Angiotensin-Converting Enzyme Inhibition With Enalapril Slows Progressive Intima-Media Thickening of the Common Carotid Artery in Patients With Non–Insulin-Dependent Diabetes Mellitus

Abstract

Background and Purpose-Whether angiotensin-converting enzyme (ACE) inhibitors have any clinically significant antiatherogenic effects in humans remains unproven. We undertook a prospective randomized clinical trial of 98 patients with non-insulin-dependent diabetes mellitus (NIDDM) to examine the efficacy of ACE inhibition with enalapril for preventing intima-media (IM) thickening of the carotid wall as measured ultrasonographically. Methods-Ninety-eight NIDDM patients were randomly assigned either to enalapril at 10 mg/d (nϭ48) or to a control group (nϭ50); the planned duration of the trial was 2 years. All patients were seen at baseline (study entry) and 2 subsequent formal annual evaluations, in addition to standard clinical management for NIDDM. IM thickening and vascular lumen diameters were determined for all patients on the basis of baseline and 2 subsequent annual evaluations with carotid ultrasonography. We performed an intent-to-treat analysis to assess changes in IM thickening over the course of the study.

Carotid Intima-Media Thickness for Atherosclerosis

“…A recent meta-analysis of 21 randomized clinical studies (6,317 patients) published before December 2011 found that statin therapy is associated with a favorable decrease in the CCA-IMT ( 0.029 mm, 95% CI: 0.045, 0.013) 93) . Other clinical trials using antihypertensive, antidiabetic or antithrombotic drugs have also evaluated the carotid IMT as a surrogate marker for subclinical atherosclerosis 15, 16,20,94) . A meta-analysis of eight randomized 2012 88) .…”

“…Therefore, the 2010 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines advocated the use of carotid IMT at a class IIa level for the assessment of cardiovascular risk in asymptomatic adults with an intermediate risk of CVD 11) . Multiple clinical trials using lipid-lowering, antihypertensive, and/or antidiabetic drugs have used the carotid IMT as a surrogate clinical endpoint [12][13][14][15][16][17][18][19][20] . However, a meta-analysis of 41 randomized trials showed that decreases in the carotid IMT do not predict a reduction in the cardiovascular events 21) .…”

Changes in carotid intima‐media thickening in patients with type 2 diabetes mellitus: Subanalysis of the Sitagliptin Preventive Study of Intima‐Media Thickness Evaluation

“…These data suggest that treatment with dipeptidyl peptidase‐4 inhibitors seems to prevent the progression of carotid atherosclerosis regardless of disease burden. Previous studies showed that treatment with statins and angiotensin‐converting enzyme inhibitors reduces the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus3, 4. In this subgroup analysis, sitagliptin still attenuated the progression of carotid IMT, even in patients who were receiving those therapies.…”

Effect of atenolol and enalapril treatment on oxidative stress parameters in patients with essential hypertension

“…In addition, Ang II can also directly activate NAD(P)H by inducing translocation of GTPase rac1 protein to the cell membrane, 19 or by phosphorylating and translocating p47phox to cell membrane. 20 Activation of NAPDH oxidase provides superoxide that reacts with eNOS-derived NO and leads to eNOS uncoupling in hypertension. 21 In addition, xanthine oxidase expression and activity are also increased by Ang II in a NADPH oxidase-dependent manner.…”

“…22 Thus ACEI may decrease the oxidative stress in part by limiting Ang II induced superoxide production by NAD(P)H oxidase and reduce the downstream effects of superoxide. 20 ACEI therapy may also down regulate activation of redox-sensitive proinflammatory signals and limit lipid peroxidation and peroxynitrite generation. This study brings new evidence in humans that supports the hypothesis that ACEI increase antioxidant activity and decrease lipid peroxidation.…”