Review
Endothelial dysfunction in metabolic syndrome: Prevalence, pathogenesis and management

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Abstract

The metabolic syndrome (MetS) is characterized by the presence of central obesity, impaired glucose metabolism, dyslipidemia and hypertension. Several studies showed that MetS is associated with increased risk for type 2 diabetes mellitus (T2DM) and vascular events. All components of MetS have adverse effects on the endothelium. Endothelial dysfunction plays a role in the pathogenesis of atherosclerosis and might also increase the risk for insulin resistance and T2DM. We review the prevalence and pathogenesis of endothelial dysfunction in MetS. We also discuss the potential effects of lifestyle measures and pharmacological interventions on endothelial function in these patients. It remains to be established whether improving endothelial function in MetS will reduce the risk for T2DM and vascular events.

Introduction

The metabolic syndrome (MetS) is characterized by the presence of central obesity, impaired fasting glucose (IFG), dyslipidemia and hypertension [1]. The prevalence of MetS is approximately 34.6% in the United States [2], 17.8–34.0% in Europe [3], [4] and 12.8–41.1% in Asia [3]. Several studies showed that MetS is associated with increased risk for type 2 diabetes mellitus (T2DM) [5] and vascular morbidity and mortality [6].

Endothelial dysfunction appears to play a role in the pathogenesis of atherosclerosis [7], [8]. Prospective studies showed that endothelial dysfunction predicts vascular events in patients with or without established vascular disease [8]. Endothelial dysfunction also appears to be implicated in the pathogenesis of T2DM [9], [10], [11]. Since all components of MetS have adverse effects on the endothelium [12], [13], [14], [15], [16], endothelial dysfunction might be more prevalent in patients with MetS and could play a role in the increased risk for vascular disease and T2DM in this population.

We review the prevalence and pathogenesis of endothelial dysfunction in MetS. We also discuss the potential effects of lifestyle measures and pharmacological interventions on endothelial function in patients with MetS.

Section snippets

Markers of endothelial function in patients with MetS

A detailed description of the methods of assessing endothelial function is beyond the scope of this review. Several relevant comprehensive reviews have been published [17], [18]. In brief, these methods assess: (a) endothelial dysfunction, which is mainly manifested as impaired vasodilation caused by reduced nitric oxide (NO) availability. Endothelium-dependent vasodilation (EDV) is evaluated in response to interventions that stimulate NO release [either pharmacological (mainly acetylcholine)

Pathogenesis of endothelial dysfunction in MetS

Several mechanisms are implicated in the pathogenesis of endothelial dysfunction. Decreased NO availability appears to play a major role and may result from reduced NO production and/or increased inactivation by reactive oxygen species [17]. In addition, reduced availability of other vasodilating agents (including prostacyclin and endothelium-derived hyperpolarizing factors) and/or increased production or activity of vasoconstrictive substances (including endothelin-1 and angiotensin II) are

Lifestyle measures

According to current guidelines, lifestyle measures are the first-line treatment of MetS [1,w28]. In the Diabetes Prevention Program [3234 overweight patients with IFG or impaired glucose tolerance (IGT); 53% had MetS], lifestyle changes reduced the prevalence of MetS [w29]. A reduction in MetS prevalence with lifestyle modification was also reported in smaller studies [w30,w31]. In overweight patients with IFG or IGT, intensive lifestyle intervention also reduced the risk for developing MetS

Conclusions

Endothelial dysfunction is observed in patients with MetS. Abdominal obesity, dyslipidemia, hypertension and impaired glucose metabolism appear to contribute to the pathogenesis of endothelial dysfunction in these patients. Limited data suggest that both lifestyle measures and pharmacological intervention might partly restore endothelial function in MetS. It is also unclear whether an improvement in endothelial function will reduce vascular risk in patients with MetS.

Conflict of interest

This review was written independently; no company or institution supported it financially. Some of the authors have attended conferences, given lectures and participated in advisory boards or trials sponsored by various pharmaceutical companies. Konstantinos Tziomalos is supported by a grant from the Hellenic Atherosclerosis Society.

References (60)

  • L. Lind

    Endothelium-dependent vasodilation, insulin resistance and the metabolic syndrome in an elderly cohort: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

    Atherosclerosis

    (2008)
  • L.M. Blanco-Colio et al.

    Elevated ICAM-1 and MCP-1 plasma levels in subjects at high cardiovascular risk are diminished by atorvastatin treatment. Atorvastatin on Inflammatory Markers study: a substudy of Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration

    Am Heart J

    (2007)
  • S.B. Williams et al.

    Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus

    J Am Coll Cardiol

    (1996)
  • C.J. Rodriguez et al.

    Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus

    Am J Cardiol

    (2005)
  • R.M. Henry et al.

    Type 2 diabetes is associated with impaired endothelium-dependent, flow-mediated dilation, but impaired glucose metabolism is not; The Hoorn Study

    Atherosclerosis

    (2004)
  • L.M. Title et al.

    Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamins C and E

    J Am Coll Cardiol

    (2000)
  • G. Lupattelli et al.

    Direct association between high-density lipoprotein cholesterol and endothelial function in hyperlipemia

    Am J Cardiol

    (2002)
  • P. Lundman et al.

    Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine

    J Am Coll Cardiol

    (2001)
  • G.B. Schnell et al.

    Impaired brachial artery endothelial function is not predicted by elevated triglycerides

    J Am Coll Cardiol

    (1999)
  • P.J. Chowienczyk et al.

    Preserved endothelial function in patients with severe hypertriglyceridemia and low functional lipoprotein lipase activity

    J Am Coll Cardiol

    (1997)
  • S.M. Grundy et al.

    Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

    Circulation

    (2005)
  • E.S. Ford

    Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S

    Diabetes Care

    (2005)
  • S.M. Grundy

    Metabolic syndrome pandemic

    Arterioscler Thromb Vasc Biol

    (2008)
  • V.G. Athyros et al.

    The prevalence of the metabolic syndrome using the National Cholesterol Educational Program and International Diabetes Federation definitions

    Curr Med Res Opin

    (2005)
  • E.S. Ford et al.

    Metabolic syndrome and incident diabetes: current state of the evidence

    Diabetes Care

    (2008)
  • R. Ross

    Atherosclerosis—an inflammatory disease

    N Engl J Med

    (1999)
  • J.A. Kim et al.

    Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms

    Circulation

    (2006)
  • R. Rossi et al.

    Endothelial-dependent vasodilation and incidence of type 2 diabetes in a population of healthy postmenopausal women

    Diabetes Care

    (2005)
  • F. Perticone et al.

    Endothelial dysfunction and C-reactive protein are risk factors for diabetes in essential hypertension

    Diabetes

    (2008)
  • E.J. Benjamin et al.

    Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study

    Circulation

    (2004)

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