Key result
High respiratory self-similarity linked to ~69% higher incident CVD risk in cohort analysis.
Why the study?
Pathological respiratory chemoreflex activation (high loop gain) in sleep apnea may induce excessive sympathetic nerve output and independently increase adverse outcome risk. Whether high loop gain during sleep, estimated by respiratory self-similarity and algorithm-derived central respiratory event index, is associated with new-onset CVD and CVD-related mortality was uncertain.
Does a high loop gain sleep apnea endotype (estimated by respiratory self-similarity and central respiratory event index) predict new-onset cardiovascular disease and CVD-related mortality in participants from the SHHS and MESA cohorts?
Cohort
Yes
Does a high loop gain sleep apnea endotype (estimated by respiratory self-similarity and central respiratory event index) predict new-onset cardiovascular disease and CVD-related mortality in participants from the SHHS and MESA cohorts?
A sleep apnea endotype reflecting high respiratory loop gain (respiratory self-similarity) is associated with an increased risk of incident cardiovascular disease and cardiovascular mortality, particularly in men, though associations attenuate when adjusting for continuous age.
Answers are grounded in this paper and cite their sources.
High respiratory self-similarity may aid CVD risk stratification in sleep apnea; extends loop-gain observations but leaves open causal and therapeutic implications.
STUDY OBJECTIVES: Pathological respiratory chemoreflex activation (high loop gain) in sleep apnea may activate the carotid body and induce excessive sympathetic nerve output, and independently add to the risk of adverse outcomes. This study aims to determine whether a high loop gain of the respiratory control system during sleep, estimated by respiratory self-similarity (SS) and the algorithm-derived central respiratory event index (CREI), is associated with new-onset cardiovascular disease (CVD) and CVD-related mortality. METHODS: A secondary analysis of The Sleep Heart Health Study (SHHS) and Multi-Ethnic Study of Atherosclerosis (MESA). High SS% and CREI were defined as the highest quartile. Lasso regression and restricted cubic spline assessed the relationship between SS%, CREI and CVD, CVD-mortality and all-cause mortality. A cumulative incidence function and a Fine-Gray subdistribution hazard model were used to evaluate this outcome accounting for competing risks. RESULTS: In adjusted models with age as a categorical variable divided by 65 years old, the highest quartile of SS% (HR 1.693, p: 0.017 in MESA and HR 1.240, p : 0.009 in SHHS) was associated with the incidence of CVD and was more prominent in males. A positive relationship between SS% (MESA: HR 1.429, p: 0.039; SHHS HR1.176, p:0.018 ) for the continuous metrics and CVD mortality in both cohorts was more apparent in men than in women. The categorical high-exposure association with CVD mortality was not consistent across cohorts.The associations were significantly attenuated when adjusted by age as a continuous metric. CONCLUSIONS: An endotype of sleep apnea reflecting high loop gain is associated with CVD and CVD mortality, especially in males.
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Ni et al. (2026) conducted a cohort in Sleep apnea. High loop gain of the respiratory control system (estimated by respiratory self-similarity [SS%] and central respiratory event index [CREI]) vs. Lower quartiles of SS% and CREI was evaluated on New-onset cardiovascular disease (CVD) and CVD-related mortality (HR 1.693, p=0.017). High respiratory self-similarity (highest quartile) was associated with increased incident CVD in MESA (HR 1.693, p=0.017) and SHHS (HR 1.240, p=0.009) and higher CVD mortality.
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