Metabolic Syndrome, Insulin Resistance, and Brachial Artery Vasodilator Function in Framingham Offspring Participants Without Clinical Evidence of Cardiovascular Disease

      The metabolic syndrome (MS), a clustering of metabolic disturbances, is associated with increased cardiovascular risk. Limited information is available about the relations between MS, insulin resistance, and vascular function. We measured brachial artery flow-mediated dilation (n = 2,123) and reactive hyperemia (n = 1,521) in Framingham Offspring participants without diabetes or clinical cardiovascular disease (mean age 59 ± 9 years, 57% women). MS, determined by National Cholesterol Education Program criteria, was present in 36% of participants. Insulin resistance was determined using Homeostatic Model Assessment. In age- and gender-adjusted models, MS was associated with lower flow-mediated dilation and reactive hyperemia. There was progressively lower vasodilator function with increasing number of MS components (p for trend <0.0001). In multivariable models adjusting for the 5 MS components as continuous variables, MS (presence vs absence) remained associated with lower flow-mediated dilation (2.84 ± 0.12% vs 3.17 ± 0.08%, p = 0.0496) and reactive hyperemia (50.8 ± 1.0 vs 54.4 ± 0.7 cm/s, p = 0.009). Insulin resistance was inversely associated with flow-mediated dilation and reactive hyperemia in age- and gender-adjusted models, but these relations were not significant in models adjusting for the MS components. In conclusion, our observations are consistent with the hypothesis that MS and insulin resistance impair vascular function predominantly through the influence of the component metabolic abnormalities that comprise MS.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lakka H.M.
        • Laaksonen D.E.
        • Lakka T.A.
        • Niskanen L.K.
        • Kumpusalo E.
        • Tuomilehto J.
        • Salonen J.T.
        The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.
        JAMA. 2002; 288: 2709-2716
        • Girman C.J.
        • Rhodes T.
        • Mercuri M.
        • Pyorala K.
        • Kjekshus J.
        • Pedersen T.R.
        • Beere P.A.
        • Gotto A.M.
        • Clearfield M.
        The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS).
        Am J Cardiol. 2004; 93: 136-141
      1. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults.
        JAMA. 2001; 285 (Adult Treatment Panel III): 2486-2497
        • Reaven G.
        Metabolic syndrome: pathophysiology and implications for management of cardiovascular disease.
        Circulation. 2002; 106: 286-288
        • Ford E.S.
        • Giles W.H.
        • Mokdad A.H.
        Increasing prevalence of the metabolic syndrome among U.S. Adults.
        Diabetes Care. 2004; 27: 2444-2449
        • Widlansky M.E.
        • Gokce N.
        • Keaney Jr., J.F.
        • Vita J.A.
        The clinical implications of endothelial dysfunction.
        J Am Coll Cardiol. 2003; 42: 1149-1160
        • Benjamin E.J.
        • Larson M.G.
        • Keyes M.J.
        • Mitchell G.F.
        • Vasan R.S.
        • Keaney Jr, J.F.
        • Lehman B.T.
        • Fan S.
        • Osypiuk E.
        • Vita J.A.
        Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study.
        Circulation. 2004; 109: 613-619
        • Rodriguez C.J.
        • Miyake Y.
        • Grahame-Clarke C.
        • Di Tullio M.R.
        • Sciacca R.R.
        • Boden-Albala B.
        • Sacca R.L.
        • Homma S.
        Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus.
        Am J Cardiol. 2005; 96: 1273-1277
        • Kuvin J.T.
        • Patel A.R.
        • Sidhu M.
        • Rand W.M.
        • Sliney K.A.
        • Pandian N.G.
        • Karas R.H.
        Relation between high-density lipoprotein cholesterol and peripheral vasomotor function.
        Am J Cardiol. 2003; 92: 275-279
        • Wheatcroft S.B.
        • Williams I.L.
        • Shah A.M.
        • Kearney M.T.
        Pathophysiological implications of insulin resistance on vascular endothelial function.
        Diabet Med. 2004; 20: 255-268
        • Kannel W.B.
        • Feinleib M.
        • McNamara P.M.
        • Garrison R.J.
        • Castelli W.P.
        An investigation of coronary heart disease in families.
        Am J Epidemiol. 1979; 110: 281-290
        • Abbott R.D.
        • McGee D.L.
        The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease, Section 37: The Probability of Developing Certain Cardiovascular Diseases in Eight Years at Specified Values of Some Characteristics.
        National Heart, Lung, and Blood Institute, Bethesda, MD1987
        • Mitchell G.F.
        • Parise H.
        • Vita J.A.
        • Larson M.G.
        • Warner E.
        • Keaney Jr, J.F.
        • Keyes M.J.
        • Levy D.
        • Vasan R.S.
        • Benjamin E.J.
        Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study.
        Hypertension. 2004; 44: 134-139
        • Grundy S.M.
        • Cleeman J.I.
        • Daniels S.R.
        • Donato K.A.
        • Eckel R.H.
        • Franklin B.A.
        • Gordon D.J.
        • Krauss R.M.
        • Savage P.J.
        • Smith Jr., S.C.
        • Spertus J.A.
        • Costa F.
        Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement.
        Circulation. 2005; 112: 2735-2752
        • Meigs J.B.
        • Dupuis J.
        • Herbert A.G.
        • Liu C.
        • Wilson P.W.
        • Cupples L.A.
        The insulin gene variable number tandem repeat and risk of type 2 diabetes in a population-based sample of families and unrelated men and women.
        J Clin Endocrinol Metab. 2005; 90: 1137-1143
        • Matthews D.R.
        • Hosker J.P.
        • Rudenski A.S.
        • Naylor B.A.
        • Treacher D.F.
        • Turner R.C.
        Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
        Diabetologia. 1985; 28: 412-419
        • Balkau B.
        • Charles M.A.
        Comment on the provisional report from the WHO consultation.
        Diabet Med. 1999; 16: 442-443
        • SAS Institute Inc
        SAS Procedures Guide, Version 8.
        SAS Institute, Cary, NC1999
        • Brook R.D.
        • Bard R.L.
        • Rubenfire M.
        • Ridker P.M.
        • Rajagopalan S.
        Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults.
        Am J Cardiol. 2001; 88: 1264-1269
        • Wang T.D.
        • Chen W.J.
        • Lin J.W.
        • Chen M.F.
        • Lee Y.T.
        Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome.
        Am J Cardiol. 2004; 93: 362-365
        • Sola S.
        • Mir M.Q.
        • Cheema F.A.
        • Khan-Merchant N.
        • Menon R.G.
        • Parthasarathy S.
        • Khan B.V.
        Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study.
        Circulation. 2005; 111: 343-348
        • Lteif A.A.
        • Han K.
        • Mather K.J.
        Obesity, insulin resistance, and the metabolic syndrome: determinants of endothelial dysfunction in whites and blacks.
        Circulation. 2005; 112: 32-38
        • Kahn R.
        • Buse J.
        • Ferrannini E.
        • Stern M.
        The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes.
        Diabetes Care. 2005; 28: 2289-2304
        • Sundstrom J.
        • Vallhagen E.
        • Riserus U.
        • Byberg L.
        • Zethelius B.
        • Berne C.
        • Lind L.
        • Ingelsson I.
        Risk associated with the metabolic syndrome versus the sum of its individual components.
        Diabetes Care. 2006; 29: 1673-1674
        • Steinberg H.O.
        • Chaker H.
        • Leaming R.
        • Johnson A.
        • Brechtel G.
        • Baron A.D.
        Obesity/insulin resistance is associated with endothelial dysfunction: implications for the syndrome of insulin resistance.
        J Clin Invest. 1996; 97: 2601-2610
        • de Jongh R.T.
        • Serne E.H.
        • Ijzerman R.G.
        • de Vries G.
        • Stehouwer C.D.
        Impaired microvascular function in obesity: implications for obesity-associated microangiopathy, hypertension, and insulin resistance.
        Circulation. 2004; 109: 2529-2535
        • Balletshofer B.M.
        • Rittig K.
        • Enderle M.D.
        • Volk A.
        • Maerker E.
        • Jacob S.
        • Matthaei S.
        • Rett K.
        • Haring H.U.
        Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance.
        Circulation. 2000; 101: 1780-1784
        • Meigs J.B.
        • Hu F.B.
        • Rifai N.
        • Manson J.E.
        Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus.
        JAMA. 2004; 291: 1978-1986
        • Tulis D.A.
        • Unthank J.L.
        • Prewitt R.L.
        Flow-induced arterial remodeling in rat mesenteric vasculature.
        Am J Physiol. 1998; 274: H874-H882
        • Steinberg H.O.
        • Baron A.D.
        Vascular function, insulin resistance and fatty acids.
        Diabetologia. 2002; 45: 623-634