Ab0466 dysfunction of the autonomic nervous system is associated with low-grade inflammation in patients with systemic lupus erythematosus.

BackgroundSystemic lupus erythematosus (SLE) is characterized by chronic, systemic inflammation, organ damage and -dysfunction. Autonomic nervous system dysfunction is highly prevalent in SLE patients (up to 54%); compared to controls the prevalence may be up to 12 times increased.1 These numbers parallel findings in other chronic conditions such as diabetes.2Heart rate variability (HRV) reflects autonomic activity, and low variability indicates impaired activity, denoted as autonomic dysfunction (AD). AD is associated with low-grade inflammation in healthy subjects and patients with diabetes or cardiovascular disease.3 The causality hereof is not fully understood: AD may impair the vagally mediated anti-inflammatory reflex, thus leading to increased systemic inflammation, but inflammatory mediated microvascular and neuronal damage may also impair autonomic function.ObjectivesTo determine if markers of low-grade inflammation are associated with AD in SLE patients.MethodsSLE patients (n=111) from the Copenhagen based PLUSheart (Prospective Lupus Study on Cardiovascular Risk Factors) cohort were included for this cross-sectional analysis. The cohort has previously been described1 with the following characteristics in 2018-2019: 89.2% women, mean age: 51.5 (SD ±12.7) years, mean BMI: 25.1 (±5.0), mean disease duration: 19.9 (±9.5) years, median SLEDAI 2K score: 3 (IQR 1-4), and median SLE Damage Index score: 2 (1-4).Low-grade inflammation was evaluated by plasma levels of C-reactive protein (CRP) and soluble urokinase-type plasminogen activator receptor (suPAR). Autonomic function was assessed with 5-min resting lead-I electrocardiograms using the VagusTM device. Subsequent HRV analyses comprised RMSSD (the root mean square of successive interval differences between normal heartbeats), reflecting parasympathetic function, and SDNN (standard deviation of normal-to-normal heartbeat intervals), reflecting mixed parasympathetic-sympathetic function.ResultsAll HRV- and inflammatory markers were non-normally distributed. The median SDNN was 30.4 (IQR 24.1-40.4), the median RMSSD was 19.7 (12.6-31.7). The median CRP level was 1 (1-3) and suPAR level was 3.2 (2.5-4.6).For parametric analyses, all markers were logarithmically transformed. Both SDNN and RMSSD associated with CRP and suPAR levels in univariate analyses. When adjusting for age and SLE disease activity as per the SLEDAI-score, SDNN remained associated with suPAR and CRP and RMSSD with suPAR only (Table 1).Table 1.Association between low-grade inflammation and autonomic nervous system functionSDNN *RMSSD *UnivariateAdjustedUnivariateAdjustedβPβPβPβPCRP *-0.2410.011-0.1970.035-0.2150.024-0.1680.072suPAR *-0.2390.014-0.1970.038-0.2680.006-0.2270.016Univariate and multivariate linear regression analyses adjusted for age and disease activity of correlations between log-transformed (*) low-grade inflammation markers (CRP and suPAR) and heart rate variability markers (RMSSD and SDNN). β=standardized coefficients. Statistically significance (P<0.05) is marked with bold.ConclusionIn SLE, HRV impairments reflecting both decreased parasympathetic and mixed parasympathetic-sympathetic autonomic function were associated with markers of low-grade inflammation independently of SLE disease activity and age. Longitudinal prospective studies are needed to determine causality.References[1]Zinglersen AH, et. al. Characteristics of cardiovascular autonomic dysfunction and association with quality of life in patients with systemic lupus erythematosus. doi:10.1136/lupus-2021-000507[2]Spallone V. Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet. Diabetes Metab J. doi:10.4093/dmj.2018.0259[3]Haensel A, et. al. The relationship between heart rate variability and inflammatory markers in cardiovascular diseases. Psychoneuroendocrinology. doi:10.1016/j.psyneuen.2008.08.007Disclosure of InterestsAmanda Hempel Zinglersen: None declared, Katrine Kjær Iversen: None declared, Jesper Eugen-Olsen Shareholder of: Co-founder, shareholder and CSO of ViroGates (suPAR assay), Jesper Fleischer Shareholder of: Co-inventor of the VagusTM-device (HRV measurement), Søren Jacobsen: None declared