Lipids and familial hypercholesterolaemia
- 1. LipidsDr Thomas FoxST5 Diabetes and EmdocrinologyDerriford Hospital
- 2. OutlineLipid physiologyFamilial HypercholesterolamiaType I DiabetesType II DiabetesPrimary preventionCase studyPharmacotherapy
- 3. Lipid physiologyTG - fuel sourceCholesterolSteroid hormone synthesisCell membrane synthesisBile acid synthesisApoliporpteinsAssembly of lipoproteinsStructural integrityEnzyme co-activatorsReceptor ligands
- 4. LipoproteinsPackages to transport insoluble lipids in the bloodChylomicrons (carry TG from gut to adipose tissues and skeletal muscle)Chylomicron remnantsVLDL (carries TG from liver)LDL (carries cholesterol fromliver)IDL HDL (carries cholestero to the liver)
- 6. Familial HypercholesterolaemiaHeterozygous genetic conditionHypercholesterolaemiaPremature CV diseaseXanthomasFrequency 1:500In UK only 15% of 115.000 diagnosed
- 8. Causes3 major mutationsLDL-RApolipoproteinBAn enzyme involved in the degradation of the receptor PCSK9
- 9. DiagnosisOn 4 clinical criteriaPossible FHDefinite FHThese patients are screened for DNA mutationIf DNA mutation found in index case then 100% sensitive and specificCascade testing (first and second degree)
- 10. Cascade ScreeningRelatives of FH should be screened before age 10 withGenetics if mutation knownLDLC if mutation unknownDo not use Framingham risk
- 11. ManagementHigh intensity statin therapy for all FH lifelongadd in ezetemibeSpecialist referralAdvice RE pregnancyAim to reduce LDL C by 50% from baselineLifestyle adviceHomozygous FHConsider referral to cardiologist
- 12. Management 2LDL apheresisLiver transplantation
- 13. Lipid management in Type I diabetesPatients with Increased ACR, or2 or more features of metabolic syndromeBP>135/80HDL < 1.2 (women) and 1.0 (men)TG > 1.8Waist circumference 80cm (women) 100cm (Men)Evidence of insulin resistance (>1 Unit/kg/day)Smoking, age, FH of CVDShould be assumed to be at high arterial risk and started on statin
- 14. Lipid management in type II DiabetesIF >40 years consider high risk of CVD unlessNot overweightNormotensive (<140/80mm/Hg)No microalbuminuriaNon-smokerNo high risk lipid profileNo history or FHx of CVDThen use UKPDS risk engine http://www.dtu.ox.ac.uk/riskengine/
- 16. Lipid management in type II DiabetesIf <40 years use statins if at high risk of CVDOnce started on cholesterol lowering therapySimvastatin 40mgReassess after 3 monthsYearly measurement thereafterAim for LDL< 2.0mmol/LTC < 4mmol/L
- 17. Case study 150 year-old maleType II diabeticObesity (BMI 36)Recurrent pancreatitisTreatmentsNR 80 units tdsGlargin 180 units at nightFenofibrate 267mgMetformin 850mg bdAspirin
- 18. Case study 2HbA1C 9.5%TC 8.3TG 20.66HDL 1.0LDL not result
- 19. TG and type II diabetesIf high TG perform full fasting sampleAssess secondary causesEtOHHypothyroidism Renal impairmentHyperglycaemiaIf TG remain>4.5mmol/Lstart fenofibrate
- 20. Primary preventionIn those aged 40-75If CV risk is >20% in next 10years treat after modifying other risk factorsGPs should screen their population and use risk assessmentTreatment with simvastatin 40mg and no need to recheck or treat to target LDLDo not use fibrate, ezetemibe or anion exchange resins
- 21. StatinsHMG CoAreductase inhibitorReduces intracellular cholesterolIncrease LDLR and cholesterol uptakeReduces LDL Increases HDL
- 23. Other drugsNiacin/nicotinic acid (Niaspan)Decreases hepatic VLDL productionReduces LDL and TGFibratesIncrease lipoprotein lipase activityBoth increase HDLEzetemibeReduces cholesterol absorption from gutReduces LDL (no effect on HDL)
- 24. Omacor (omega 3 fatty acids)Reduces TGReduced death - secondary prevention of MI
- 25. Dietary adviceFat should make up<30% of calorie intakeSaturated fat <10% of calorie intakeCholesterol <300mg/day5 a day2 portions oily fish per week
- 26. Lifestyle Advice30 mins exercise 3 times per weekStop smoking advice
- 27. SummaryStatins are an effective treatment for hypercholesterolaemiaTreat patients if C risk >20% over 10yearsAlmost all type II diabeteics are considered high risk and should be treated to targets ofTC <4mmol/LLDL <2mmol/L