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Advanced Lipid testing for the Assessment of Cardiac Risk

This article discusses the limitations of LDL-C as a predictor of cardiac risk and explores the use of advanced lipid testing, such as Apo.B and LDL particle concentration, for a more accurate assessment of cardiovascular risk.

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Advanced Lipid testing for the Assessment of Cardiac Risk

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  1. Advanced Lipid testing for the Assessment of Cardiac Risk Tara Dall, MD Advanced Lipidology Delafield, Wisconsin Diplomate, American Board of Clinical Lipidology

  2. Is Lowering LDL-C Enough? • Despite on-therapy LDL-C <80 mg/dL, a significant number of patients still have events1,2 • Major statin trials consistently show an approximate 25%–40% risk reduction for cardiovascular events, regardless of baseline LDL-C levels3,4 • Despite LDL-C lowering, residual risk remains high for at least 2 years following the index event, with about two thirds of CHD events not avoided1 • There is a great need for further reducing cardiovascular risk, as 65%-70% of major cardiac events still occur5 CHD = coronary heart disease. 1. Cannon CP, et al. N Engl J Med. 2004;350:1495-1504; 2. de Lemos JA, et al. JAMA. 2004;292:1307-1316; 3. LaRosa J, et al. JAMA. 1999;282:2340-2346; 4. HPS Collaborative Group. Lancet. 2002;360:7-22; 5. Assmann G, Gotto AM Jr. Circulation. 2004;109(suppl III):8-14.

  3. Atherogenic Cholesterol and Lipoproteins • NonHDL-C = [Total-C] minus [HDL-C] • Can be accurately measured in nonfasting state • Apo B concentration represents total number of lipoprotein particles in LDL + IDL + VLDL • This may be called “non-HDL” cholesterol or “atherogenic cholesterol” • All apo B-containing lipoproteins may truly possess similar atherogenic potential? Grundy, et al, Circulation. 1997;95:1-4

  4. Measures of Atherogenic LipoproteinsNon HDL = Apo B = LDL particle Concentration (NMR) >90 % Apo B is on LDL

  5. Up to 70% More Particles 100 mg/dL 100 mg/dL Large LDL Small LDL Cholesterol Balance Small LDL Particles Contain Less Cholesterol Than Large LDL Particles

  6. Up to 40% More Particles 100 mg/dL 100 mg/dL Normal Cholesterol Per Particle Less Cholesterol Per Particle Cholesterol Balance Even LDL Particles of the Same Size can Differ in Cholesterol Content

  7. LDL-P (NMR) vs LDL-C Prospective CVD Outcome Studies MESA & Framingham * Independent predictors in multivariate models adjusted for lipids

  8. 40 80 120 160 200 240 280 High Triglycerides Are Associated With LDL Subclass Pattern B 100 Pattern A 80 60 Cumulative Percent Pattern B 40 20 0 TGs (mg/dL) LDL=low-density lipoprotein; TG=triglyceride. Austin MA, King MC, Vranizan KM, Krauss RM. Circulation. 1990;82:495-506.

  9. CHD Event Associations of NMR LDL Particle Number (LDL-P) versus LDL Cholesterol (LDL-C)

  10. Advanced Lipoprotein testing • Berkeley Heartlab, Quest • Particle size, Apo B • Liposcience NMR • Subparticle size, LDL particle concentration • Atherotech VAP • Subparticle cholesterol content

  11. Conclusions • Non HDL-C , Apo B, LDL particle conc improve risk assessment compared to LDL-C • Non HDL-C and Apo B may be better than LDL-C for assessing optimal lipid therapy particulary in patients with high TG • Non HDL-C should be included in the written lab reports by all labs • Achieving Non HDL-C targets in clinical practice will require more intensive therapy than currently practiced

  12. Treatment Goals for LDL-C, Non–HDL-C, and Apo B Grundy SM. Circulation 2002;106:2526–2529.

  13. Linear Regression of Non-HDL-C vs Apo B On statin: Achieving target apo B <90 mg/dL requires lower non-HDL-C Ballantyne CM et al. J Am Coll Cardiol 2008;52:626-632.

  14. Clinical Cutpoints for LDL Percentile: 20th 50th 80th Optimal High LDL Cholesterol Percent of Subjects Framingham Offspring 70 100 130 160 190 220 250 mg/dL LDL Particle Number Percent of Subjects MESA 700 1000 1300 1600 1900 2200 2500 nmol/L

  15. LDL Particle Number Goals Using the same approach to risk assessment and management outlined by ATP III, percentile-equivalent LDL particle number goals are defined as follows:

  16. Primary Prevention High-risk history (family) Isolated lipid abnormalities High triglyceride Low HDL cholesterol Assess “residual risk” near NCEP values Metabolic syndrome Diabetes Secondary Prevention Few or no modifiable risk factors Assess “residual risk” near NCEP goal Recurrent events Diabetes Metabolic syndrome Candidates for Quantitative Lipoprotein Testing

  17. Treatment Considerations Combination therapy (statin + other agent[s]) may be necessary to achieve both goals. Combination agents which increase LDL size (niacin or fibrates) generally lower LDL-P more than LDL-C.

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