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

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ecurrent stroke compared with the subgroup of patients with the lowest levels of Lp-PLA2. However, the reviewed studies overestimated the magnitude of the predictive ability of the PLAC test by subdividing the study populations into 3 or 4 subgroups and comparing only those patients who have the highest and lowest levels of Lp-PLA2. A study by Wallach in 2007 suggested that an elevated Lp- PLA2 with low LDL-C increases risk of heart disease by two times and that increased Lp-PLA2 with high CRP increases risk of heart disease by three times. Davidson et al (2008), in an expert consensus panel, evaluated how Lp-PLA2 might be used for determining CVD risk and concluded that it is not recommended for the general populations or persons who are at lower risk. However, the panel does recommend testing in moderate- or high-risk persons to further stratify risk. The 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults designated Lp-PLA2 a Class IIb indication, meaning the benefit outweighed the risk and the procedure may be considered. However, the guideline did not include the Lp-PLA2 Studies Collaboration (LSC), a meta-analysis of 32 prospective studies which found that Lp-PLA2 levels remained an important risk factor for heart disease even after adjusting for existing risk factors such as high cholesterol and high blood pressure. This information can probably increase the current IIb recommendation to a higher level designation. As a highly specific biomarker for vascular inflammation, elevated Lp-PLA2 levels should prompt consideration of increasing the cardiovascular risk category from moderate to high or high to very high risk. Because intensification of lifestyle changes and low-density lipoprotein (LDL) cholesterol lowering is beneficial in high-risk patients, regardless of baseline LDL cholesterol levels, consideration should be given to lowering the LDL cholesterol target by 30 mg/dL in patients with high levels of Lp- PLA2. Lp-PLA2 is currently recommended as a diagnostic test for vascular inflammation to better identify patients at high or very high risk who will benefit from intensification of lipid-modifying therapies. However, it is not presently known whether lowering Lp-PLA2 levels will decrease the incidence of coronary disease or stroke and improve clinical health outcomes. G. Vertical Auto Profile (VAP). The VAP (Vertical Auto Profile) Cholesterol Test was developed in 2006 by the privately held Atherotech, Inc., a cardio-diagnostic company. VAP utilizes the patented vertical density gradient ultracentrifugation method. The VAP test claims it detects a higher number of lipid abnormalities because it reports 15 different tests compared to four in the standard lipid test. It measures direct low-density lipoprotein (LDL) which is unaffected by triglycerides. It is the only available test that meets the new American Diabetes Association and American College of Cardiology (ADA-ACC) consensus guidelines because it reports all three measurements including apo B in addition to LDL and non-HDL in high-risk patients. The VAP provides LDL size phenotypes (A, B or AB) which represent either the small, dangerous particles, or the larger, more benign particles. It measures the HDL subtypes (HDL1 or HDL2), HDL2 being more beneficial. It also measures Lp(a) cholesterol content (see discussion above). It also provides non-HDL cholesterol, Triglycerides (TG), Intermediate Density Lipoprotein (IDL) cholesterol, and “real” LDL cholesterol values. A study by Maki et al published in January 2012 reported that the atherogenic lipoprotein phenotype identified by the VAP Test, which included higher TG-rich lipoprotein cholesterol, lower HDL-C and HDL-C subfractions, and greater proportion of LDL-C carried by more dense LDL particles was more strongly associated with carotid intimal media thickening (CIMT) progression. These atherogenic phenotypes may have an important role in the initiation and progression of early atherosclerosis. However, at this time, there is no available RCT in the peer-reviewed medical literature to support the efficacy of the VAP (Vertical Auto Profile) Cholesterol Test or determine if outcomes are equal to or better than testing currently being used. Comprehensive Lipid Profile Testing in the Evaluation of Cardiovascular Disease Page 10 of 14
H. LDL Particle Number. LDL particle number is an emerging area of research. It can be measured by nuclear magnetic resonance (NMR), ultracentrifugation, and high pressure liquid chromatography (HPLC). In theory, small size LDL particles are more atherogenic as they are easily deposited into the coronary artery intima compared to large LDL particles. In addition, many studies have shown that individuals with predominantly small LDL particles (pattern B) experience greater CHD risk. However, the Multi-Ethnic Study of Atherosclerosis (MESA) multivariate analyses showed that both small and large LDL were strongly associated with subclinical atherosclerosis. The VA-HIT trial also showed both small and large particles to be significantly related to CHD events. These two studies seem to suggest that the association between small LDL and CVD may be due to the increased number of LDL particles. The more accurate method in measuring LDL particle number has been by NMR. With this method, the LDL particle number has consistently been shown to be a strong, independent predictor of CHD. The utility of NMR particle number testing is, however, limited by its availability and its relatively high cost. Also, there is a lack of independent data confirming the accuracy of the method and whether its CHD predictive power can be consistent across various ethnicities, ages, and conditions that affect lipid metabolism. U.S. FOOD AND DRUG ADMINISTRATION (FDA) The US Food and Drug Administration (FDA) has approved an immunoturbidimetric test for the quantitative determination of apo A-I and apo B in serum and plasma. In addition, the FDA has approved the product Apolipoprotein Control Serum CHD for use as a quality control material to monitor accuracy and precision of human serum protein assays, such as tests for the quantitative immunochemical determination of apo A-I and apo B using RID, the Behring Nephelometer Systems, and the TurbiTime System. The diaDexus PLAC® Test received initial 510(k) approval (K030477) from the FDA on July 18, 2003. It was approved at that time as an enzyme immunoassay for the quantitative determination of Lp-PLA2 in human plasma, to be used in conjunction with clinical evaluation and patient risk assessment as an aid in predicting risk for coronary heart disease. On June 15, 2005, a second 510(k) approval (K050523) was issued for the PLAC Test for the same indications but also incorporating approval for prediction of risk of ischemic stroke associated with atherosclerosis. The FDA has approved a number of devices and reagents for testing blood levels of Lp(a). However, these approvals neither imply that the tests used for measuring Lp(a) are standardized nor that they are of value for coronary heart disease (CHD) risk prediction and patient management. LDL subclass testing, apoE testing, homocysteine testing and HDL subclass testing must be performed in accordance with the quality standard established in 1988 by the Clinical Laboratory Improvement Amendments (CLIA). Comprehensive Lipid Profile Testing in the Evaluation of Cardiovascular Disease Page 11 of 14
Page 1 and 2: COMPREHENSIVE LIPID PROFILE TESTING
Page 3 and 4: Indications and Limitations of Cove
Page 5 and 6: is well known that CAD alone is the
Page 7 and 8: Apolipoproteins are proteins on the
Page 9: However, a recent study questioned
Page 13 and 14: Pearson TA, et al: Markers of infla

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