Statins modulate feedback regulation mechanisms between advanced glycation end-products and C-reactive protein: evidence in patients with acute myocardial infarction

Eur J Pharm Sci. 2013 Jul 16;49(4):512-8. doi: 10.1016/j.ejps.2013.05.001. Epub 2013 May 9.

Abstract

Objective: High sensitivity C-reactive protein (hsCRP) and advanced glycation end-products (AGEs) have been proposed as mediators in inflammation and atherosclerosis. Therefore, we studied the relation between AGE and hsCRP in patients with acute myocardial infarction (AMI).

Methods: Patients with AMI diagnosis and satisfying our inclusion criteria were included during 2009-2011 in an unicentre registry of AMI patients for a cross-sectional study. The final cohort was composed of 156 patients (46.2% STEMI and 27.6% with type-2 diabetes). AGE and hsCRP were measured in plasma.

Results: Diabetic patients were older than non-diabetics (68.6 ± 10.6 vs. 60.4 ± 13.9 years; p<0.05), presented more incidence of hypertension (62.8 vs. 36.3%; p<0.05) and were in a higher Killip class (p<0.05). The mean values of fluorescent AGE and hsCRP levels were 61.3 ± 49.8 AU and 2.4 ± 4.0 mg/L, respectively, and there were no differences in these parameters between diabetic and non-diabetic patients. A direct association between AGE and hsCRP levels was observed, mainly in diabetic patients (r=0.258; p=0.018). Importantly, this association disappeared in patients who had been treated with statins before their AMI (r=-0.055; p=0.845), but it was maintained in non-diabetic patients naïve for statins treatment (r=0.634; p<0.001), independently of other treatments and confounding parameters.

Conclusions: This is the first evidence in humans of a feedback regulation mechanism between CRP and the AGE-RAGE axis modulated by statins.

Keywords: Acute myocardial infarction; Advanced glycation end-products (AGEs); Cardiovascular biomarkers; High sensitivity C-reactive protein (hsCRP); Statins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • C-Reactive Protein / metabolism*
  • Diabetes Mellitus, Type 2 / blood*
  • Female
  • Glycated Hemoglobin / metabolism
  • Glycation End Products, Advanced / metabolism*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • hemoglobin A1c protein, human
  • C-Reactive Protein