Implications of sympathetic activation for objective versus self-reported daytime sleepiness in obstructive sleep apnea, 2022, Chen et al

[nataliezzz]

Implications of sympathetic activation for objective versus self-reported daytime sleepiness in obstructive sleep apnea
Baixin Chen, Virend K Somers, Qimeng Sun, Yanyuan Dai, Yun Li
https://academic.oup.com/sleep/article/45/7/zsac076/6562985 (PDF Available)

Study objectives: Objective excessive daytime sleepiness (EDS) is associated with systemic inflammation and a higher risk of cardiometabolic morbidity in obstructive sleep apnea (OSA). We hypothesized that OSA with objective EDS is associated with higher levels of sympathetic nerve activity (SNA) when compared with self-reported EDS. We, therefore, examined the associations between objective and self-reported EDS with SNA in patients with OSA.

Methods: We studied 147 consecutive male patients with OSA from the institutional sleep clinic. Objective EDS and self-reported EDS were defined based on Multiple Sleep Latency Test (MSLT) latency ≤ 8 minutes and Epworth Sleepiness Scale (ESS) > 10, respectively. Twenty-four-hour urinary norepinephrine was used for assessing SNA. Blood pressure (BP) was measured both in the evening and in the morning.

Results: Twenty-four-hour urinary norepinephrine was significantly higher in patients with OSA with objective EDS compared with those without objective EDS (p = 0.034), whereas it was lower in patients with OSA with self-reported EDS compared with those without self-reported EDS (p = 0.038) after adjusting for confounders. Differences in the sympathetic drive were most striking in those with an objective but not self-reported EDS versus those with self-reported but not objective EDS (p = 0.002). Moreover, shorter MSLT latency was significantly associated with higher diastolic BP (β = -0.156, p = 0.049) but not systolic BP. No significant association between ESS scores and BP was observed.

Conclusions: Objective, but not self-reported EDS, is associated with increased SNA and diastolic BP among males with OSA, suggesting that objective EDS is a more severe phenotype of OSA that is accompanied by higher sympathetic drive, higher BP, and possibly greater cardiovascular morbidity and mortality.

 

[Clio]

I just skimmed the paper after seeing p values close to 0.05, couldn't find any mention of MCID, was that taken into account?

 

[nataliezzz]

I just skimmed the paper after seeing p values close to 0.05, couldn't find any mention of MCID, was that taken into account?

I haven't actually read this paper (besides the abstract) yet lol, sorry, I just added it because it was cited in the other paper I made a thread on that discussed differences in objective markers between OSA patients with objective vs. subjective sleepiness: [Edit to link full post]

Post in thread 'Objective versus subjective excessive daytime sleepiness in OSA: Quantifying the impact of fatigue, 2026, Gold et al.'

Mar 31, 2026

Re: the pathophysiology of objective excessive daytime sleepiness (EDS) ("OSA Phenotype 1") vs. subjective EDS / fatigue ("OSA Phenotype 2"):

In recent years, a series of studies in patients with OSA have considered whether the presence of objective EDS (MSLT) and subjective EDS (ESS) correlated with the following parameters:
• inflammation – levels of IL-6 and cortisol [6].
• sympathetic activation – urinary norepinephrine and blood pressure measurements [7].
• glucose metabolism - blood glucose, insulin, HOMA-IR, serum metabolomics, fecal microbiota [8].
• all cause and...

• nataliezzz

• 

 

[nataliezzz]

I've read the whole paper now. Here is the most important finding. Self-reported/subjective excessive daytime sleepiness (EDS) was defined as Epworth Sleepiness Scale (ESS) >10. Objective EDS was defined as mean multiple sleep latency test (MSLT) ≤ 8 min.

Patients with OSA with purely objective EDS [MSLT ≤ 8 and ESS ≤ 10] had significantly higher 24-hour urinary norepinephrine compared with those with purely self-reported EDS [ESS > 10 and MSLT > 8] (60.98 ± 4.79 vs. 34.03 ± 7.09 μg; p = 0.002)

Notably, subjects with purely self-reported EDS also had significantly lower 24-hour urine norepinephrine than those with no self-reported or objective EDS, supporting that there are different physiological processes underlying objective and subjective EDS in OSA.

Moreover, patients with OSA with purely self-reported EDS (34.03 ± 7.09 μg) also had significantly lower 24-hour urinary norepinephrine compared with those with both self-reported and objective EDS (53.09 ± 4.53 μg, p = 0.024) and those with no EDS (54.95 ± 4.62 μg; p = 0.016). These results remained similar when adjusted for minimum oxygen saturation instead of AHI. In sensitivity analyses after excluding patients taking anti-hypertensive medications, the findings remained similar.

Discussion of possible mechanisms underlying the associations. So basically, in the purely objectively sleepy OSA phenotype (which one would expect to report subjective sleepiness and to be more impaired in terms vigilance etc.) the increased "sympathetic drive" - i.e. sympathetic nerve activity (SNA) as measured by 24-hour urine norepinephrine - may actually counteract subjective sleepiness and decreased alertness/vigilance.

The higher SNA in objective EDS patients might be partly mediated by impaired baroreflex sensitivity. The arterial baroreceptors, located in the carotid sinuses and aortic arch, respond to changes in carotid or aortic stretch elicited by increased arterial pressure and thereby provide direct input on SNA [30, 31]. Impaired baroreflex sensitivity is not only associated with the development of hypertension [28] but also associated with objective daytime sleepiness [15]. Moreover, enhanced efferent sympathetic discharge plays a critical role in the alerting response and maintaining wakefulness [32, 33]. Thus, increased SNA with consequent increased alertness in patients with OSA with objective EDS might also have a counteracting effect against self-reported perceptions of sleepiness, resulting in attenuated measures of self-reported sleepiness. Indeed, we noted the highest levels of sympathetic drive in those patients with OSA without symptoms of self-reported sleepiness despite the presence of objective sleepiness evident by MSLT ≤8 minutes. In contrast, the lowest levels of sympathetic drive were evident in those with self-reported but not objective sleepiness. Thus, our data suggest that while increased sympathetic activation may attenuate self-reported perceptions of sleepiness, the heightened sympathetic drive does not appear to mitigate objective measures of sleepiness as measured by the MSLT.

In contrast to objective EDS, we found that OSA with self reported EDS was associated with lower sympathetic drive, consistent with previous studies [16, 17]. In a recent report, we demonstrated a link between self-reported EDS and impaired behavioral alertness/sustained attention among patients with OSA [34]. Thus, the effects of sympathetic activation on levels of alertness [16, 17] may help explain the association between self-reported EDS (probably accompanied by impaired alertness) and lower SNA.

Patients with cardiovascular diseases (aside from hypertension) were excluded in the study.

Because cardiovascular diseases are highly associated with sympathetic dysfunction and increased BP, we also excluded patients with cardiovascular diseases (ie, atrial fibrillation, heart failure, and ischemic heart disease and/or stroke, which may cause a confounding effect on SNA and/or BP) except hypertension.