Lots of studies have reported that the risk of cardiovascular (CV) events decreases with low density lipoprotein-cholesterol (LDL-C) reduction, and the risk of recurrent cardiovascular events and survival improvement in patients with acute myocardial infarction (AMI) is reduced by using statin.1)2) Therefore, statin is a class IA American College of Cardiology (ACC)/American Heart Association (AHA) recommendation for secondary prevention of atherosclerotic coronary heart disease.3)

In 2011, the European Atherosclerosis Society (EAS)/European Society of Cardiology (ESC) joint guidelines emphasized that LDL-C is still the most important marker to treat targets, regardless of LDL-C levels, with target LDL-C <70 mg/dL, statin therapy should be initiated after AMI,4)5) However, there are still arguments for the use of statin in low LDL-C patients; on the other hands, lots of hyperlipidemia patients with AMI in current practice do not attain the guideline-recommended target LDL-C level.6)7) In addition, the influence of the intensity of statin therapy as represented by the achieved level of LDL-C on cardiovascular outcomes in patients with AMI has not been fully evaluated.8)

Now, the clinical outcome of patients suffering from AMI undergoing percutaneous coronary intervention (PCI) with or without achievement of target LDL-C has little known information. This study investigated is target LDL-C level (below 70 mg/dL) achievements in patients with AMI showed better clinical outcomes or not.

The Korean Acute Myocardial Infarction Registry (KAMIR), is a prospective, open, observational, multicenter, online, nationwide registry of AMI, conducted from November 2005 to January 2008, and its successor, the Korean Myocardial Infarction (KorMI) registry, conducted from January 2008; these registries were supported by the Korean Working Group of Acute Myocardial Infarction. The aims and protocols of the registries have been published. The protocols of the two prospective cohorts were similar. Participating centers included 53 university or community hospitals that have high volumes of patients with facilities for primary PCI and onsite cardiac surgery. The study protocol was reviewed and approved by the institutional review board at each participating center. AMI was diagnosed by characteristic clinical presentations, serial changes on the electrocardiogram suggesting infarction or injury, and increase in cardiac enzymes. We analyzed baseline demographic characteristics, initial presentation, initial vital signs, electrocardiographic findings, results of laboratory tests, procedural data, and medications. Blood samplings for baseline laboratory tests, except for the lipid measurement, were collected at admission or before PCI. Patients were required to fasting overnight and the following day blood was sampled for lipid levels. The LDL-C levels were calculated by the Friedewald formula. Patients with a triglyceride (TG) level ≥400 mg/dL were excluded. A left ventricular ejection fraction was determined by 2-dimensional echocardiography. In-hospital complications and their management were also recorded. 12-month major adverse cardiac events (MACEs) were defined as the composite of a 1-year MACEs including cardiac death, recurrent myocardial infarction (MI), target lesion revascularization (TLR) and coronary artery bypass grafting (CABG). Follow up data were obtained by reviewing medical records and telephone interviews with patients. All data were recorded on an electronic Web page–based case-report form.

Elevation of total cholesterol and LDL-C has received the most attention, particularly because it can be modified by lifestyle changes and drug therapies. Significant associations between higher total cholesterol and LDL-C levels and a higher incidence of cardiovascular events have been repeatedly published.9)10)11) Meta-analyses of many trials show a clear dose-dependent relative reduction in cardiovascular disease with LDL-C lowering.12)13)14) Every 1.0 mmoL/L reduction in LDL-C is associated with a corresponding 20-25% reduction in cardiovascular mortality and non-fatal myocardial infarction.14)15)16)17)18) More recently, trials have confirmed that lowering LDL-C to <1.8 mmoL/L (70 mg/dL) is associated with the lowest risk of recurrent cardiovascular events in secondary prevention populations. Therefore, LDL-C is a cornerstone of secondary prevention and reporting evidence-based approached to risk reduction after an AMI. Based on the results from the TNT and other randomized controlled studies, “the lower, the better” hypothesis has been widely advocated with regard to optimal treatment LDL-C levels in patients with coronary artery disease.1) However, it has not yet been proven whether a lower level of LDL-C itself was the predominant mechanism of better outcomes in the atorvastatin 80 mg group of the TNT study.1)

Statin, by decreasing LDL-C, reduces cardiovascular morbidity and mortality as well as the need for coronary artery interventions. Statin effectively reduces LDL-C by 50% also seems to halt progression or even contribute to regression of coronary atherosclerosis. Experimental studies have demonstrated that statin therapy decreases the extent of myocardial necrosis, preserves myocardial viability, and results in increased ventricular function in models of myocardial ischemia reperfusion injury. Statins' cardioprotective effect after AMI during long-term treatment can be partly explained by their pleiotropic effects, such as anti-inflammatory, antiplatelet, and antithrombotic properties, and improvements in endothelial function. It is obvious that statin therapy with its LDL-C lowering effect provides clinical benefits in the secondary prevention for AMI patients. However, a considerable number of untreated patients with AMI are still eligible for statin therapy.19)20)21)22)23) There are still arguments of the use of statin in having patients with a low LDL-C.24)25)

The main finding of this study is that achieved target LDL-C levels <70 mg/dL were not associated with a lower risk for cardiovascular events as compared with target LDL-C non-achievers. Although the nonachiever's LDL-C levels are relatively low (96.3±24.3 mg/dL) and 78.8% of patients use statin, we can suggest that just a low LDL-C level itself, regardless use of statin, is not always related to better clinical outcomes, suggesting that the LDL-C level itself might not critically influence the risk for cardiovascular events. Thus, “the lower the better” may not be always applicable. It also might be possible that even with less LDL-C reduction, the pleiotropic effects of the statin influenced the risk reduction even in the LDL-C ≥70 mg/dL group. We do not currently know the specific threshold level of LDL-C above which the high level of LDL-C level itself can be an independent risk factor for future cardiovascular events.26)27)28) This study may suggest that LDL-C levels ≥70 mg/dL might not be a risk for future cardiovascular events. And “makes LDL-C lower with statin” should be always addressed in secondary prevention, however more intensive LDL-C lowering may not be recommended just only based on LDL-C level.