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. doi Plasma metabolomic profiles predict near-term death among individuals with lower extremity peripheral arterial disease
    Chiang Ching Huang
    Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Ill
    J Vasc Surg 58:989-96.e1. 2013
  2. pmc Higher body mass index is associated with more adverse changes in calf muscle characteristics in peripheral arterial disease
    Zankhana Raval
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill, USA
    J Vasc Surg 55:1015-24. 2012
  3. pmc The Walking Impairment Questionnaire stair-climbing score predicts mortality in men and women with peripheral arterial disease
    Atul Jain
    Division of General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    J Vasc Surg 55:1662-73.e2. 2012
  4. pmc Comparative effectiveness study of self-directed walking exercise, lower extremity revascularization, and functional decline in peripheral artery disease
    Mary M McDermott
    Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    J Vasc Surg 57:990-996.e1. 2013
  5. doi Declining walking impairment questionnaire scores are associated with subsequent increased mortality in peripheral artery disease
    Atul Jain
    Department of Medicine, The University of Chicago, Chicago, Illinois, USA
    J Am Coll Cardiol 61:1820-9. 2013
  6. pmc Decline in functional performance predicts later increased mobility loss and mortality in peripheral arterial disease
    Mary M McDermott
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    J Am Coll Cardiol 57:962-70. 2011
  7. doi Comparison of effects of statin use on mortality in patients with peripheral arterial disease with versus without elevated C-reactive protein and d-dimer levels
    Himabindu Vidula
    Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    Am J Cardiol 105:1348-52. 2010
  8. pmc Leg symptom categories and rates of mobility decline in peripheral arterial disease
    Mary M McDermott
    Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    J Am Geriatr Soc 58:1256-62. 2010
  9. pmc Leg strength predicts mortality in men but not in women with peripheral arterial disease
    Nimarta Singh
    Feinberg School of Medicine, Northwestern University, Chicago, Ill, USA
    J Vasc Surg 52:624-31. 2010
  10. doi Women with peripheral arterial disease experience faster functional decline than men with peripheral arterial disease
    Mary M McDermott
    Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Am Coll Cardiol 57:707-14. 2011

Scientific Experts

  • Mary Mcgrae McDermott
  • Natalie S Evans
  • Laura J Zimmermann
  • Victor Aboyans
  • Bernice Ruo
  • Lynette L Craft
  • Kiang Liu
  • Lu Tian
  • Luigi Ferrucci
  • Michael H Criqui
  • Jack M Guralnik
  • Atul Jain
  • Huimin Tao
  • Yihua Liao
  • Himabindu Vidula
  • Parveen K Garg
  • David Green
  • Chiang Ching Huang
  • Zankhana Raval
  • Nimarta Singh
  • Seth D Herman
  • Jin Tan
  • Philip Greenland
  • Jay Giri
  • San Yuan Wang
  • Yufeng Jane Tseng
  • Ching Hua Kuo
  • Robert Sufit
  • Takashi Nishida
  • Paul Ridker
  • Daniel B Garside
  • Jack Guralnik
  • Paul M Ridker
  • Nader Rifai
  • William H Pearce
  • Joseph R Schneider

Detail Information

Publications39

  1. doi Plasma metabolomic profiles predict near-term death among individuals with lower extremity peripheral arterial disease
    Chiang Ching Huang
    Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Ill
    J Vasc Surg 58:989-96.e1. 2013
    ..This pilot study determined whether metabolomic profiling can accurately identify patients with PAD who are at increased risk of near-term mortality...
  2. pmc Higher body mass index is associated with more adverse changes in calf muscle characteristics in peripheral arterial disease
    Zankhana Raval
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill, USA
    J Vasc Surg 55:1015-24. 2012
    ....
  3. pmc The Walking Impairment Questionnaire stair-climbing score predicts mortality in men and women with peripheral arterial disease
    Atul Jain
    Division of General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    J Vasc Surg 55:1662-73.e2. 2012
    ..We determined whether poorer WIQ scores are associated with higher all-cause and cardiovascular disease (CVD) mortality in individuals with and without PAD...
  4. pmc Comparative effectiveness study of self-directed walking exercise, lower extremity revascularization, and functional decline in peripheral artery disease
    Mary M McDermott
    Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    J Vasc Surg 57:990-996.e1. 2013
    ....
  5. doi Declining walking impairment questionnaire scores are associated with subsequent increased mortality in peripheral artery disease
    Atul Jain
    Department of Medicine, The University of Chicago, Chicago, Illinois, USA
    J Am Coll Cardiol 61:1820-9. 2013
    ....
  6. pmc Decline in functional performance predicts later increased mobility loss and mortality in peripheral arterial disease
    Mary M McDermott
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    J Am Coll Cardiol 57:962-70. 2011
    ..We hypothesized that a greater 2-year decline in office-based functional performance measures would be associated with greater mobility loss and mortality in people with peripheral arterial disease (PAD)...
  7. doi Comparison of effects of statin use on mortality in patients with peripheral arterial disease with versus without elevated C-reactive protein and d-dimer levels
    Himabindu Vidula
    Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    Am J Cardiol 105:1348-52. 2010
    ..The favorable association of statin use with mortality was not influenced significantly by the baseline CRP or D-dimer level...
  8. pmc Leg symptom categories and rates of mobility decline in peripheral arterial disease
    Mary M McDermott
    Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    J Am Geriatr Soc 58:1256-62. 2010
    ..To determine whether asymptomatic lower extremity peripheral arterial disease (PAD) and leg symptoms other than intermittent claudication (IC) in PAD are associated with faster functional decline than in people with both PAD and IC...
  9. pmc Leg strength predicts mortality in men but not in women with peripheral arterial disease
    Nimarta Singh
    Feinberg School of Medicine, Northwestern University, Chicago, Ill, USA
    J Vasc Surg 52:624-31. 2010
    ..To establish associations between leg strength and mortality in men and women with lower extremity peripheral arterial disease (PAD)...
  10. doi Women with peripheral arterial disease experience faster functional decline than men with peripheral arterial disease
    Mary M McDermott
    Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Am Coll Cardiol 57:707-14. 2011
    ..We hypothesized that women with lower extremity peripheral arterial disease (PAD) would have greater mobility loss and faster functional decline than men with PAD...
  11. pmc Relation of interleukin-6 and vascular cellular adhesion molecule-1 levels to functional decline in patients with lower extremity peripheral arterial disease
    Mary M McDermott
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    Am J Cardiol 107:1392-8. 2011
    ..In conclusion, in participants with peripheral arterial disease, persistently high IL-6 levels are associated with faster functional decline compared to those with fluctuating or persistently low IL-6 levels...
  12. pmc Associations of calf skeletal muscle characteristics and peripheral nerve function with self-perceived physical functioning and walking ability in persons with peripheral artery disease
    Natalie S Evans
    Department of Medicine, Northwestern University s Feinberg School of Medicine, Chicago, IL, USA
    Vasc Med 16:3-11. 2011
    ..031). In summary, adverse calf muscle characteristics and poorer peripheral nerve function are associated significantly and independently with impairments in self-perceived physical functioning and walking ability in PAD persons...
  13. doi Greater sedentary hours and slower walking speed outside the home predict faster declines in functioning and adverse calf muscle changes in peripheral arterial disease
    Mary M McDermott
    Feinberg School of Medicine, Northwestern University, Chicago, IL USA
    J Am Coll Cardiol 57:2356-64. 2011
    ....
  14. doi Poorer clock draw test scores are associated with greater functional impairment in peripheral artery disease: the Walking and Leg Circulation Study II
    Laura J Zimmermann
    Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    Vasc Med 16:173-81. 2011
    ..Longitudinal studies are necessary to explore whether baseline CDT scores and changes in CDT scores over time can predict long-term decline in functional performance in individuals with and without PAD...
  15. pmc Lower extremity nerve function, calf skeletal muscle characteristics, and functional performance in peripheral arterial disease
    Parveen K Garg
    Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    J Am Geriatr Soc 59:1855-63. 2011
    ..To determine whether poor lower extremity nerve function is associated with less-favorable calf muscle characteristics and greater functional impairment in people with and without peripheral arterial disease (PAD)...
  16. pmc Calf muscle characteristics, strength measures, and mortality in peripheral arterial disease: a longitudinal study
    Mary M McDermott
    Department of Medicine, Northwestern University Feinberg School of Medicine, 750 North Lake Shore Drive, Chicago, IL 60611, USA
    J Am Coll Cardiol 59:1159-67. 2012
    ..This study analyzed whether lower calf muscle density and poorer upper and lower extremity strength are associated with higher mortality rates in men and women with peripheral arterial disease (PAD)...
  17. pmc 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)...
  18. pmc 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...
  19. pmc 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...
  20. pmc 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...
  21. pmc 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)...
  22. 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...
  23. 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...
  24. 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
    ..We determined whether statin use (vs. non-use) is associated with less annual decline in lower-extremity functioning in patients with and without lower-extremity peripheral arterial disease (PAD) over three-year follow-up...
  25. 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
    ....
  26. pmc 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...
  27. pmc 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
    ..We determined whether patients with lower-extremity peripheral arterial disease (PAD) who are more physically active during daily life have lower mortality rates than PAD patients who are less active...
  28. pmc 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...
  29. pmc 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)...
  30. 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...
  31. pmc 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
    ....
  32. pmc 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...
  33. pmc 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
    ....
  34. pmc 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...
  35. pmc 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...
  36. pmc 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...
  37. pmc 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)...
  38. doi 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)...
  39. 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...