CAR039 Comprehensive Lipid Profile Testing in the Evaluation of ...
CAR039 Comprehensive Lipid Profile Testing in the Evaluation of ...
CAR039 Comprehensive Lipid Profile Testing in the Evaluation of ...
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obust. Among <strong>the</strong> earliest trials <strong>in</strong>clude <strong>the</strong> Fram<strong>in</strong>gham Heart Study, <strong>the</strong> Multiple Risk Factor<br />
Intervention Trial (MRFIT), and <strong>the</strong> <strong>Lipid</strong> Research Cl<strong>in</strong>ics (LRC) trials which established that<br />
lower<strong>in</strong>g LDL cholesterol <strong>in</strong> patients with multiple cardiovascular risk factors lowers coronary heart<br />
disease (CHD) event rates.<br />
B. HDL. The most important function <strong>of</strong> HDL-C is reverse cholesterol transport. The data <strong>in</strong>dicates<br />
that HDL cholesterol levels are strong <strong>in</strong>verse predictors <strong>of</strong> CHD events. Randomized <strong>in</strong>tervention<br />
studies have demonstrated significant <strong>in</strong>hibition <strong>of</strong> a<strong>the</strong>rosclerosis and/or improvement <strong>in</strong><br />
cardiovascular event rates <strong>in</strong> treatments that <strong>in</strong>crease HDL-cholesterol. The Veterans Adm<strong>in</strong>istration<br />
HDL Intervention Trial (VA-HIT) trial demonstrated <strong>the</strong> benefits <strong>of</strong> Gemfibrozil <strong>in</strong> patients with low<br />
HDL levels with CHD. The HDL A<strong>the</strong>rosclerosis Treatment Study (HATS) trial demonstrated a<br />
reduction <strong>in</strong> major cardiovascular events <strong>of</strong> 90% vs. placebo <strong>in</strong> patients randomized to nicot<strong>in</strong>ic acid<br />
and Simvastat<strong>in</strong>. In addition, patients <strong>in</strong> <strong>the</strong> Coronary Drug Project benefited from a significant<br />
reduction <strong>in</strong> mortality after 15 years, 9 years after <strong>the</strong> trial ended. However, it has been difficult to<br />
determ<strong>in</strong>e whe<strong>the</strong>r rais<strong>in</strong>g HDL cholesterol <strong>in</strong>dependently reduces CVD events because <strong>in</strong>terventions<br />
that raise HDL also affect <strong>the</strong> concentration <strong>of</strong> o<strong>the</strong>r lipoprote<strong>in</strong>s. The NCEP report states that<br />
although <strong>the</strong> potential benefit <strong>of</strong> HDL-rais<strong>in</strong>g <strong>the</strong>rapy has evoked considerable <strong>in</strong>terest, "current<br />
documentation <strong>of</strong> risk reduction through controlled cl<strong>in</strong>ical trials is not sufficient to warrant sett<strong>in</strong>g a<br />
specific goal value for rais<strong>in</strong>g HDL-C." The AIM-High trial's purpose was to determ<strong>in</strong>e if, <strong>in</strong> <strong>the</strong><br />
sett<strong>in</strong>g <strong>of</strong> well-treated LDL and low HDL, <strong>the</strong>re was an <strong>in</strong>cremental benefit <strong>of</strong> add<strong>in</strong>g extended-release<br />
niac<strong>in</strong>. The study was halted prematurely by <strong>the</strong> FDA as it met <strong>the</strong> criterion <strong>of</strong> “futility”. The<br />
evidence to correct low HDL-C <strong>in</strong> addition to reduc<strong>in</strong>g LDL-C <strong>the</strong>refore awaits support from a larger<br />
randomized controlled trial, HPS-2-THRIVE, which should help guide cl<strong>in</strong>ical decision as to <strong>the</strong><br />
benefit <strong>of</strong> rais<strong>in</strong>g HDL.<br />
C. Triglycerides, <strong>in</strong> <strong>the</strong> fast<strong>in</strong>g state, are primarily found <strong>in</strong> VLDL. Triglycerides are <strong>the</strong>refore used as<br />
a surrogate measure <strong>of</strong> VLDL. Because triglycerides are highly l<strong>in</strong>ked to abnormalities <strong>in</strong> HDL and<br />
LDL, triglycerides are <strong>of</strong>ten not an <strong>in</strong>dependent predictor <strong>in</strong> multivariate analyses. There has been no<br />
cl<strong>in</strong>ical trial establish<strong>in</strong>g that lower<strong>in</strong>g triglycerides <strong>in</strong> <strong>in</strong>dividuals leads to lower CHD event rates<br />
when adjusted for HDL cholesterol.<br />
D. Non-HDL. Non-HDL cholesterol <strong>in</strong>cludes all lipoprote<strong>in</strong>s that conta<strong>in</strong> apo B. The ATP III<br />
guidel<strong>in</strong>es suggest non-HDL as a secondary target <strong>of</strong> <strong>the</strong>rapy <strong>in</strong> patients with high triglycerides, after<br />
target<strong>in</strong>g LDL cholesterol levels. The targeted level for non-HDL cholesterol is <strong>the</strong> LDL cholesterol<br />
target plus 30. Some authors advocate that measur<strong>in</strong>g non-HDL cholesterol is more practical than<br />
directly measur<strong>in</strong>g apo B and is predictive <strong>of</strong> heart disease <strong>in</strong> <strong>in</strong>dividuals who have high triglycerides<br />
(see discussion on apo B below). Because many studies have demonstrated non-HDL's superiority <strong>in</strong><br />
predict<strong>in</strong>g CHD risk over LDL cholesterol, its ease <strong>of</strong> calculation from non fast<strong>in</strong>g samples (total<br />
cholesterol-HDL), as well as its lack <strong>of</strong> additional expense <strong>in</strong> patients already gett<strong>in</strong>g lipid panel<br />
measurements, a consensus statement from <strong>the</strong> American Diabetes Association and American College<br />
<strong>of</strong> Cardiology Foundation (Brunzell, et al., 2008) recommend <strong>the</strong> calculation <strong>of</strong> non-HDL cholesterol<br />
<strong>in</strong> cardio-metabolic risk <strong>in</strong>dividuals with low to moderate LDL levels.<br />
II. ADVANCED LABORATORY TESTS<br />
A. Apolipoprote<strong>in</strong>s. Because cholesterol is <strong>in</strong>soluble <strong>in</strong> blood, cholesterol is carried by lipoprote<strong>in</strong>s.<br />
<strong>Comprehensive</strong> <strong>Lipid</strong> <strong>Pr<strong>of</strong>ile</strong> <strong>Test<strong>in</strong>g</strong> <strong>in</strong> <strong>the</strong> <strong>Evaluation</strong> <strong>of</strong> Cardiovascular Disease Page 6 <strong>of</strong> 14