Assessment of sympathetic neural activity in chronic insomnia: evidence for elevated cardiovascular risk

Abstract

Study objectives: Chronic insomnia affects up to 15 per cent of adults. Recent cross-sectional and prospective epidemiological studies report an association between insomnia and hypertension, including incident hypertension, yet mechanisms underlying the association remain unknown. We hypothesized that participants with chronic insomnia would have elevated sympathetic neural outflow, blunted baroreflex sensitivity, and augmented sympathetic neural and cardiovascular reactivity to stress when compared with good-sleeper controls.

Methods: Twelve participants with chronic insomnia (11 women, 1 man) and 12 controls (8 women, 4 men) underwent one night of laboratory polysomnography, two weeks of at-home wrist actigraphy, and one night of controlled laboratory sleep prior to a comprehensive morning autonomic function test. The autonomic function test consisted of simultaneous recordings of muscle sympathetic nerve activity (MSNA; microneurography), beat-to-beat blood pressure (finger plethysmography), and heart rate (electrocardiogram) during a 10 min supine baseline and a 2 min cold pressor test.

Results: Baseline blood pressure, heart rate, and MSNA were not different between groups, but sympathetic baroreflex sensitivity was significantly blunted in participants with insomnia (-2.1 ± 1.0 vs. -4.3 ± 1.3 bursts/100 heartbeats/mm Hg; p < 0.001). During the cold pressor test, systolic arterial pressure reactivity (Δ21 ± 11 vs. Δ14 ± 8 mm Hg; time × group = 0.04) and total MSNA reactivity (Δ127%, 54%-208% vs. Δ52%, 30%-81%; time × group = 0.02) were augmented in chronic insomnia.

Conclusions: Participants with chronic insomnia demonstrated impaired sympathetic baroreflex function and augmented neural cardiovascular responsiveness to stress, when compared with controls. These findings support growing evidence of cardiovascular risk and physiological hyperarousal in chronic insomnia.

Clinical trial registration: NCT02048878. https://clinicaltrials.gov/ct2/show/NCT02048878.

Figure 1.

Study consort diagram. Consort diagram depicting how the a priori goal of n = 12 participants with chronic insomnia and n = 12 habitual good sleeper controls with successful microneurographic recordings was achieved.

Figure 2.

Sympathetic BRS in patients with insomnia. (A) Sympathetic BRS was significantly lower in patients with insomnia compared with controls. Data represented as mean ± standard error; *p < 0.05 vs. controls. (B) Representative slope analyses for one insomniac and one control. DAP = diastolic arterial pressure; MSNA = muscle sympathetic nerve activity.

Figure 3.

Cardiovascular and sympathetic neural reactivity in patients with insomnia. (A) Total MSNA responsiveness to the cold pressor test was significantly higher in patients with chronic insomnia compared with controls. Data expressed as a box-and-whisker diagram. The line in the box represents the median and the box represents the interquartile range (IQR; the difference between 25th and 75th percentile). The upper whisker represents the 75th percentile plus 1.5 times the IQR, whereas the lower whisker represents the 25th percentile minus 1.5 times the IQR. Any value beyond the whiskers was defined as an outlier and not graphed. *p < 0.05 vs. controls. (B) Representative microneurographic recordings from a good sleeper control (top) and a participant with chronic insomnia (bottom). Exposure to the cold pressor test increased the number of bursts (i.e. burst frequency/incidence) in both groups, but the increased amplitude/area of those bursts was significantly higher in patients with chronic insomnia. Dotted line represents amplitude normalization to the highest sympathetic burst during baseline condition. Results were similar when total MSNA was normalized by amplitude or area (Table 2).