Homocysteine Concentration Levels May Predict Risk and Severity of Obstructive Sleep Apnea


The findings show that those with higher plasma homocysteine concentrations experienced more sleep apnea events per hour compared with those with lower concentrations.

According to study findings published in European Archives of Oto-Rhino-Laryngology, measuring the levels of a certain amino acid, homocysteine, that is in the blood may help predict an individual’s risk of developing obstructive sleep apnea. Prior evidence shows that unusually high levels of homocysteine in the blood (more than 15 µmol/L) can cause alterations in the blood vessel walls and potentially lead to the development of coronary disease, thrombosis, heart attacks, and strokes. Additionally, sleep apnea can accelerate cellular aging and increase the risk of conditions such as high blood pressure, diabetes, and heart failure as well as impair concentration and memory.1

Man with sleep apnea snoring -- Image credit: ryanking999 | stock.adobe.com

Image credit: ryanking999 | stock.adobe.com

“We don’t yet know whether apnea causes the rise in blood levels of homocysteine or the rise in levels of this amino acid causes severe apnea. Our hypothesis is that it’s a 2-way correlation,” said study author Monica Levy Andersen, professor at Sleep Institute and the Federal University of São Paulo (UNIFESP), in a news release. “It would be a good idea for more physicians in all specialties to include a homocysteine test in the blood work prescribed for checkups of people over 40 [years of age]…The results could provide more information on this correlation, at the very least.”1

The investigators aimed to assess the potential association between sleep apnea and blood levels of homocysteine. A total of 1042 participants aged 20 to 80 years were enrolled in an initial study in 2007, and included polysomnographic evaluations to measure participants’ apnea-hypopnea index (AHI), questionnaires on participants’ sleep and general health, and biochemical analyses. After an 8-year period, 715 of the initial population were invited to participate in a follow-up assessment, which commenced in 2015.1,2

The polysomnographic evaluation assesses the severity of one’s sleep apnea by counting the number of times that breathing slows or stops during an average hour of sleep. According to the investigators, up to 5 events per hour is considered “normal,” 5 through 15 is “mild,” 15 through 30 is “moderate,” and more than 30 is “severe.” According to the 2007 portion of the study, approximately 54.4% of participants had no apnea, 24.4% had mild, 12.4% had moderate, and 8.8% had severe. Additionally, the participants in the 2007 round were classified according to their blood levels of homocysteine, with up to 10 µmol/L being considered “normal,” 10-15 µmol/L “moderate,” and over 15 µmol/L “high.” In the 2015 portion, the sample size decreased to 561, and of this population, 29.8% presented no apnea, 31.2% mild, 19.4% moderate, and 19.6% severe.1

The findings also demonstrate that homocysteine was a predictor for an increased AHI, and AHI also increased over time. Those who had plasma homocysteine concentrations of 15 µmol/L experienced an average AHI increase of 7.43 events per hour over time (β = 7.43; 95% CI 2.73-12.13), compared to those with plasma concentrations of 10 µmol/L. Similarly, a trend was also observed in participants with homocysteine concentrations of 10 and up to 15 µmol/L, who had an AHI increase with an average of 3.20 events per hour (95% CI 1.01-5.39) compared with those who had plasma homocysteine concentrations of 10 µmol/L.2

“When we cross-tabulated the data, we saw that subjects with high levels of homocysteine also had a higher AHI. Those with more than 15 µmol/L had an AHI that was 7.43 higher on average than those with less than 10 µmol/L,” said first study author Vanessa Cavalcante-Silva, postdoctoral researcher at UNIFESP, in the news release. “In this stage, the aim was to find out whether homocysteine was a risk factor for the development of apnea, so we excluded participants who had apnea in 2007 and analyzed the data for those who were then sleeping normally. In this subgroup, a rise of 1 µmol/L in the 2007 level of homocysteine represented a rise of 0.98% in the risk of a diagnosis of apnea in 2015.”1

The findings demonstrate that increased plasma homocysteine concentrations may be considered a risk factor for the development of obstructive sleep apnea. The data, according to the investigators, demonstrate that elevations in levels may be able to predict the severity of patients’ apnea, emphasizing the believed association between homocysteine and sleep apnea. In addition, the investigators note wanting to conduct further research to gain more extensive data.1,2

“It’s a low risk, but it exists. The fact is that we presented a novel factor which is easy to measure and has clinical and practical applicability,” said Andersen in the news release. “Now it would be interesting to conduct a study with a different format, in which the participants are assessed annually and we could obtain more extensive data.”1


1. Fundação de Amparo à Pesquisa do Estado de São Paulo. Blood test can help predict risk of obstructive sleep apnea. News release. July 1, 2024. Accessed July 2, 2024. https://www.eurekalert.org/news-releases/1050064
2. Cavalcante-Silva, V, Morelhão, PK, Fernandes, GL, D’Almedida, V, Tufik, S, Andersen, ML. Homocysteine as a predictor of apnea–hypopnea index in obstructive sleep apnea: a longitudinal epidemiological study (EPISONO). Eur Arch Otorhinolaryngol 281, 3237–3243 (2024) doi:10.1007/s00405-024-08614-z
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