When is Muscle Sympathetic Nerve Activity ‘Abnormal’?

The sympathetic nervous system participates in both short‐ and long‐term cardiovascular regulation. The microneurographic technique, enabling in humans direct recordings from the populations of post‐ganglionic sympathetic neurons innervating the skeletal muscle vasculature (i.e. muscle sympathetic nerve activity; MSNA), has yielded key insights into mechanisms of sympathetic regulation of the circulation in health, and, importantly, its contributions to cardiovascular disease development and progression. Due to its invasive nature, as well as the technical challenges involved in site acquisition and burst quantification, its application has been limited primarily to trained investigators studying small, selected cohorts, rather than populations. In healthy individuals, MSNA burst frequency or burst incidence, as measured under supine resting conditions, exhibit considerable inter‐individual variability, yet are highly reproducible within individuals over time. However, such variability, as well as the limited data, has impaired the establishment of age‐ and sex‐dependent normative values. Therefore, we aimed to develop resting MSNA reference charts, representing MSNA percentile curves, in a large cohort of young and older men and women. Specifically, we retrospectively assembled a dataset of 654 healthy, unmedicated normotensive (<140/90 mmHg) individuals from four participating Canadian laboratories, including 396 men (aged 18–71 yrs) and 258 women (aged 18–81 yrs), in whom baseline resting MSNA was evaluated over a minimum of 5 min. Quantile regression was used to estimate the 5 th , 20 th , 50 th (i.e. median), 80 th , and 95 th percentiles for resting MSNA burst frequency and burst incidence in men and women as a function of age. Quantiles were parameterized as functions of age by both a one‐ and two‐term fractional polynomial model with power selected from a ladder of values (i.e. −2, −1, −0.5, 0.5, 1, 2, 3). Next, an iterative fitting approach was applied to the MSNA versus age data to determine the fractional coefficients and the combination of values for the two powers from the ladder that provided the greatest goodness of fit (i.e. lowest χ 2 ). The 5 th , 20 th , 50 th , 80 th , and 95 th percentiles for MSNA burst frequency and burst incidence in men and women as a function of age are displayed in the figure below. In conclusion, these MSNA percentile curves, developed from a large sample of men and women, provide age‐ and sex‐related reference values for resting MSNA levels in healthy, normotensive individuals, and, furthermore, by establishing 95% confidence limits, may help inform comparative studies of disease states referenced to age‐ and sex‐matched controls.