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NMR Lipoprofile : More than LDL -P

NMR Lipoprofile : More than LDL -P. Tara Dall, MD, FNLA Advanced Lipidology Delafield, Wisconsin Diplomate , American Board of Clinical Lipidology www.advlip.com. Weight of Evidence LDL-P more predictive than LDL-C. 213 NMR related papers published to Date.

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NMR Lipoprofile : More than LDL -P

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  1. NMR Lipoprofile:More than LDL -P Tara Dall, MD, FNLA Advanced Lipidology Delafield, Wisconsin Diplomate, American Board of Clinical Lipidology www.advlip.com

  2. Weight of Evidence LDL-P more predictive than LDL-C 213 NMR related papers published to Date

  3. LDL-P and LDL-C Discordance in MESA CVD Event Rates in Subgroups with Low LDL Residual Risk Otvos et al. J ClinLipidol 2011;5:105-13

  4. LDL-P and LDL-C Discordance in MESA CVD Event Rates in Subgroups with Low LDL Discorcordant High LDL-P Residual Risk Concordant Discorcordant Low LDL-P Need Additional LDL-C Lowering? Otvos et al. J ClinLipidol 2011;5:105-13

  5. Clinical Application

  6. 40 yr old female Primary prevention LDL –C 171 • Wt 147 lbs Ht 65.6 BMI 24 • Waist 33 inches • BP 100/60 • PMH: hypothyroid stable nl TSH • FH: no premature CAD • SH: nonsmoker, healthy diet, exercises 150 min/week

  7. Initial Presentation40 yr old female Primary prevention LDL –C 171 LDL-P 1267 (optimal <1300) Sm LDL-P <90 LDL-C 171 HDL-C 82 TG 113 Total Chol 276 Disconnect high LDL-C but low LDL -P

  8. Population Equivalent Cutpoints for Alternate LDL Measures (LDL-C, Measured Apo B and NMR LDL-P) LDL_C LDL-P 1 Contois, et al. Clinical Chemistry 2009;55:407-419 2 Cromwell WC. Clinical Challenges in Lipid Disorders. Oxford:Clinical Publishing, 2008:249-259.

  9. 2 New Patient referralsSecondary Prevention 3/2011 • Both patients recent Myocardial Infarction referred for lipid treatment and work up genetic etiology • Both patients on Moderate dose stain at time NMR drawn

  10. 53 yr Male BMI 29, 122/83 Total Chol143 LDL-C 57 HDL-C 43 TG 152 Non HDL-C 100 LDL particle # LDL-P 1835 58 yr Male BMI 29, BP 122/78 Total chol 121 LDL-C 60 HDL c 45 TG 81 Non HDL-C 76 LDL particle # LDL-P 1006 2 Men Secondary Prevention on Moderate Dose Statin post MI

  11. Cholesterol per particle increases with: • niacin • fibrates • pioglitazone • omega 3 FAs • exercise • low carb diet • Cholesterol per particle decreases with: • statins • statin + ezetimibe • estrogen replacement therapy • low fat, high carb diet LDL-C More LDL-P More Treatments that Alter the Cholesterol Content of LDL Change LDL-C and LDL-P Differentially

  12. Beyond LDL: Combination TherapyStatinvsStatin/Niacin FATS10 YR WOSCOPS 4S CARE HPS FATS HATS 0 -10 -20 -24 -30 -25 -31 -34 -40 Percent -50 -60 -70 -80 -80 -90 -90 -95 -100 Reduction in CV Events Brown BG, et al. N Engl J Med. 2001;345:1583-1592.

  13. Same Day 2 Consults Completely different decision making based on NMR results

  14. NMR lipoprofile Beyond LDL –P ….

  15. Results From the Insulin Resistance Atherosclerosis Study NMR Lipoprotein Particle Concentrations In Normal Glucose Tolerance (NGT), Impaired Glucose Tolerance (IGT), Diabetes (DM) Subjects Goff, Metabolism 2005;54:264-70

  16. Women’s Health Study Adjusted hazard ratios for the association of lipoprotein measure with incident type 2 diabetes in quintiles 1 through 5 Mora et al. 2010. Diabetes

  17. Insulin Resistance Possibly years before Diabetes diagnosis Presents with abnormal Glucose IR SCORE >45 abnormal

  18. 2008 1994 2000 2008 1994 2000 No Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0% Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes Obesity (BMI ≥30 kg/m2) Diabetes No Data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% >9.0% CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics

  19. Low prevalence rate (<4%) Medium prevalence rate (4–8%) High prevalence rate (≥8%) 40 +43% Diabetes: A global pandemic GlobalPrevalence 438m in 2030 (+54%) 55m Europe North America 66m+20% 37m 53m +43% 285m in 2010 South-east Asia 27m 77m 59m Eastern Mediterranean and Middle East 113m +47% 52m +93% 101m +71% Western Pacific South and Central America Africa 18 m 12m 30m +67% 24m+100% Source: IDF Diabetes Atlas 2010. www.diabetesatlas.org/map. Accessed 7 Sept 2010

  20. Time Course of the Pathogenesis of Type 2 Diabetes Diabetes diagnosis

  21. Medications for Prediabetes • No medications are U.S. FDA approved to prevent progression to diabetes • Research has shown that metformin and acarbose seem promising at preventing progression from prediabetes to diabetes • Acarbose not in ADA guidelines – use should be case by case • Consider using these in high risk patients (such as people with CV disease) • Metformin has also been shown to reduce the incidence of diabetes in overweight and obese non-diabetic patients Diabetes Care. 1999;22:623–634 Chaisson JL, et al. Lancet. 2002;359:2072–2077 Andreadis EA, et al; Exp ClinEndocrinol Diabetes. 2008 Dec 3.

  22. UKPDS 33 / 34: Effect of intensive glucose control on microvascular and macrovascular events *Any diabetes-related endpoint: sudden death, death from hyperglycemia or hypoglycemia, fata l or non-fatal MI, angina, heart failure, stroke, renal failure, amputation, vitreous hemorrhage, retinopathy, blindness, cataract Brown et al, Nat Rev Cardiol 2010;7:369-375

  23. UKPDS :Ten-year follow-up of intensive glucose control in type 2 diabetes Holman RR, Paul SJ, Bethel MA, et al. N Engl J Med 2008

  24. Meta-analysis 40 Randomized Controlled Trials • Patients with type 2 diabetes may have a lower risk of cardiovascular death when treated with metformin • 26% Relative risk reduction in cardiovascular mortality with Metformin compared with other drugs or placebo AND IT IS VERY INEXPENSIVE THERAPY Selvin E, et al " Arch Intern Med 2008; 168: 2070-2080.

  25. Case Study Application NMR defined Insulin resistance

  26. 45 yr Female Dyslipidemia • Excellent diet (low glycemic) and exercises daily • FH: no premature CAD, Diabetes mother and mgma • Maximized TLC and dyslipidemia persists

  27. 45 yr Female Dyslipidemia max TLC • Lipids • Total Cholesterol 250 • LDL-C 150 • HDL-C 56 • Triglycerides 220 • Non HDL C 194 • Fasting Glucose 100 • HgAIC 5.6 • hsCRP 3 • BP 120/82 • BMI 25

  28. AHA CVD Prevention Guidelines for Women 2011 Criteria Risk Status Cigarette smoking SBP ≥ 120 mm Hg, DBP ≥ 80 mm Hg or treated HTN TC ≥ 200 mg/dL, HDL-C < 50 mg/dL or treated dyslipidemia Obesity, particularly central adiposity Poor diet Physical inactivity Family history of premature CVD occurring in first degree relatives In men < 55 y of age or in women < 65 y of age Metabolic syndrome Poor exercise capacity on treatment on treadmill test and/or abnormal heart rate recovery after stopping exercise Systemic autoimmune collagen vascular disease (eg, lupus, rheumatoid arthritis) History of preeclampsia, gestational diabetes or pregnancy-induced hypertension At risk (≥ 1 major risk factor[s] Mosca, L. et al. Circulation 2011;123:

  29. AHA CVD Prevention Guidelines for Women Clinical Recommendations Major Risk Factor Interventions • Lipids; Pharmacotherapy for LDL-C lowering: other at- risk women • LDL-C lowering therapy with lifestyle therapy is useful if LDL-C is ≥ 130 mg/dL, there are multiple risk factors, and the 10-y absolute risk is 10-20% (Class I; Level of Evidence B) • LDL-C lowering therapy with lifestyle therapy is useful if LDL-C is ≥ 160 mg/dL, there are multiple risk factors, even if the 10-y absolute risk is <10% (Class I; Level of Evidence B) • LDL-C lowering therapy with lifestyle therapy is useful if LDL-C is 190 mg/dL, regardless of the presence or absence of other risk factors (Class I; Level of Evidence B) Mosca, L. et al. Circulation 2011;123:

  30. 45 yr Female Dyslipidemia max TLC LDL-P 2552 (very high) Sm LDL-P 1732 (very high ) LDL-C 150 HDL-C 56 TG 220 Total Chol 250 Non HDL-C 194 IR SCORE 65 (abnormal >45) HgAIC 5.6, Glucose normal

  31. Treatment options ?LDL-P 2552, LDL-C 150, TG 220 • Statin • Niaspan • Fibrate • Combination • Metformin • Pioglitazone • Others

  32. 2 month follow up • LDL-P 1440 (1068 pt drop) • Small LDL-P 592 (1140 pt drop) • What intervention caused this drop? • Metformin ER 1500 mg/day • 5 pound weight loss

  33. Other lab changes • LDL-C 147 (150) • TG 99 (220) • HDL 62 (56) • hsCRP 1 (3) • IR Score 42 (65)

  34. Metformin an easy sell… • You lose weight • LDL P decreases • Triglycerides decrease • HDL may increase • Shown to prevent progression to diabetes • Cardiovascular mortality benefit • Pregnancy Category B • And it’s a very inexpensive generic drug

  35. Conclusions: LDL-P (via NMR) for Risk Assessment Primary Prevention: risk stratify more accurately, target therapy appropriately Avoid overtreatment of high LDL –C when LDL-P optimal Pediatric patients : better assess who should be treated more aggressively with statins

  36. Risk Management Identify Metabolic syndrome/Insulin resistance before traditional tests become abnormal Its our “window into Diabetes” Treating this common secondary cause may prevent need for lifelong lipid lowering therapy NMR clinical benefits beyond LDL–P

  37. Questions?taradall@advlip.comwww.advlip.com

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