Lipoprotein Particle Profile

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1 Lipoprotein Particle Profile 50% of people at risk for HEART DISEASE are not identified by routine testing. Why is LPP Testing The Most Comprehensive Risk Assessment? u Provides much more accurate cardiovascular risk assessment and treatment guidelines than conventional cholesterol testing u Detects all new NCEP risk factors, including Lp(a), RLP, HDL2b and small, dense LDL u Accurately measures the lipoprotein subgroups of VLDL, LDL and HDL u Helps identify the 50% of patients that are at risk for cardiovascular disease but have normal cholesterol levels Measures Particle Density & Number u Directly measures lipoprotein particles both number and density (which directly correlates to size) u Takes into account cholesterol-depleted and cholesterol-enriched patients which can mislead risk assessment u Enables clinician to treat atherogenic lipoprotein profiles before overt dyslipidemia becomes apparent Superior Technology u Separates lipoproteins by analytical ultracentrifugation, which is considered the CDC gold standard u Counts lipoprotein particles using proprietary technology u Uses a continuous gradient through the entire lipoprotein density range u Low end of gradient is g/ml for accurate VLDL results u Separation by analytical ultracentrifugation at 120,000 rpm Additional Risk Factor Measurements u Independent chemical assay of Lp(a) u Gives clinician overall cardiovascular lipoprotein particle profile with subgroups and inflammation risk assessment Easy-To-Understand Reporting u Lists all lipid-related metabolic syndrome traits u Graphical results are included with every report u Clinical suggestions with treatment recommendations on each report u Cumulative reporting available Easy Sample Collection u Complete test kit and transportation provided u Small sample size (less than 4 ml serum) u Quick turnaround (less than one week) u LPP is very cost effective and is covered by most insurances and medicare.

2 Atherosclerotic Plaque Formation SpectraCell s Lipoprotein Particle Profile (LPP ) identifies all the National Cholesterol Education Program s (NCEP) Lipoprotein Risk Factors. PLAQUE RUPTURES DUE TO INFLAMMATION Foam Cells Build Plaque Foam Cell 3 Lp(a) 5 2 LDL RLP DENSE LDL OXIDIZED LDL 1 HDL2b HDL3 ARTERIAL LUMEN MONOCYTE CELL DAMAGED MACROPHAGE CELL 4 ENDOTHELIUM CELL ARTERIAL INTIMA 1 2 Small, Dense LDL is three times more atherogenic than buoyant LDL due to the additional number of LDL particles per cholesterol equivalent and the rapid penetration of small LDL particles through the arterial endothelium. RLP (Remnant Lipoprotein) is readily scavenged by macrophage cells without having to be oxidized (like other LDL) and becomes a major component of plaque. 3 Lp(a) are small, dense LDL s and that are easily oxidized. Lp(a) is prothrombotic in many of the genetic variations. 4 5 HDL Removes Excess Lipids HDL2b is formed from HDL3 as it removes excess lipids. High HDL2b is an indicator of functional reverse cholesterol transport. LDL Oxidation is when LDL is oxidized in the intima of the vessel wall and is scavenged by macrophage cells to form foam cells. The foam cells are the building blocks of plaque. Antioxidants, measured by Spectrox, can retard LDL oxidation. The LPP test from SpectraCell Laboratories provides physicians with the actual LDL particle count, allowing healthcare providers to accurately determine and diagnose cardiovascular risk in their practice. Each patient shown below has the same LDL cholesterol of 125 mg/dl, but particles differ. (normal) (depleted) (enriched) (depleted)

3 LPP Sample Test Report - Page 1 SAMPLE

4 Clinical Interpretation Guide to the LPP Test Clinical Interpretation Guide to the LPP TM Test Step 1. Primary Risk Assessment Lipoprotein non-hdl particle numbers and other lipid and non-lipid risk factors may show a greater patient risk than a standard lipid panel and therefore, a greater LDL reduction than indicated by a standard lipid panel. Non-HDL lipoprotein particle numbers and/or Apo B-100 are measures of the number of atherogenic lipoprotein particles and are compliant with the recent consensus statement from the American Diabetes Association and the American College of Cardiology 1 stating that lipoprotein particle numbers are more predictive of CVD risk than cholesterol. Moderate to elevated triglycerides can cause the lipoproteins to be cholesterol depleted or triglyceride enriched and these patients will show a greater CVD risk from non-hdl particle numbers or Apo B-100 than from a standard lipid panel. This occurs in about 30% of the population. Step 2. Modify Risk Using Metabolic Syndrome Traits, Lp(a) and Inflammation Risk Markers Evaluate possible Metabolic Syndrome by combining the lipid traits from the LPP TM test with possible hypertension, obesity and high glucose. Three total traits is a diagnosis of Metabolic Syndrome and raises the CVD risk to the next level. Also check for insulin resistance using the LPP fasting insulin value. Take into account additional risk from elevated Lp(a) or inflammation markers such as hs-crp or Lp-PLA2 if ordered, in determining the final treatment goals. Also consider non-lipid risk factors such as hypertension, obesity, high glucose, smoking, family history and other medical history. The risk assessment and treatment goal from Step 1 should be adjusted in light of the presence of these additional Biomarkers and Risk Factors. A standard directly measured cholesterol Lipid Panel is presented at the bottom of the report for comparison to previously determined lipid results. Step 3. Determine Therapeutic Approach Based On the Lipid Subgroup Distribution, Lp(a) and Therapeutic Guidelines Using the risk level established in Step 2 and treatment goals from the NCEP guidelines, determine if VLDL, LDL subgroups, HDL subgroups and/or Lp(a) should be therapeutic targets. The LPP particle numbers by subgroup and Lp(a) each have a specific therapeutic approach that is most effective. Often, combination therapy is needed to address the different risk areas. A special HDL species enriched in Apo C-1 is atherogenic but displays health attributes 2. It is generally identified by high HDL>70mg/dL, high HDL 2b > 4000 nmol/l with a high HDL peak or hump extending into LDL IV region and low TG s < 70 mg/dl. Check for CVD development with a CIMT, a Coronary Calcium Score or other method to confirm. Refer to the LPP Therapeutic Guidelines for lipoprotein subgroup specific information. 1. Diabetes Care, Volume 31, Number 4, April Kwiterovich P., et al. JAMA 2005; 293(15): 1891

5 LPP Sample Test Report - Page 2 SAMPLE

6 Lipoprotein Particle Profile Testing Lipoprotein Abnormality Lifestyle Changes (diet & exercise) Statins Niacin Fibrates Oral Estrogens Resins Absorption Inhibitors Omega-3 s EPA & DHA Alcohol (moderate) LDL I & II Buoyant LDL III - Dense HDL 2b - Buoyant Therapeutic Beneficial Little or No Effect Negative Effect

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