Elevated Levels of Inflammation, D-Dimer, and Homocysteine Are Associated With Adverse Calf Muscle Characteristics and Reduced Calf Strength in Peripheral Arterial Disease

Mary M. McDermott; Luigi Ferrucci; Jack M. Guralnik; Lu Tian; David Green; Kiang Liu; Jin Tan; Yihua Liao; William H. Pearce; Joseph R. Schneider; Paul Ridker; Nader Rifai; Frederick Hoff; Michael H. Criqui

doi:10.1016/j.jacc.2007.05.017

Elevated Levels of Inflammation, D-Dimer, and Homocysteine Are Associated With Adverse Calf Muscle Characteristics and Reduced Calf Strength in Peripheral Arterial Disease

Mary M. McDermott^*, Luigi Ferrucci, Jack M. Guralnik, Lu Tian, David Green, Kiang Liu, Jin Tan, Yihua Liao, William H. Pearce, Joseph R. Schneider, Paul Ridker, Nader Rifai, Frederick Hoff, Michael H. Criqui

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

Abstract

Objectives: 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.

Original language	English (US)
Pages (from-to)	897-905
Number of pages	9
Journal	Journal of the American College of Cardiology
Volume	50
Issue number	9
DOIs	https://doi.org/10.1016/j.jacc.2007.05.017
State	Published - Aug 28 2007

Funding

Supported by grants R01-HL58099, R01-HL64739, R01-HL71223, and R01-HL076298 from the National Heart, Lung, and Blood Institute and by grant #RR-00048 from the National Center for Research Resources, National Institutes of Health (NIH). Supported in part by the Intramural Research Program, National Institute on Aging, NIH. Dr. Ridker is a co-inventor of the assay used for analyzing C-reactive protein. R. Wayne Alexander served as Guest Editor for this article.

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacc.2007.05.017

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McDermott, M. M., Ferrucci, L., Guralnik, J. M., Tian, L., Green, D., Liu, K., Tan, J., Liao, Y., Pearce, W. H., Schneider, J. R., Ridker, P., Rifai, N., Hoff, F., & Criqui, M. H. (2007). Elevated Levels of Inflammation, D-Dimer, and Homocysteine Are Associated With Adverse Calf Muscle Characteristics and Reduced Calf Strength in Peripheral Arterial Disease. Journal of the American College of Cardiology, 50(9), 897-905. https://doi.org/10.1016/j.jacc.2007.05.017

@article{b0f3d4d9bea04f2c9b5d8ee2e815f9b4,

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 = "Objectives: 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.",

author = "McDermott, {Mary M.} and Luigi Ferrucci and Guralnik, {Jack M.} and Lu Tian and David Green and Kiang Liu and Jin Tan and Yihua Liao and Pearce, {William H.} and Schneider, {Joseph R.} and Paul Ridker and Nader Rifai and Frederick Hoff and Criqui, {Michael H.}",

note = "Funding Information: Supported by grants R01-HL58099, R01-HL64739, R01-HL71223, and R01-HL076298 from the National Heart, Lung, and Blood Institute and by grant #RR-00048 from the National Center for Research Resources, National Institutes of Health (NIH). Supported in part by the Intramural Research Program, National Institute on Aging, NIH. Dr. Ridker is a co-inventor of the assay used for analyzing C-reactive protein. R. Wayne Alexander served as Guest Editor for this article. ",

year = "2007",

month = aug,

day = "28",

doi = "10.1016/j.jacc.2007.05.017",

language = "English (US)",

volume = "50",

pages = "897--905",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier Inc.",

number = "9",

}

McDermott, MM, Ferrucci, L, Guralnik, JM, Tian, L, Green, D , Liu, K, Tan, J, Liao, Y, Pearce, WH , Schneider, JR, Ridker, P, Rifai, N, Hoff, F & Criqui, MH 2007, 'Elevated Levels of Inflammation, D-Dimer, and Homocysteine Are Associated With Adverse Calf Muscle Characteristics and Reduced Calf Strength in Peripheral Arterial Disease', Journal of the American College of Cardiology, vol. 50, no. 9, pp. 897-905. https://doi.org/10.1016/j.jacc.2007.05.017

Elevated Levels of Inflammation, D-Dimer, and Homocysteine Are Associated With Adverse Calf Muscle Characteristics and Reduced Calf Strength in Peripheral Arterial Disease. / McDermott, Mary M.; Ferrucci, Luigi; Guralnik, Jack M. et al.
In: Journal of the American College of Cardiology, Vol. 50, No. 9, 28.08.2007, p. 897-905.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Elevated Levels of Inflammation, D-Dimer, and Homocysteine Are Associated With Adverse Calf Muscle Characteristics and Reduced Calf Strength in Peripheral Arterial Disease

AU - McDermott, Mary M.

AU - Ferrucci, Luigi

AU - Guralnik, Jack M.

AU - Tian, Lu

AU - Green, David

AU - Liu, Kiang

AU - Tan, Jin

AU - Liao, Yihua

AU - Pearce, William H.

AU - Schneider, Joseph R.

AU - Ridker, Paul

AU - Rifai, Nader

AU - Hoff, Frederick

AU - Criqui, Michael H.

N1 - Funding Information: Supported by grants R01-HL58099, R01-HL64739, R01-HL71223, and R01-HL076298 from the National Heart, Lung, and Blood Institute and by grant #RR-00048 from the National Center for Research Resources, National Institutes of Health (NIH). Supported in part by the Intramural Research Program, National Institute on Aging, NIH. Dr. Ridker is a co-inventor of the assay used for analyzing C-reactive protein. R. Wayne Alexander served as Guest Editor for this article.

PY - 2007/8/28

Y1 - 2007/8/28

N2 - Objectives: 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.

AB - Objectives: 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.

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DO - 10.1016/j.jacc.2007.05.017

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SN - 0735-1097

VL - 50

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JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

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ER -

Elevated Levels of Inflammation, D-Dimer, and Homocysteine Are Associated With Adverse Calf Muscle Characteristics and Reduced Calf Strength in Peripheral Arterial Disease

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