Heart rate responses to autonomic challenges in obstructive sleep apnea

Abstract

Obstructive sleep apnea (OSA) is accompanied by structural alterations and dysfunction in central autonomic regulatory regions, which may impair dynamic and static cardiovascular regulation, and contribute to other syndrome pathologies. Characterizing cardiovascular responses to autonomic challenges may provide insights into central nervous system impairments, including contributions by sex, since structural alterations are enhanced in OSA females over males. The objective was to assess heart rate responses in OSA versus healthy control subjects to autonomic challenges, and, separately, characterize female and male patterns. We studied 94 subjects, including 37 newly-diagnosed, untreated OSA patients (6 female, age mean ± std: 52.1 ± 8.1 years; 31 male aged 54.3 ± 8.4 years), and 57 healthy control subjects (20 female, 50.5 ± 8.1 years; 37 male, 45.6 ± 9.2 years). We measured instantaneous heart rate with pulse oximetry during cold pressor, hand grip, and Valsalva maneuver challenges. All challenges elicited significant heart rate differences between OSA and control groups during and after challenges (repeated measures ANOVA, p<0.05). In post-hoc analyses, OSA females showed greater impairments than OSA males, which included: for cold pressor, lower initial increase (OSA vs. control: 9.5 vs. 7.3 bpm in females, 7.6 vs. 3.7 bpm in males), OSA delay to initial peak (2.5 s females/0.9 s males), slower mid-challenge rate-of-increase (OSA vs. control: -0.11 vs. 0.09 bpm/s in females, 0.03 vs. 0.06 bpm/s in males); for hand grip, lower initial peak (OSA vs. control: 2.6 vs. 4.6 bpm in females, 5.3 vs. 6.0 bpm in males); for Valsalva maneuver, lower Valsalva ratio (OSA vs. control: 1.14 vs. 1.30 in females, 1.29 vs. 1.34 in males), and OSA delay during phase II (0.68 s females/1.31 s males). Heart rate responses showed lower amplitude, delayed onset, and slower rate changes in OSA patients over healthy controls, and impairments may be more pronounced in females. The dysfunctions may reflect central injury in the syndrome, and suggest autonomic deficiencies that may contribute to further tissue and functional pathologies.

Figure 1. Cold pressor heart rate responses.

A: 37 OSA and 57 control subjects; B: 6 OSA and 20 control female subjects, and 31 OSA and 37 control male subjects. Ai, Bi: Raw heart rate during the complete sequence. Aii, Bii, Biii: Change in heart rate relative to baseline (group mean ± SE), with time-points of significant increase or decrease relative to baseline within-group, and time-points of between-group differences (RMANOVA, p<0.05). Shaded areas indicate challenge periods.

Figure 2. Cold pressor indices.

A: heart rate increase from baseline to initial peak (i); B: sustained heart rate elevation during mid-challenge period (area-under curve, ii); C: rate of change (slope) during mid-challenge increase (iii). Time trend graph illustrates the mean heart rate of the 57 subjects in the control group, with a simplified representation (thick black line) overlaid on the measured values (gray line). Shaded area indicates challenge period.

Figure 3. Hand grip heart rate responses.

A: 37 OSA and 57 control subjects; B: 6 OSA and 20 control female subjects, and 31 OSA and 37 control male subjects. Aii, Bii: Raw heart rate during the complete sequence. Aii, Bii, Biii: Change in heart rate relative to baseline (group mean ± SE) averaged over 4 challenges, with time-points of significant increase or decrease relative to baseline within-group, and time-points of between-group differences (RMANOVA, p<0.05). Gray rectangles (hg) indicate challenge periods.

Figure 4. Hand grip indices.

A: heart rate increase from baseline to initial peak (i); B: sustained heart rate elevation during main challenge period (area-under curve, ii). Time trend graph illustrates the mean heart rate of the 57 subjects in the control group, with a simplified representation (thick black line) overlaid on the measured values (gray line). Shaded area indicates challenge period.

Figure 5. Valsalva maneuver heart rate responses.

A: 37 OSA and 57 control subjects; B: 6 OSA and 20 control female subjects, and 31 OSA and 37 control male subjects. Ai, Bi, Raw heart rate and Aii load pressure during the complete sequence. Aiii,Bii, Biii: change in signals relative to baseline (group mean ± SE) averaged over 4 challenges, with time-points of significant increase or decrease relative to baseline within-group, and time-points of between-group differences (RMANOVA, p<0.05). Shaded areas (Val) indicate challenge periods.

Figure 6. Hand grip indices.

A: tachycardia ratio (TR; peak during i/baseline); B: heart rate increase from baseline to initial peak (i); C: Valsalva ratio (VR; peak during ii/minimum during recovery); D: rate of change (slope) during phase II increase (iii). Time-trend graph illustrates the mean heart rate of the 57 subjects in the control group, with a simplified representation (thick black line) overlaid on the measured values (gray line). Shaded area indicates challenge period.