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The Importance of HDL-Cholesterol in Risk Reduction of CHD
By Lawrence M. Prescott, Ph.D.
A large-scale meta-analysis of 17 landmark clinical trials of mono and
combination lipid interventions pointed out that changes in high density
lipoprotein-cholesterol (HDL-C) and HDL-C-inclusive parameters are the
strongest predictors of coronary heart disease (CHD) risk reduction in
lipid intervention trials, according to Richard Karas, M.D., Ph.D., in a
presentation at the American Heart Association Scientific Sessions 2004.
"Our analysis found that the effects on patients' HDL-C levels were
considerably better than the effect on patients' LDL-C levels in
predicting their risk of future heart disease," said Dr. Karas, Associate
Professor of Medicine, Division of Cardiology, and Director of Preventive
Cardiology, Tufts New England Medical Center, Boston, Massachusetts. "The
results should send a wake-up call to alert both healthcare providers and
patients to the importance of addressing HDL-C in addition to LDL-C."
The Scope of the Problem
The benefit of lipid lowering altering interventions has been well
documented in many clinical trials. While many of these trials are
generally considered LDL-lowering studies, the extent to which
intervention-induced changes in lipid parameters correlate with the
observed reduction in cardiovascular risk has not been studied. An
analysis was carried out, therefore, to determine the relative importance
of treatment-induced changes on specific lipid parameters in predicting
risk reduction with lipid-altering therapies.
A systematic review identified active treatment arms from 17 landmark,
randomized, clinical trials of mono or combination lipid values, including
HDL-C, as well as the incidence of clinical CHD in both treatment and
control arms. The meta-analysis included 44,170 patients who had a total
of 3,869 CHD events. Univariate and multivariate regression analyses were
used to assess the relationships of treatment-induced changes in lipids to
the observed risk reduction in CHD, defined as fatal or non-fatal
myocardial infarction (MI). The on-treatment percent change from baseline
in total cholesterol (TC), LDL-C, HDL-C, non-HDL-C, triglycerides (TG),
and TC/HDL ratio were correlated with the relative risk reduction in CHD.
The Importance of HDL-C in Risk Reduction
In univariate models, the rank order of R2 values was TC/HDL>HDL>non-HDL>TC>LDL>TG,
either as a curvilinear relationship or a linear relationship. Changes in
HDL-inclusive parameters such as TC/HDL, HDL, and non-HDL were
consistently better predictors of CHD risk reduction. The weakest
association was between the percent change in TG and CHD outcomes, with a
relatively moderate association between the percent change in LDL and
relative risk reduction in CHD.
In a multivariate model, only the percent change in HDL (p<0.001) and TC
(p=0.015) were independently predictive of relative risk reduction in CHD.
The relationships between percent change in LDL (p=0.1) and TG (p=0.06)
and relative risk reduction in CHD were of borderline significance.
"Raising good cholesterol levels demonstrated a nearly first order
relationship with event risk reduction, meaning that risk of heart attack
fell immediately and continuously with a steady increase in HDL-C level,"
Dr. Karas concluded. "The LDL-C showed a 'threshold effect,' where lipid
levels had to be improved considerably before having a large impact on
risk reduction."
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The author Lawrence M. Prescott, Ph.D., may be contacted via e-mail at
sprescott@aol.com.
Source: D&MD
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