Key words: atherosclerosis, inflammation, intima-media thickness, PPARγ, statins.
IntroductionAtherosclerosis is a complex process that progresses through various functional and morphological alterations in the vessel wall, cumulating in overt cardiovascular disease. Measurement of the intima-media thickness (IMT) of the common carotid artery (CCA) by ultrasound has been established as a reliable screening tool for atherosclerosis and has been shown to predict the risk for stroke and ischaemic heart disease.1 Further, increased arterial stiffness measured by applanation tonometry is predictive for stroke, myocardial infarction and other macrovascular complications.2 In addition to these vascular measurements, laboratory markers of lipid metabolism, inflammation, adhesion molecules and new laboratory markers characterise the metabolic syndrome. Recently, intact proinsulin and adiponectin have been established as criteria of the metabolic syndrome and as predictors of cardiovascular risk in this high-risk population.
3,4The most common intervention to contain the atherosclerotic process and to reduce cardiovascular risk is treatment with 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, or statins. 5,6 Besides lowering of plasma lipids, treatment with statins has been shown to exert several pleiotropic effects, including a reduction in IMT and an improvement in arterial elasticity. 7,8 During recent years, increasing attention has been paid to the role of insulin resistance and the metabolic syndrome in the development of atherosclerosis and cardiovascular disease. Peroxisome proliferator-activated receptor (PPAR)γ agonists (thiazolidinediones), such as pioglitazone, are a class In a recent study, pioglitazone in addition to simvastatin treatment was shown to improve insulin resistance, to inhibit low-grade inflammation and to improve the overall cardiovascular risk profile even in non-diabetic patients with cardiovascular disease (CVD). 15,16 The aim of this study was to evaluate the effect of pioglitazone in addition to atorvastatin compared to atorvastatin alone on intimamedia thickness, vascular elasticity and several cardiovascular risk markers in a non-diabetic patient population at cardiovascular risk.
MethodsThis study was a two-centre, prospective, double-blind, placebo-controlled trial, evaluating the effects of pioglitazone in addition to atorvastatin on IMT, arterial stiffness, endothelial function and several laboratory markers predictive for cardiovascular risk. The study was performed according to the Declaration of Helsinki and Good Clinical Practice, it was approved by the local ethical review board and all patients gave their written informed consent prior to study entry.Patients and study procedure Non-diabetic patients at increased cardiovascular risk, defined as those with an IMT greater than 0.8 mm and a previous medical history of myocardial infarction, coronary angiography with proven CVD, unstable angina pectoris, cervical or leg vessels with atherosclerotic alterations demon...