title: Coenzyme Q10 levels are low and may be associated with the inflammatory cascade in septic shock.
abstract: BACKGROUND
  Mitochondrial dysfunction is associated with increased mortality in septic shock. Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial respiratory chain, but whether CoQ10 is depleted in septic shock remains unknown. Moreover, statin therapy may decrease CoQ10 levels, but whether this occurs acutely remains unknown. We measured CoQ10 levels in septic shock patients enrolled in a randomized trial of simvastatin versus placebo.
  
  
  METHODS
  We conducted a post hoc analysis of a prospective, randomized trial of simvastatin versus placebo in patients with septic shock (ClinicalTrials.gov ID: NCT00676897). Adult patients with suspected or confirmed infection and the need for vasopressor support were included in the initial trial. For the current analysis, blood specimens were analyzed for plasma CoQ10 and low-density lipoprotein (LDL) levels. The relationship between CoQ10 levels and inflammatory and vascular endothelial biomarkers was assessed using either the Pearson or Spearman correlation coefficient.
  
  
  RESULTS
  We analyzed 28 samples from 14 patients. CoQ10 levels were low, with a median of 0.49 (interquartile range 0.26 to 0.62) compared to levels in healthy control patients (CoQ10 = 0.95 μmol/L ± 0.29; P < 0.0001). Statin therapy had no effect on plasma CoQ10 levels over time (P = 0.13). There was a statistically significant relationship between plasma CoQ10 levels and levels of vascular cell adhesion molecule (VCAM) (r2 = 0.2; P = 0.008), TNF-α (r2 = 0.28; P = 0.004), IL-8 (r2 = 0.21; P = 0.015), IL-10 (r2 = 0.18; P = 0.025), E-selectin (r2 = 0.17; P = -0.03), IL-1ra (r2 = 0.21; P = 0.014), IL-6 (r2 = 0.17; P = 0.029) and IL-2 (r2 = 0.23; P = 0.009). After adjusting for LDL levels, there was a statistically significant inverse relationship between plasma CoQ10 levels and levels of VCAM (r2 = 0.24; P = 0.01) (Figure 3) and IL-10 (r2 = 0.24; P = 0.02).
  
  
  CONCLUSIONS
  CoQ10 levels are significantly lower in septic shock patients than in healthy controls. CoQ10 is negatively associated with vascular endothelial markers and inflammatory molecules, though this association diminishes after adjusting for LDL levels.
authors.affiliation: Department of Emergency Medicine, Beth Israel Deaconess Medical Center, One Deaconess Road, West Clinical Center 2, Boston, MA 02215, USA. mdonnino@bidmc.harvard.edu
authors.forename: Michael W
authors.initials: MW
authors.lastname: Donnino
authors.forename: Michael N
authors.initials: MN
authors.lastname: Cocchi
authors.forename: Justin D
authors.initials: JD
authors.lastname: Salciccioli
authors.forename: Daniel
authors.initials: D
authors.lastname: Kim
authors.forename: Ali B
authors.initials: AB
authors.lastname: Naini
authors.forename: Catherine
authors.initials: C
authors.lastname: Buettner
authors.forename: Praveen
authors.initials: P
authors.lastname: Akuthota
mesh_terms: D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects; D014815:Vitamins / Q000097:blood*
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D014815:Vitamins; D014451:Ubiquinone; C024989:coenzyme Q10