Obstructive sleep apnea (OSA) is estimated to affect 83.7 million adult patients in the United States (1). OSA is associated with several diseases, such as hypertension, coronary artery disease and depression, as well as economic burden (2), including a loss in productivity of US $86.9 billion annually (2). Studies have shown that OSA severity may be associated with coronary artery disease, including coronary calcification or atherosclerosis (3,4). In one study, patients with OSA and an apnea-hypopnea index (AHI) of ≥15 events/h demonstrated significantly higher N-terminal pro B-type natriuretic peptide (275.8 vs. 131.9 pg/ml) and high-sensitivity cardiac troponin T levels (0.011 vs. 0.008 ng/ml) than patients with an AHI <15 events/h (3).

The American Academy of Sleep Medicine recommends either in-laboratory polysomnography or a home sleep apnea test (HSAT) to diagnose OSA (5). Although HSATs outperform in-laboratory polysomnography in terms of cost, patient satisfaction and wait times (6), they have some limitations, particularly regarding scores for respiratory effort-related arousal (RERA). RERA is defined as a period encompassing a sequence of breaths of ≥10 sec, with a flattening of the inspiratory portion of the nasal pressure followed by arousal, that does not meet criteria for apnea or hypopnea (7,8). Unlike apnea or hypopnea events, RERA events begin with a partial narrowing or functional instability of the upper airway leading to progressive inspiratory effort to maintain adequate ventilation. This increasing effort results in elevated negative intrathoracic pressure during inspiration, a condition known as flow limitation. Cortical arousal in the brain restores muscle tone of the upper airway to open the passage (5,8). In patients with OSA, RERA is associated with prevalent hypertension with a sensitivity of 75% and a specificity of 83% (9).

High RERA score may result in more severe OSA or a higher respiratory disturbance index (RDI). Because OSA severity may be misclassified when relying on HSATs alone, undertreatment with a continuous positive airway pressure machine (CPAP) may occur, which can result in early cardiovascular diseases and/or other consequences (10). For patients who tend to have an RDI higher than AHI, in-laboratory polysomnography may be preferred, whereas patients with an RDI equal to AHI may proceed with HSATs to save diagnostic costs. However, data remain limited about the phenotypes of patients with OSA who have RDIs higher than AHIs (11). Therefore, the present study aimed to evaluate whether any clinical factors predict RDIs higher than AHIs in patients with OSA.

Of the 72 patients with OSA who met the inclusion criteria, 27 (37.50%) had an RDI higher than AHI. Clinical features of both groups are shown in Tables I and II. No significant difference in clinical features emerged between the groups in terms of age, sex, comorbidity or physical features. The RDI>AHI group had more patients with obesity (81.48 vs. 60.00%) and a higher body weight (85 vs. 70 kg) than the RDI=AHI group.

RDI>AHI group had a higher AHI (40.7 vs. 27.3 times/h) and RDI (53.6 vs. 27.3 times/h) than the RDI=AHI group (Table III). The lowest oxygen saturation was comparable between the groups (84 vs. 86%).

There were five factors in the predictive model for RDI higher than AHI: Age, sex, hypertension, diabetes, BMI and STOP-BANG score (Table IV). Only BMI was independently associated with RDI>AHI, with an adjusted odds ratio of 1.10 (95% confidence interval: 1.01, 1.19). The Hosmer-Lemeshow χ² value of the model was 4.03, which indicates goodness of fit. The ROC curve of BMI for RDI>AHI was 60.66% (95% confidence interval: 46.53%, 74.78%; Fig. 1). BMI cutoff points for RDI>AHI are shown in Table V. A BMI of ≥26.03 kg/m² had a sensitivity of 81.48% and a specificity of 33.33%.

Of all participants, 37.5% had an RDI higher than AHI; higher BMI is suggestive for RDI >AHI in patients with OSA. A previous study on the general population showed that the prevalence of patients with a RERA index ≥5 events/h is 3.8%, with a RERA index of 7.1 events/h, an RDI of 23.2 events/h and an AHI of 16.1 events/h (11). In the present study, 37.5% of patients with OSA had a higher RDI than AHI, with an RDI of 53.6 and AHI of 40.7 events/h. These differences may be explained by different study populations; the aforementioned study was a population-based study, whereas the present study was conducted with patients with OSA. As expected, the severity of OSA in patients with an RDI higher than AHI was more severe; the median RDI was 53.6 events/h, categorized as ‘severe OSA’, whereas the median RDI for individuals with an RDI equal to AHI was 27.3 events/h, classified as ‘moderate OSA’ (5). The RDI>AHI group may have demonstrated more severe OSA compared with the RDI=AHI group, with OSA severity potentially ranging from mild to severe and a median inter-group difference of 26.3 events/h. These findings are clinical significance, as the severity progression from mild to severe OSA has important treatment implications-specifically, severe OSA typically necessitates CPAP therapy (5).

The present study also showed that individuals with a high BMI, particularly >26.03 kg/m², may be at risk of having an RDI higher than AHI, with a sensitivity of 84.84%. Those patients may benefit from in-laboratory polysomnography more than HSATs because they may have more severe OSA defined by in-laboratory polysomnography. These results may differ from a previous study conducted with obese vs. non-obese patients with OSA in India (17). In the aforementioned study, there was a significantly lower proportion of patients with a RERA index >5 events/h in obese patients than in the non-obese group (29.16 vs. 52.12%). The aforementioned study classified obesity as a BMI of 27.5 kg/m², whereas the present study adopted a cutoff point of 26.03 kg/m² for having RDI higher than AHI. Moreover, the aforementioned study examined RERA index >5 events/h, whereas the present study focused on the median RDI index. Further studies are required to confirm the present results.

BMI and RERA are related. A previous study showed that patients with OSA with a low arousal threshold have significantly higher body fat than non-OSA patients based on visceral fat score (10.95 vs. 6.35) and body fat percentage (28.61 vs. 26.61) (18). The BMI among patients with a low arousal threshold and OSA was significantly higher than in the non-OSA group (25.99 vs. 22.74 kg/m²). Those findings may indicate that having high BMI and OSA may be associated with a low arousal threshold that leads to higher RERA and RDI.

Although BMI may be a notable predictor of having an RDI higher than AHI, it has low specificity (33.33%). Therefore, clinical decision-making should integrate other factors such as oropharyngeal anatomy. BMI ≥26.03 kg/m² had a sensitivity of 81.48%; this cutoff point may be useful in screening. In patients with suspected OSA and with a BMI <26.03 kg/m², having RDI higher than AHI is unlikely, and using HSATs may be justified. By contrast, in-laboratory polysomnography may be suitable for patients with a BMI ≥26.03 kg/m².

The present study had limitations. First, the median BMI of the study population was ~30 kg/m². Thus, the present results may not be generalized to other populations such as non-obese or severely morbid obese patients. Differences in ethnic, anthropometric, healthcare systems and lack of external validation may also limit their applicability. Furthermore, variations in socioeconomic status, the presence of comorbidities, genetic polymorphisms and phenotypes may prevent generalized implementation. Second, RERA scoring may be scorer-dependent and lab-specific, with variability that may affect RERA burden and validity. An RDI higher than AHI also reflected RERA burden. Third, HSATs were not performed. Typically, AHIs based on HSATs are less than those based on in-laboratory polysomnography for 10 events/h (19), emphasizing the need for in-laboratory polysomnography. Fourth, no cardiovascular outcomes were measured. The area under the ROC curve for BMI was 60.66%, which indicated modest predictive ability. Finally, the study was conducted in a single center with a sample size that could have led to model instability. Additional large-sample studies with external validation are required to confirm the present results.

In conclusion, patients with suspected OSA with BMI ≥26.03 kg/m² may have higher RDI than AHI due to moderate to severe OSA. These patients may require in-laboratory polysomnography, whereas other patients may be tested by HSAT, which may report comparable AHI values.