Risk factors for progression of peripheral arterial disease in large and small vessels

Circulation. 2006 Jun 6;113(22):2623-9. doi: 10.1161/CIRCULATIONAHA.105.608679. Epub 2006 May 30.


Background: Data on the natural history of peripheral arterial disease (PAD) are scarce and are focused primarily on clinical symptoms. Using noninvasive tests, we assessed the role of traditional and novel risk factors on PAD progression. We hypothesized that the risk factors for large-vessel PAD (LV-PAD) progression might differ from small-vessel PAD (SV-PAD).

Methods and results: Between 1990 and 1994, patients seen during the prior 10 years in our vascular laboratories were invited for a new vascular examination. The first assessment provided baseline data, with follow-up data obtained at this study. The highest decile of decline was considered major progression, which was a -0.30 ankle brachial index decrease for LV-PAD and a -0.27 toe brachial index decrease for SV-PAD progression. In addition to traditional risk factors, the roles of high-sensitivity C-reactive protein, serum amyloid-A, lipoprotein(a), and homocysteine were assessed. Over the average follow-up interval of 4.6+/-2.5 years, the 403 patients showed a significant ankle brachial index and toe brachial index deterioration. In multivariable analysis, current smoking, ratio of total to HDL cholesterol, lipoprotein(a), and high-sensitivity C-reactive protein were related to LV-PAD progression, whereas only diabetes was associated with SV-PAD progression.

Conclusions: Risk factors contribute differentially to the progression of LV-PAD and SV-PAD. Cigarette smoking, lipids, and inflammation contribute to LV-PAD progression, whereas diabetes was the only significant predictor of SV-PAD progression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Ankle / blood supply
  • Brachial Artery / physiopathology*
  • C-Reactive Protein / analysis
  • C-Reactive Protein / physiology
  • Cholesterol, HDL / blood
  • Diabetes Mellitus / physiopathology
  • Diabetic Angiopathies / physiopathology*
  • Disease Progression
  • Female
  • Homocysteine / blood
  • Homocysteine / physiology
  • Humans
  • Inflammation / complications
  • Inflammation / physiopathology*
  • Lipoprotein(a) / blood
  • Lipoprotein(a) / physiology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peripheral Vascular Diseases / blood
  • Peripheral Vascular Diseases / etiology*
  • Peripheral Vascular Diseases / physiopathology*
  • Predictive Value of Tests
  • Regression Analysis
  • Risk Factors
  • Serum Amyloid A Protein / analysis
  • Serum Amyloid A Protein / physiology
  • Smoking / adverse effects
  • Smoking / physiopathology*
  • Toes / blood supply


  • Cholesterol, HDL
  • Lipoprotein(a)
  • Serum Amyloid A Protein
  • Homocysteine
  • C-Reactive Protein