM; N3: stage 3 of non-REM; min: minute; Min.–Max.: minimum–maximum; %: percentage

Table 3 shows that the patients had substantially greater AHI and ODI than controls (30.1 ± 17 and 9.2 ± 6.2 versus 1.5 ± 1.2 and 2.2 ± 2, respectively); p values (< 0.001 and < 0.001, respectively). And considerably lower SaO₂ than the controls (76.8 ± 13 Versus 190.7 ± 5.3, p value < 0.001). Based on the AHI, the patients were categorized as follows: 5 patients (25.0%) had mild OSA, seven patients (35.0%) had moderate OSA, and eight patients (40.0%) had severe OSA (Table 4).

Table 3

Sleep abnormalities among the participants

	Patient (n = 20)	Control (n = 20)	Test of Sig.	p
	Mean ± SD Median (Min.–Max.)	Mean ± SD Median (Min.–Max.)	Test of Sig.	p
AHI	30.1 ± 17	1.5 ± 1.2	t = 7.484	< 0.001*
	27 (8.1–64.6)	1 (0–4)	t = 7.484	< 0.001*
AHI non-REM	30.2 ± 17	1.5 ± 1.2	U = 0.000*	< 0.001*
	26.6 (8–66)	1 (0–4)	U = 0.000*	< 0.001*
AHI in REM	24.6 ± 11.4	1.7 ± 1.4	U = 0.000*	< 0.001*
	21.1 (10.5–50.1)	1 (0–4)	U = 0.000*	< 0.001*
O₂ desaturation index	9.2 ± 6.2	2.2 ± 2	U = 48.000*	< 0.001*
	8.5 (0–24.1)	2.1 (0–6.4)	U = 48.000*	< 0.001*
Lowest SaO₂	76.8 ± 13.1	90.7 ± 5.3	t = 4.379	0.001*
	82 (50–94)	92 (81–97)	t = 4.379	0.001*
SaO₂ in REM	94.9 ± 2.3	97.2 ± 1.7	t = 3.518	< 0.001*
	95 (90.9–98.1)	97.4 (92.2–99)	t = 3.518	< 0.001*
SaO₂ in non-REM	94.7 ± 2.5	97.3 ± 1.3	t = 4.159	< 0.001*
	94.8 (90.2–98)	97.6 (92.8–98.5)	t = 4.159	< 0.001*

REM rapid eye movement, Chi-square test (χ²); standard deviation (SD); p: p value; O₂ saturation (SaO₂₎; Student’s t-test (t); *: statistically significant at p ≤ 0.05; Mann–Whitney test (U); Non-REM non-rapid eye movement, MC Monte Carlo, AHI apnea–hypopnea index, Min.–Max. minimum–maximum

Table 4

Degree of obstructive sleep apnea among the participants

Obstructive sleep apnea	Patient (n = 20)	Control (n = 20)	Test of Sig.	p
Obstructive sleep apnea	Mean ± SD Median (Min.–Max.)	Mean ± SD Median (Min.–Max.)	Test of Sig.	p
No (AHI < 5)	0 (0.0%)	20 (100.0%)	χ² = 45.002*	^MCp < 0.001*
Mild (AHI ≥ 5)	5 (25.0%)	0 (0.0%)
Moderate (AHI ≥ 15)	7 (35.0%)	0 (0.0%)
Severe (AHI ≥ 30)	8 (40.0%)	0 (0.0%)

Chi-square test (χ²); AHI apnea–hypopnea index standard deviation (SD); p: p value, MC Monte Carlo

*Statistically significant at p ≤ 0.05; Min.–Max.: minimum–maximum

Table 5 shows that the patient's plasma fibrinogen levels were substantially more significant than the controls' (399.8 ± 54.7 versus 309.8 ± 26.7 mg/dL, respectively), with a p-value of less than 0.001. the patient's CRP was substantially higher than the control group's (mean values were 10.6 ± 5.2 and 2.4 ± 1.1, respectively). Table 6 shows no statistically significant variation in the plasma levels of CRP and fibrinogen among patients based on gender.

Table 5

Plasma fibrinogen level and C-reactive protein among the participants

	Patient (n = 20)	Control (n = 20)	Test of Sig.	p
	Mean ± SD Median (Min.–Max.)	Mean ± SD Median (Min.–Max.)	Test of Sig.	p
Plasma fibrinogen (mg/dL)	399.8 ± 54.7	309.8 ± 26.7	t = 6.612*	< 0.001*
	397.5 (295–480)	300 (280–350)	t = 6.612*	< 0.001*
C-reactive protein	10.6 ± 5.2	2.4 ± 1.1	U = 6.000*	< 0.001*
	12 (3–19)	2 (1–4)	U = 6.000*	< 0.001*

Standard deviation (SD); p: p value; deviation Student’s t-test (t); *: statistically significant at p ≤ 0.05; Mann–Whitney test (U), Min.–Max.: minimum–maximum.; mg/dL: milligrams per deciliter

Table 6

Comparing the plasma fibrinogen and C-reactive protein levels between male and female patients

	Male (n = 9)	Female (n = 11)	Test of Sig	p
	Mean ± SD Median (Min.–Max.)	Mean ± SD Median (Min.–Max.)	Test of Sig	p
Plasma fibrinogen (mg/dL)	422.2 ± 52.4	390.4 ± 51.6	t = 1.749	0.097
	430(350–480)	400 (295–470)	t = 1.749	0.097
C-reactive protein	10.8 ± 5.3	9.4 ± 4.3	U = 30.50	0.152
	11(− 18)	10(4–18)	U = 30.50	0.152

Standard deviation (SD); p: p value; deviation Student’s t-test (t); *: statistically significant at p ≤ 0.05; Mann–Whitney test (U); mg/dL: milligrams per deciliter; Min.–Max.: minimum–maximum

Table 7 shows that the plasma levels of fibrinogen in controls (mean = 309.8 ± 26.7 mg/dL) and mild OSA patients (mean = 335 ± 27.8 mg/dL) did not differ statistically (p = 0.219). However, the levels in moderate OSA patients (mean = 383.6 ± 20.6 mg/dL) and severe OSA patients (mean = 454.4 ± 25.6 mg/dL) were statistically higher than in controls (p < 0.001 and p < 0.001). The patients with mild OSA showed lower fibrinogen levels than those with moderate OSA (p1 = 0.013). In contrast, patients with severe OSA showed more significant levels of fibrinogen than those with moderate OSA (p3 < 0.001).

Table 7

Plasma fibrinogen level and C-reactive protein in controls and patients with mild, moderate, and severe obstructive sleep apnea

	Normal (n = 20)	Mild OSA (n = 5)	Moderate OSA (n = 7)	Severe OSA (n = 8)	Test of Sig	p
Plasma fibrinogen (mg/dL)
Mean ± SD	309.8 ± 26.7	335 ± 27.8	383.6 ± 20.6	454.4 ± 25.6	F = 64.556*	< 0.001*
Median (Min.–Max.)	300 (280–350)	330 (295–370)	380 (350–410)	465 (415–480)	F = 64.556*	< 0.001*
p₀		0.219	< 0.001*	< 0.001*
Sig. bet. groups		p₁ = 0.013, p₂ < 0.001, p₃ < 0.001*
C-reactive protein (CRP)					H = 32.309	< 0.001*
Mean ± SD	2.4 ± 1.1	4.40 ± 1.67	9.4 ± 2.6	15.6 ± 3.2
Median (Min.–Max.)	2(1–4)	3.0 (3.0–7.0)	10 (4–12)	16 (12–19)
p₀		0.036*	0.001*	< 0.001*
Sig. bet. groups		p₁ = 0. 01, p₂ = 0.001, p₃ = 0.001*

F: F for one-way ANOVA test and pairwise comparison bet. each two groups were done using post hoc test (Tukey)

H: H for Kruskal–Wallis test, pairwise comparison bet. Each two groups were done using a post hoc test (Dunn's for multiple comparisons test)

OSA obstructive sleep apnea

*Statistically significant at p ≤ 0.05 Sig. Bet. Grps: significance between groups; Min.–Max.: minimum–maximum; mg/dL: milligrams per deciliter

p: p-value for comparing the different groups p₀: p-value for comparing normal and each group

p₁: p-value for comparing mild and moderate p₂: p-value for comparing mild and severe

p₃: p-value for comparing moderate and severe

Table 7 shows that the CRP levels were more significant in individuals with mild, moderate, and severe OSA than in the control group (4.40 ± 1.67, 9.4 ± 2.6, and 15.6 ± 3.2) (p = 0.036, 0.001, and < 0.001, respectively). The CRP levels were statistically higher in moderate and severe OSA patients compared to mild OSA patients (p1 = 0.01 and p2 < 0.001) and in severe OSA patients compared to moderate OSA patients (p3 < 0.001).

Table 8 shows AHI, AI, and ODI showed positive correlations with plasma fibrinogen (r = 0.953, 0.888, and 0.894, p = < 0.001, < 0.001, and < 0.001, respectively), while total sleep time, sleep efficiency, N3%, REM%, and lowest SaO₂ showed negative correlations (r = − 0.860, − 0.877, − 0.611, − 0.844, and − 0.745, p = < 0.001, < 0.001, < 0.001, and < 0.001, respectively).

Table 8

Correlation between plasma fibrinogen, C-reactive protein, and different parameters in patients (n = 20)

	Plasma fibrinogen		C-reactive protein
	r	p	r_s	p
Age (years)	0.126	0.548	0.174	0.462
Body mass index	0.119	0.617	0.285	0.223
Epworth Sleepiness Scale	0.861	< 0.001*	0.757	< 0.001*
Apnea–hypopnea index	0.953	< 0.001*	0.635	< 0.001*
Total sleep time	− 0.860	< 0.001*	-0.468	< 0.002*
Sleep efficiency (%)	− 0.877	< 0.001*	-0.555	< 0.001*
Arousal index	0.888	< 0.001*	0.693	< 0.001*
N3%	− 0.611	< 0.001*	− 0.523	< 0.001*
REM%	− 0.844	< 0.001*	− 0.464	< 0.003*
O2 desaturation index	0.894	< 0.001*	0.610	< 0.001*
Lowest O₂ saturation	− 0.745	< 0.001*	− 0.471	< 0.002*
C-reactive protein (CRP)	0.598	< 0.001*	–	–

Spearman coefficient (r_s); REM rapid eye movement; Pearson coefficient (r); *: statistically significant at p ≤ 0.05; N3: stage 3 of non-REM; %: percentage

Table 8 shows AHI, AI, and ODI showed positive correlations with CRP (r = 0.635, 0.693, and 0.610, p = < 0.001, < 0.001, and 0.001, respectively), while total sleep time, sleep efficiency, N3%, REM%, and lowest SaO₂ showed negative correlations (r = − 0.468, − 0.555, − 0.523, − 0.464, and − 0.471, p = < 0.002, < 0.001, < 0.003, < 0.001, and < 0.002, respectively).

Discussion

One of the most crucial things for CVD and systemic hypertension is the presence of OSA [15, 16]. Diastolic dysfunction and left ventricular hypertrophy were more common in patients with moderate-to-severe OSA [17]. Another established association between OSA and generalized atherosclerosis symptoms, including carotid atherosclerosis, was approved [18]. Although vascular inflammation has been implicated in these associations, the underlying pathophysiologic mechanisms are still not fully understood. Researchers have focused on inflammatory biomarkers in their studies of OSA patients because of the extensive research on low-grade inflammation and its role in cardiovascular abnormalities. We assessed the correlation between OSA and plasma fibrinogen and CRP as two circulating inflammatory biomarkers in OSA patients to learn more about the potential changes to early inflammatory pathways in OSA.

This study only included individuals who had recently been diagnosed with OSA, had never had therapy for OSA before, and did not have any other preexisting conditions. Obese patients were not included in the study because obesity has a major impact on fibrinogen levels. Research demonstrates that elevated quantities of fibrinogen are independently correlated with BMI, which may complicate the connection between fibrinogen levels and OSA [19, 20]. To ensure more precise results unique to OSA pathophysiology, the study attempts to isolate the effect of OSA on fibrinogen without interference from the inflammatory and metabolic effects of obesity by excluding obese patients [21, 22]. This method helps reduce confounding variables and produces more accurate information about how OSA affects fibrinogen levels and associated cardiovascular risks on its own, apart from obesity. Thus, the elevated levels of CRP and plasma fibrinogen in patients with moderate-to-severe OSA were not due to any preexisting acute or chronic illnesses.

According to our findings, patients with moderate-to-severe OSA had higher plasma fibrinogen levels than both controls and patients with mild OSA. However, there was no discernible difference in plasma fibrinogen levels between the patients with mild OSA and the controls.

According to our study, plasma fibrinogen levels in moderate and severe OSA (383.6 ± 20.6 mg/dL and 454.4 ± 25.6 mg/dL, respectively) were significantly higher than in controls (309.8 ± 26.7 mg/dL) and mild OSA patients (335 ± 27.8 mg/dL). According to Shamsuzzaman et al. [23], patients with moderate-to-severe OSA exhibited notably higher plasma fibrinogen levels when compared to both controls (398 ± 18 mg/dL versus 331 ± 25 mg/dL, p = 0.003) and patients with mild OSA (398 ± 18 mg/dL versus 334 ± 25 mg/dL, p = 0.02). Similarly according to, Celikhisar et al. [24], patients with moderate-to-severe OSA exhibited notably higher plasma fibrinogen levels when compared to controls (440 ± 12 mg/dL versus 350 ± 16 mg/dL; p: 0.025).

One established biomarker for cardiovascular risk is fibrinogen. The liver produces this acute-phase protein in response to infections and inflammation [25]. The inflammatory process and coagulation profile are disrupted in OSA, particularly regarding cytokines and fibrinogen [26].

According to previous research, OSA is associated with hypercoagulation caused by increased clotting factors, a decline in fibrinolysis, and an increase in platelet activity [27, 28]. As a result of elevated catecholamine levels, the sympathetic nervous system becomes more active during many sleep apneic episodes, which is likely the underlying cause of this hypercoagulable state [29]. Patients with OSA are more likely to develop thrombosis because of elevated levels of fibrinogen, decreased fibrinolytic function, and increased platelet aggregation and activation [26, 30]. Edema and plasma cell infiltration are potential mechanisms by which OSA may raise plasma fibrinogen levels. Also, inflammation of the soft palate worsens upper airway blockage while you sleep [31].

Wessendorf et al. [32] stated that patients with ischemic stroke had greater OSA prevalence and fibrinogen levels, and there was an independent association between OSA and high levels of plasma fibrinogen. There was an inverse correlation between fibrinogen and minimum SaO₂, although a positive correlation was also discovered with mean oxygen desaturation and respiratory distress index (RDI). They hypothesized that fibrinogen levels may be involved in the mechanism that increases the risk of stroke in OSAS. Consequently, we did not involve patients with a history of stroke in our study.

In another study, morning plasma fibrinogen levels were more significant in OSA patients compared to afternoon values, and following treatment with continuous positive airway pressure (CPAP), a drop in the elevated morning fibrinogen level was also noted [33]. Another study demonstrated that treatment with CPAP did not affect fibrinogen levels, whereas OSA patients had increased plasma viscosity and fibrinogen levels regardless of the time of day [34].

Additionally, according to our findings, patients with OSA had a direct correlation between plasma fibrinogen level and AHI, AI, and ODI and an inverse correlation with lowest oxygen saturation during sleep. Our research also demonstrated that in patients with OSA without any other medical conditions, CRP levels were related to OSA severity. This association remained statistically significant even after controlling gender and body mass index.

Previous research found that levels of plasma fibrinogen in OSA patients might be higher for a variety of reasons, including hypoxic conditions caused by the disease and sleep architecture disruptions caused by recurrent awakenings. There was a relationship between AHI and CRP and fibrinogen; however, this association was significantly reduced after controlling BMI and comorbidities [35]. Several researchers have demonstrated that CRP is a significant risk factor for atherosclerosis. Moreover, even in healthy individuals, greater C-reactive protein levels are linked to a greater risk of cardiovascular morbidity and death [36].

It is challenging to explore the relative consequences of OSA severity in inflammatory biomarker variations due to obesity, which is a strongly confounding factor. Therefore, in our study, obese patients were not included as the results from studies examining the AHI and CRP levels association in patients with OSA have been inconsistent, which may be attributable to the impact of obesity [37‐39]. Another meta-analysis found that OSA severity positively correlated with a significantly higher CRP level in OSA patients [40]. Persistent low-grade inflammation has a correlation with obesity, particularly visceral adiposity. A study of obese women and their first-degree relatives identified a correlation between waist circumference and elevated CRP and fibrinogen levels with BMI [41]. On the other hand, a study including obese patients found that patients with OSAS had more significant C-reactive protein and fibrinogen values than non-OSAS patients [42].

Additionally, this study revealed that ESS was significantly greater in patients with OSA than in the controls. Previous population-based research has also found that most people with OSA suffer from excessive sleepiness [43, 44]. Furthermore, this study revealed that fibrinogen levels were significantly correlated with ESS. In prior research, obesity and EDS were found to be more strongly associated with inflammatory indicators than AHI [45, 46].

This study demonstrated that newly diagnosed OSA patients without comorbidities had higher plasma fibrinogen and C-reactive protein levels than controls and these levels were substantially linked with sleep apnea severity, as measured by apneic episodes and oxygen desaturation regardless of age, BMI, blood pressure, smoking, or alcohol use.

Limitations of the study

There are various limitations to the current investigation. At first, it was not possible to demonstrate a cause-and-effect relationship between inflammatory biomarkers and OSA because of the cross-sectional nature of our work. Moreover, the only patients without comorbidities made up the study population; thus, conclusions should be approached with caution when applied to patients who do not meet this profile. In addition, to ascertain whether OSA therapy can prevent an elevation in plasma fibrinogen concentration, this investigation must be replicated in larger, autonomous prospective trials that encompass an ideal representation of all OSA severity categories.

Conclusion

Acknowledgements

The authors are grateful to all patients and volunteers for their willingness to participate in this study.

Declarations

The study was approved by the Ethics committee of Suez Canal Faculty of medicine on April 11, 2023. Committee Number: 5237. An informed written consent was taken from all the participants in the study.

Not applicable.

Competing interests

The authors declare that they have no competing interests (financial or non-financial).

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Metadaten
Literatur

Titel: Relationship between plasma fibrinogen level and obstructive sleep apnea
Verfasst von: Reda Abd El-Razek
Tarek Elnahriry
Abdullah Hashish
Osama Shehab
Publikationsdatum: 01.12.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: The Egyptian Journal of Neurology, Psychiatry and Neurosurgery / Ausgabe 1/2024
Elektronische ISSN: 1687-8329
DOI: https://doi.org/10.1186/s41983-024-00909-6

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Erweiterte Suche

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Springer Medizin

Relationship between plasma fibrinogen level and obstructive sleep apnea

Abstract

Background

Results

Conclusion

Publisher's Note

Background

Methods

Statistical analysis

Results

Discussion

Limitations of the study

Conclusion

Acknowledgements

Declarations

Competing interests

Publisher's Note

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Declarations

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Consent for publication

Competing interests

Publisher's Note