Treatment of Dyslipidaemias & The New Grampian Guidelines

1. Treatment of Dyslipidaemias & The New Grampian Guidelines Professor Iain Broom Director, Centre for Obesity Research and Epidemiology The Robert Gordon University Professor of Metabolic Medicine, University of Aberdeen Consultant in Clinical Biochemistry and Metabolic Medicine, NHS Grampian

2. SECONDARY PREVENTION PRIMARY PREVENTION (CV Risk Assessment)

3. PRIMARY PREVENTION • GLOBAL RISK SCORE (Cholesterol is only one of many Risk Factors) • RISK ASSESSMENT TOOL • > 20% RISK OF CV EVENT IN 10 YEARS (40 Years of Age)

4. What do we know about CV risk? INTERHEART • Large, international, standardised, case-control study of acute myocardial infarction (AMI) in 52 countries • To determine the strength of association between various risk factors and AMI • 15,142 cases and 14,820 controls enrolled to the study • 9 risk factors were studied Yusuf S, et al.Lancet 2004; 364: 937–952.

5. Nine risk factors represent 90.4% of the risk of AMI • Current or former smoking • History of diabetes • History of hypertension • Abdominal obesity • Combined psychosocial stressors • Irregular consumption of fruits and vegetables • No alcohol intake • Avoidance of regular exercise • Raised plasma lipids Yusuf S, et al.Lancet 2004; 364: 937–952.

6. Substantial residual CV risk in statin-treated patients The MRC/BHF Heart Protection Study 30 20 Patients with major vascular events (%) 10 19.8% of statin-treatedpatients had a majorCV event by 5 years 0 0 1 2 3 4 5 6 BHF=British Heart Foundation MRC=Medical Research Council Year of follow-up Risk reduction=24% Placebo Statin p<0.0001 Heart Protection Study Collaborative Group. Lancet 2002; 360: 7–22.

7. Abdominal Fat DistributionObesity and Risk BP 150/95 Chol 5.8 LDL 4.5 HDL 0.8 TGs 2.3 BP 120/70 Chol 4.4 LDL 2.7 HDL 1.6 TGs 1.0

8. HDL HDL  TG  TG  Effect of Triacylglycerol & HDL Cholesterol on Atherogenicity apo B Lipoprotein apo B Lipoprotein

9. High/Intensive Doseage with Statins • PROVE-IT (2004) • Acute coronary syndromes • 80 mg Atorvastatin v 40 mg Pravastatin • 3.9% Absolute Risk Reduction • 16% Relative Risk Reduction

10. High/Intensive Doseage with Statins • TNT (2005) • Stable Coronary Disease • 80 mg Atorvastatin v 10 mg Atorvastatin • 2.2% Absolute Risk Reduction • 22% Relative Risk Reduction • 6 x  in LFT Derangement

11. High/Intensive Doseage with Statins • SPARCL (2006) • Post CVA or TIA, no known CHD • 80 mg Atorvastatin v Placebo • 2.2% Absolute Risk Reduction in Stroke (5 years) BUT Small Increase in Haemorrhagic Stroke • 3.5% Absolute Risk Reduction in CV Event (5 years) • No Difference in Mortality

12. High/Intensive Doseage with Statins • ASTEROID (2006) [Galaxy Studies] • Assessment of Coronary Atheroma Burden. 0 & 24 Months Post-Therapy • 40 mg Rosuvastatin • LDL-CHOL 53.2% Reduction HDL OHOL 14.7% Increase • 6.8% Median Reduction Atheroma Volume Other studies with high dose Rosuvastatin are underway as part of the GALAXY GROUP

13. CONCLUSIONS • CHOLESTEROL (LDL-CHOLESTEROL) IS IMPORTANT • CURRENTLY POWERFUL DRUGS TO REDUCE EFFECTS • SHOULD BE USED IN PRIMARY & SECONDARY PREVENTION • SIDE-EFFECTS ARE IMPORTANT & CAN MARKEDLY EFFECT QUALITY OF LIFE • LIPID PROFILE IS IMPORTANT FOR CORRECT DRUG USAGE • DO NOT FORGET TRIACYLGLYCEROL  STATINS ARE NOT THE DRUG OF CHOICE