High-dose atorvastatin versus moderate dose on early vascular protection after ST-elevation myocardial infarction

Background and aim Clinical benefits of early high-dose statin therapy after acute coronary syndromes are widely known; however, there is poor evidence on the specific setting of ST-elevation myocardial infarction (STEMI) and dose-dependent effects of this therapy on endothelial function and inflammatory biomarkers in the most vulnerable phase after acute coronary syndromes: the postdischarge period. In our study, we compared the short-term effects of high (80 mg) vs moderate doses of atorvastatin (20 mg) in patients with STEMI undergoing primary percutaneous coronary intervention on endothelial function and vascular inflammation. The aim of our study was the evaluation of dose-dependent short-term effects. Subjects and methods We enrolled 52 patients within 48 hours of a STEMI to atorvastatin 80 mg (n=26) or 20 mg (n=26). Every patient underwent endothelial function evaluation by the reactive hyperemia–peripheral arterial tonometry (RH-PAT) index on the first day and 1 month after the STEMI. At the same time, we measured lipid profile and serum levels of high-sensitivity CRP, IL6, TNFα, and oxidized LDL. Results After 1 month of therapy, we observed differences in high-sensitivity CRP levels (0.04±0.02 mg/dL vs 0.36±0.3 mg/dL, P=0.001), IL6 (1.12±0.93 pg/mL vs 3.13±2.84 pg/mL, P=0.03), and improvement in RH-PAT index (1.96±0.16 vs 1.72±0.19, P=0.002) in the group treated with high-dose vs moderate-dose atorvastatin. There was no significant difference in levels of TNFα or oxidized LDL with atorvastatin 20 mg, while there was a reduction in these variables in the group treated with atorvastatin 80 mg. We observed a correlation between high-sensitivity polymerase chain reaction and RH-PAT index on the 30th day after STEMI (r=0.5, P=0.001). Conclusion Higher dose statin therapy in patients with STEMI undergoing primary percutaneous coronary intervention showed early greater vascular protective effects that moderate dose.

[1]  A. Keech,et al.  Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease , 2017, The New England journal of medicine.

[2]  P. Camici,et al.  Novel insights into an "old" phenomenon: the no reflow. , 2015, International journal of cardiology.

[3]  A. Unlu,et al.  Comparative effects of high-dose atorvastatin versus moderate-dose rosuvastatin on lipid parameters, oxidized-LDL and inflammatory markers in ST elevation myocardial infarction. , 2015, Atherosclerosis.

[4]  R. Califf,et al.  Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. , 2015, The New England journal of medicine.

[5]  S. Shiraishi,et al.  Effect of a hydrophilic and a hydrophobic statin on cardiac salvage after ST-elevated acute myocardial infarction - a pilot study. , 2014, Atherosclerosis.

[6]  Gemma A. Figtree,et al.  Biological markers of oxidative stress: Applications to cardiovascular research and practice☆ , 2013, Redox biology.

[7]  Jian Li,et al.  C‐reactive protein promotes adhesion of monocytes to endothelial cells via NADPH oxidase‐mediated oxidative stress , 2012, Journal of cellular biochemistry.

[8]  Zhaohui J. Cai,et al.  Pretreatment data is highly predictive of liver chemistry signals in clinical trials , 2012, Drug design, development and therapy.

[9]  H. Hod,et al.  Statins have an early antiplatelet effect in patients with acute myocardial infarction , 2011, Platelets.

[10]  Akiko Maehara,et al.  A prospective natural-history study of coronary atherosclerosis. , 2011, The New England journal of medicine.

[11]  R. Collins,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010, The Lancet.

[12]  Y. Jang,et al.  Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial. , 2010, JACC. Cardiovascular interventions.

[13]  Wei-Qing Chen,et al.  Early C-reactive protein in the prediction of long-term outcomes after acute coronary syndromes: a meta-analysis of longitudinal studies , 2010, Heart.

[14]  A. Colombo,et al.  Novel approaches for preventing or limiting events (Naples) II trial: impact of a single high loading dose of atorvastatin on periprocedural myocardial infarction. , 2009, Journal of the American College of Cardiology.

[15]  A. Balbarini,et al.  Inflammatory markers and cardiac function in acute coronary syndrome: difference in ST-segment elevation myocardial infarction (STEMI) and in non-STEMI models. , 2009, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[16]  Guangping Li,et al.  Prognostic role of brachial reactivity in patients with ST myocardial infarction after percutaneous coronary intervention , 2009, Coronary artery disease.

[17]  V. Pasceri,et al.  Efficacy of atorvastatin reload in patients on chronic statin therapy undergoing percutaneous coronary intervention: results of the ARMYDA-RECAPTURE (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) Randomized Trial. , 2009, Journal of the American College of Cardiology.

[18]  Michael Weis,et al.  [Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation]. , 2009, Giornale italiano di cardiologia.

[19]  Takamitsu Nakamura,et al.  Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease. , 2009, Journal of the American College of Cardiology.

[20]  C. Stefanadis,et al.  Beneficial effects of statins on endothelial dysfunction and vascular stiffness. , 2007, Current vascular pharmacology.

[21]  V. Pasceri,et al.  Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. , 2007, Journal of the American College of Cardiology.

[22]  C. Cannon,et al.  Relation between soluble intercellular adhesion molecule-1, statin therapy, and long-term risk of clinical cardiovascular events in patients with previous acute coronary syndrome (from PROVE IT-TIMI 22). , 2006, The American journal of cardiology.

[23]  S. Verma,et al.  C-Reactive Protein Upregulates Receptor for Advanced Glycation End Products Expression in Human Endothelial Cells , 2006, Hypertension.

[24]  J. D. de Lemos,et al.  Effects of early treatment with statins on short-term clinical outcomes in acute coronary syndromes: a meta-analysis of randomized controlled trials. , 2006, JAMA.

[25]  D. Morrow,et al.  Is C-reactive protein an innocent bystander or proatherogenic culprit?: The Verdict Is Still Out , 2006, Circulation.

[26]  A. Aggarwal Inflammatory response after intervention assessed by serial C-reactive protein measurements correlates with restenosis in patients treated with coronary stenting. , 2006, American heart journal.

[27]  W. Markiewicz,et al.  Early inflammation and risk of long-term development of heart failure and mortality in survivors of acute myocardial infarction predictive role of C-reactive protein. , 2006, Journal of the American College of Cardiology.

[28]  J. Ornato,et al.  ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention). , 2006, Circulation.

[29]  Joseph P Ornato,et al.  ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). , 2006, Journal of the American College of Cardiology.

[30]  C. Cannon,et al.  The potential relevance of the multiple lipid-independent (pleiotropic) effects of statins in the management of acute coronary syndromes. , 2005, Journal of the American College of Cardiology.

[31]  J. Liao Effects of statins on 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition beyond low-density lipoprotein cholesterol. , 2005, The American journal of cardiology.

[32]  J. Lotterie,et al.  High frequency of endothelial vasomotor dysfunction after acute coronary syndromes in non-culprit and angiographically normal coronary arteries: a reversible phenomenon. , 2005, Atherosclerosis.

[33]  F. Mach,et al.  Statins Reduce Interleukin-6–Induced C-Reactive Protein in Human Hepatocytes: New Evidence for Direct Antiinflammatory Effects of Statins , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[34]  Amir Lerman,et al.  Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. , 2004, Journal of the American College of Cardiology.

[35]  M. Pfeffer,et al.  Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. , 2004, JAMA.

[36]  P. Libby,et al.  Effect of Atorvastatin on Risk of Recurrent Cardiovascular Events After an Acute Coronary Syndrome Associated With High Soluble CD40 Ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study , 2004, Circulation.

[37]  P. Libby,et al.  Inflammation, Immunity, and HMG-CoA Reductase Inhibitors: Statins as Antiinflammatory Agents? , 2004, Circulation.

[38]  Ayan R Patel,et al.  Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. , 2003, American heart journal.

[39]  P. Ridker,et al.  C-reactive protein and other inflammatory risk markers in acute coronary syndromes. , 2003, Journal of the American College of Cardiology.

[40]  Amir Lerman,et al.  Endothelial Dysfunction: A Marker of Atherosclerotic Risk , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[41]  A. Sposito,et al.  Statin Therapy in Acute Coronary Syndromes: Mechanistic Insight Into Clinical Benefit , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[42]  Sridevi Devaraj,et al.  Demonstration That C-Reactive Protein Decreases eNOS Expression and Bioactivity in Human Aortic Endothelial Cells , 2002, Circulation.

[43]  W. Rand,et al.  Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease. , 2001, Journal of the American College of Cardiology.

[44]  P. Ridker,et al.  High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. , 2001, Circulation.

[45]  James T. Willerson,et al.  Direct Proinflammatory Effect of C-Reactive Protein on Human Endothelial Cells , 2000, Circulation.

[46]  M. Pfeffer,et al.  Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. , 2000, Circulation.

[47]  J. Connell,et al.  Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. , 2000, Clinical science.

[48]  I Maruyama,et al.  Biology of endothelium , 1998, Lupus.

[49]  G. Ciliberto,et al.  Elevated levels of interleukin-6 in unstable angina. , 1996, Circulation.

[50]  M. Entman,et al.  Induction of interleukin-6 synthesis in the myocardium. Potential role in postreperfusion inflammatory injury. , 1995, Circulation.

[51]  P. Libby,et al.  Induction and Stabilization of IκBα by Nitric Oxide Mediates Inhibition of NF-κB (*) , 1995, The Journal of Biological Chemistry.

[52]  S. Wesselingh,et al.  Cytokine mRNA expression in postischemic/reperfused myocardium. , 1995, The American journal of pathology.

[53]  D. Celermajer,et al.  Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. , 1994, Journal of the American College of Cardiology.

[54]  W. Weintraub,et al.  Elevation of C-reactive protein in "active" coronary artery disease. , 1990, The American journal of cardiology.