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Metabolic Syndrome and Dyslipidemia: Effective Strategies for Lipid Management

Metabolic Syndrome and Dyslipidemia: Effective Strategies for Lipid Management. Peter W. F. Wilson, M.D. Emory University School of Medicine. Outline Insulin Resistant Patients Lipids and CVD Risk . Pathophysiology Observational Studies Clinical Trials Specific Medications

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Metabolic Syndrome and Dyslipidemia: Effective Strategies for Lipid Management

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  1. Metabolic Syndrome and Dyslipidemia:Effective Strategies for LipidManagement Peter W. F. Wilson, M.D. Emory University School of Medicine

  2. OutlineInsulin Resistant PatientsLipids and CVD Risk • Pathophysiology • Observational Studies • Clinical Trials • Specific Medications • Multivariable concepts

  3. Risk Variables for a Metabolic Syndrome Fasting Fasting Body Insulin Glucose Mass Waist/Hip Index 2-Hour Insulin BP Diastolic 2-Hour Glucose BP HDL-C Trig Systolic Meigs Diabetes 1997; 46:1594

  4. Risk Variables for a Metabolic Syndrome Impaired Glucose Tolerance Hypertension Central Metabolic Syndrome Meigs Diabetes 1997; 46:1594

  5. Lipid Metabolism and Insulin Resistance Ginsberg JCI 2000; 106: 453

  6. Serum Lipoprotein Size and Density VLDL 1.140 -- Chylomicrons 1.100 -- 1.060 -- LDL Density (g/ml) HDL-1 IDL 1.020 -- Chylomicron Remnants 1.006 -- HDL-2 HDL-3 0.950 -- Nascent HDL 60 100 140 200 280 400 600 800 1000 Diameter (Angstroms)

  7. LDL Cholesterol and LDL Particle Numbers in T2DM Patients with LDL-C < 100 mg/dL (n=2,355) 5th 20th 50th 80th percentile 37% (n=870) 63% (n=1485) LDL-C Percent of Subjects 70 100 130 160 (mg/dL) 7% (n=162) 31% (n=741) 38% (n=891) 16% (n=383) 8% (n=178) Percent of Subjects LDL-P 700 1000 1300 1600 (nmol/L) Cromwell Amer J Cardi 2006; 98: 1599

  8. Diabetes and CVD Risk in Framingham Cohort Age 35-64 Years--30 Year Follow-up 10 P<0.001 P<0.001 8 Men Women P<0.001 6 Risk Ratio P<0.001 P<0.001 4 P<0.001 P<0.001 P<0.05 P<0.001 2 0 CHD Stroke Int. Cardiac CVD Claudication Failure Total Wilson Am J Kidney Dis 1998

  9. Diabetes and Lipid Extremes Framingham Offspring Men 60 p<0.001 50 Non-Diabetic 40 Diabetic Per cent 30 p<0.001 20 p<0.001 10 0 HDL-C<35 Total-C 240+ LDL-C 160+ Trig 250+ HDL-C<35 Total-C 240+ Siegel Metabolism 1996; 96: 1267

  10. Diabetes and Lipid Extremes Framingham Offspring Women 50 p<0.001 Non-Diabetic p<0.001 40 Diabetic p<0.001 30 Per cent p<0.001 20 10 0 HDL-C<35 Total-C 240+ LDL-C 160+ Trig 250+ HDL-C<35 Trig 250+ Siegel Metabolism 1996; 96: 1267

  11. CHD Death Riskby non HDL-C, LDL-C, and DiabetesARIC, Framingham, MRFIT Usual Care Relative Risk >100 LDL-C (mg/dL) <100 Non HDL-C (mg/dL) Diabetes Present Diabetes Absent Liu Diabetes Care 2006; 28: 1916

  12. Prevalence of NCEP Metabolic Syndrome TraitsNHANES III, Framingham Offspring Study, San Antonio Heart Study Prevalence Meigs Diabetes 2003: 53 2160

  13. Nutrient Intake in Various Diets Sat Fat Mono & Poly Fat Protein Carbo 25 35 22 18 Atkins 7 33 15 45 Reaven 15 25 15 45 US Diet 10 20 15 55 AHA Step I 7 23 15 55 AHA Step 2 7 18-23 15 50-60 ATP III 6 24 30 40 The Zone 6 21 18 55 Dash 5 25 15 65 Connor 3 7 18 72 Ornish 0% 20% 40% 60% 80% 100% Per cent

  14. Effects of Fibrates on Vascular Events: VA-HIT Percent Difference vs Placebo Rubins N Engl J Med. 1999;341:410

  15. Gemfibrozil and CHD RiskVA-HIT Diabetes Results -24% risk -24% risk Vascular Event Rate (%) Diabetic Patients N=627, P=0.05 Nondiabetic Patients N=1904, P=0.004 Rubins N Engl J Med 1999.

  16. CHD Prevention Trials with Statins in Diabetic Subjects: LDL-C Lowering *LDL-C values for overall group Downs JR et al. JAMA 1998;279:1615-1622. | HPS Investigators. Presented at AHA, 2001. | Goldberg RB et al. Circulation 1998;98:2513-2519. | Pyorala K et al. Diabetes Care 1997;20:614-620. | Haffner SM et al. Arch Intern Med 1999;159:2661-2667. | LIPID Study Group. N Engl J Med 1998;339:1349-1357.

  17. CHD Prevention Trials with Statins in Diabetic Subjects: CHD Risk Reduction Downs JR et al. JAMA 1998;279:1615-1622. | HPS Investigators. Presented at AHA, 2001. | Goldberg RB et al. Circulation 1998;98:2513-2519. | Pyorala K et al. Diabetes Care 1997;20:614-620. | LIPID Study Group. N Engl J Med 1998;339:1349-1357. | Haffner SM et al. Arch Intern Med 1999;159:2661-2667.

  18. Summary of Intervention Studies Risk Reduction with Individual TreatmentsPersons with Diabetes Mellitus Blood pressure treatment 30-50% Lipid treatment 25-55% Glucose treatment 10-20%per 1% HbA1c Macrovascular Event Reduction

  19. CAD Risk Factors in Type 2 Diabetes Based on Time to First Event: UKPDS Variable Increment in Increment in risk variable of CAD LDL-C 1.0 mmol/L + 57 % (39 mg/dL) HDL-C 0.1 mmol/L - 15 % (3.9 mg/dL) SBP 10 mm Hg + 15 % HBA1C 1.0 % + 11 % Multivariate Cox proportional hazard model containing age, sex, and smoking as significant categorical risk factors. Turner RC et al, for the UKPDS Group. BMJ. 1998;316:823-828

  20. UKPDS: Order of Baseline Risk Factors for CAD Based on Time to First Event* Risk Factor P Value+ LDL-C <0.0001 HDL-C 0.0001 HbA1C 0.0022 SBP 0.0065 Smoking 0.056 *Fatal or nonfatal MI or clinical angina +Significance of risk factor after considering all other risk factors Turner RC BMJ. 1998;316:823-828

  21. Steno-2 Study: Outcomes 60 50 40 30 20 10 0 Conventional Primary Composite Endpoint (%) Intensive ASA, statins, ACE, ARB, exercise, low fat diet, smoking cessation, tight glucose control, and blood pressure control 0 12 24 26 48 60 72 84 96 Months of Follow-up Gaede N Eng J Med 2003;348:383-393.

  22. 10 5 0 -5 -10 -15 -20 30 25 20 15 10 5 0 P<0.001 22.9 +0.4 P=0.017 Change in TG (%) Change in HDL-C (%) -3.6 15.6 11.8 P<0.001 -15.7 0 12 24 36 52 Week 0 12 24 36 52 Week RIO-LipidsPercent Change in HDL-C and TG Levels At 1 Year Completers Rimonabant 20 mg Rimonabant 5 mg Placebo Despres N Engl J Med. 2005;353:2121

  23. Updated ATP III LDL-C Goals and Cutpoints for Therapy Grundy Circulation 2004;110:227

  24. Combination Lipid-Altering Drug Therapy with Statins • Medications used in combinations • Ezetimibe • Bile acid sequestrants • PPAR alpha (fibrates) • Fish oils • Niacin

  25. SummaryMetabolic Syndrome/Insulin ResistanceLipid Therapy • Lipid Abnormalities HDL Triglycerides LDL particle characteristics • Lipid Goals Aggressive lowering of LDL, nonHDL, Lowering of triglycerides • Lipid Treatment Adjuvants Weight loss (diet, drug, surgery) Diet Monotherapy, combination therapy

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