Angiopoietin-related growth factor is independently associated with lower extremity peripheral arterial disease

J Diabetes Complications. 2017 Feb;31(2):433-438. doi: 10.1016/j.jdiacomp.2016.10.019. Epub 2016 Oct 27.

Abstract

Aims: The present study investigated the association of serum levels of angiopoietin-related growth factor (AGF) with lower extremity peripheral arterial disease (LEPAD).

Methods: The study group is comprised of 105 patients with lower extremity peripheral arterial disease. The control group consisted of 80 individuals without lower extremity peripheral arterial disease. Serum AGF concentrations were determined by enzyme-linked immunosorbent assay. The relationship between AGF and clinical and biochemical parameters was studied. Besides, this study analyzed AGF levels in LEPAD patients according to disease severity and evaluated the prognostic value of AGF for amputation and mortality in LEPAD patients after a follow-up period of 1.7years.

Results: Median serum AGF levels were significantly higher in LEPAD group (103.70±64.69ng/mL) as compared with control group (53.83±37.87ng/mL) (P<0.001). In addition, T2DM patients with LEPAD exhibited markedly higher serum AGF concentrations (118.7±60.90ng/mL) than those without LEPAD (60.23±32.62ng/mL) (P<0.0001). Moreover, LEPAD positively predicted AGF concentrations in multivariate linear regression analysis (P<0.0001). Serum AGF levels were independently associated with LEPAD in binary logistic regression analysis model. Among LEPAD patients, those with critical limb ischemia (n=43) showed higher AGF levels (124.9±73.9 vs. 88.98±53.26ng/mL, P=0.01) compared with those with intermittent claudication (n=62). Furthermore, patients with the highest AGF tertile had an increased all-cause mortality and cardiovascular mortality (P=0.033 and P=0.025, respectively).

Conclusions: Our results suggested that lower extremity peripheral artery disease was positively associated with AGF serum levels. High serum AGF level was a potential risk factor for LEPAD and associates with disease severity and poor outcome in LEPAD patients.

Keywords: Angiogenic factor; Angiopoietin-related growth factor; Lower extremity; Peripheral artery disease; Type 2 diabetes mellitus.

MeSH terms

  • Aged
  • Angiopoietin-Like Protein 6
  • Angiopoietin-like Proteins / blood*
  • Biomarkers / blood
  • China / epidemiology
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetic Angiopathies / blood*
  • Diabetic Angiopathies / epidemiology
  • Diabetic Angiopathies / mortality
  • Diabetic Angiopathies / physiopathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Intermittent Claudication / etiology
  • Ischemia / etiology
  • Logistic Models
  • Lower Extremity / blood supply
  • Male
  • Middle Aged
  • Mortality
  • Prospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Up-Regulation*

Substances

  • ANGPTL6 protein, human
  • Angiopoietin-Like Protein 6
  • Angiopoietin-like Proteins
  • Biomarkers