doi: 10.1161/01.CIR.0000141736.76561.78
(Circulation. 2004;110:1507-1512.)
© 2004 American Heart Association, Inc.
New Drugs and Technologies |
Renin-Angiotensin System and Angiotensin Receptor Blockers in the Metabolic Syndrome
From the Division of Cardiovascular Diseases and Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minn (A.P.), and Division of Cardiology, Emory University Hospital, Atlanta, Ga (A.A.Q.).
Correspondence to Arshed A. Quyyumi, MD, Division of Cardiology, Emory University Hospital, 1364 Clifton Rd NE, Suite F-606, Atlanta, GA 30322. E-mail aquyyum@emory.edu
Key Words: angiotensin • diabetes mellitus • atherosclerosis • obesity • risk factors
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Activation of the renin-angiotensin system (RAS) occurs in many cardiovascular disorders, and its modulation with angiotensin-converting enzyme (ACE) inhibitors is now established therapy for hypertension, left ventricular dysfunction, diabetic nephropathy, and atherosclerosis. More recently, angiotensin type 1 receptor blockers (ARBs) have shown similar promise.1,2 Research is currently focused on the role of the RAS in the metabolic syndrome (MetS), a disorder characterized primarily by insulin resistance that has emerged as a major risk factor for cardiovascular disease.3 Here, we review how cross talk between angiotensin II (AII) and insulin signaling contributes to the pathophysiology of the MetS and raises the potential for therapeutic use of angiotensin antagonists in its management.
Metabolic Syndrome
The MetS, also known as syndrome X, is an intermediate state between normal metabolism and type 2 diabetes mellitus.3,4 It is characterized by a constellation of atherogenic risk factors that include dyslipidemia, hypertension, and hyperglycemia; a susceptible genomic substrate; and superimposed proinflammatory and prothrombotic milieu. Although the underlying mechanisms for the MetS have not been entirely elucidated, resistance to the cellular actions of insulin is known to be a cardinal feature. The MetS is prevalent in nearly 20% of the adult US population; the likelihood of developing MetS increases with advancing age, higher body mass index, postmenopausal status, smoking, and physical inactivity.5
Insulin Resistance, Hyperinsulinemia, and Atherosclerosis
Important organ systems involved in the MetS include the vasculature, heart, adipose tissue, liver, and skeletal muscle. Hyperinsulinemia and insulin resistance are both implicated in the pathogenesis of hypertension, obesity, type 2 diabetes, and atherosclerosis (Figure).
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