title: Impact of heart rate variability, a marker for cardiac health, on lupus disease activity.
abstract: Decreased heart rate variability (HRV) is associated with adverse outcomes in cardiovascular diseases and has been observed in patients with systemic lupus erythematosus (SLE). We examined the relationship of HRV with SLE disease activity and selected cytokine pathways.
  
  
  
  Fifty-three patients from the Oklahoma Lupus Cohort were evaluated at two visits each. Clinical assessments included the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), British Isles Lupus Assessment Group (BILAG) index, physician global assessment (PGA), and Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI Flare Index. HRV was assessed with a 5-minute electrocardiogram, and the following HRV parameters were calculated: square root of the mean of the squares of differences between adjacent NN intervals (RMSSD), percentage of pairs of adjacent NN intervals differing by more than 50 milliseconds (pNN50), high-frequency power (HF power), and low frequency to high frequency (LF/HF) ratio, which reflects sympathetic/vagal balance. Plasma cytokine levels were measured with a multiplex, bead-based immunoassay. Serum B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) were measured with an enzyme-linked immunosorbent assay. Linear regression analysis was applied.
  
  
  
  Baseline HRV (pNN50, HF power, LF/HF ratio) was inversely related to disease activity (BILAG, PGA) and flare. Changes in RMSSD between visits were inversely related to changes in SLEDAI (p = 0.007). Age, caffeine, tobacco and medication use had no impact on HRV. Plasma soluble tumor necrosis factor receptor II (sTNFRII) and monokine induced by interferon gamma (MIG) were inversely related with all baseline measures of HRV (p = 0.039 to <0.001). Plasma stem cell factor (SCF), interleukin (IL)-1 receptor antagonist (IL-1RA), and IL-15 showed similar inverse relationships with baseline HRV, and weaker trends were observed for interferon (IFN)-α, interferon gamma-induced protein (IP)-10, and serum BLyS. Changes in the LF/HF ratio between visits were also associated with changes in sTNFRII (p = 0.021), MIG (p = 0.003), IFN-α (p = 0.012), SCF (p = 0.001), IL-1RA (p = 0.023), and IL-15 (p = 0.010). On the basis of multivariate linear regression, MIG was an independent predictor of baseline HRV after adjusting for plasma IL-1RA, SCF, IFN-α, IP-10, and serum BLyS. In a similar model, the sTNFRII impact remained significant after adjusting for the same variables.
  
  
  
  Impaired HRV, particularly the LF/HF ratio, is associated with lupus disease activity and several cytokines related to IFN type II and TNF pathways. The strongest association was with MIG and sTNFRII, expanding previous immune connections of vagal signaling.
authors: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, OK, 73104, USA. aikaterini-thanou@omrf.org.
authors: Aikaterini
authors: 0000-0002-1161-7618
authors: A
authors: Thanou
authors: Heart Rhythm Institute, University of Oklahoma Health Sciences Center, 1200 Mark Everett Drive, TCH 6E103, Oklahoma City, OK, 73104, USA.
authors: Stavros
authors: S
authors: Stavrakis
authors: Heart Rhythm Institute, University of Oklahoma Health Sciences Center, 1200 Mark Everett Drive, TCH 6E103, Oklahoma City, OK, 73104, USA.
authors: John W
authors: JW
authors: Dyer
authors: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, OK, 73104, USA.
authors: Melissa E
authors: ME
authors: Munroe
authors: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, OK, 73104, USA.|Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors: Judith A
authors: JA
authors: James
authors: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, OK, 73104, USA.
authors: Joan T
authors: JT
authors: Merrill
mesh_terms: D000328:Adult; D015331:Cohort Studies; D016207:Cytokines / Q000276:immunology; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged
chemical_list: D016207:Cytokines
keywords: Cytokines; Disease activity; Heart rate variability; Systemic lupus erythematosus