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

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.