HDL cholesterol as a predictor for the incidence of lower extremity amputation and wound-related death in patients with diabetic foot ulcers

Atherosclerosis. 2015 Apr;239(2):465-9. doi: 10.1016/j.atherosclerosis.2015.02.006. Epub 2015 Feb 7.


Objective: We examined whether HDL cholesterol levels are a predictor for an incidence of lower-extremity amputation (LEA) and wound-related death in patients with diabetic foot ulcers (DFUs).

Research design and methods: This was a single-center, observational, longitudinal historical cohort study of 163 Japanese ambulatory patients with DFUs, 45 woman and 118 men, with a mean (standard deviation) age of 62 (14) years. The primary composite endpoint was defined as the worst of the following outcomes for each individual; (1) minor amputation, defined as amputation below the ankle, (2) major amputation, defined as amputation above the ankle, and (3) wound-related death.

Results: During the median follow-up period of 5.1 months, 67 patients (41.1%) reached the endpoint (43 minor amputations, 16 major amputations, and 8 wound-related deaths). In the univariate Cox proportional hazard model analysis, lower HDL cholesterol levels (mmol/L) were significantly associated with the incidence of the primary composite endpoint (hazard ratio 0.16 [95% CI 0.08-0.32], p < 0.001). In the multivariate Cox proportional hazard model analysis using a stepwise variable-selecting procedure, HDL cholesterol levels in addition to the presence of ankle brachial index <0.9 or ≥1.4 and serum albumin levels were selected as independent risk factors for the incidence of the endpoint (hazard ratio 0.30 [95% CI 0.14-0.63], p = 0.002). Similar results were obtained when HDL cholesterol levels were treated as a categorical variable (≥1.03 mmol/L or less).

Conclusions: HDL cholesterol levels might be a novel clinical predictor for the incidence of LEA and wound-related death in patients with DFUs.

Keywords: Diabetic foot ulcer; HDL cholesterol; Lower extremity amputation.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Amputation, Surgical / adverse effects
  • Amputation, Surgical / mortality*
  • Ankle Brachial Index
  • Biomarkers / blood
  • Cholesterol, HDL / blood*
  • Diabetic Foot* / blood
  • Diabetic Foot* / diagnosis
  • Diabetic Foot* / mortality
  • Diabetic Foot* / surgery
  • Female
  • Humans
  • Japan / epidemiology
  • Kaplan-Meier Estimate
  • Longitudinal Studies
  • Lower Extremity / blood supply*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Risk Factors
  • Serum Albumin / analysis
  • Serum Albumin, Human
  • Time Factors
  • Treatment Outcome


  • ALB protein, human
  • Biomarkers
  • Cholesterol, HDL
  • Serum Albumin
  • Serum Albumin, Human