Nocturnal Respiratory Rate and Variability Predict Long-term Mortality in Stable Outpatients with Cardiovascular Disease

Background: Respiratory rate (RR) predicts short-term mortality in acute care settings, yet its prognostic significance in clinically stable outpatients remains poorly defined. Objectives: To determine whether the median and variability of nocturnal respiratory rate (NRR) are independently associated with long-term cardiovascular and all-cause mortality in outpatients with cardiovascular disease. Methods: We analyzed overnight chest belt waveforms from elective polysomnography in 5,679 older adults with cardiovascular disease enrolled in the Sleep Heart Health Study (SHHS). NRR was quantified at 30-second resolution, and per-subject median NRR and within-night variability (standard deviation) were derived. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate associations with cardiovascular and all-cause mortality over 3-year and 15-year follow-up periods, adjusting for demographic characteristics, cardiopulmonary comorbidities, and sleep apnea severity. Results: Higher median NRR and greater NRR variability were each associated with increased cardiovascular and all-cause mortality. Combining these metrics identified a high-risk group characterized by elevated median and high variability of NRR, with approximately five-fold higher 3-year all-cause mortality compared with a low-risk group; this association remained significant in Cox models (unadjusted HR: 2.61; 95% CI: 1.65, 4.14; p<0.001; adjusted HR: 2.15; 95% CI: 1.30, 3.55; p=0.003). Conclusions: Both the baseline level and variability of NRR independently predict mortality in clinically stable outpatients with cardiovascular disease. Densely profiled NRR represents a promising, underutilized biomarker for long-term risk stratification.