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One-Year Consumption of a Grape Nutraceutical Containing Resveratrol Improves the Inflammatory and Fibrinolytic Status of Patients in Primary Prevention of Cardiovascular Disease

      The search for complementary treatments in primary prevention of cardiovascular disease (CVD) is a high-priority challenge. Grape and wine polyphenol resveratrol confers CV benefits, in part by exerting anti-inflammatory effects. However, the evidence in human long-term clinical trials has yet to be established. We aimed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD. Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded, randomized, parallel, dose–response, placebo-controlled, 1-year follow-up trial. Patients, allocated in 3 groups, consumed placebo (maltodextrin), a resveratrol-rich grape supplement (resveratrol 8 mg), or a conventional grape supplement lacking resveratrol, for the first 6 months and a double dose for the next 6 months. In contrast to placebo and conventional grape supplement, the resveratrol-rich grape supplement significantly decreased high-sensitivity C-reactive protein (−26%, p = 0.03), tumor necrosis factor-α (−19.8%, p = 0.01), plasminogen activator inhibitor type 1 (−16.8%, p = 0.03), and interleukin-6/interleukin-10 ratio (−24%, p = 0.04) and increased anti-inflammatory interleukin-10 (19.8%, p = 0.00). Adiponectin (6.5%, p = 0.07) and soluble intercellular adhesion molecule-1 (−5.7%, p = 0.06) tended to increase and decrease, respectively. No adverse effects were observed in any patient. In conclusion, 1-year consumption of a resveratrol-rich grape supplement improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk (i.e., with diabetes or hypercholesterolemia plus ≥1 other CV risk factor). Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold standard therapy in the primary prevention of CVD.
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      References

        • Renaud S.
        • de Lorgeril M.
        Wine, alcohol, platelets, and the French paradox for coronary heart disease.
        Lancet. 1992; 339: 1523-1526
        • Bertelli A.
        • Bertelli A.A.
        • Gozzini A.
        • Giovannini L.
        Plasma and tissue resveratrol concentrations and pharmacological activity.
        Drugs Exp Clin Res. 1998; 24: 133-138
        • Petrovski G.
        • Gurusamy N.
        • Das D.K.
        Resveratrol in cardiovascular health and disease.
        Ann N Y Acad Sci. 2011; 1215: 22-33
        • Reiner Z.
        • Catapano A.L.
        • De Backer G.
        • Graham I.
        • Taskinen M.R.
        • Wiklund O.
        • Agewall S.
        • Alegria E.
        • Chapman M.J.
        • Durrington P.
        • Erdine S.
        • Halcox J.
        • Hobbs R.
        • Kjekshus J.
        • Filardi P.P.
        • Riccardi G.
        • Storey R.F.
        • Wood D.
        • European Association for Cardiovascular Prevention and Rehabilitation, ESC Committee for Practice Guidelines (CPG) 2008–2010 and 2010–2012 Committees
        ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS).
        Eur Heart J. 2011; 32: 1769-1818
        • Banegas J.R.
        • López-García E.
        • Dallongeville J.
        • Guallar E.
        • Halcox J.P.
        • Borghi C.
        • Massó-González E.L.
        • Jiménez F.J.
        • Perk J.
        • Steg P.G.
        • De Backer G.
        • Rodríguez-Artalejo F.
        Achievement of treatment goals for primary prevention of cardiovascular disease in clinical practice across Europe: the EURIKA study.
        Eur Heart J. 2011; 32: 2143-2152
        • Libby P.
        • Crea F.
        Clinical implications of inflammation for cardiovascular primary prevention.
        Eur Heart J. 2010; 31: 777-783
        • Braunwald E.
        Creating controversy where none exists: the important role of C-reactive protein in the CARE, AFCAPS/TexCAPS, PROVE IT, REVERSAL, A to Z, JUPITER, HEART PROTECTION, and ASCOT trials.
        Eur Heart J. 2012; 33: 430-432
        • Ridker P.M.
        • Rifai N.
        • Clearfield M.
        • Downs J.R.
        • Weis S.E.
        • Miles J.S.
        • Gotto Jr, A.M.
        • Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators
        Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.
        N Engl J Med. 2001; 344: 1959-1965
        • Weil B.R.
        • Greiner J.J.
        • DeSouza C.A.
        • Stauffer B.L.
        Relation of C-reactive protein to endothelial fibrinolytic function in healthy adults.
        Am J Cardiol. 2011; 108: 1675-1679
        • Koenig W.
        • Sund M.
        • Fröhlich M.
        • Fischer H.G.
        • Löwel H.
        • Döring A.
        • Hutchinson W.L.
        • Pepys M.B.
        C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992.
        Circulation. 1999; 99: 237-242
        • Mora S.
        • Musunuru K.
        • Blumenthal R.S.
        The clinical utility of high-sensitivity C-reactive protein in cardiovascular disease and the potential implication of JUPITER on current practice guidelines.
        Clin Chem. 2009; 55: 219-228
        • Ridker P.M.
        • Danielson E.
        • Fonseca F.A.
        • Genest J.
        • Gotto A.M.
        • Kastelein J.J.
        • Koenig W.
        • Libby P.
        • Lorenzatti A.J.
        • MacFadyen J.G.
        • Nordestgaard B.G.
        • Shepherd J.
        • Willerson J.T.
        • JUPITER Study Group
        Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
        N Engl J Med. 2008; 359: 2195-2207
        • Pearson T.A.
        • Mensah G.A.
        • Alexander R.W.
        • Anderson J.L.
        • Cannon III, R.O.
        • Criqui M.
        • Fadl Y.Y.
        • Fortmann S.P.
        • Hong Y.
        • Myers G.L.
        • Rifai N.
        • Smith Jr, S.C.
        • Taubert K.
        • Tracy R.P.
        • Vinicor F.
        • Centers for Disease Control and Prevention, American Heart Association
        Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association.
        Circulation. 2003; 107: 499-511
        • Jain M.K.
        • Ridker P.M.
        Anti-inflammatory effects of statins: clinical evidence and basic mechanisms.
        Nat Rev Drug Discov. 2005; 4: 977-987
        • Vang O.
        • Ahmad N.
        • Baile C.A.
        • Baur J.A.
        • Brown K.
        • Csiszar A.
        • Das D.K.
        • Delmas D.
        • Gottfried C.
        • Lin H.Y.
        • Ma Q.Y.
        • Mukhopadhyay P.
        • Nalini N.
        • Pezzuto J.M.
        • Richard T.
        • Shukla Y.
        • Surh Y.J.
        • Szekeres T.
        • Szkudelski T.
        • Walle T.
        • Wu J.M.
        What is new for an old molecule?.
        PLoS ONE. 2011; 6: e19881
        • Cesari M.
        • Penninx B.W.
        • Newman A.B.
        • Kritchevsky S.B.
        • Nicklas B.J.
        • Sutton-Tyrrell K.
        • Rubin S.M.
        • Ding J.
        • Simonsick E.M.
        • Harris T.B.
        • Pahor M.
        Inflammatory markers and onset of cardiovascular events: results from the Health ABC study.
        Circulation. 2003; 108: 2317-2322
        • Gorog D.A.
        Prognostic value of plasma fibrinolysis activation markers in cardiovascular disease.
        J Am Coll Cardiol. 2010; 55: 2701-2709
        • Bisoendial R.J.
        • Boekholdt S.M.
        • Vergeer M.
        • Stroes E.S.
        • Kastelein J.J.
        C-reactive protein is a mediator of cardiovascular disease.
        Eur Heart J. 2010; 31: 2087-2091
        • Bernstein L.E.
        • Berry J.
        • Kim S.
        • Canavan B.
        • Grinspoon S.K.
        Effects of etanercept in patients with the metabolic syndrome.
        Arch Intern Med. 2006; 166: 902-908
        • Lyngdoh T.
        • Vollenweider P.
        • Waeber G.
        • Marques-Vidal P.
        Association of statins with inflammatory cytokines: A population-based Colaus study.
        Atherosclerosis. 2011; 219: 253-258
        • Fujitaka K.
        • Otani H.
        • Jo F.
        • Jo H.
        • Nomura E.
        • Iwasaki M.
        • Nishikawa M.
        • Iwasaka T.
        • Das D.K.
        Modified resveratrol Longevinex improves endothelial function in adults with metabolic syndrome receiving standard treatment.
        Nutr Res. 2011; 31: 842-847
        • Brasnyó P.
        • Molnár G.A.
        • Mohás M.
        • Markó L.
        • Laczy B.
        • Cseh J.
        • Mikolás E.
        • Szijártó I.A.
        • Mérei A.
        • Halmai R.
        • Mészáros L.G.
        • Sümegi B.
        • Wittmann I.
        Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients.
        Br J Nutr. 2011; 106: 383-389
        • Kruithof E.K.
        Regulation of plasminogen activator inhibitor type 1 gene expression by inflammatory mediators and statins.
        Thromb Haemost. 2008; 100: 969-975
        • Maruyama S.
        • Shibata R.
        • Ohashi K.
        • Ohashi T.
        • Daida H.
        • Walsh K.
        • Murohara T.
        • Ouchi N.
        Adiponectin ameliorates doxorubicin-induced cardiotoxicity through Akt protein-dependent mechanism.
        J Biol Chem. 2011; 286: 32790-32800
        • Penumathsa S.V.
        • Thirunavukkarasu M.
        • Koneru S.
        • Juhasz B.
        • Pant R.
        • Menon V.P.
        • Otani H.
        • Maulik N.
        Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat.
        J Mol Cell Cardiol. 2007; 42: 508-516