EDITORIAL COMMENT
Lipid Levels in the Post-Acute
Coronary Syndrome Setting
Destabilizing Another Myth?*
Michael Miller, MD, FACC
Baltimore, Maryland
For many years, the proclamation that coronary heart disease
(CHD) was not attributable to traditional risk factors in up to
50% of cases (1,2) was finally submerged after careful and
detailed re-analysis (3,4). In this issue of the Journal, Pitt
et al. (5) take aim at another long-held notion: that clinically
significant alterations in lipids occur after an acute coronary
syndrome (ACS), thereby precluding meaningful interpre-
tation until well beyond hospital discharge.
See page 1440
Modifications of serum lipids after ACS have been
recognized for at least 50 years (6). They include reductions
in total cholesterol (TC), low-density lipoprotein cholesterol
(LDL-C), and high-density lipoprotein cholesterol (HDL-C)
in the range of 10% to 20%, with reciprocal increases in
triglycerides approximating 20% to 30%. These changes were
believed to commence approximately 24 h after presentation
and to last up to several months (7–11). Several mechanisms
accounting for these changes include the acute phase re-
sponse (12,13) associated with up-regulation of low-density
lipoprotein (LDL) receptor activity (14) and reduction in
several pivotal high-density lipoprotein (HDL) regulatory
proteins (15). In addition, stress-induced myocardial injury
and necrosis facilitates adrenergic mediated adipocyte lipol-
ysis leading to free fatty acid mobilization, enhanced hepatic
very-low-density lipoprotein (VLDL) secretion, triglyceride
(TG) elevation, and alteration in LDL and HDL particle
composition (16,17). In-hospital therapy and lifestyle changes
are additional contributors to post-ACS lipid changes. For
example, heparinization results in reduced concentrations of
TG and LDL-C owing to lipoprotein lipase (LPL)–mediated
hydrolysis of TG-rich lipoproteins and facilitated uptake of
cholesterol by the LDL receptor (18). Conversely, nonselective
beta-blockers may reduce HDL-C and increase TG by unop-
posed alpha-adrenergic–mediated suppression of hormone-
sensitive lipase (19). Additional contributors to lipid alterations
include nonspecific postural effects (20) and reductions in
saturated fat intake that may reduce LDL-C and HDL-C
levels (21). Based on these acute changes, the American
College of Cardiology/American Heart Association (ACC/
AHA) have supported a Class I recommendation for a fasting
lipid profile analysis to be obtained within 24 h of admission
for ACS (22).
The study by Pitt et al. (5) suggests that lipid levels
remain relatively stable during the initial 96 h after ACS
based on data from the LUNAR (Limiting UNdertreat-
ment of lipids in ACS with Rosuvastatin) study, a prospec-
tive trial comparing the efficacy of LDL-C lowering with 2
different statins (rosuvastatin and atorvastatin) after hospi-
talization for ACS. As part of the trial, lipid and lipoprotein
levels were assessed on 3 different occasions during the first
4 hospital days. Although fasting blood samples were not
mandated on the admission baseline test, subsequent sam-
ples collected on days 2 and 4 were in the fasting state. Five
hundred seven patients were evaluated, representing more
than twice the number of participants from the earlier
studies combined (7–11), and for which direct LDL-C
measurements and fasting TG levels were available. Overall,
the results indicated a similar trend of reduced TC, LDL-C,
and HDL-C between baseline and the day 2 sample.
However, these changes were small (2% to 5%) and short-
lived, with rebound increases observed by day 4. From a
clinical standpoint, these data provide reassurance that lipid
levels remain relatively stable within the first 96 h after
ACS. Unfortunately, what cannot be deduced from the
present study or its predecessors is the magnitude of LDL-C
reduction compared with the pre-ACS free-living state.
Because the most profound alterations in lipids and lipopro-
teins are proportional to the extent and severity of myocar-
dial necrosis (9), clinical trials such as LUNAR that gener-
ally exclude complicated patients (e.g., Killip class III/IV,
ventricular dysrhythmia) are also likely to underestimate the
potentially greater lipid alterations that may have otherwise
resulted with their inclusion. To this end, it is also not
surprising that older studies, especially those performed in
the pre-thrombolytic and pre-PCI era (6 –10), were associ-
ated with bigger lipid effects after ACS compared with more
recent studies that, in addition to the LUNAR study,
showed smaller changes in post-ACS lipids and/or quicker
reversion to baseline levels (14,23–24).
How should clinicians apply the results of the present
study to their practice? All patients presenting with ACS
deserve lipid and lipoprotein evaluation in the hospital. This
decision is not predicated on whether to institute in-patient
lipid-lowering therapy, as previously reflected by evidence-
based data supporting intensive LDL-C reduction post-
ACS (25). Rather it serves to reinforce the importance of
initiating lifestyle and therapeutic measures in-hospital to
*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the University of Maryland Medical Center, Division of Cardiology, Baltimore,
Maryland. Dr. Miller receives research grants and honoraria from AstraZeneca,
Merck–Schering-Plough, and Pfizer.
Journal of the American College of Cardiology Vol. 51, No. 15, 2008
© 2008 by the American College of Cardiology Foundation ISSN 0735-1097/08/$34.00
Published by Elsevier Inc. doi:10.1016/j.jacc.2007.12.039