Association of Decreased Docosahexaenoic Acid Level After Statin Therapy and Low Eicosapentaenoic Acid Level with In-Stent Restenosis in Patients with Acute Coronary Syndrome

Aim: It is speculated that statin therapy modulates the synthesis of polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, the data available on the effects of statin therapy on the serum levels of PUFA and the subsequent impact on in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) are limited. Methods: A total of 120 ACS patients who received emergent coronary stent implantation, follow-up coronary angiography to evaluate ISR, and new statin therapy were enrolled. We measured the serum levels of the PUFA and lipids at the onset of ACS and at the follow-up coronary angiography. Results: The follow-up coronary angiography revealed 38 ISR cases. New statin therapy significantly reduced the serum levels of DHA and low-density lipoprotein cholesterol (LDL-C), while it did not affect EPA level. Single regression analysis revealed that a decreased serum level of LDL-C was associated with decreased DHA level. The multiple logistic regression analysis revealed that the decreased DHA level after statin therapy and low serum level of EPA on admission were determinants of prevalence of ISR. Conclusion: Statin therapy decreased the serum level of DHA with a parallel reduction in LDL-C level in patients with ACS. Decreased DHA level after statin therapy and low EPA level on admission are risk factors for ISR, indicating that in patients with ACS, decreased serum levels of DHA may be a residual target for the prevention of ISR.

[1]  K. Aihara,et al.  n-3 Polyunsaturated Fatty Acids: Promising Nutrients for Preventing Cardiovascular Disease , 2017, Journal of atherosclerosis and thrombosis.

[2]  J. Jakobsen,et al.  Drug-eluting stents versus bare-metal stents for acute coronary syndrome. , 2017, The Cochrane database of systematic reviews.

[3]  Tomoaki Tanaka,et al.  Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells , 2017, Molecular medicine reports.

[4]  Y. Higashikuni,et al.  Combination of n-3 polyunsaturated fatty acids reduces atherogenesis in apolipoprotein E-deficient mice by inhibiting macrophage activation. , 2016, Atherosclerosis.

[5]  A. Kirtane,et al.  Mechanisms and Patterns of Intravascular Ultrasound In-Stent Restenosis Among Bare Metal Stents and First- and Second-Generation Drug-Eluting Stents. , 2015, The American journal of cardiology.

[6]  K. Aihara,et al.  Reduced ratio of eicosapentaenoic acid and docosahexaenoic acid to arachidonic acid is associated with early onset of acute coronary syndrome , 2015, Nutrition Journal.

[7]  V. Kocka,et al.  Bioresorbable vascular scaffolds in acute ST-segment elevation myocardial infarction: a prospective multicentre study ‘Prague 19’ , 2014, European heart journal.

[8]  N. Yokoyama,et al.  Effects of eicosapentaenoic acid on platelet function in patients taking long-term aspirin following coronary stent implantation. , 2014, International heart journal.

[9]  S. Hwang,et al.  Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis , 2013, Proceedings of the National Academy of Sciences.

[10]  A. Sato,et al.  Effects of Statins on Serum n-3 to n-6 Polyunsaturated Fatty Acid Ratios in Patients With Coronary Artery Disease , 2013, Journal of cardiovascular pharmacology and therapeutics.

[11]  I. Komuro,et al.  Low levels of serum n-3 polyunsaturated fatty acids are associated with worse heart failure-free survival in patients after acute myocardial infarction. , 2013, Circulation journal : official journal of the Japanese Circulation Society.

[12]  P. Serruys,et al.  Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial , 2012, The Lancet.

[13]  L. Räber,et al.  Effect of biolimus-eluting stents with biodegradable polymer vs bare-metal stents on cardiovascular events among patients with acute myocardial infarction: the COMFORTABLE AMI randomized trial. , 2012, JAMA.

[14]  K. Aihara,et al.  Effects of Statins on Cardiorenal Syndrome , 2012, International journal of vascular medicine.

[15]  J.,et al.  The New England Journal of Medicine , 2012 .

[16]  T. Murohara,et al.  Impact of omega-3 polyunsaturated fatty acids on coronary plaque instability: an integrated backscatter intravascular ultrasound study. , 2011, Atherosclerosis.

[17]  Gary S Mintz,et al.  In-stent restenosis in the drug-eluting stent era. , 2010, Journal of the American College of Cardiology.

[18]  J. Brophy,et al.  Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of randomized controlled trials , 2010, BMC cardiovascular disorders.

[19]  S. Yoshida,et al.  Endothelial Nitric Oxide Synthase–Independent Protective Action of Statin Against Angiotensin II–Induced Atrial Remodeling via Reduced Oxidant Injury , 2010, Hypertension.

[20]  Y. Matsuzawa,et al.  Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease. , 2009, Circulation journal : official journal of the Japanese Circulation Society.

[21]  M. Pencina,et al.  In-hospital and 1-year outcomes among percutaneous coronary intervention patients with chronic kidney disease in the era of drug-eluting stents: a report from the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) registry. , 2009, JACC. Cardiovascular interventions.

[22]  Ken-ichi Aihara,et al.  Pitavastatin, an HMG-CoA Reductase Inhibitor, Exerts eNOS-Independent Protective Actions Against Angiotensin II–Induced Cardiovascular Remodeling and Renal Insufficiency , 2008, Circulation research.

[23]  八木 秀介 Pitavastatin, an HMG-CoA reductase inhibitor, exerts eNOS-independent protective actions against angiotensin 2-induced cardiovascular remodeling and renal insufficiency , 2008 .

[24]  Y. Matsuzawa,et al.  Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis , 2007, The Lancet.

[25]  T. Terano,et al.  Eicosapentaenoic acid suppressed the proliferation of vascular smooth muscle cells through modulation of various steps of growth signals , 2007, Lipids.

[26]  I. Morita,et al.  Eicosapentaenoic acid inhibits tube formation of vascular endothelial cellsin vitro , 1991, Lipids.

[27]  R. Huupponen,et al.  Effects of Diet and Simvastatin on Fatty Acid Composition in Hypercholesterolemic Men: A Randomized Controlled Trial , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[28]  A. O'Connor The Cochrane Database of Systematic Reviews , 2004 .

[29]  M. Makuuchi,et al.  Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis , 2002, Nature Medicine.

[30]  P. Serruys,et al.  Reference chart derived from post-stent-implantation intravascular ultrasound predictors of 6-month expected restenosis on quantitative coronary angiography. , 1999, Circulation.

[31]  C. Di Mario,et al.  Stented segment length as an independent predictor of restenosis. , 1999, Journal of the American College of Cardiology.

[32]  Roberto Marchioli,et al.  Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. , 1999 .

[33]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[34]  H. Arnesen,et al.  n-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study , 1999 .

[35]  M. Hadamitzky,et al.  Predictive factors of restenosis after coronary stent placement. , 1997, Journal of the American College of Cardiology.

[36]  Sayon Roy,et al.  ω-3 Polyunsaturated fatty acids inhibit migration of human vascular smooth muscle cells in vitro , 1997 .

[37]  D. Kyle,et al.  The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans , 1997, Lipids.

[38]  S. Roy,et al.  Omega-3 polyunsaturated fatty acids inhibit migration of human vascular smooth muscle cells in vitro. , 1997, Life sciences.

[39]  J. Cairns,et al.  Fish oils and low-molecular-weight heparin for the reduction of restenosis after percutaneous transluminal coronary angioplasty. The EMPAR Study. , 1996, Circulation.

[40]  M. Leon,et al.  Patterns and mechanisms of in-stent restenosis. A serial intravascular ultrasound study. , 1996, Circulation.

[41]  A. Jacobs,et al.  Do fish oils prevent restenosis after coronary angioplasty? , 1994, Circulation.

[42]  T. Terano,et al.  Eicosapentaenoic acid and docosahexaenoic acid suppress the proliferation of vascular smooth muscle cells. , 1993, Atherosclerosis.

[43]  J. Gapinski,et al.  Preventing restenosis with fish oils following coronary angioplasty. A meta-analysis. , 1993, Archives of internal medicine.

[44]  C. Hennekens,et al.  A meta-analysis of randomized trials of fish oil in prevention of restenosis following coronary angioplasty. , 1992, American Journal of Preventive Medicine.

[45]  P. Elwood,et al.  EFFECTS OF CHANGES IN FAT, FISH, AND FIBRE INTAKES ON DEATH AND MYOCARDIAL REINFARCTION: DIET AND REINFARCTION TRIAL (DART) , 1989, The Lancet.