Elevated levels of inflammation, d-dimer, and homocysteine are associated with adverse calf muscle characteristics and reduced calf strength in peripheral arterial disease.
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.
McDermott
Mary M
MM
Department of Medicine and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. mdm608@northwestern.edu
Ferrucci
Luigi
L
Guralnik
Jack M
JM
Tian
Lu
L
Green
David
D
Liu
Kiang
K
Tan
Jin
J
Liao
Yihua
Y
Pearce
William H
WH
Schneider
Joseph R
JR
Ridker
Paul
P
Rifai
Nader
N
Hoff
Frederick
F
Criqui
Michael H
MH
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
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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