BLOOD FACTORS AND PERIPHERAL ARTERIAL DISEASE OUTCOMES

Summary

Principal Investigator: Mary Mcgrae McDermott
Affiliation: Northwestern University
Country: USA
Abstract: DESCRIPTION: This study will prospectively assess associations between hemostatic and inflammatory blood factors and progression of lower extremity arterial ischemia and cardiovascular events in 499 men and women with lower extremity peripheral arterial disease (PAD) and 241 men and women without PAD. The proposed study is ancillary to an NHLBI funded prospective study of functional and cardiovascular outcomes in men and women with PAD, the Walking and Leg Circulation Study (WALCS). The blood factors we will study, fibrinogen, PAI-1, TPA antigen, d-dimer, prothrombin 1.2, and C-reactive protein (CRP), are associated with progression of coronary atherosclerosis in proposed models of the pathogenesis of coronary atherosclerosis, but are not well studied in PAD. Our primary specific aims are as follows. First, we will determine whether higher baseline blood factor levels are associated with a) progression of lower extremity arterial ischemia (decline in ankle brachial index >= 0.15, lower extremity gangrene, ulcer, revascularization, or amputation);, b) functional decline over 48 month follow-up. Second, we will determine whether higher baseline blood factor levels are associated with new cardiovascular events over 48 month follow-up. We hypothesize that higher blood factor levels at baseline will be associated with PAD progression, functional decline, and higher rates of cardiovascular morbidity and mortality Pilot data from the Cardiovascular Health Study (CHS) show that relative risks of fibrinogen, D-dimer and CRP levels for cardiovascular events are highest for events occurring more proximate to baseline blood factor measurements. Therefore, we will also determine whether blood factor levels measured at the most recent examination prior to cardiovascular events or PAD progression are higher than the levels that do not immediately precede cardiovascular events or PAD progression. We hypothesize that blood factor levels at the most recent examination prior to cardiovascular events or PAD progression will be higher than blood factor levels that do not immediately precede cardiovascular events or PAD progression. The specific aims of this study cannot be answered by the CHS, the Women's Health Study or the Atherosclerosis Risk in Community study. Unique comparisons of the proposed study include the wide spectrum of PAD severity in the WALCS cohort, the large number of PAD participants, the breadth of functional assessments, and the inherent generalizability of our findings to patients routinely encountered by practicing physicians. Much of the data collection is currently funded as part of the WALCS, reducing the marginal cost of our application. Results are expected to lead to subsequent studies identifying mechanisms of any associations demonstrated and lead to interventions that prevent progression of lower extremity arterial ischemia, functional decline, and cardiovascular events in men and women with PAD.
Funding Period: 2001-01-01 - 2005-12-31
more information: NIH RePORT

Top Publications

  1. ncbi D-dimer and inflammatory markers as predictors of functional decline in men and women with and without peripheral arterial disease
    Mary M McDermott
    Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Am Geriatr Soc 53:1688-96. 2005
  2. ncbi Baseline functional performance predicts the rate of mobility loss in persons with peripheral arterial disease
    Mary M McDermott
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    J Am Coll Cardiol 50:974-82. 2007
  3. ncbi Biomarkers of inflammation and thrombosis as predictors of near-term mortality in patients with peripheral arterial disease: a cohort study
    Himabindu Vidula
    Feinberg School of Medicine, Northwestern University, Chicago, Illinois University of California at San Diego, San Diego, California, USA
    Ann Intern Med 148:85-93. 2008
  4. ncbi Associations between lower extremity ischemia, upper and lower extremity strength, and functional impairment with peripheral arterial disease
    Mary M McDermott
    Department of Medicine, National Institute on Aging, Bethesda, Maryland, USA
    J Am Geriatr Soc 56:724-9. 2008
  5. ncbi Prognostic value of functional performance for mortality in patients with peripheral artery disease
    Mary M McDermott
    Department of Medicine, Northwestern University s Feinberg School of Medicine, Chicago, Illinois, USA
    J Am Coll Cardiol 51:1482-9. 2008
  6. ncbi Asymptomatic peripheral arterial disease is associated with more adverse lower extremity characteristics than intermittent claudication
    Mary M McDermott
    Feinberg School of Medicine, Northwestern University, Chicago, Ill, USA
    Circulation 117:2484-91. 2008
  7. ncbi Circulating blood markers and functional impairment in peripheral arterial disease
    Mary M McDermott
    Department of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University Cicago, IL, USA
    J Am Geriatr Soc 56:1504-10. 2008
  8. ncbi Physical activity during daily life and circulating biomarker levels in patients with peripheral arterial disease
    Lynette L Craft
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    Am J Cardiol 102:1263-8. 2008
  9. ncbi Associations of borderline and low normal ankle-brachial index values with functional decline at 5-year follow-up: the WALCS (Walking and Leg Circulation Study)
    Mary M McDermott
    Department of Medicine, Northwestern University s Feinberg School of Medicine, 750 North Lake Shore Drive, Chicago, IL 60611, USA
    J Am Coll Cardiol 53:1056-62. 2009
  10. ncbi Pathophysiological changes in calf muscle predict mobility loss at 2-year follow-up in men and women with peripheral arterial disease
    Mary Mcgrae McDermott
    Feinberg School of Medicine, Northwestern University, Chicago, Ill, USA
    Circulation 120:1048-55. 2009

Scientific Experts

Detail Information

Publications23

  1. ncbi D-dimer and inflammatory markers as predictors of functional decline in men and women with and without peripheral arterial disease
    Mary M McDermott
    Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Am Geriatr Soc 53:1688-96. 2005
    ..To determine whether higher circulating levels of inflammatory and thrombotic markers are associated with greater decline in lower extremity performance...
  2. ncbi Baseline functional performance predicts the rate of mobility loss in persons with peripheral arterial disease
    Mary M McDermott
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    J Am Coll Cardiol 50:974-82. 2007
    ..We compared rates of mobility loss among persons with versus without peripheral arterial disease (PAD). Associations between baseline functional performance and mobility loss in persons with and without PAD were studied...
  3. ncbi Biomarkers of inflammation and thrombosis as predictors of near-term mortality in patients with peripheral arterial disease: a cohort study
    Himabindu Vidula
    Feinberg School of Medicine, Northwestern University, Chicago, Illinois University of California at San Diego, San Diego, California, USA
    Ann Intern Med 148:85-93. 2008
    ..Traditional atherosclerotic risk factors predict long-term cardiovascular disease events but are poor predictors of near-term events...
  4. ncbi Associations between lower extremity ischemia, upper and lower extremity strength, and functional impairment with peripheral arterial disease
    Mary M McDermott
    Department of Medicine, National Institute on Aging, Bethesda, Maryland, USA
    J Am Geriatr Soc 56:724-9. 2008
    ..To determine whether poorer strength may mediate poorer lower extremity performance in persons with lower arterial brachial index (ABI) levels...
  5. ncbi Prognostic value of functional performance for mortality in patients with peripheral artery disease
    Mary M McDermott
    Department of Medicine, Northwestern University s Feinberg School of Medicine, Chicago, Illinois, USA
    J Am Coll Cardiol 51:1482-9. 2008
    ..Among persons with lower extremity peripheral artery disease (PAD), we determined whether objective measures of walking performance predict mortality independently of the ankle brachial index (ABI)...
  6. ncbi Asymptomatic peripheral arterial disease is associated with more adverse lower extremity characteristics than intermittent claudication
    Mary M McDermott
    Feinberg School of Medicine, Northwestern University, Chicago, Ill, USA
    Circulation 117:2484-91. 2008
    ..This study assessed functional performance, calf muscle characteristics, peripheral nerve function, and quality of life in asymptomatic persons with peripheral arterial disease (PAD)...
  7. ncbi Circulating blood markers and functional impairment in peripheral arterial disease
    Mary M McDermott
    Department of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University Cicago, IL, USA
    J Am Geriatr Soc 56:1504-10. 2008
    ..To determine whether higher levels of inflammatory blood markers, D-dimer, and homocysteine were associated with greater impairment in lower extremity functioning in persons with peripheral arterial disease (PAD)...
  8. ncbi Physical activity during daily life and circulating biomarker levels in patients with peripheral arterial disease
    Lynette L Craft
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    Am J Cardiol 102:1263-8. 2008
    ..033). In conclusion, higher levels of physical activity were associated independently with lower levels of inflammatory markers, homocysteine, and D-dimer in patients with PAD...
  9. ncbi Associations of borderline and low normal ankle-brachial index values with functional decline at 5-year follow-up: the WALCS (Walking and Leg Circulation Study)
    Mary M McDermott
    Department of Medicine, Northwestern University s Feinberg School of Medicine, 750 North Lake Shore Drive, Chicago, IL 60611, USA
    J Am Coll Cardiol 53:1056-62. 2009
    ..We studied associations of borderline and low normal ankle-brachial index (ABI) values with functional decline over a 5-year follow-up...
  10. ncbi Pathophysiological changes in calf muscle predict mobility loss at 2-year follow-up in men and women with peripheral arterial disease
    Mary Mcgrae McDermott
    Feinberg School of Medicine, Northwestern University, Chicago, Ill, USA
    Circulation 120:1048-55. 2009
    ..Associations of pathophysiological calf muscle characteristics with functional decline in people with lower extremity peripheral arterial disease are unknown...
  11. ncbi 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
    Department of Medicine and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    J Am Coll Cardiol 50:897-905. 2007
    ....
  12. ncbi Persistent depressive symptoms and functional decline among patients with peripheral arterial disease
    Bernice Ruo
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    Psychosom Med 69:415-24. 2007
    ..Because depressive symptoms are prevalent among patients with peripheral arterial disease (PAD), our goal was to study the effect of depressive symptoms over time on functional decline among patients with PAD...
  13. ncbi Physical activity, walking exercise, and calf skeletal muscle characteristics in patients with peripheral arterial disease
    Mary Mcgrae McDermott
    Department of Medicine, Feinberg School of Medicine, Northwestern University, 676 N St Clair, Chicago, IL 60611, USA
    J Vasc Surg 46:87-93. 2007
    ....
  14. ncbi Functional decline in lower-extremity peripheral arterial disease: associations with comorbidity, gender, and race
    Mary M McDermott
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    J Vasc Surg 42:1131-7. 2005
    ..We also determined whether female sex and black race were associated with greater functional decline than male sex and white race, respectively, in PAD...
  15. ncbi Physical performance in peripheral arterial disease: a slower rate of decline in patients who walk more
    Mary Mcgrae McDermott
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    Ann Intern Med 144:10-20. 2006
    ..However, it is unknown whether patients with PAD who walk for exercise regularly have less functional decline than those with less walking activity...
  16. ncbi Statin use and functional decline in patients with and without peripheral arterial disease
    Jay Giri
    Massachusetts General Hospital, Boston, Massachusetts, USA
    J Am Coll Cardiol 47:998-1004. 2006
    ..CONCLUSIONS: The PAD patients on statins have less annual decline in lower-extremity performance than PAD patients who are not taking statins...
  17. ncbi Functional decline in patients with and without peripheral arterial disease: predictive value of annual changes in levels of C-reactive protein and D-dimer
    Mary M McDermott
    Northwestern University s Feinberg School of Medicine, Chicago, Illinois, USA
    J Gerontol A Biol Sci Med Sci 61:374-9. 2006
    ....
  18. ncbi Obesity, weight change, and functional decline in peripheral arterial disease
    Mary M McDermott
    Department of Medicine, Northwestern University s Feinberg School of Medicine, Chicago, IL 60611, USA
    J Vasc Surg 43:1198-204. 2006
    ..We hypothesized that baseline obesity and weight gain during follow-up would each be associated with functional declines in persons with PAD...
  19. ncbi Physical activity during daily life and mortality in patients with peripheral arterial disease
    Parveen K Garg
    New York University School of Medicine, New York City, NY, USA
    Circulation 114:242-8. 2006
    ..Further study is needed to determine whether interventions that increase physical activity during daily life are associated with improved survival in patients with PAD...
  20. ncbi Lower extremity nerve function in patients with lower extremity ischemia
    Mary M McDermott
    Department of Medicine, Northwestern University Feinberg School of Medicine, 676 N St Clair, Suite 200, Chicago, IL 60611, USA
    Arch Intern Med 166:1986-92. 2006
    ..We determined whether lower extremity ischemia, as measured by the ankle brachial index (ABI), is associated with impaired lower extremity nerve function...
  21. ncbi Lower extremity ischemia, calf skeletal muscle characteristics, and functional impairment in peripheral arterial disease
    Mary M McDermott
    Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Am Geriatr Soc 55:400-6. 2007
    ..To determine whether lower ankle brachial index (ABI) levels are associated with lower calf skeletal muscle area and higher calf muscle percentage fat in persons with and without lower extremity peripheral arterial disease (PAD)...
  22. ncbi The vital prognosis of subclavian stenosis
    Victor Aboyans
    Department of Family and Preventive Medicine, University of California San Diego, La Jolla, California 92093 0607, USA
    J Am Coll Cardiol 49:1540-5. 2007
    ..This study sought to assess the prognosis of subclavian stenosis (SS) as a potential marker of total and cardiovascular disease (CVD) mortality...
  23. ncbi Baseline lower extremity strength and subsequent decline in functional performance at 6-year follow-up in persons with lower extremity peripheral arterial disease
    Seth D Herman
    Department of Physical Medicine and Rehabilitation, Rehabilitation Institute of Chicago, Chicago, IL 60611, USA
    J Am Geriatr Soc 57:2246-52. 2009
    ..To evaluate associations between baseline lower extremity strength and decline in functional performance over 6 years of follow-up in men and women with lower extremity peripheral arterial disease (PAD)...