Spontaneous baroreflex sensitivity: sequence method at rest does not quantify causal interactions but rather determines the heart rate to blood pressure variability ratio

In order to quantify spontaneous baroreflex sensitivity (BRS) many groups use the sequence method (SME). In this paper we test the hypothesis that SME is quantifying causal interactions of spontaneous BRS at rest rather than, alternatively, being solely dominated by heart rate variability (HRV) and/or systolic blood pressure variability (BPV). Therefore, we retrospectively analyzed 1828 beat-to-beat time series and their corresponding systolic blood pressure during resting conditions. We found a high correlation between short-term HRV and the SME of baroreflex sensitivity of r = 0.85 ( p < 0.001). The correlation is even higher between SME and the root mean square ratio of HRV and BPV ( r = 0.93, p < 0.001). Surrogate analyses revealed that SME is not able to quantify causal relationships between both signals, it cannot differentiate between random and baroreflex driven sequences, and rather determines the HRV-BPV variability ratio. We conclude that SME has a potentially large methodological bias in the characterization of the capacity of the arterial baroreflex during resting conditions.