Skip to main content
SpringerLink
Log in

Progression of Peripheral Artery Disease to Critical Limb Ischemia

  • Chapter
  • First Online:
Critical Limb Ischemia

  • 2516 Accesses

Abstract

Critical limb ischemia (CLI), often considered the end stage of peripheral artery disease (PAD), is a tipping point in the balance between metabolic supply and demand of the lower extremity. This balance hinges on many factors, and the progression from stable PAD to CLI depends on the complex interplay of these variables. Despite the fact that PAD is classically categorized by disease severity, the natural history of PAD progression and general development of CLI does not follow a strictly linear path, a fact characterized by the often insidious clinical presentation of CLI. From a pathophysiologic perspective, CLI is the final result of the common atherogenic pathway that causes PAD. However, CLI manifests only in selected case largely due to a loss of compensatory mechanisms that leads to overt tissue ischemia. Many of the risk factors that contribute to the development of PAD are also responsible for its progression and ultimately for development of CLI, and important information can be gleaned from their modification both in PAD and CLI.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg. 2007;45(Suppl S):S5–67.

    Google Scholar 

  2. Minar E. Critical limb ischaemia. Hamostaseologie. 2009;29(1):102–9.

    CAS  PubMed  Google Scholar 

  3. Mohler ER 3rd, Bundens W, Denenberg J, Medenilla E, Hiatt WR, Criqui MH. Progression of asymptomatic peripheral artery disease over 1 year. Vasc Med. 2012;17(1):10–16.

    Google Scholar 

  4. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286(11):1317–24.

    Article  CAS  PubMed  Google Scholar 

  5. van der Feen C, Neijens FS, Kanters SD, Mali WP, Stolk RP, Banga JD. Angiographic distribution of lower extremity atherosclerosis in patients with and without diabetes. Diabet Med. 2002;19(5):366–70.

    Article  PubMed  Google Scholar 

  6. Rogers R, Hiatt W. Pathophysiology and treatment of critical limb ischemia. http://www.vascularmed.org/clinical_archive/Pathophysiology-Treatment-of-CLI_11Feb2013.pdf. Accessed 8 Apr 2014.

  7. Varu VN, Hogg ME, Kibbe MR. Critical limb ischemia. J Vasc Surg. 2010;51(1):230–41.

    Article  PubMed  Google Scholar 

  8. Baser O, Verpillat P, Wang L. Prevalence, incidence, and outcomes of critical limb ischemia in the US medicare population. http://www.vasculardiseasemanagement.com/content/prevalence-incidence-and-outcomes-critical-limb-ischemia-us-medicare-population. Updated 2013. Accessed 8 Apr 2014.

  9. Goodney PP, Travis LL, Nallamothu BK, et al. Variation in the use of lower extremity vascular procedures for critical limb ischemia. Circ Cardiovasc Qual Outcomes. 2012;5(1):94–102.

    Article  PubMed  Google Scholar 

  10. Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJ, Carotid Endarterectomy Trialists Collaboration. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet. 2004;363(9413):915–24.

    Google Scholar 

  11. Weitz JI, Byrne J, Clagett GP, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation. 1996;94(11):3026–49.

    Article  CAS  PubMed  Google Scholar 

  12. Fowkes FG, Housley E, Cawood EH, Macintyre CC, Ruckley CV, Prescott RJ. Edinburgh artery study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. Int J Epidemiol. 1991;20(2):384–92.

    Article  CAS  PubMed  Google Scholar 

  13. Nehler MR, Peyton BD. Is revascularization and limb salvage always the treatment for critical limb ischemia? J Cardiovasc Surg (Torino). 2004;45(3):177–84.

    CAS  Google Scholar 

  14. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the american association for vascular Surgery/Society for vascular surgery, society for cardiovascular angiography and interventions, society for vascular medicine and biology, society of interventional radiology, and the ACC/AHA task force on practice guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease): endorsed by the american association of cardiovascular and pulmonary rehabilitation; national heart, lung, and blood institute; society for vascular nursing; TransAtlantic inter-society consensus; and vascular disease foundation. Circulation. 2006;113(11):e463–654.

    Google Scholar 

  15. Dormandy J, Heeck L, Vig S. The natural history of claudication: risk to life and limb. Semin Vasc Surg. 1999;12(2):123–37.

    CAS  PubMed  Google Scholar 

  16. McDermott MM, Criqui MH, Greenland P, et al. Leg strength in peripheral arterial disease: associations with disease severity and lower-extremity performance. J Vasc Surg. 2004;39(3):523–30.

    Article  PubMed  Google Scholar 

  17. Muluk SC, Muluk VS, Kelley ME, et al. Outcome events in patients with claudication: a 15-year study in 2777 patients. J Vasc Surg. 2001;33(2):251–7. discussion 257–8.

    Article  CAS  PubMed  Google Scholar 

  18. Cronenwett JL, Warner KG, Zelenock GB, et al. Intermittent claudication. current results of nonoperative management. Arch Surg. 1984;119(4):430–6.

    Article  CAS  PubMed  Google Scholar 

  19. Smith I, Franks PJ, Greenhalgh RM, Poulter NR, Powell JT. The influence of smoking cessation and hypertriglyceridaemia on the progression of peripheral arterial disease and the onset of critical ischaemia. Eur J Vasc Endovasc Surg. 1996;11(4):402–8.

    Article  CAS  PubMed  Google Scholar 

  20. Dormandy J, Belcher G, Broos P, et al. Prospective study of 713 below-knee amputations for ischaemia and the effect of a prostacyclin analogue on healing. Hawaii study group. Br J Surg. 1994;81(1):33–7.

    Article  CAS  PubMed  Google Scholar 

  21. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (PROspective pioglitAzone clinical trial in macroVascular events): a randomised controlled trial. Lancet. 2005;366(9493):1279–89.

    Article  CAS  PubMed  Google Scholar 

  22. Falluji N, Mukherjee D. Critical and acute limb ischemia: an overview. Angiology. 2014;65(2):137–46.

    Article  PubMed  Google Scholar 

  23. Price JF, Mowbray PI, Lee AJ, Rumley A, Lowe GD, Fowkes FG. Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh artery study. Eur Heart J. 1999;20(5):344–53.

    Article  CAS  PubMed  Google Scholar 

  24. Walsh DB, Gilbertson JJ, Zwolak RM, et al. The natural history of superficial femoral artery stenoses. J Vasc Surg. 1991;14(3):299–304.

    Article  CAS  PubMed  Google Scholar 

  25. Coran AG, Warren R. Arteriographic changes in femoropopliteal arteriosclerosis obliterans. A five-year follow-up study. N Engl J Med. 1966;274(12):643–7.

    Article  CAS  PubMed  Google Scholar 

  26. McDermott MM, Liu K, O’Brien E, Guralnik JM, Criqui MH, Martin GJ, et al. Measuring physical activity in peripheral arterial disease: a comparison of two physical activity questionnaires with an accelerometer. Angiology. 2000;51(2):91–100.

    Article  CAS  PubMed  Google Scholar 

  27. Sieminski DJ, Gardner AW. The relationship between free-living daily physical activity and the severity of peripheral arterial occlusive disease. Vasc Med. 1997;2(4):286–91.

    Article  CAS  PubMed  Google Scholar 

  28. Paraskevas KI, Hamilton G, Mikhailidis DP, Liapis CD. Optimal medical management of peripheral arterial disease. Vasc Endovascular Surg. 2007;41(1):87.

    Article  PubMed  Google Scholar 

  29. Murabito JM, D’Agostino RB, Silbershatz H, Wilson WF. Intermittent claudication. A risk profile from the framingham heart study. Circulation. 1997;96(1):44–9.

    Article  CAS  PubMed  Google Scholar 

  30. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the united states: results from the national health and nutrition examination survey, 1999–2000. Circulation. 2004;110(6):738–43.

    Article  PubMed  Google Scholar 

  31. Bartholomew JR, Olin JW. Pathophysiology of peripheral arterial disease and risk factors for its development. Cleve Clin J Med. 2006;73 Suppl 4:S8–14.

    Article  PubMed  Google Scholar 

  32. Harris LM, Peer R, Curl GR, Pillai L, Upson J, Ricotta JJ. Long-term follow-up of patients with early atherosclerosis. J Vasc Surg. 1996;23(4):576–80. discussion 581.

    Article  CAS  PubMed  Google Scholar 

  33. Valentine RJ, Myers SI, Inman MH, Roberts JR, Clagett GP. Late outcome of amputees with premature atherosclerosis. Surgery. 1996;119(5):487–93.

    Article  CAS  PubMed  Google Scholar 

  34. Lo RC, Bensley RP, Dahlberg SE, et al. Presentation, treatment, and outcome differences between men and women undergoing revascularization or amputation for lower extremity peripheral arterial disease. J Vasc Surg. 2014;59(2):409–18.e3.

    Google Scholar 

  35. Miller M, Byington R, Hunninghake D, Pitt B, Furberg CD. Sex bias and underutilization of lipid-lowering therapy in patients with coronary artery disease at academic medical centers in the united states and canada. prospective randomized evaluation of the vascular effects of norvasc trial (PREVENT) investigators. Arch Intern Med. 2000;160(3):343–7.

    Article  CAS  PubMed  Google Scholar 

  36. Chou AF, Brown AF, Jensen RE, Shih S, Pawlson G, Scholle SH. Gender and racial disparities in the management of diabetes mellitus among medicare patients. Womens Health Issues. 2007;17(3):150–61.

    Article  PubMed  Google Scholar 

  37. Gottsater A. Managing risk factors for atherosclerosis in critical limb ischaemia. Eur J Vasc Endovasc Surg. 2006;32(5):478–83.

    Article  CAS  PubMed  Google Scholar 

  38. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC working group. TransAtlantic inter-society consensus (TASC). J Vasc Surg. 2000;31(1 Pt 2):S1–296.

    CAS  PubMed  Google Scholar 

  39. Ingolfsson IO, Sigurdsson G, Sigvaldason H, Thorgeirsson G, Sigfusson N. A marked decline in the prevalence and incidence of intermittent claudication in icelandic men 1968–1986: a strong relationship to smoking and serum cholesterol–the reykjavik study. J Clin Epidemiol. 1994;47(11):1237–43.

    Article  CAS  PubMed  Google Scholar 

  40. Marso SP, Hiatt WR. Peripheral arterial disease in patients with diabetes. J Am Coll Cardiol. 2006;47(5):921–9.

    Article  PubMed  Google Scholar 

  41. Freund KM, Belanger AJ, D’Agostino RB, Kannel WB. The health risks of smoking. the framingham study: 34 years of follow-up. Ann Epidemiol. 1993;3(4):417–24.

    Article  CAS  PubMed  Google Scholar 

  42. Cimminiello C. PAD. epidemiology and pathophysiology. Thromb Res. 2002;106(6):V295–301.

    Article  CAS  PubMed  Google Scholar 

  43. Aronow WS. Peripheral arterial disease in women. Maturitas. 2009;64(4):204–11.

    Article  PubMed  Google Scholar 

  44. Juergens JL, Barker NW, Hines EA. Arteriosclerosis obliterans: review of 520 cases with special reference to pathogenic and prognostic factors. Circulation. 1960;21:188–95.

    Article  CAS  PubMed  Google Scholar 

  45. Jude EB, Oyibo SO, Chalmers N, Boulton AJ. Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome. Diabetes Care. 2001;24(8):1433–7.

    Article  CAS  PubMed  Google Scholar 

  46. Faglia E, Favales F, Quarantiello A, et al. Angiographic evaluation of peripheral arterial occlusive disease and its role as a prognostic determinant for major amputation in diabetic subjects with foot ulcers. Diabetes Care. 1998;21(4):625–30.

    Article  CAS  PubMed  Google Scholar 

  47. Kannel WB. Risk factors for atherosclerotic cardiovascular outcomes in different arterial territories. J Cardiovasc Risk. 1994;1(4):333–9.

    Article  CAS  PubMed  Google Scholar 

  48. Porth C. Pathophysiology: Concepts of Altered Health States. Philadelphia: Lippincott; 1995. p. 203–22.

    Google Scholar 

  49. Diehm N, Schmidli J, Setacci C, et al. Chapter III: Management of cardiovascular risk factors and medical therapy. Eur J Vasc Endovasc Surg. 2011;42 Suppl 2:S33–42.

    Article  PubMed  Google Scholar 

  50. Bild DE, Selby JV, Sinnock P, Browner WS, Braveman P, Showstack JA. Lower-extremity amputation in people with diabetes. epidemiology and prevention. Diabetes Care. 1989;12(1):24–31.

    Google Scholar 

  51. Barani J, Nilsson JA, Mattiasson I, Lindblad B, Gottsater A. Inflammatory mediators are associated with 1-year mortality in critical limb ischemia. J Vasc Surg. 2005;42(1):75–80.

    Article  PubMed  Google Scholar 

  52. Virkkunen J, Heikkinen M, Lepantalo M, Metsanoja R, Salenius JP, Finnvasc Study Group. Diabetes as an independent risk factor for early postoperative complications in critical limb ischemia. J Vasc Surg. 2004;40(4):761–7.

    Article  PubMed  Google Scholar 

  53. AhChong AK, Chiu KM, Wong MW, Hui HK, Yip AW. Diabetes and the outcome of infrainguinal bypass for critical limb ischaemia. ANZ J Surg. 2004;74(3):129–33.

    Article  PubMed  Google Scholar 

  54. Bosevski M, Meskovska S, Tosev S, Peovska I, Asikov I, Georgievska-Ismail LJ. Risk factors for development of critical limb ischemia – a survey of diabetic vs. nondiabetic population. Prilozi. 2006;27(2):89–96.

    CAS  PubMed  Google Scholar 

  55. Mehler PS, Coll JR, Estacio R, Esler A, Schrier RW, Hiatt WR. Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes. Circulation. 2003;107(5):753–6.

    Article  PubMed  Google Scholar 

  56. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703–13.

    Google Scholar 

  57. De Backer G, Ambrosioni E, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice. third joint task force of european and other societies on cardiovascular disease prevention in clinical practice. Eur Heart J. 2003;24(17):1601–10.

    Article  PubMed  Google Scholar 

  58. Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.

    Article  Google Scholar 

  59. The Scandinavian Simvastatin Survival Study (4S). Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease. Lancet. 1994;344(8934):1383–89.

    Google Scholar 

  60. Aung PP, Maxwell HG, Jepson RG, Price JF, Leng GC. Lipid-lowering for peripheral arterial disease of the lower limb. Cochrane Database Syst Rev. 2007;(4):CD000123.

    Google Scholar 

  61. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol. 2001;21(11):1712–9.

    Article  CAS  PubMed  Google Scholar 

  62. Curtis AM, Edelberg J, Jonas R, Rogers WT, Moore JS, Syed W, et al. Endothelial microparticles: sophisticated vesicles modulating vascular function. Vasc Med. 2013;18(4):204–14.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Schillinger M, Exner M, Mlekusch W, et al. Statin therapy improves cardiovascular outcome of patients with peripheral artery disease. Eur Heart J. 2004;25(9):742–8.

    Article  CAS  PubMed  Google Scholar 

  64. Mohler ER 3rd, Hiatt WR, Creager MA. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation. 2003;108(12):1481–6.

    Google Scholar 

  65. Giri J, McDermott MM, Greenland P, Guralnik JM, Criqui MH, Liu K, et al. Statin use and functional decline in patients with and without peripheral arterial disease. J Am Coll Cardiol. 2006;47(5):998–1004.

    Article  CAS  PubMed  Google Scholar 

  66. Cheng SW, Ting AC. Lipoprotein (a) level and mortality in patients with critical lower limb ischaemia. Eur J Vasc Endovasc Surg. 2001;22(2):124–9.

    Article  CAS  PubMed  Google Scholar 

  67. Bismuth J, Kofoed SC, Jensen AS, Sethi A, Sillesen H. Serum lipids act as inverse acute phase reactants and are falsely low in patients with critical limb ischemia. J Vasc Surg. 2002;36(5):1005–10.

    Article  PubMed  Google Scholar 

  68. Conte MS, Bandyk DF, Clowes AW, Moneta GL, Namini H, Seely L. Risk factors, medical therapies and perioperative events in limb salvage surgery: observations from the PREVENT III multicenter trial. J Vasc Surg. 2005;42(3):456–64. discussion 464–5.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Schanzer A, Hevelone N, Owens CD, Beckman JA, Belkin M, Conte MS. Statins are independently associated with reduced mortality in patients undergoing infrainguinal bypass graft surgery for critical limb ischemia. J Vasc Surg. 2008;47(4):774–81.

    Article  PubMed  Google Scholar 

  70. Garg PK, Tian L, Criqui MH, Liu K, Ferrucci L, Guralnik JM, et al. Physical activity during daily life and mortality in patients with peripheral arterial disease. Circulation. 2006;114(3):242–8.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Gardner AW, Poehlman ET. Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis. JAMA. 1995;274(12):975–80.

    Article  CAS  PubMed  Google Scholar 

  72. Murphy TP, Cutlip DE, Regensteiner JG, Mohler ER, Cohen DJ, Reynolds MR, et al. Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease: six-month outcomes from the claudication: exercise versus endoluminal revascularization (CLEVER) study. Circulation. 2012;125(1):130–9.

    Article  PubMed  Google Scholar 

  73. McDermott MM, Liu K, Ferrucci L, et al. Physical performance in peripheral arterial disease: a slower rate of decline in patients who walk more. Ann Intern Med. 2006;144(1):10–20.

    Article  PubMed  Google Scholar 

  74. O’Hare AM, Vittinghoff E, Hsia J, Shlipak MG. Renal insufficiency and the risk of lower extremity peripheral arterial disease: results from the heart and estrogen/progestin replacement study (HERS). J Am Soc Nephrol. 2004;15(4):1046–51.

    Article  PubMed  Google Scholar 

  75. Mya MM, Aronow WS. Increased prevalence of peripheral arterial disease in older men and women with subclinical hypothyroidism. J Gerontol A Biol Sci Med Sci. 2003;58(1):68–9.

    Article  PubMed  Google Scholar 

  76. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation. 1998;97(5):425–8.

    Article  CAS  PubMed  Google Scholar 

  77. McDermott MM, Guralnik JM, Corsi A, Albay M, Macchi C, Bandinelli S, et al. Patterns of inflammation associated with peripheral arterial disease: The InCHIANTI study. Am Heart J. 2005;150(2):276–81.

    Article  PubMed  Google Scholar 

  78. McDermott MM, Ferrucci L, Liu K, Criqui MH, Greenland P, Green D, et al. D-dimer and inflammatory markers as predictors of functional decline in men and women with and without peripheral arterial disease. J Am Geriatr Soc. 2005;53(10):1688–96.

    Article  PubMed  Google Scholar 

  79. Ubbink DT, Vermeulen H. Spinal cord stimulation for critical leg ischemia: a review of effectiveness and optimal patient selection. J Pain Symptom Manage. 2006;31(4 Suppl):S30–5.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael J. McArdle MD

  2. Cardiovascular Division, Department of Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd 11-103, Philadelphia, PA, 19104, USA

    Jay Giri MD, MPH & Emile R. Mohler III MD

Authors
  1. Michael J. McArdle MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jay Giri MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emile R. Mohler III MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Loyola University Medical Center, Maywood, Illinois, USA

    Robert S. Dieter

  2. Northwestern Medicine Central DuPage Hospital, Glen Ellyn, Illinois, USA

    Raymond A. Dieter, Jr

  3. The University of Tennessee Medical Center, Knoxville, Tennessee, USA

    Raymond A. Dieter, III

  4. West Virginia University, Charleston, West Virginia, USA

    Aravinda Nanjundappa

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

McArdle, M.J., Giri, J., Mohler, E.R. (2017). Progression of Peripheral Artery Disease to Critical Limb Ischemia. In: Dieter, R., Dieter, Jr, R., Dieter, III, R., Nanjundappa, A. (eds) Critical Limb Ischemia. Springer, Cham. https://doi.org/10.1007/978-3-319-31991-9_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-31991-9_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-31989-6

  • Online ISBN: 978-3-319-31991-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation