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

SECONDARY PREVENTION PRIMARY PREVENTION (CV Risk Assessment)

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)

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.

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.

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

Abdominal Fat Distribution Obesity and Risk BP150/95 Chol5.8 LDL4.5 HDL0.8 TGs2.3 BP120/70 Chol4.4 LDL2.7 HDL1.6 TGs1.0

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

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

High/Intensive Doseage with Statins II.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

High/Intensive Doseage with Statins III.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

High/Intensive Doseage with Statins IV.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

CONCLUSIONS 1.CHOLESTEROL (LDL-CHOLESTEROL) IS IMPORTANT 2.CURRENTLY POWERFUL DRUGS TO REDUCE EFFECTS 3.SHOULD BE USED IN PRIMARY & SECONDARY PREVENTION 4.SIDE-EFFECTS ARE IMPORTANT & CAN MARKEDLY EFFECT QUALITY OF LIFE 5.LIPID PROFILE IS IMPORTANT FOR CORRECT DRUG USAGE 6.DO NOT FORGET TRIACYLGLYCEROL  STATINS ARE NOT THE DRUG OF CHOICE