The Renin-Angiotensin-Aldosterone System: Approaches to Guide Angiotensin-Converting Enzyme Inhibition in Patients with Coronary Artery Disease

Abstract

Drugs that modulate the renin-angiotensin-aldosterone system (RAAS) play an important role in modern cardiovascular prevention strategies. Inhibitors of the RAAS, in particular angiotensin-converting enzyme (ACE) inhibitors, have been proven to be beneficial in specific patient groups, including patients with hypertension, heart failure, diabetes mellitus and stable coronary artery disease. Although clinical trials demonstrated a rather consistent beneficial effect of ACE inhibitors across groups of patients based on clinical characteristics, the variability in treatment response on the individual patient level is extensive. Recent publications suggest that genetic polymorphisms in the RAAS are related to cardiovascular risk. Genetic variability also seems associated with the response to ACE inhibitor therapy, and can probably be used to tailor treatment. This review discusses several approaches to guide ACE inhibitor therapy in patients with coronary artery disease. In addition, the potential impact of pharmacogenetics regarding this particular topic is highlighted.

A pharmacogenetic analysis of determinants of hypertension and blood pressure response to angiotensin-converting enzyme inhibitor therapy in patients with vascular disease and healthy individuals

“…Prior genetic research on the RAAS and hypertension has mainly focused on the angiotensin-converting enzyme (ACE) I/D polymorphism and the M235T polymorphism in the angiotensinogen (AGT) gene [5][6][7][8][9][10]. However, the investigation of only one or two polymorphisms within a single gene ignores the well documented feedback mechanisms within the RAAS and the presence of two angiotensin II receptors (AT1 and AT2) with counteracting effects [4]. A further limitation of most prior studies is their limited sample size.…”

Sulfhydryl Angiotensin-Converting Enzyme Inhibitor Promotes Endothelial Cell Survival through Nitric-Oxide Synthase, Fibroblast Growth Factor-2, and Telomerase Cross-Talk

“…This initial hypothesis has been disputed because of clinical evidence indicating that, even with marginal decreases of blood vessel tone, ACEI provide significant benefits (e.g., decreased mortality) in a large number of patients suffering from cardiac heart failure, acute myocardial infarction, and diabetes complications (Yusuf et al, 2000; Boss and Dawes, 2004;Kjeldsen and Julius, 2004;Brugts et al, 2009). The common thread linking these diverse diseases is endothelium dysfunction, widely recognized as one of the factors implicated in these pathologies.…”

The Rationale and Design of the Perindopril Genetic Association Study (PERGENE): A Pharmacogenetic Analysis of Angiotensin-Converting Enzyme Inhibitor Therapy in Patients with Stable Coronary Artery Disease

“…In previous studies, several genetic polymorphisms in RAAS genes have been associated with high blood pressure levels or an increased cardiovascular risk [22,23]. Nearly all these studies focused at two polymorphisms, the ACE I/ D polymorphism and the M235T polymorphism in the angiotensinogen gene.…”