Should heart rate variability be "corrected" for heart rate? Biological, quantitative, and interpretive considerations

Abstract

Metrics of heart period variability are widely used in the behavioral and biomedical sciences, although somewhat confusingly labeled as heart rate variability (HRV). Despite their wide use, HRV metrics are usually analyzed and interpreted without reference to prevailing levels of cardiac chronotropic state (i.e., mean heart rate or mean heart period). This isolated treatment of HRV metrics is nontrivial. All HRV metrics routinely used in the literature exhibit a known and positive relationship with the mean duration of the interval between two beats (heart period): as the heart period increases, so does its variability. This raises the question of whether HRV metrics should be "corrected" for the mean heart period (or its inverse, the heart rate). Here, we outline biological, quantitative, and interpretive issues engendered by this question. We provide arguments that HRV is neither uniformly nor simply a surrogate for heart period. We also identify knowledge gaps that remain to be satisfactorily addressed with respect to assumptions underlying existing HRV correction approaches. In doing so, we aim to stimulate further progress toward the rigorous use and disciplined interpretation of HRV. We close with provisional guidance on HRV reporting that acknowledges the complex interplay between the mean and variability of the heart period.

Keywords: autonomic; behavioral medicine; heart rate; heart rate variability.

Figure 1

HRV metrics expressed as an exponential function of HR (bpm) and a linear function of IBI (ms). Data sources for SDNN and pvRSA are sleep (N = 1,320), leisure time (N = 1,277), and workday (N = 958) averages obtained from ambulatory recordings on participants from the Netherlands Twin Register (NTR). Data sources for RMSSD and HF are the baseline (N = 1,874), and math (N = 1,778) and Stroop (N = 1,794) condition averages from participants in the MIDUS II and Refresher Biomarker Studies. Left: Exponential fit (+ 95% CIs) of the HRV metrics against HR. Right: Linear fit (+ 95% CIs) of the HRV metrics against IBI

Figure 2

Models relating observable heart rate variability (HRV) and heart period to unobserved cardiac vagal activity

Figure 3

Effects of ACh release on the diastolic depolarization rate of the pacemaker cells in the SA. (a) Fixed angle scenario. The same amount of ACh release decreases the slope of diastolic depolarization by a fixed angle (α) at shorter (400 ms, left column) and longer (850 ms, middle column) diastolic depolarization intervals. This change prolongs the heart period less when the mean heart period is shorter (with faster mean diastolic depolarization of the pacemaker cells) than when mean heart period is longer (+50 ms vs. +250 ms). The graph on the right provides an illustration of this strong accumulative vagal prolongation effect across a heart period range of 600 to 1,200 ms. (b) Relative angle scenario. The same amount of ACh release decreases the slope of diastolic depolarization of the pacemaker cells by angles (α) or (β) that scale with the mean ongoing slope of diastolic depolarization. Hence, the effect on heart period is rather similar across shorter (400 ms, left column) and longer (850 ms, middle column) durations of the diastolic depolarization interval (+50 ms vs. +70 ms). The graph on the right provides an illustration of this weak vagal prolongation effect across a heart period range of 600 to 1,200 ms

Figure 4

Structural equation model using HRV and heart period as observable indicators (facets) of a latent factor representing vagal nerve activity to test the association of vagal activity with BMI. Parameters b_{V_BMI} and Ɛ_{NV_BMI} are set to values that cause vagal activity to explain 10% of the variance in BMI. As in Figure 2, b_{V_HRV} and b_{V_HP} capture the vagal effects on HRV and heart period, and b_direct the (putative) direct effect of heart period on HRV. Nonvagal (NV) and error (Ɛ) terms capture all other sources of variance in heart period and HRV

Figure 5

Spontaneous depolarization in the pacemaker cells in the SA node is prolonged by ACh, which, in turn, prolongs the heart period. Main ionic currents related to vagal activity are depicted only; complete rendering would add various sodium currents, the potassium delayed rectifying current, and sodium‐potassium and sodium‐calcium exchangers

Figure 6

Vagal gating giving rise to respiratory sinus arrhythmia. This is a higher‐order conceptual representation only. In reality, cardiac effector responses to respiration‐related, episodic ACh release do not solely depend on quantity, but also on the timing of its release and clearance, and the ongoing kinetics of the multiple other signal transduction pathways involved in sinoatrial depolarization. (a) High tonic vagal firing (~12 Hz) is reduced during inspiration compared to expiration giving rise to differential amounts of ACh release at the SA effector junction. (b) Gating of lower tonic vagal firing (~6 Hz) will also produce inspiration/expiration differences in the amounts of ACh release, but they are less pronounced as those in (a) where tonic vagal firing is higher