title: Elevated levels of inflammation, d-dimer, and homocysteine are associated with adverse calf muscle characteristics and reduced calf strength in peripheral arterial disease.
abstract: OBJECTIVE
  This study determined whether increased levels of inflammatory blood markers, D-dimer, and homocysteine were associated with smaller calf skeletal muscle area, increased calf muscle percent fat, reduced calf muscle density, and poorer calf strength in persons with lower extremity peripheral arterial disease (PAD).
  
  
  BACKGROUND
  Elevated levels of inflammatory markers and D-dimer are associated with greater functional impairment and functional decline in persons with PAD. Mechanisms of these associations are unknown.
  
  
  METHODS
  Participants were 423 persons with PAD. Calf muscle area, percent fat, and density were measured with computed tomography. Physical activity levels were measured objectively over 7 days with the Caltrac (Muscle Dynamics Fitness Network, Inc., Rocklin, California) vertical accelerometer. Isometric plantarflexion strength was measured. Analyses were adjusted for age, gender, race, comorbidities, the ankle-brachial index, and other potential confounders.
  
  
  RESULTS
  Higher levels of D-dimer (p = 0.014), C-reactive protein (CRP) (p = 0.002), interleukin (IL)-6 (p < 0.001), and soluble vascular cellular adhesion molecule (sVCAM)-1 (p = 0.008) were associated with smaller calf muscle area. Higher sVCAM-1 (p = 0.004) and IL-6 (p = 0.017) were associated with higher calf muscle percent fat. Higher D-dimer (p < 0.001), sVCAM-1 (p < 0.001), and homocysteine (p = 0.014) were associated with lower calf muscle density. These associations were generally unchanged after additional adjustment for physical activity. Higher sVCAM-1 (p = 0.013) was associated with lower calf strength.
  
  
  CONCLUSIONS
  These data show, for the first time, that higher levels of inflammation, D-dimer, and homocysteine are associated with more adverse calf muscle characteristics in persons with PAD. These associations may contribute to previously established associations between elevated biomarkers and functional impairment and functional decline in PAD.
authors: Department of Medicine and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. mdm608@northwestern.edu
authors: Mary M
authors: MM
authors: McDermott
authors: Luigi
authors: L
authors: Ferrucci
authors: Jack M
authors: JM
authors: Guralnik
authors: Lu
authors: L
authors: Tian
authors: David
authors: D
authors: Green
authors: Kiang
authors: K
authors: Liu
authors: Jin
authors: J
authors: Tan
authors: Yihua
authors: Y
authors: Liao
authors: William H
authors: WH
authors: Pearce
authors: Joseph R
authors: JR
authors: Schneider
authors: Paul
authors: P
authors: Ridker
authors: Nader
authors: N
authors: Rifai
authors: Frederick
authors: F
authors: Hoff
authors: Michael H
authors: MH
authors: Criqui
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D015897:Comorbidity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D018737:Hand Strength; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007866:Leg / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength / Q000502:physiology*; D018482:Muscle, Skeletal / Q000503:physiopathology*; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; C036309:fibrin fragment D; D006710:Homocysteine; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein
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