Comment on: use of blood biomarkers to screen for obstructive sleep apnea.

Dear editor

The recently published paper in Nature and Science of Sleep1 describes a combination of blood biomarkers for obstructive sleep apnea (OSA) screening which is shown to have better sensitivity and selectivity than any one individually. The combination comprises elevated levels of glycated hemoglobin (HbA1c), C-reactive protein, and erythropoeitin. The combination algorithm alluded to in the paper requires a sufficiently elevated level above a threshold of the combination of the three constituents for further diagnostic testing to be recommended. Of course, OSA would have to have been present long enough for the elevated levels to occur in order for the proposed biomarker to indicate its likely presence. My comment on this paper questions not whether this screening tool is valid, but whether it is valid early enough in the development of OSA to initiate diagnosis and treatment before some irreversible life-threatening consequence of OSA develops.

In particular, I focus on HbA1c, which when elevated above 5.7% indicates prediabetes or diabetes, a recognized common consequence of OSA which risks the quality and length of life. The meta-analyses in2,3 conclude that overcoming OSA does not generally reduce HbA1c, although it may improve insulin sensitivity. Insulin insufficiency from beta cell dysfunction and mass reduction remains to keep HbA1c elevated, and diabetes is still a threat.

There is another biomarker, although not a blood biomarker, which appears earlier in the development of OSA. It is the formation of monosodium urate crystals on patellar, biceps, or quadriceps tendons, where they are detectable by ultrasonic means.4 The intermittent hypoxemia which results from OSA causes three effects which quickly elevate the concentration of serum uric acid, often leading to the precipitation of mono-sodium urate crystals: 1) intermittent cell catabolism which culminates irreversibly in the generation of excess uric acid fed into the blood; 2) concurrent intermittent serum acidosis and hypercapnia which reduces the solubility of uric acid in the blood; and 3) gradual reduction of the kidneys’ glomerular filtration rate which slows removal of serum uric acid. Once formed, the crystals dissolve very slowly, which allows for their detection at any time convenient for OSA screening.

Dear editor

We would like to thank Burton Abrams, MS, for the letter in response to our recently published article.

Mr Abrams questions whether our new screening tool is valid early enough in the development of OSA to initiate diagnosis and treatment before irreversible life-threatening consequences of OSA develop. We would like to reiterate that the algorithm score derived from a combination of three biomarkers correlated with severity of disease (none, mild, moderate, severe), allowing sleep centers to identify and triage lower- to higher-risk patients for sleep study testing and treatment. In addition, the combination of biomarkers performed significantly better than current screening methods. Given that up to 90% of individuals with obstructive sleep apnea (OSA) remain undiagnosed and untreated, this new screening tool represents a substantial improvement in early identification of OSA.

Mr Abrams’ work on ultrasonic detection of monosodium urate is interesting, and we commend any effort to improve upon the early detection of OSA.