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Lipids 201. James Mold, M.D., M.P.H. LDL. Atherogenicity appears to be correlated with the number of LDL particles, not the total amount of LDL cholesterol Patients with Type 2 DM tend to have large numbers of smaller, denser LDL particles associated with Lp(a) total LDL may be near normal

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Lipids 201


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    1. Lipids 201 James Mold, M.D., M.P.H.

    2. LDL • Atherogenicity appears to be correlated with the number of LDL particles, not the total amount of LDL cholesterol • Patients with Type 2 DM tend to have large numbers of smaller, denser LDL particles associated with Lp(a) • total LDL may be near normal number X content = measured amount

    3. LDL Size Certainly Seems to Matter “The mean concentration of LDL cholesterol in those with type 2 diabetes is not significantly different from that in those individuals who do not have diabetes.” “However, qualitative changes in LDL cholesterol may be present. Patients with diabetes tend to have a higher proportion of smaller and denser LDL particles which are more susceptible to oxidation and may therefore increase the risk of cardiovascular events.” Diabetes Care 2004;27:S68

    4. 130 mg/dL 130 mg/dL LDL Cholesterol Balance 20+ years of studies: Patients with smaller LDL size have greater CHD risk at any given level of LDL-C. Lower risk Higher risk Large LDL (Pattern A) Small LDL (Pattern B) But they also have more particles!

    5. Small, Dense Low-Density Lipoprotein Particles as a Predictor of the Risk of Ischemic Heart Disease in Men • Prospective Results From the Quebec Cardiovascular Study • Circulation 1997;95:69-75 6.2 Risk of IHD 2.1 1.0 1.0 LDL particle number (apoB) LDL particle size

    6. Concordant with LDL-C Carotid IMT (microns) Q1 <1055 Q2 1055-1285 Q3 1285-1545 Q4 >1545 Carotid Atherosclerosis in MESA* LDL-C <100 mg/dL (n=1,425) n=32 Ptrend = 0.006 n=153 n=352 n=888 LDL Particle Number (nmol/L) *Adjusted for age, sex, race, hypertension, smoking, diabetes, TG and HDL-C

    7. Concordant with LDL-C Carotid Atherosclerosis in MESA* LDL-C = 100-118 mg/dL (n=1,362) Ptrend <0.001 n=143 n=371 n=499 Carotid IMT (microns) n=349 Q1 <1055 Q2 1055-1285 Q3 1285-1545 Q4 >1545 LDL Particle Number (nmol/L) *Adjusted for age, sex, race, hypertension, smoking, diabetes, TG and HDL-C

    8. Treatment • Statins lower total LDL but don’t change particle size • Niacin, fenofibrate, aspirin, exercise, and weight loss increase LDL particle size

    9. HDL • Not all HDLs are equally protective • There are 5 types (2a, 2b, 2c, 3a, and 3b) • HDL2b inhibits atherogenesis • HDL3b may actually promote atherogenesis

    10. Treatment • Exercise, smoking cessation • Niacin • Some statins raise HDL2 levels • Best statins for raising HDL2 are Crestor and Zocor. • Worst is Lipitor (lowers HDL2). • Aggressive LDL lowering reduces the impact of a low HDL2 or high HDL3

    11. VLDL • Transports triglycerides • Comes in various sizes • Larger VLDL particles (VLDL1,2)shift LDL to smaller, denser forms • Smaller, denser VLDL particles (VLDL3 are directly atherogenic

    12. Treatment • Low carb diet, exercise • Fibrates, niacin, statins, fish oil

    13. Total Cholesterol LDL VLDL HDL HDL2 Lp(a) VLDL1,2 IDL HDL3 VLDL3 LDL-R

    14. Effects of Various Medications

    15. Testing Currently available options are: • Measure amounts of various lipid subtypes and LP(a) (VAP – DLO, LabCorp) • Count the numbers of various LDL particles (NMR Lipoprofile Test – Labcorp)

    16. VAP Lipid Profile CPT: 83716, 84478 Cost: DLO $188 LabCorp $244

    17. V6 V5 V4 V3 V2 V1 IDL L3 L2 L1 H5 H4 H3 H2 H1 Subclass Particle Numbers (nmol/L) Weighted Ave VLDL, LDL, HDL Particle Sizes (nm) NMR Lipoprotein Particle Number Analysis Large VLDL Medium VLDL Small VLDL IDL Large LDL Small LDL Large HDL Med HDL Small HDL CPT: 82465, 83704 Cost: Labcorp $167 Clin Lab 2002;48:171-80

    18. Addendum DLO now offers a Lipid Panel with reflex direct measurement of LDL when triglycerides are elevated “Lipid Panel W/REFL LDL”