The pulse-rate response to apneas and hypopneas, defined as the difference between the maximum pulse rate following an airway-opening event and the minimum pulse rate during the respiratory event.

Click on the following link to read about methodology for calculating change in heart rate response to respiratory events- (https://doi.org/10.1164/rccm.202010-3900oc)

The below PSG tracing shows how to calculate change in heart rate associated with one respiratory event. In the red box, minimum pulse rate during the respiratory event is 127 and maximum pulse rate at the end of the respiratory event is 138. Change in heart rate/pulse rate will be 11.

Association with Cardiovascular Outcomes:

• A heightened change in heart rate (DHR) is associated with an increased risk of cardiovascular (CV) morbidity and mortality, particularly in patients with moderate-to-severe obstructive sleep apnea (OSA).
• Both high and low DHR values (U-shaped relationship) are linked to elevated CV risk, with midrange DHR values (5.8–10.1 bpm) being the least risky.

Heart rate change response (ΔHR) is divided into quartiles based on the Multi-Ethnic Study of Atherosclerosis (MESA) data. These ranges are: (https://doi.org/10.1164/rccm.202010-3900oc)

Low ΔHR (1st Quartile): <5.8 beats per minute (bpm)

• Associated with higher cardiovascular risk due to potentially impaired autonomic response or existing comorbidities (e.g., heart disease or diabetes).
• In patients with CAD and OSA without EDS, there is Limited cardiovascular benefit from CPAP therapy, with a potential trend toward harm in some cases. https://doi.org/10.1164/rccm.202111-2608oc

Midrange ΔHR (2nd and 3rd Quartiles): 5.8–10.1 bpm

• Represents the optimal range with the lowest cardiovascular risk and all-cause mortality.
• In patients with CAD and OSA without EDS, CPAP therapy may still provide some benefit, but the risk is already relatively low in this group. https://doi.org/10.1164/rccm.202111-2608oc

High ΔHR (4th Quartile): >10.1 bpm

• Indicates an exaggerated autonomic response and is linked to an increased risk of cardiovascular morbidity and mortality.
• In patients with CAD and OSA without EDS, these individuals experience the greatest cardiovascular benefit from CPAP therapy, with significant reductions in risk (up to 59%). https://doi.org/10.1164/rccm.202111-2608oc

These ranges provide insight into autonomic activity during apneas/hypopneas, helping identify patients at different risk levels. Some of the main findings from a recent study are- (https://doi.org/10.1164/rccm.202010-3900oc)

ΔHR as a Prognostic Biomarker: (https://doi.org/10.1164/rccm.202010-3900oc)

• The apnea-specific heart rate response (ΔHR) serves as a novel and significant biomarker for predicting cardiovascular (CV) morbidity and all-cause mortality in individuals with obstructive sleep apnea (OSA).
• Both low and high ΔHR values (U-shaped relationship) are associated with higher cardiovascular risks, while midrange ΔHR (5.8–10.1 bpm) corresponds to the lowest risk.

High ΔHR and Cardiovascular Risk: (https://doi.org/10.1164/rccm.202010-3900oc)

• A high ΔHR reflects exaggerated autonomic responses to apneas and hypopneas, including heightened sympathetic activation and vagal activity. This overactivation contributes to an increased risk of nonfatal and fatal cardiovascular events.
• The strongest associations were observed in individuals with moderate-to-severe OSA (AHI >15 events/hour) and those with substantial hypoxic burden.

Low ΔHR and Existing Comorbidities: (https://doi.org/10.1164/rccm.202010-3900oc)

• A low ΔHR likely reflects reduced autonomic responsiveness due to pre-existing conditions such as heart disease, diabetes, or autonomic dysfunction. While it indicates risk, these risks are less likely to be directly modifiable through OSA treatment.

Hypoxic Burden as a Moderator: (https://doi.org/10.1164/rccm.202010-3900oc)

• The association between ΔHR and adverse outcomes is stronger in individuals with high hypoxic burden, emphasizing the interplay between oxygen desaturation severity and autonomic response.

Gender and Sleep Stage Variations: (https://doi.org/10.1164/rccm.202010-3900oc)

• Women with high ΔHR showed stronger CV and all-cause mortality associations compared to men, though the difference was not statistically significant.
• Non-REM sleep ΔHR was more consistently associated with outcomes compared to REM sleep, likely due to fewer events and measurement noise in REM sleep.

Findings from RICCADSA Trial regarding Heart rate responses to respiratory events in CAD with OSA patients without EDS

The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the DHR. Specifically, patients with higher DHR exhibit greater cardiovascular benefit from CPAP therapy. (https://doi.org/10.1164/rccm.202111-2608oc) The main findings of this study were-

Elevated ΔHR as a Predictor of Cardiovascular Risk: (https://doi.org/10.1164/rccm.202111-2608oc)

• Individuals with obstructive sleep apnea (OSA) who exhibit a higher heart rate response to respiratory events (ΔHR) are at increased risk for adverse cardiovascular outcomes, such as myocardial infarction, stroke, and cardiovascular mortality.

CPAP Therapy Benefits: (https://doi.org/10.1164/rccm.202111-2608oc)

• Continuous positive airway pressure (CPAP) treatment significantly reduces cardiovascular risk in individuals with elevated ΔHR. Patients with ΔHR ≥6 beats per minute (bpm) experience the most pronounced benefit, with an estimated 59% reduction in risk.
• Patients with lower ΔHR (<6 bpm) showed limited benefit from CPAP, with a potential trend toward harm.

U-Shaped Relationship of ΔHR and Risk: (https://doi.org/10.1164/rccm.202111-2608oc)

• A U-shaped relationship exists between ΔHR and cardiovascular outcomes. Both low and high ΔHR values are associated with increased risk, but only the risk linked to high ΔHR is reversible with CPAP therapy.

ΔHR as a Phenotypic Marker: (https://doi.org/10.1164/rccm.202111-2608oc)

• ΔHR reflects the severity of OSA-related autonomic dysregulation. It serves as a phenotypic marker to identify patients who are most likely to benefit from CPAP therapy, particularly those with more severe respiratory event-related autonomic responses.

Mechanisms Behind Elevated ΔHR: (https://doi.org/10.1164/rccm.202111-2608oc)

• High ΔHR may result from exaggerated autonomic nervous system responses, including sympathetic overactivation during apneic events. This autonomic stress could contribute to long-term cardiovascular complications.

Implications for Clinical Practice: (https://doi.org/10.1164/rccm.202111-2608oc)

• ΔHR could help guide treatment decisions by identifying high-risk patients who might benefit the most from CPAP therapy. It provides a more personalized approach than traditional metrics like the apnea-hypopnea index (AHI).

Limitations and Future Directions: (https://doi.org/10.1164/rccm.202111-2608oc)

• The study cohort predominantly included older men with coronary artery disease (CAD) and OSA, limiting generalizability to other populations.
• Further research is needed to validate ΔHR as a biomarker in diverse populations and to explore its utility in routine clinical practice.
• Development of simpler, scalable tools to measure ΔHR in home settings is encouraged.

These findings highlight the importance of ΔHR as a prognostic marker and emphasize its role in refining treatment strategies for OSA-related cardiovascular risk.