Consensus and Recommendations for LDL-P

Brunzell et al. Diabetes Care (4): “Measurement of LDL cholesterol (the cholesterol within LDL particles) has been the standard approach to approximate LDL levels.” 2.“However, the cholesterol content of LDL particles varies from person to person and is influenced by metabolic abnormalities such as insulin resistance and hyperglycemia.” 3.“Hence, measurement of LDL cholesterol may not accurately reflect the true burden of atherogenic LDL particles, especially in those with the typical lipoprotein abnormalities of cardio-metabolic risk.” Recommendations from ADA/ACC Consensus Statement on Lipoprotein Management in Patients with Cardiometabolic Risk

Brunzell et al. Diabetes Care (4): “A more accurate way to capture the risk posed by LDL may be to measure the number of LDL particles directly using nuclear magnetic resonance (NMR).” 5.“Measurements of apoB or LDL particle number by NMR may more closely quantitate the atherogenic lipoprotein load. Some studies suggest that both are better indices of CVD risk than LDL cholesterol or non-HDL cholesterol and more reliable indexes of on-treatment residual CVD risk.” 6.“ApoB or LDL particle number also appear to be more discriminating measures of the adequacy of LDL lowering therapy than are LDL cholesterol or non-HDL cholesterol.”

National Lipid Association Expert Panel Recommendations

1.“Any measure of LDL-C, including the b-quantification reference method, suffers from the fact that measurement of the cholesterol component of LDL does not consistently reflect the concentration of LDL particles in serum/plasma.” 2.“Despite a high correlation, these markers are only modestly concordant, indicating that one cannot simply substitute for another in classifying patients into risk categories.” Contois, et al. Clinical Chemistry 2009;55: Position Statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices

3.“Importantly, on-treatment non HDL-C concentrations may not reflect residual risk associated with increased LDL particle number.” 4.“We believe that the medical decision cutpoints should be set so that the apoB and LDL-P cutpoints are equivalent to those for LDL-C in terms of population percentiles.” Contois, et al. Clinical Chemistry 2009;55: Position Statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices

“The National Lipid Association convened a panel of clinical experts to evaluate the use of selected biomarkers in clinical practice as either tools to improve risk assessment or as markers to adjust therapy once a decision to treat had been made.” “These panel recommendations are intended to provide practical advice to clinicians who wrestle with the challenges of identifying the patients who are most likely to benefit from therapy, or intensification of therapy, to provide the optimum protection from CV risk.” Davidson, et al. J Clin Lipidol 2011;5: Recommendations from the NLA Expert Panel on Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing Dr Basu and team- Please find attached revised version of your poster titled “Effects of Lidocaine 3% Gel Delivered Rectally in Anorectal Dysfunction Induced by Telaprevir Therapy in Chronic Hepatitis C: A Randomized, Placebo-Controlled Study” with your comments incorporated. As you are reviewing, please note that we have included several highlighted queries that we would appreciate your assistance in addressing. Please send any comments/answers to queries by end of day 1/30. Thank you for your time in this review, we look forward to your feedback. Thanks! Lisa

Specific Clinical Populations Considered: 1.Low risk (patients with 0-1 risk factors and < 5% 10-year CHD event risk on the basis of NCEPATP III Framingham risk scoring) 2.Intermediate risk (patients with 2 or more risk factors or 5%-20% 10- year CHD event risk on the basis of NCEPATP III Framingham risk scoring) 3.CHD or CHD equivalent (i.e., diabetes, atherosclerotic CV disease [CVD], or more than 20% 10-year CHD event risk by ATP III Framingham risk scoring) 4.Patients with a family history of premature CHD 5.Patients with CVD and recurrent events despite apparently ‘‘optimal’’ medical therapy Recommendations from the NLA Expert Panel on Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing Davidson, et al. J Clin Lipidol 2011;5:

Categories of recommendations for specific clinical populations under discussion : 1.Recommended for routine measurement; 2.Reasonable for many patients under discussion; 3.Consider in selected patients; 4.Not recommended Recommendations from the NLA Expert Panel on Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing Davidson, et al. J Clin Lipidol 2011;5:

2011 Recommendations from the NLA Expert Panel on Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing Summary of Recommendations for Measurement for Initial Clinical Assessment Davidson, et al. J Clin Lipidol 2011;5:

2011 Recommendations from the NLA Expert Panel on Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing Summary of Recommendations for Measurement for Initial Clinical Assessment “There is a substantial number of patients for whom LDL-C may not accurately reflect CVD risk, and data show that discordantly elevated LDL-P is more strongly associated with incident CVD risk than LDL-C.” Davidson, et al. J Clin Lipidol 2011;5:

2011 Recommendations from the NLA Expert Panel on Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing Summary of Recommendations for Measurement for Initial Clinical Assessment “When LDL-P is discordantly elevated, consideration should be given to initiating LDL lowering therapy.” Davidson, et al. J Clin Lipidol 2011;5:

2011 Recommendations from the NLA Expert Panel on Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing Summary of Recommendations for Measurement for On-Treatment Management Decisions Davidson, et al. J Clin Lipidol 2011;5:

2011 Recommendations from the NLA Expert Panel on Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing Summary of Recommendations for Measurement for On-Treatment Management Decisions “Use of LDL-P measurement is reasonable for many patients… to adjudicate the adequacy of LDL lowering therapy.” Davidson, et al. J Clin Lipidol 2011;5:

2011 Recommendations from the NLA Expert Panel on Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing Summary of Recommendations for Measurement for On-Treatment Management Decisions “When LDL-P is discordantly elevated, consideration should be given to intensifying LDL lowering therapy.” Davidson, et al. J Clin Lipidol 2011;5: