Editorial |
From the Departments of Medicine (J.R.C.) and Public Health Sciences (C.D.F.), Wake Forest University School of Medicine, Winston-Salem, NC.
Correspondence to Curt D. Furberg, MD, PhD, Department of Public Health Sciences, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1063. E-mail cfurberg@wfubmc.edu
Low density lipoprotein cholesterol (LDL-C)
is the appropriate focus of primary and secondary prevention of
coronary heart disease (CHD) in patients with
hypercholesterolemia. Basic investigation and
evidence from animal models and epidemiological studies lend robust
support to its role as a major risk factor for CHD.
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
reduce plasma concentrations of LDL-C and have consistently
shown substantial benefits in primary and secondary prevention.
However, although treatment has dramatically reduced the risk of
recurrent CHD in secondary prevention trials, it is becoming
increasingly evident that even reduction of LDL-C to 100 mg/dL may not
be adequate to restore the risk levels of such patients to the risk
levels of those individuals free of CHD. Despite mean on-treatment
LDL-C concentrations ranging from 97 to 113 mg/dL, recurrent CHD event
rates in 3 secondary prevention trials were all
2% per
year.1 2 3 The CHD event rate in the 40% subset of
participants in the Scandinavian Simvastatin Survival Study
who lowered their LDL-C levels to <100 mg/dL (mean 95 mg/dL) was also
2% per year.4 These event rates are unacceptably high,
and 2 approaches are being explored to determine whether there is room
for improvement: (1) more aggressive lowering of LDL-C and (2)
treatment of the "lipoprotein complex."
Although the first of these appears intuitively attractive,
careful examination of curves relating CHD event rates to on-treatment
LDL-C in the trials outlined above suggests an asymptotic relationship.
The CHD risk appears to "flatten out" at 2% per year for LDL-C
levels <120
This article has been cited by other articles:
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R. A. Kreisberg and A. Oberman Lipids and Atherosclerosis: Lessons Learned from Randomized Controlled Trials of Lipid Lowering and Other Relevant Studies J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 423 - 437. [Full Text] [PDF] |
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