|Year : 2019 | Volume
| Issue : 1 | Page : 14-20
A study of serum uric acid and lactate level in patients with obstructive sleep apnea syndrome
Mona A.E. Taha Elgazzar1, Adel S Bediwy1, Ghada A Attia1, Sahar M Eldin Hazzaa2, Wafaa S El-Shimy1
1 Department of Chest Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt
|Date of Submission||26-Apr-2017|
|Date of Acceptance||01-Oct-2017|
|Date of Web Publication||17-Sep-2019|
Mona A.E. Taha Elgazzar
Department of Chest Diseases, Faculty of Medicine, Tanta University, Tanta
Background Tissue hypoxia due to repeated sleep apneas leads to evolution of reactive oxygen stress and serum levels of uric acid (UA) and lactate in patients with obstructive sleep apnea syndrome (OSAS).
Objective The objective of this study was to determine whether there is an association between OSAS and both serum UA and lactate levels as potential markers of tissue hypoxia and their relation with OSAS severity.
Participants and methods Thirty participants were classified into two groups. Group I included 10 control persons matched to obstructive sleep apnea (OSA) patients by sex, age, and BMI. Group II included 20 patients with OSA as diagnosed by polysomnography [apnea–hypopnea index (AHI)≥5]. The following were conducted: full history, clinical examination, complete overnight polysomnography to detect AHI, oxygen saturation parameters, and snoring index. Finally serum lactate and UA levels were assessed through two samples of peripheral arterial blood: one before sleep and the second at the end of polysomnography.
Results In OSA patients, the mean levels of serum UA and lactate both before and after sleep were significantly higher compared with controls with significant overnight increase after sleep and high percent of change of serum UA and lactate levels. These higher levels were independent of age, sex, and BMI. Moreover, UA and lactate levels after sleep in OSA patients were significantly correlated with OSA severity (AHI) and degree of nocturnal hypoxia through positive correlation with (%TST<90%, %TST<80%, and oxygen desaturation index) and negative correlation with average SpO2% and lowest SpO2%. This correlation was not affected by age or obesity as confirmed by regression models.
Conclusion Both serum UA and lactate may be considered as potential markers of tissue hypoxia and related to OSAS severity. Their levels were significantly elevated after sleep with significant overnight rise and significant positive correlation with AHI, %TST<80%, %TST<90%, oxygen desaturation index, and negative correlation with average and lowest SpO2%. This correlation was not affected by age or obesity.
Keywords: lactate level, obstructive sleep apnea syndrome, serum uric acid
|How to cite this article:|
Elgazzar MT, Bediwy AS, Attia GA, Eldin Hazzaa SM, El-Shimy WS. A study of serum uric acid and lactate level in patients with obstructive sleep apnea syndrome. Tanta Med J 2019;47:14-20
|How to cite this URL:|
Elgazzar MT, Bediwy AS, Attia GA, Eldin Hazzaa SM, El-Shimy WS. A study of serum uric acid and lactate level in patients with obstructive sleep apnea syndrome. Tanta Med J [serial online] 2019 [cited 2020 Dec 1];47:14-20. Available from: http://www.tdj.eg.net/text.asp?2019/47/1/14/267019
| Introduction|| |
Sleep is a naturally recurring state characterized by reduced or lacking consciousness, relatively suspended sensory activity and inactivity of nearly all voluntary muscles .
There are three types of sleep apnea: central sleep apnea, obstructive sleep apnea (OSA), and complex or mixed (i.e. combination of central and obstructive) constituting 0.4, 84, and15% of cases, respectively .
OSA is a clinical condition characterized by recurrent, episodes of complete obstruction (apnea), or partial obstruction (hypopnea) of the upper airway, leading to increased negative intrathoracic pressure, sleep fragmentation, and intermittent hypoxia during sleep .
Symptoms of OSA include: sleep episodes during wakefulness, daytime sleepiness, unrefreshing sleep, fatigue, insomnia, waking up, breath holding, gasping or choking and loud snoring .
Obstructive sleep apnea syndrome (OSAS) is defined as five or more episodes of apnea or hypopnea per hour of sleep (called apnea–hypopnea index or AHI) .
Apneas present in patients with OSAS cause a decrease in arterial oxygen saturation and tissue hypoxia, followed by reoxygenation after the termination of apneas. These multiple cycles of hypoxia/reoxygenation are associated with evolution of hypoxic oxidative stress (HOS). Owing to HOS the production of ATP (ATP from ADP is impaired, leading to a net degradation of ATP to ADP and AMP. This cascade leads to the release of intermediates of purine nucleotide (adenosine, inosine, hypoxanthine, and xanthine). Uric acid (UA) is biosynthesized from these purine catabolic products .
HOS also triggers exaggerated degradation of glucose through the glycolytic pathway, resulting in an accumulation of pyruvate. Lactate dehydrogenase converts accumulated pyruvate to lactate .
The lack of ATP in a state of hypoxemia markedly impairs the utilization of lactate by a process of gluconeogenesis in the liver ( Cori cycle More Details) and renal cortex. Tissue hypoxia results in hyperlactatemia and lactic acidosis. So, hyperuricemia and hyperlactatemia are considered markers of tissue HOS in OSA patients .
| Patients and methods|| |
This study was conducted after approval of Tanta Research and Ethical Committee in the Sleep Laboratory Unit, Chest Department, Tanta University Hospital on 30 participants during the period from July 2015 to February 2016. The 30 participants were classified into two groups:
- Group I: Included 10 control persons, matched to OSA patients by sex, age, and BMI. All control persons have normal physical examination and laboratory tests and AHI less than 5/h.
- Group II: Included 20 patients with OSA as diagnosed by polysomnography (AHI≥5).
All patients with OSAS as confirmed by AHI of at least 5 was included in this study, and their BMI less than 40 kg/m2.
- Patient receiving UA and lactate-lowering medications.
- Patient’s with gout.
- Other medical diseases such as anemia, hepatic, and renal diseases.
The following were done to all patients after having an informed consent: Personal and medical history taking, clinical examination including: measurement of blood pressure and heart rate, calculation of BMI, measurement of waist–hip ratio (WHR) and neck circumference, subjective evaluation of daytime sleepiness using the Epworth Sleepiness Scale (ESS), complete overnight polysomnography (6–8 h) using SOMON screen plus PSG+ (SOMNO Medics GmbH Am Sonnenstuhl 63 D-97236 Randersacker, Germany) which is computer-based high technology polysomnography and finally serum UA and lactate levels by two samples of peripheral arterial blood one before sleep and the second one at the end of polysomnography. Immediately, blood was transported to the biochemical laboratory for the estimation of lactate in a fluorized tube and UA in a plain glass bottle. The serum UA and lactate was measured by spectrophotometry method and by percentage of change in UA and lactate calculated as: [(a−b)/b×100] where a is the change before sleep and b is the change after sleep.
Statistical analysis of the data
Data were fed to the computer and analyzed using IBM SPSS software package, version 20.0. Qualitative data were described using number and percent. Quantitative data were described using range (minimum and maximum), mean, SD, and median. Significance of the obtained results was judged at the 5% level.
| Results|| |
- Regarding AHI in OSA patients: OSA was mild in three patients, moderate in five, and severe in 12 patients and AHI was in the range 8.70–109.0 events/h with mean±SD of 47.67±31.50 event/h ([Table 1]).
|Table 1 Classification of obstructive sleep apnea group according to apnea–hypopnea index|
Click here to view
- Regarding ESS in studied groups: There were nine participants who had normal ESS in the control group and four patients in the OSA group; one patient had abnormal ESS in the control group and 16 patients in the OSA group and the range of the score was 3.0–10.0 with mean±SD of 5.80±2.10 in the control group, whereas the range in the OSA group was 8.0–22.0 with mean±SD of 16.0±4.4 with statistically significant difference between both groups ([Table 2]).
- Regarding different oxygen saturation parameters between the two studied groups ([Table 3]).
- Average SpO2%: ranged in the control group 94–98% with mean±SD of 96.90±1.45%, whereas in OSA patients the range was 63–98% with mean±SD of 90.15±7.58% with statistically significant decrease in OSA patients than the control group (P=0.001).
- Lowest SpO2%: range in the control group 94–98% with mean±SD of 97.20±1.55%, whereas in the OSA patients the range was 45–87% with mean±SD of 74.10±13.02 with statistically significant decrease in OSA patients than the control group (P=0.001).
- TST (min): ranged in both control and OSA patients 360–450 min with mean±SD of 372.70±27.93 min with no statistically significant difference between both groups.
- TST<90%: ranged in control group 0.0–0.0 min, whereas in OSA patients ranged 1.08–360 min with mean±SD of 113.91±102.55 min with statistically significant increase in OSA patients than the control group (P<0.001).
- %TST<90%: ranged in control group 0.0%, whereas in OSA patients it was 0.30–100.0% with mean±SD of 30.69±27.80% of total sleep time (TST) with statistically significant increase in OSA patients than the control group (P<0.001).
- TST<80%: ranged in control group 0.0–0.0 min, whereas in OSA patients it was 0–159.48 min with mean±SD of 26.61±44.55 min and show statistically significant increase with the control group (P=0.003).
- %TST<80%: ranged in control group 0.0%, whereas in OSA patients it was 0.0–44.30% with mean±SD of 7.45±12.32% of TST with statistically significant increase in OSA patients than the control group (P<0.001).
- Oxygen desaturation index (ODI): ranged in control group 0.0–0.0, whereas in OSA patients 0.0–129 desaturation events/h with mean±SD of 64.11±36.91 desaturation events/h with statistically significant increase in OSA patients than the control group (P=0.001).
- Arousal index: ranged in control group 6.0–13.0 arousal/h with mean±SD of 10.20±2.10, whereas in OSA patients it was 12.80–8.0 arousal/h with mean±SD of 34.86±17.31with statistically significant increase in OSA patients than the control group (P<0.001).
|Table 3 Different polysomnographic oxygen saturation parameters between the two studied groups|
Click here to view
- Comparing the levels of serum UA before and after sleep between the two studied groups: showed significant increase of their levels in OSAS patients than controls with significant overnight increase after sleep (P=0.049, P<0.001, respectively) and higher percent of change after sleep in OSAS patients (P<0.001) ([Table 4]).
|Table 4 Comparing the levels of serum uric acid before and after sleep between the two studied groups|
Click here to view
- Comparing the levels of serum lactate before and after sleep between the two studied groups: showed significant increase of their levels in OSAS patients than controls with significant overnight increase after sleep (P=0.007, P<0.001, respectively) and higher percent of change after sleep in OSAS patients (P<0.001) ([Table 5]).
|Table 5 Comparing levels of serum lactate before and after sleep between the two studied groups|
Click here to view
- Correlation between different polysomnographic parameters and serum levels of UA and lactate after sleep in the OSA group: showed significant positive correlation between their levels after sleep study and AHI, %TST<80, %TST<90%, and ODI, whereas significant negative correlation with average and lowest SpO2% ([Table 6]).
|Table 6 Correlation between different polysomnographic parameters and serum levels of uric acid and lactate after sleep in obstructive sleep apnea patients|
Click here to view
- Respective multiple regression models controlling for age, BMI, and WHR showed significant correlation with AHI and %TST<90% serum UA ([Table 7]).
- Respective multiple regression models controlling for age, BMI, and WHR showed significant correlation with AHI, %TST<90%, %TST<80%, and lactate level ([Table 8]).
| Discussion|| |
OSA is the most common form of sleep disordered breathing and represents a major public health problem that affects 2 and 4% of middle-aged women and men, respectively. It is caused by repetitive collapse of a narrow upper airway during sleep with periodic cessation of breathing (>10 s). These events usually result in fragmented sleep, intermittent hypoxia, and lead to excessive daytime sleepiness .
Several studies have suggested that OSA is associated with increased levels of oxidative stress markers or decreased antioxidant defense. UA and lactate are examples for these markers. Apneas present in OSAS causes a decrease in arterial oxygen saturation and tissue hypoxia followed by reoxygenation after the termination of apneas. These multiple cycles of hypoxia/reoxygenation are associated with evolution of reactive oxygen stress (ROS) that lead to impairment of ATP that increase the release of purine nucleotides and UA, which are biosynthesized from these purine catabolic products .
ROS also triggers exaggerated degradation of glucose through glycolytic pathway, resulting in the accumulation of pyruvate that is converted to lactate. The lack of ATP in hypoxemia impairs the utilization of lactate by gluconeogenesis in the liver and renal cortex .
As regards the level of serum UA: In this study, the mean level of serum UA both before and after sleep in OSA patients (6.10±0.34, 7.38±0.53 mg/dl, respectively) was significantly higher as compared with that in the control group (5.72±0.49, 5.81±0.46 mg/dl, respectively).These higher levels of serum UA were independent of age, sex, and BMI. Moreover, the present study reported overnight significant increase of UA levels after sleep in OSA patients than controls with significantly high percent of change in OSA patients (21.01±8.16%) than controls (1.63±1.10%).
The raised levels of serum UA after sleep in OSA patients were significantly correlated with high AHI and with the degree of nocturnal hypoxia through positive correlation with the percentage of TST<90%, <80%, ODI, arousal index, and negative correlation with lowest SpO2%. This correlation is not affected by age or obesity as confirmed by regression models. The increase in the UA level can be explained by the evolution of ROS from multiple cycles of hypoxia/reoxygenation that lead to impairment of ATP and increased release of purine nucleotides and UA biosynthesized from these purine catabolic products.
The Garcia et al.’s  study results were in agreement with the present study results and found a significant correlation between UA levels and some sleep parameters (number of respiratory events, number of desaturations, and the cumulative percentage of time with oxygen saturation<90%). In addition, they showed that those patients with severe OSAS (AHI>30) had higher UA levels than those with mild or no OSAS.
Verhulst et al.  have demonstrated a relationship between the severity of sleep apnea and increased levels of serum UA in overweight adolescents, independent of abdominal adiposity. Their explanation was that high respiratory disturbance index during sleep was associated with the higher ODI and increased percentage of TST spent with arterial oxygen saturation less than 90% that lead to increased serum UA levels.
Kaditis et al.  found that severity of nocturnal hypoxemia and frequency of upper airway obstructive events in Greeks patients with SDB were significantly and positively associated with UA excretion even after adjustments for age, sex, and BMI.
Moreover, Hirotsu et al.  in a large epidemiological study found that individuals diagnosed with OSAS had higher levels of serum UA than those without OSAS and this effect remained significant after adjustment for confounding factors such as sex, age, BMI. Besides, their study demonstrated important associations between high UA levels and common OSAS-related parameters.
In contrast to the present study results, Braghiroli et al.  reported that the index of UA excretion in OSAS had poor sensitivity in detecting nocturnal hypoxemia and not correlated with indexes of apnea-associated arterial oxygen desaturation.
Moreover, Saito et al.  found that UA excretion was a marker of tissue hypoxia but not necessarily parallel apnea severity or arterial desaturation indexes in sleep apnea syndrome.
Hira et al.  were in disagreement with the present study results as they considered the measurement of UA not a sensitive marker of HOS and OSAS severity. They reported no correlation between AHI and serum UA levels and could not demonstrate the effect of hypoxia during sleep or the rise in the serum UA level after sleep due to the small number of OSAS patients and slow metabolism of serum UA level that could not be detected by a short-time sleep study (6–8 h).
As regards lactate levels, the present study showed that the mean lactate levels before and after sleep in OSA patients (1.35±0.19, 2.94±0.68 mmol/l, respectively) were significantly higher in comparison to the mean values in controls before and after sleep (1.11±0.26, 1.20±0.27 mmol/l, respectively). These higher levels of lactate were independent of age, sex, and BMI.
Besides, our data showed an overnight significant increase of lactate levels after sleep in OSA patients, whereas the controls showed no significant increase, and the percent of change of lactate levels after sleep was significantly higher in OSA patients (119.96±57.74%) than controls (8.94±10.29%).
This overnight increase in lactate levels after sleep was significantly positively correlated with the severity of OSAS (AHI), and degree of hypoxia with a high percent of TST<90%,<80%, ODI, arousal index, and lowest SpO2%. The correlation is also not affected by age or obesity as confirmed by regression models. This increase in lactate level can be explained by ROS that exaggerated degradation of glucose through glycolytic pathway, results in the accumulation of pyruvate which is converted to lactate. The lack of ATP in hypoxemia impairs the utilization of lactate by gluconeogenesis in the liver and renal cortex.
In accordance to our results, Vanuxem et al.  reported connection between lactate elimination with AHI and nocturnal desaturation in OSAS patients. They explained the decrease in lactate elimination by a defect in the oxidative metabolism in OSAS patients due to chronic nocturnal hypoxemia.
Ucar et al.’s  study conducted on 80 sleep-related breathing-disordered (SRBD) patients found that arterial lactate after sleep was higher in SRBD patients than in the No-SRBD group and was related with nocturnal hypoxemia. They explained higher lactate levels to intermittent nocturnal hypoxemia that increase myocardial stress by sympathetic activation; also sleep fragmentation with poor sleep quality increase lactate production and decrease its elimination. The study reported that age and BMI did not affect the high lactate levels.
Hira et al.’s  study on 40 OSAS patients’ was in agreement with our data. They found that lactate measurement was a sensitive marker for the degree of HOS and was related to OSAS severity. This is due to rapid metabolism of lactate with a half-life of 20 min that facilitates measuring transient night-time hypoxemia in OSAS patients and detection of overnight increase that significantly correlated with OSAS severity and the correlation not influenced by age and obesity variables.
In contrast, the study by Bonanni et al.  did not find a relation between lactate level and AHI. They denied the role of sympathetic activation in OSAS patients in the increased lactate production. This overproduction may be due to the primary defect in muscle oxidative metabolism caused by adaptation to chronic nocturnal hypoxemia in OSAS.
The present study assessed the levels of serum UA and lactate simultaneously in patients and healthy controls and found that lactate seems to be more sensitive than UA as a marker of HOS and OSAS severity. In agreement with these results, Hira et al.  reported that the measurement of UA was not a sensitive marker of the overnight rise and HOS owing to its slower metabolism as compared with that of lactate.
| Conclusion|| |
Both serum UA and lactate may be considered as potential markers of tissue hypoxia and are related to OSAS severity. Measurement of their levels before and after sleep might be used for the detection of severe cases of OSAS especially in large epidemiological studies where sleep studies are expensive and not always available. Long-term studies are needed to evaluate their level changes after CPAP treatment.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cirelli C, Tononi G. Is sleep essential? PLoS Biol 2008; 6:1605–1611.
Schwab RJ, Pasirstein M, Pierson R. Identification of upper airway anatomic risk factors for sleep apnea. Am J Respir Crit Care Med 2003; 168:522–530.
Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep apnea,cardiometabolic risk in obesity and metabolic syndrome. J Am Coll Cardiol 2013; 62:569–576.
Fernandez-Mendoza J, Shea S, Vgontzas AN, Calhoum SL, Liao D, Bixler EO. Sleep misperception and chronic insomnia in the general population: role of objective sleep duration and psychological profiles. Psychosom Med 2011; 73:88–97.
Ballard RD. Management of patients with obstructive sleep apnea. J Fam Pract 2008; 57:524–530.
Rodwell VW. Metabolism of purine and pyrimidine nucleotides. In: Murray RK, Granner DK, Rodwell VW, editors. Harpers illustrated biochemistry. 27th ed. NY: American McGraw-Hill Education; 2006. pp. 301–310.
Bender DA, Mayes PA. Glycolysis and oxidation of pyrvate. In: Murray RK, Granner DK, Rodwell VW, editors. Harpers illustrated biochemistry. 27th ed. NY: American McGraw-Hill Education; 2006. pp. 145–150.
Bellomo R. Bench to bedside review: lactate and the kidney. Crit Care 2002; 6:322–326.
Drager FL, Togeiro MS, Polotsky YV, Lorenzi-Filho G. Obstructive sleep apnea in obesity and the metabolic syndrome. J Am Coll Cardiol 2013; 62:569–576.
García AR, Armengol AS, Crespo E, García AD, Romero FA, Carmona BC, Capote F. Blood uric acid levels in patients with sleepdisorderedbreathing. Arch Bronconeumol 2006; 42:492–500.
Verhulst SL, Van Hoeck K, Schrauwen N, Haentjens D, Raoul Rooman R, Van Gaal L et al.
Sleep-disordered breathing and uric acid in overweight and obese children and adolescents. Chest 2007; 132:76–80.
Kaditis A, Gozal D, Snow AB, Kheirandish-Gozal L, Alexopoulos E, Varlami V. Uric acid excretion in North American and Southeast European children with obstructive sleep apnea. Sleep Med 2010; 11:489–493.
Hirotsu C, Tufik S, Guindalini C, Mazzotti DR, Bittencourt LR, Andersen ML. Association between uric acid levels and obstructive sleep apnea syndrome. in a large epidemiological sample. PLoS One 2010; 8:e66891.
Braghiroli A, Sacco C, Erbetta M, Ruga V, Donner CF. Overnight urinary uric acid for detectio of sleep hypoxemia: validation study in chronic obstructive pulmonary disease and obstructive sleep apnea before and after treatment with nasal continuou positive airway pressure. Am Rev Respir Dis 1993; 148:173–178.
Saito H, Nishimura M, Shibuya E, Makita H, Tsujino I, Miyamoto K, Kawakami Y. Tissue hypoxia in sleep apnea syndrom assessed by uric acid and adenosine. Chest 2002; 22:1686–1694.
Hira HS, Shukla A, Kaur A, Kapoor S. Serum uric acid and lactate levels among patients with obstructive sleep apnea syndrome: which is a better marker of hypoxemia? Ann Saudi Med 2012; 32:37–42.
Vanuxem D, Badier M, Guillot C, Delpierre S, Jahjah F, Vanuxem P. Impairment of muscle energy metabolism in patients with sleep apnoea syndrome. Respir Med 1997; 91:551–557.
Ucar ZZ, Taymaz Z, Erbaycu AE, Kirakli C, Tuksavul F, Guclu SZ. Nocturnal hypoxia and arterial lactate levels in sleep-related breathing disorders. South Med J 2009; 102:693–700.
Bonanni E, Pasquali L, Manca ML, Maestri M, Prontera C, Fabbrini M et al.
Lactate production and catecholamin profile during aerobic exercise in normotensive OSAS patients. Sleep Med 2004; 5:137–145.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]