Text: Karina Toledo | FAPESP Agency
Measuring blood levels of an amino acid called homocysteine can help predict a person’s risk of developing obstructive sleep apnea – a condition characterized by recurrent interruptions in breathing caused by relaxation of the throat muscles when sleeping. This simple blood test can also help the doctor predict the risk of worsening of the disorder in patients already affected by the mild or moderate form.
The conclusion is from a study conducted by researchers from the Sleep Institute and the Federal University of São Paulo (Unifesp), with support from FAPESP. The data was disclosed in April in European Archives of Oto-Rhino-Laryngology.
“We still don’t know whether it is the apnea that causes the elevation of homocysteine in the blood or whether it is the increased level of this amino acid that worsens the apnea. Our hypothesis is that it is a bidirectional correlation”, explains Monica Levy Andersen, professor at Unifesp and research coordinator. “It would be interesting if more doctors, from all specialties, requested this exam in the check-up of patients over 40 years old. It’s something simple and doesn’t burden the SUS [Sistema Único de Saúde]. And the results could, at the very least, provide more information about this correlation”, argues the author.
Homocysteine has been a concern for cardiologists for a long time, as there is strong evidence that high levels of the substance – above 15 micromoles per liter of blood (µmol/l) – can cause changes in the walls of blood vessels and favor the emergence of coronary disease, thrombosis, heart attack and even cerebrovascular accident (CVA), also known as cerebrovascular accident (CVA).
“A deficiency of B complex vitamins – particularly B6, B9 and B12 – predisposes to hyperhomocysteinemia. Eating foods that contain these nutrients or even supplementation can be a strategy to modulate the levels of this amino acid in the blood”, informs Vanessa Cavalcante-Silva, postdoctoral fellow at Unifesp and first author of the article.
Sleep epidemiology
Under the coordination of the Unifesp professor Sergio Tufik, the Sleep Epidemiological Study (Episono) has been conducted for over 15 years, the objective of which is to evaluate the quality of sleep and the influence of sleep disorders on the health of a representative sample of the population of the city of São Paulo. Data from Episono 2007, released by the group in another study, indicate that 42% of São Paulo residents snore three times a week or more and almost 33% have sleep apnea.
In addition to family fights instigated by noise at bedtime and concentration and memory problems associated with sleep deficit, apnea accelerates cellular aging and increases the risk of several other diseases, such as hypertension, diabetes and heart failure (Read more at: agencia.fapesp.br/41898).
To investigate the correlation between this disorder and blood levels of homocysteine, the team coordinated by Andersen selected a sample of Episono volunteers who underwent evaluation of the so-called apnea and hypopnea index (AHI). Measured through polysomnography, this indicator represents the number of respiratory events (partial or total obstruction of breathing) recorded per hour and is one of the parameters used to stratify the severity of the disease.
“Up to five events per hour is considered normal. From five to 15, mild apnea; from 15 to 30 is already moderate and, above 30, severe apnea”, says Cavalcante-Silva.
Initially, the team analyzed the AHI of 854 volunteers who participated in Episono in 2007. Of these, 54.4% did not have apnea, 24.4% had a mild condition, 12.4% moderate and 8.8% severe. These participants were also classified according to homocysteine levels in their blood, with a value up to 10 µmol/l being considered normal, moderate from 10 to 15 µmol/l and high above 15 µmol/l.
“When crossing the data, we observed that volunteers with high homocysteine levels also had a higher AHI. Those above 15 µmol/l had an average increase in AHI of 7.43 when compared to those with levels below 10 µmol/l”, says the postdoctoral student. The influence of factors such as weight, biological sex and age was corrected using statistical methods.
In a second stage, data from a reassessment carried out in 2015 with the same volunteers were analyzed. As part of the group was unable to participate in this new phase of Episono, the sample for this second phase covered 561 people. The rate of those without apnea had fallen to 29.8%. The number of participants with mild conditions rose to 31.2%, those with moderate conditions rose to 19.4% and another 19.6% were diagnosed with severe apnea.
“In this case, the objective was to discover whether homocysteine would be a risk factor for the development of apnea. To do this, we excluded participants who already had the disease in 2007 and analyzed data from those who, at the time, had normal sleep. In this subgroup, we observed that the unit increase (1 µmol/l) in homocysteine concentrations in 2007 represented a 0.98% increase in the risk of apnea diagnosis in 2015”, says Cavalcante-Silva.
“It’s a low risk, but it exists. The fact is that we present a new factor, simple to measure and with clinical and practical applicability”, comments Andersen. “It would now be interesting to carry out a study with another format, in which participants are assessed annually, to obtain more comprehensive data.”
The article Homocysteine as a predictor of apnea–hypopnea index in obstructive sleep apnea: a longitudinal epidemiological study (Episono) can be read: https://link.springer.com/article/10.1007/s00405-024-08614-z.
