Longitudinal effect of nocturnal R-R intervals changes on cardiovascular outcome in a community-based cohort

Abstract

Rationale: Sleep-disordered breathing (SDB) is strongly linked to adverse cardiovascular outcomes (cardiovascular diseases (CVD)). Whether heart rate changes measured by nocturnal R-R interval (RRI) dips (RRI dip index (RRDI)) adversely affect the CVD outcomes is unknown.

Objectives: To test whether nocturnal RRDI predicts CVD incidence and mortality in the Wisconsin Sleep Cohort study (WSCS), independent of the known effects of SDB on beat-to-beat variability.

Methods: The study analysed electrocardiograph obtained from polysomnography study to assess the nocturnal total RRDI (the number of RRI dips divided by the total recording time) and sleep RRDI (the number of RRI dips divided by total sleep time). A composite CVD risk as a function of total and sleep RRDI was estimated by Cox proportional hazards in the WSCS.

Results: The study sample consisted of 569 participants from the WSCS with no prior CVD at baseline were followed up for up to 15 years. Nocturnal total RRDI (10-unit change) was associated with composite CVD event(s) (HR, 1.24 per 10-unit increment in RRDI (95% CI 1.10 to 1.39), p<0.001). After adjusting for demographic factors (age 58±8 years old; 53% male; and body mass index 31±7 kg/m²), and apnoea-hypopnoea index (AHI 4%), individuals with highest total nocturnal RRDI category (≥28 vs<15 dips/hour) had a significant HR for increased incidence of CVD and mortality of 7.4(95% CI 1.97 to 27.7), p=0.003). Sleep RRDI was significantly associated with new-onset CVD event(s) (HR, 1.21 per 10-unit increment in RRDI (95% CI 1.09 to 1.35), p<0.001) which remained significant after adjusting for demographic factors, AHI 4%, hypoxemia and other comorbidities.

Conclusion: Increased nocturnal RRDI predicts cardiovascular mortality and morbidity, independent of the known effects of SDB on beat-to-beat variability. The frequency of RRDI is higher in men than in women, and is significantly associated with new-onset CVD event(s) in men but not in women.

Keywords: cardiac epidemiology; cardiovascular disease; epidemiology; heart rate; sleep medicine.

Figure 1

(A) A representative polygraph from one subject in the WSCS that illustrate changes in respective heart rate and computed RRI tracing during sleep. (B) A magnified segment of ECG illustrating RRI following respiratory event (apnoea). The RRI tracing was retro-graphed from the exported signal that calculates RRI from raw ECG recordings. Open arrows indicate oxygen desaturation following apnoea and closed arrows indicate RRI dip following apnoea. EEG, electroencephalogram; EMG, electromyogram;; RRI, R-R interval; WSCS, Wisconsin Sleep Cohort Study.

Figure 2

A representative computed data of RRI and oxygen saturation (SaO₂) from one individual during sleep. The red dots represent the RRI dips throughout the duration of the PSG recording (approximately 8 hours). The RRDI at 90% threshold for this participant was 54.5 dips/hour, the average heart rate was 61.1 bpm and the ODI (3%) was 2.3 de-saturations/hour (from the original PSG recording). The RRI tracing was retro-graphed from the exported signal that calculates RRI and SaO₂ from raw ECG and pulse oximetry recordings, respectively. ODI, oxygen desaturation index; PSG, polysomnography; RRI, R-R intervals; RRDI, RRI dips index; SaO₂, oxygen saturation.

Figure 3

The WSCS study sample. CPAP, continuous  positive airway pressure; PSG, polysomnography; WSCS, Wisconsin Sleep Cohort Study.

Figure 4

Incidence of composite CVD and hazard ratio across different total RRDI severity: Category 1 as a reference (RRDI <15.1), category 2 (RRDI 15.1-<28.4) and category 3 (RRDI ≥28.4) (n=569). (*) versus unadjusted model (1) RRDI <15.1 dips/hour, p<0.01; (**) versus adjusted model (3) RRDI <15.1 dips/hour, p<0.01. CVD, Cardiovascular  disease; RRDI, R-R interval dips index.

Figure 5

Kaplan-Meier estimates of the likelihood of survival according to total RRDI severity: Category 1 as a reference (RRDI <15.1), category 2 (RRDI 15.1–<28.4) and category 3 (RRDI ≥28.4) (n=569); log-rank test for differences in survival by RRDI category; survival was lower for category 3 compared with group 1 and 2. RRDI is a mean number of RRI dips/hour of total recording time of PSG. PSG, polysomnography; RRDI, R-R interval dips index.