Advertisement

Impact of Chronic Pre-Treatment of Statins on the Level of Systemic Inflammation and Myocardial Perfusion in Patients Undergoing Primary Angioplasty

Published:December 03, 2010DOI:https://doi.org/10.1016/j.amjcard.2010.09.008
      Statins have many favorable pleiotropic effects beyond their lipid-lowering properties. The aim of this study was to evaluate the impact of long-term statin pretreatment on the level of systemic inflammation and myocardial perfusion in patients with acute myocardial infarctions. This was a retrospective study of 1,617 patients with acute ST-segment elevation myocardial infarctions who underwent primary percutaneous coronary intervention <12 hours after the onset of symptoms. Angiographic no-reflow was defined as postprocedural Thrombolysis In Myocardial Infarction (TIMI) flow grade ≤2. Long-term statin pretreatment was significantly less common in the no-reflow group (6.2% vs 21%, p <0.001). The serum lipid profiles of the groups were similar (p >0.05 for all parameters). Baseline C-reactive protein levels (10 ± 8.2 vs 15 ± 14 mg/L, p <0.001) and the frequency of angiographic no-reflow (3.9% vs 14%, p <0.001) were significantly lower, and myocardial blush grade 3 was more common (50% vs 40%, p = 0.006) in the statin pretreatment group (n = 306). Moreover, the frequency of complete ST-segment resolution (>70%) (70% vs 59%, p <0.001) and the left ventricular ejection fraction were higher (49 ± 7.5% vs 46 ± 8.3%, p <0.001) and peak creatine kinase-MB was lower (186 ± 134 vs 241 ± 187 IU/L, p <0.001) in the statin-treated group. In conclusion, long-term statin pretreatment is associated with lower C-reactive protein levels on admission and better myocardial perfusion after primary percutaneous coronary intervention, leading to lower enzymatic infarct area and a more preserved left ventricular ejection fraction. This is a group effect independent of lipid-lowering properties.
      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:

      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

      References

        • Baigent C.
        • Keech A.
        • Kearney P.M.
        • Blackwell L.
        • Buck G.
        • Pollicino C.
        • Kirby A.
        • Sourjina T.
        • Peto R.
        • Collins R.
        • Simes R.
        • Cholesterol Treatment Trialists' (CTT) Collaborators
        Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.
        Lancet. 2005; 366: 1267-1278
        • Fonarow G.C.
        • Wright R.S.
        • Spencer F.A.
        • Fredrick P.D.
        • Dong W.
        • Every N.
        • French W.J.
        • National Registry of Myocardial Infarction 4 Investigators
        Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality.
        Am J Cardiol. 2005; 96: 611-616
        • Laufs U.
        • La Fata V.
        • Plutzky J.
        • Liao J.K.
        Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors.
        Circulation. 1998; 97: 1129-1135
        • 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
        • Son J.W.
        • Koh K.K.
        • Ahn J.Y.
        • Jin D.K.
        • Park G.S.
        • Kim D.S.
        • Shin E.K.
        Effects of statin on plaque stability and thrombogenicity in hypercholesterolemic patients with coronary artery disease.
        Int J Cardiol. 2003; 88: 77-82
        • Jones S.P.
        • Teshima Y.
        • Akao M.
        • Marban E.
        Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes.
        Circ Res. 2003; 93: 697-699
        • Merla R.
        • Reddy N.K.
        • Wang F.W.
        • Uretsky B.F.
        • Barbagelata A.
        • Birnbaum Y.
        Meta-analysis of published reports on the effect of statin treatment before percutaneous coronary intervention on periprocedural myonecrosis.
        Am J Cardiol. 2007; 100: 770-776
        • Iwakura K.
        • Ito H.
        • Kawano S.
        • Okamura A.
        • Kurotobi T.
        • Date M.
        • Inoue K.
        • Fujii K.
        Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction.
        Eur Heart J. 2006; 27: 534-539
        • Hoffmann R.
        • Haager P.
        • Suliman H.
        • Christott P.
        • Radke P.
        • Blindt R.
        • Kelm M.
        Effect of statin therapy before q-wave myocardial infarction on myocardial perfusion.
        Am J Cardiol. 2008; 101: 139-143
        • van 't Hof A.W.
        • Liem A.
        • Suryapranata H.
        • Hoorntje J.C.
        • de Boer M.J.
        • Zijlstra F.
        • Zwolle Myocardial Infarction Study Group
        Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade.
        Circulation. 1998; 97: 2302-2306
        • de Lemos J.A.
        • Braunwald E.
        ST segment resolution as a tool for assessing the efficacy of reperfusion therapy.
        J Am Coll Cardiol. 2001; 38: 1283-1294
        • Reffelmann T.
        • Kloner R.A.
        The no-reflow phenomenon: basic science and clinical correlates.
        Heart. 2002; 87: 162-168
        • Ito H.
        • Okamura A.
        • Iwakura K.
        • Masuyama T.
        • Hori M.
        • Takiuchi S.
        • Negoro S.
        • Nakatsuchi Y.
        • Taniyama Y.
        • Higashino Y.
        • Fujii K.
        • Minamino T.
        Myocardial perfusion patterns related to thrombolysis in myocardial infarction perfusion grades after coronary angioplasty in patients with acute anterior wall myocardial infarction.
        Circulation. 1996; 93: 1993-1999
        • Niccoli G.
        • Burzotta F.
        • Galiuto L.
        • Crea F.
        Myocardial no-reflow in humans.
        J Am Coll Cardiol. 2009; 54: 281-292
        • Pruefer D.
        • Scalia R.
        • Lefer A.M.
        Simvastatin inhibits leukocyte-endothelial cell interactions and protects against inflammatory processes in normocholesterolemic rats.
        Arterioscler Thromb Vasc Biol. 1999; 19: 2894-2900
        • Rezaie-Majd A.
        • Prager G.W.
        • Bucek R.A.
        • Schernthaner G.H.
        • Maca T.
        • Kress H.G.
        • Valent P.
        • Binder B.R.
        • Minar E.
        • Baghestanian M.
        Simvastatin reduces the expression of adhesion molecules in circulating monocytes from hypercholesterolemic patients.
        Arterioscler Thromb Vasc Biol. 2003; 23: 397-403
        • Libby P.
        • Aikawa M.
        Mechanisms of plaque stabilization with statins.
        Am J Cardiol. 2003; 91: S4B-S8B
        • Bonetti P.O.
        • Wilson S.H.
        • Rodriguez-Porcel M.
        • Holmes D.R.
        • Lerman L.O.
        • Lerman A.
        Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering.
        J Am Coll Cardiol. 2002; 40: 546-554
        • Walter D.H.
        • Rittig K.
        • Bahlmann F.H.
        • Kirchmair R.
        • Silver M.
        • Murayama T.
        • Nishimura H.
        • Losordo D.W.
        • Asahara T.
        • Isner J.M.
        Statin therapy accelerates re-endothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells.
        Circulation. 2002; 105: 3017-3024
        • Bell R.M.
        • Yellon D.M.
        Atorvastatin, administered at the onset of reperfusion, and independent of lipid lowering, protects the myocardium by up-regulating a pro-survival pathway.
        J Am Coll Cardiol. 2003; 41: 508-515
        • Ledoux S.
        • Laouari D.
        • Essig M.
        • Runembert I.
        • Trugnan G.
        • Michel J.B.
        • Friedlander G.
        Lovastatin enhances ecto-5′-nucleotidase activity and cell surface expression in endothelial cells: implication of rho-family GTPases.
        Circ Res. 2002; 90: 420-427
        • Thuc L.C.
        • Teshima Y.
        • Takahashi N.
        • Nagano-Torigoe Y.
        • Ezaki K.
        • Yufu K.
        • Nakagawa M.
        • Hara M.
        • Saikawa T.
        Mitochondrial K+ ATP channels-derived reactive oxygen species activate pro-survival pathway in pravastatin-induced cardioprotection.
        Apoptosis. 2010; 15: 669-678
        • Pastuszczak M.
        • Kotlarz A.
        • Mostowik M.
        • Zalewski J.
        • Zmudka K.
        • Undas A.
        Prior simvastatin treatment is associated with reduced thrombin generation and platelet activation in patients with acute ST-segment elevation myocardial infarction.
        Thromb Res. 2010; 125: 382-386
        • Bybee K.A.
        • Kopecky S.L.
        • Williams B.A.
        • Murphy J.G.
        • Scott Wright R.
        Reduced creatine kinase release with statin use at the time of myocardial infarction.
        Int J Cardiol. 2004; 96: 461-466
        • Danesh J.
        • Wheeler J.G.
        • Hirschfield G.M.
        • Eda S.
        • Eiriksdottir G.
        • Rumley A.
        • Lowe G.D.
        • Pepys M.B.
        • Gudnason V.
        C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease.
        N Engl J Med. 2004; 350: 1387-1397
        • Pasceri V.
        • Willerson J.T.
        • Yeh E.T.
        Direct proinflammatory effect of C-reactive protein on human endothelial cells.
        Circulation. 2000; 102: 2165-2168
        • Griselli M.
        • Herbert J.
        • Hutchinson W.L.
        • Taylor K.M.
        • Sohail M.
        • Krausz T.
        • Pepys M.B.
        C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction.
        J Exp Med. 1999; 190: 1733-1740
        • Ørn S.
        • Manhenke C.
        • Ueland T.
        • Damås J.K.
        • Mollnes T.E.
        • Edvardsen T.
        • Aukrust P.
        • Dickstein K.
        C-reactive protein, infarct size, microvascular obstruction, and left-ventricular remodelling following acute myocardial infarction.
        Eur Heart J. 2009; 30: 1180-1186