CAR039 Comprehensive Lipid Profile Testing in the Evaluation of ...

obust. Among the earliest trials include the Framingham Heart Study, the Multiple Risk Factor
Intervention Trial (MRFIT), and the Lipid Research Clinics (LRC) trials which established that
lowering LDL cholesterol in patients with multiple cardiovascular risk factors lowers coronary heart
disease (CHD) event rates.
B. HDL. The most important function of HDL-C is reverse cholesterol transport. The data indicates
that HDL cholesterol levels are strong inverse predictors of CHD events. Randomized intervention
studies have demonstrated significant inhibition of atherosclerosis and/or improvement in
cardiovascular event rates in treatments that increase HDL-cholesterol. The Veterans Administration
HDL Intervention Trial (VA-HIT) trial demonstrated the benefits of Gemfibrozil in patients with low
HDL levels with CHD. The HDL Atherosclerosis Treatment Study (HATS) trial demonstrated a
reduction in major cardiovascular events of 90% vs. placebo in patients randomized to nicotinic acid
and Simvastatin. In addition, patients in the Coronary Drug Project benefited from a significant
reduction in mortality after 15 years, 9 years after the trial ended. However, it has been difficult to
determine whether raising HDL cholesterol independently reduces CVD events because interventions
that raise HDL also affect the concentration of other lipoproteins. The NCEP report states that
although the potential benefit of HDL-raising therapy has evoked considerable interest, "current
documentation of risk reduction through controlled clinical trials is not sufficient to warrant setting a
specific goal value for raising HDL-C." The AIM-High trial's purpose was to determine if, in the
setting of well-treated LDL and low HDL, there was an incremental benefit of adding extended-release
niacin. The study was halted prematurely by the FDA as it met the criterion of “futility”. The
evidence to correct low HDL-C in addition to reducing LDL-C therefore awaits support from a larger
randomized controlled trial, HPS-2-THRIVE, which should help guide clinical decision as to the
benefit of raising HDL.
C. Triglycerides, in the fasting state, are primarily found in VLDL. Triglycerides are therefore used as
a surrogate measure of VLDL. Because triglycerides are highly linked to abnormalities in HDL and
LDL, triglycerides are often not an independent predictor in multivariate analyses. There has been no
clinical trial establishing that lowering triglycerides in individuals leads to lower CHD event rates
when adjusted for HDL cholesterol.
D. Non-HDL. Non-HDL cholesterol includes all lipoproteins that contain apo B. The ATP III
guidelines suggest non-HDL as a secondary target of therapy in patients with high triglycerides, after
targeting LDL cholesterol levels. The targeted level for non-HDL cholesterol is the LDL cholesterol
target plus 30. Some authors advocate that measuring non-HDL cholesterol is more practical than
directly measuring apo B and is predictive of heart disease in individuals who have high triglycerides
(see discussion on apo B below). Because many studies have demonstrated non-HDL's superiority in
predicting CHD risk over LDL cholesterol, its ease of calculation from non fasting samples (total
cholesterol-HDL), as well as its lack of additional expense in patients already getting lipid panel
measurements, a consensus statement from the American Diabetes Association and American College
of Cardiology Foundation (Brunzell, et al., 2008) recommend the calculation of non-HDL cholesterol
in cardio-metabolic risk individuals with low to moderate LDL levels.
II. ADVANCED LABORATORY TESTS
A. Apolipoproteins. Because cholesterol is insoluble in blood, cholesterol is carried by lipoproteins.
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