Acute effects of statin on reduction of angiopoietin-like 2 and glyceraldehyde-derived advanced glycation end-products levels in patients with acute myocardial infarction: a message from SAMIT (Statin for Acute Myocardial Infarction Trial)
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Experimental ischemia–reperfusion models have shown that 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, have cardioprotective effects. SAMIT (Statin Acute Myocardial Infarction Trial) is a multicenter prospective open randomized trial, designed to evaluate the effects of statin treatment from the earliest stage on cardioprotection in patients with acute myocardial infarction (AMI). Patients were randomly assigned to receive atorvastatin (initial dose of 40 mg at admission followed by the maintenance dose of 10 mg/day for 30 days) or not (control), and then immediately underwent percutaneous coronary intervention (PCI) for the culprit lesion. The primary endpoints were infarct size and left ventricular function. The secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE) and various biomarkers. There were no significant differences in baseline characteristics between 2 groups of the statin treatment group and the control group. The left ventricular ejection fraction increased at 6 months after the onset of AMI, compared with the baseline level in the atorvastatin group (P < 0.05), while it did not change in the control group. Although there were no significant differences in the MACCE, the changes in the levels of angiopoietin-like protein 2 (ANGPTL2) (P < 0.05), and glyceraldehyde-derived advanced glycation end-products, (TAGE) (P < 0.01) were suppressed at 2 weeks in the atorvastatin group, compared with the control group. Statin therapy started early after the onset reduced the levels of ANGPTL2 and TAGE, and thus, might have cardioprotective effects in patients with AMI.
KeywordsStatin Acute myocardial infarction Inflammation Oxidative stress
The authors thank Sae Katafuchi and Hiroko Takagi for their expert technical assistance during the study.
Compliance with ethical standards
This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI: Grant Number 22300264; MT).
Conflict of interest
JO belongs to the department endowed by Fukuda Denshi Co, Ltd. SY received honoraria such as lecture fees, from AstraZeneca, Astellas Pharma Inc., Pfizer Inc, Daiichi Sankyo Company, Ltd., Kowa Pharmaceutical Co, Ltd., and Shionogi & Co., Ltd. KN received remuneration, including lecture fees, from AstraZeneca, Astellas Pharma Inc., Nippon Boehringer Ingelheim Co, Ltd., Pfizer Inc, MSD K.K., Daiichi Sankyo Company, Ltd., Kowa Pharmaceutical Co, Ltd., Takeda Pharmaceutical Co, Ltd., Novartis Pharmaceuticals Japan, Mitsubishi Tanabe Pharma Corporation and Dainippon Sumitomo Pharma Co, Ltd. KN also received scholarship funds and donations granted by Astellas Pharma Inc., Nippon Boehringer Ingelheim Co, Ltd., Daiichi Sankyo Company, Ltd., Takeda Pharmaceutical Co, Ltd., Mitsubishi Tanabe Pharma Corporation and MSD K.K.
- 1.Hayashidani S, Tsutsui H, Shiomi T, Suematsu N, Kinugawa S, Ide T, Takeshita A (2002) Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation 105:868–873CrossRefPubMedGoogle Scholar
- 6.Kaneko H, Yajima J, Oikawa Y, Tanaka S, Fukamachi D, Suzuki S, Sagara K, Otsuka T, Matsuno S, Funada R, Kano H, Uejima T, Koike A, Nagashima K, Kirigaya H, Sawada H, Aizawa T, Yamashita T (2014) Effects of statin treatment in patients with coronary artery disease and chronic kidney disease. Heart Vessels 29:21–28CrossRefPubMedGoogle Scholar
- 7.Okumura S, Sakakibara M, Hayashida R, Jinno Y, Tanaka A, Okada K, Hayashi M, Ishii H, Murohara T (2014) Accelerated decline in renal function after acute myocardial infarction in patients with high low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol ratio. Heart Vessels 29:7–14CrossRefPubMedGoogle Scholar
- 8.de Lemos JA, Blazing MA, Wiviott SD, Lewis EF, Fox KA, White HD, Rouleau JL, Pedersen TR, Gardner LH, Mukherjee R, Ramsey KE, Palmisano J, Bilheimer DW, Pfeffer MA, Califf RM, Braunwald E, Investigators (2004) Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndrome: phase Z of the A to Z trial. JAMA 292:1307–1316CrossRefPubMedGoogle Scholar
- 9.Cannon CP, Braunwald E, McCabe CH, Grayston JT, Muhlestein B, Glugliano RP, Cairns R, Skene AM, Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction-22 Investigators (2004) Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 350:1495–1504CrossRefPubMedGoogle Scholar
- 11.Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I, Larsen ML, Bendiksen FS, Lindahl C, Szarek M, Tsai J, Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Study Group (2005) High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized control trial. JAMA 294:2437–2445CrossRefPubMedGoogle Scholar
- 12.Lenderink T, Boersma E, Gitt AK, Zeymer U, Wallentin L, Van de Werf F, Hasdai D, Behar S, Simoons ML (2006) Patients using statin treatment within 24H after admission for ST-elevation acute coronary syndromes had lower mortality than non-users: a report from the first Euro Heart Survey on acute coronary syndromes. Eur Heart J 27:1799–1804CrossRefPubMedGoogle Scholar
- 14.Newby LK, Kristinsson A, Bhapkar MV, Aylward PE, Dimas AP, Klein WW, McGuire DK, Moliterno DJ, Verheugt FW, Weaver WD, Califf RM, SYMPHONY and 2nd SYMPHONY Investigator (2002) Sibrafiban vs aspirin to yield maximum protection from ischemic heart events post-acute coronary syndromes. Early statin initiation and outcomes in patients with acute coronary syndromes. JAMA 287:3087–3095CrossRefPubMedGoogle Scholar
- 16.Nakamura I, Oyama J, Komoda H, Shiraki A, Sakamoto Y, Taguchi I, Hiwatashi A, Komatsu A, Takeuchi M, Yamagishi S, Inoue T, Node K (2014) Possible effects of glimepiride beyond glycemic control in patients with type 2 diabetes: a preliminary report. Cardiovasc Diabetol 13:15CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Ramasamy R, Yan SF, Herold K, Clynes R, Schmidt AM (2008) Receptor for advanced glycation end products: fundamental roles in the inflammatory response: winding the way to the pathogenesis of endothelial dysfunction and atherosclerosis. Ann N Y Acad Sci 1126:7–13CrossRefPubMedPubMedCentralGoogle Scholar