1. The Hyperlipidaemias What are they and how to treat Dr John O’Donnell Consultant Clinical Biochemist Borders General Hospital

2. The Hyperlipidaemias Familial Hypercholesterolaemia Mixed hyperlipidaemias Post menopausal hypercholesterolaemia ‘Polygenic’ hypercholesterolaemia – the bog standard high cholesterol

3. Polygenic hypercholesterolaemia Simply ‘high’ cholesterol Secondary and primary risk Management base on National and local guidelines

4. Familial hypercholesterolaemia 1 in 500 – relatively common Cholesterol > 7.5 – bear in mind family history Clinical signs – tendon xanthoma, xanthelasma, and arcus senilis Genetic testing - problems

5. Postmenopausal Hypercholesterolaemia Increase in cholesterol of 1-2 mmol/L Increased cardiovascular risk post- menopause Role of HRT – highly controversial NOT same risk as familial hypercholesterolaemia

6. Mixed Hyperlipidaemia Essentially high cholesterol and high triglyceride

7. Hypertriglyceridaemia Triglyceride above 1.7 – 3.0 Usually secondary to alcohol or diabetes Trig > 10mmol/L – risk of pancreatitis Increased cardiovascular risk Limited evidence that treating triglycerides changes risk (Field study) – but we treat it anyway!

8. HDL Cholesterol Independent risk factor for cardiovascular risk HDL less than 1.0 consider as high risk HDL > 3.0 – cardiovascular protection – Familial hyperalphalipoproteinaemia Measurement of HDL requires a fasting sample (as does triglyceride) Not much evidence that treating HDL makes any difference

9. Drugs treating lipids Anion resins – cholestyramine et al Ezetimibe Fibrates Fish oils Nicotinic acid Statins Newer agents coming to market – biologic agents

10. Resins Rarely used New capsule format introduced ??? Did work, and some patients preferred them – most did not Antiquated and barely have a role

11. Ezetimibe Recently introduced Modest reduction in cholesterol Effective in combination Few side-effects No effect on triglycerides

12. Fibrates Really only means fenofibrate Effective against triglyceride Effective against cholesterol Some side-effects Effective in combination – side-effects over exaggerated DON’T MIX GEMFIBROZIL WITH STATIN - EVER

13. Fish Oils Omacor and Maxepa Only evidence of effect is with Omacor Need a barrel of fish per week to give appropriate levels of the active fish oil Uses in hypertriglycerides Some evidence of protection post MI - Gissi trial (absence of statins)

14. Nicotinic acid In many ways ideal lipid drug Lowers LDL cholesterol Lowers Triglyceride Raises HDL cholesterol Needs high doses SIDE – EFFECTS up to 100% of patients Last line of treatment – approximately 50% tolerate it New preparation – attempting to reduce side- effects – trial stopped due to side-effect concern

15. Statins ‘All statins are equal – but some are more equal than others’ – unnamed DOH senior civil servant Undeniably scientifically proven to REDUCE DEATH Side – effects – myalgia,myositis and rhabdomyolysis Think carefully about 80mg of any statin

16. Suggested treatment strategies Predominantly High Cholesterol – then 1 st line statin 2 nd line ezetimibe 3 rd line fibrate if statin intolerant Nb fibrates tend to interfere with statin effect so do not combine in simple high cholesterol

17. Treatment strategies Predominantly high triglyceride (>6.0) Fibrate Omacor In diabetes patients (?impaired glucose tolerance) pioglitazone Treat cholesterol level appropriately with statin if need be (nb previous caution)

18. Management of patient Full history and examination (ECG) Blood tests Cholesterol, Triglyceride and HDL – FASTING Glucose LFTs, U & Es, TSH

19. Management of patient Primary or secondary Clinical guidelines – MOST are flawed Poor recognition of family history, ethnicity Use common sense (terminal cancer, dementia)

20. Some practical points Familial hypercholesterolaemia and children – refer to me Statins and fibrates(fenofibrate!) are safe Ezetimibe and fibrates are off licence – refer to me Reasonable referrals – statin intolerance, mixed hyperlipidaemias, familial hypercholesterolaemias

21. Some more practical points Increase in LFTs – no concern up to 2x upper limit of ref range Between 2x and 3x – monitor every three months > 3x ref range stop tablets and review therapy CK – Symptoms more important than level

22. Even more practical points In asymptomatic patients – CK 5x ref range check three monthly CK 10x ref range – stop drug NB Africans and Afro-Caribbean's have different ref range – usually higher Hypothyroidism can increase CK Other muscle myopathies

23. The Future? Statins in the water? More aggressive treatments Alternative treatments More guidelines