Editor's Note: Commentary based on Barth JH, Jackson BM, Farrin AJ, et al. Change in serum lipids after acute coronary syndromes: secondary analysis of SPACE ROCKET study data and a comparative literature review. Clin Chem 2010;56:1592-8.

Lipid values are commonly thought to decrease rapidly after the onset of MI. However, most studies were performed 20-30 years ago. Using data from the SPACE ROCKET Trial, the authors re-examined this relationship. The SPACE ROCKET trial was an open-label, national, multicenter, randomized, controlled trial comparing the efficacy and tolerability of 40 mg simvastatin versus 10 mg rosuvastatin in patients admitted with an acute coronary event within the preceding two weeks, requiring secondary prevention with a statin.1 Patients were not excluded if they were already taking a statin at time of admission unless it was 80 mg simvastatin or 80 mg atorvastatin per day. Participants were included in this secondary analysis if the participating hospital laboratory used the same analysis methods on the routine day one samples as the central laboratory, as significant bias has been reported between analysis methods.2

Routine hospital admission (day one) blood samples (fasting or nonfasting) were used for analysis, as well as a follow up sample obtained on days two –four. Total cholesterol, HDL cholesterol, and triglycerides were measured, and LDL cholesterol was calculated using the Friedewald equation.

A secondary objective of this report entailed a comprehensive analysis of published studies examining the effect of AMI on lipid concentrations in which the absolute concentration of cholesterol and triglycerides was given at specific time points and no lipid-modifying treatment was given during the study period. The mean changes for total cholesterol and triglycerides were calculated, weighted according to the number of participants in each study.

Of the 1263 participants enrolled into the SPACE ROCKET trial, 128 met the entry criteria for this sub-study. Total cholesterol changed from 205 to 178 mg/dL (absolute difference 27 mg/dL, relative change 8.6%) and LDL from 134 to 117 mg/dL (absolute difference 17 mg/dL, relative change 13%). In contrast, no significant difference was observed in HDL or triglyceride concentrations between day one and days two – four.

A secondary analysis reviewed 26 papers including 2122 participants in studies from 1963 – 2008. These studies reviewed total cholesterol and triglyceride concentrations at identified days post AMI. The median study size was 39 patients (range 12–565). The combined results demonstrated that total cholesterol fell by about 10% in the 14 days after ACS.

The authors concluded that the SPACE ROCKET trial data, along with a comparison of previously published data found that there was a 10% fall in total cholesterol after AMI—a difference that they concluded was of high clinical significance.

Commentary

It has been widely accepted that serum cholesterol (and by association, LDL) falls in the first few days after AMI. Sampling time immediately after AMI is required to obtain an accurate profile. As the authors note, this view was based on studies that were in general very small, ranging in size from 12 to 123 participants, with the average only 39 per trial. When the combined results were reviewed, the results were consistent with the current study, with an approximate 10% reduction in total cholesterol. Although the authors comment that this is a highly significant result, these changes are actually fairly minor and unlikely to change overall treatment plans.

In contrast, the largest study performed thus far by Pitt et.al4 enrolled 507 patients, of which approximately 40% had STEMI, 30%, had non-STEMI, and 30% had unstable angina. The initial sample was taken a median of 26 hours after symptom onset. There was a slight change in lipid values over the next 84 hours, which was not different based on presenting ACS type. Changes in values, although statistically significant, were not clinically significant.

Why the difference in results? First, an important limitation of this study is that the number of patients included is relatively small. Second, the decrease in cholesterol after acute MI is hypothesized to result from the effects of severe stress. It is possible that improvements in care and changes in the diagnostic criteria for MI patients result in only small amounts of myocardial damage, which in turn causes less stress. This may explain the finding that almost all studies reported since 20024-8 have demonstrated only small changes in cholesterol (typically <10% relative change) in contrast to studies performed in the 1960s and 1970s. Unfortunately, this study, as well as many others, failed to report the size and type of MI, making it difficult to determine the effects of MI size.

Another potential but unlikely explanation is that lipid values decrease very acutely, within the first few minutes to hours after MI onset. As most studies have some delay in obtaining the lipid profile, this acute decrease would be missed. Using a calculated LDL could also play a role; if the patient was non-fasting, triglycerides would be increased, artificially lowering the LDL value.

What are the implications of this study? Although it appears that both total cholesterol and LDL do decrease, the change does not appear clinically significant, and therefore unlikely to make a substantial clinical change in overall treatment, given current recommendations to treat all MI patients with a statin. For those who believe that lower is better and that maximal statin therapy is indicated no matter the LDL, then treatment will not change. However, for those who believe in targeting a specific LDL goal, knowing the initial LDL level could allow better targeting of statin dose. This has become more important given the substantial cost differential between generic, low-cost, less potent statins, and more potent but non-generic statins.

The results of this study, in conjunction with their review of prior ones, dispels the myth that lipids obtained after the first 24 hours are not valid. Lipid values, even if obtained two-three days later after admission (with the caveat that it may not apply to patients with very large MIs or those in cardiogenic shock) will be relatively equivalent to the patient’s baseline values.

References

1. Barth JH, Jackson BM, Farrin AJ,et al. Change in serum lipids after acute coronary syndromes: secondary analysis of SPACE ROCKET study data and a comparative literature review. Clin Chem 2010;56:1592-8.
2. Hall AS, Jackson BM, Farrin AJ, et al. A randomised controlled trial of simvastatin versus rosuvastatin in patients with acute myocardial infarction: the Secondary Prevention of Acute Coronary Events—Reduction Of Cholesterol to Key European Targets (SPACEROCKET) trial. Eur J Cardiovasc Prev Rehab 2009;16:712–21.
3. Cramb R, French J, Mackness M, Neely RDG, Caslake M, MacKenzie F. Lipid external quality assessment: commutability between external quality assessment and clinical specimens. Ann Clin Biochem 2008;45:260–65.
4. Pitt B, Loscalzo J, Ycas J, Raichlen JS. Lipid levels after acute coronary syndromes. J Am Coll Cardiol 2008;51:1440–5.
5. Ko D, Alter D, Newman A, Donovan L, Tu J. Association between lipid testing and statin therapy in acute myocardial infarction patients. Am Heart J 2005;150:419–25.
6. Henkin Y, Crystal E, Goldberg Y, Friger M, Lorber J, Zuili I, Shany S. Usefulness of lipoprotein changes during acute coronary syndromes for predicting postdischarge lipoprotein levels. Am J Cardiol 2002;89:7–11.
7. Barbagallo CM, Rizzo M, Cefalu AB, et al. Changes in plasma lipids and low-density lipoprotein peak particle size during and after acute myocardial infarction. Am J Cardiol 2002;89:460–2.
8. Nawaz H, Comerford BP, Njike VY, Dhond AJ, Plavec M, Katz DL. Repeated serum lipid measurements during the peri-hospitalization period. Am J Cardiol 2006;98:1379–82.

Keywords: Fluorobenzenes, Heptanoic Acids, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Laboratories, Hospital, Pyrimidines, Pyrroles, Secondary Prevention, Simvastatin, Sulfonamides

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