Cholesterol Richard Cleve Medical Biochemist C.J. Coady Associates Overview H3C What is cholesterol? What is it? Why is it bad? 1 Future CH3 CH3 3 CH3 2 HO The sample What do we Need to watch For? 4 H3C Treatment Drugs? Lifestyle? Protocols What is it? What is my risk? What is cholesterol? Definition? What is good and bad cholesterol? Is it really that bad? “Cholesterol” vs “lipids” In the general press: synonyms In the medical literature: almost interchangable Biochemically: • Cholesterol is a specific sterol • Lipids is a broad class of compounds including cholesterol What is Cholesterol then? Fat-like substance Essential for life • • • • Hormone synthesis Membrane fluidity Bile acids Vitamin D Photo courtesy Prof. K. Gough U. Manitoba Photo courtesy D. Vukmanic & M. Colgan Brock University How are cholesterol and HDL/LDL related? Cholesterol is insoluble in water and blood Lipoproteins transport cholesterol through the blood stream HDL and LDL are lipoproteins What is a Lipoprotein? phospholipid apoprotein cholesterol cholesterol ester & triglycerides Image: www.peprotech.com What do HDL and LDL stand for? HDL = High density lipoprotein LDL = Low density lipoprotein <0.950 g/mL 0.950 – 1.006 1.006 – 1.019 1.019 – 1.063 1.063 – 1.21 1.21 – 1.25 18 h @ 45K RPM chylomicrons VLDL IDL LDL HDL VHDL Airfuge? Where does cholesterol come from? 1. Diet 2. Liver synthesis Where does cholesterol come from? LDL HDL chylomicron Which foods contain cholesterol? Why is Cholesterol Bad? 1. Block artery 2. Plaque rupture www.web-books.com Is cholesterol really that bad? Cholesterol smoker DM High BP Abdominal obesity “stress” Vegetables & fruit daily Alcohol Exercise OR 1.47-3.87 2.27 3.08 2.48 2.24 2.51 0.90 0.79 0.72 PAR 54.1% 36.4% 12.3% 23.4% 33.7% 28.8% 12.9% 13.9% 25.5% Yusuf et al. 2004 Lancet 364: 912 Cholesterol around the world Stehle et al. 1991 Klin. Wochenschr 69: 629 Cholesterol & ethnicity Participants from Canada from different ethnic groups. Conclusion: ethnic group has minimal impact when weight is corrected for Razak et al. 2005 Int. J. Obesity 29(6): 656. Cholesterol risk around the World High cholesterol caries same risk around the world. Yusuf et al. 2004 Lancet 364: 912 Collection Considerations How can you tell if someone’s cholesterol is high? What do we need to watch for? Features of high cholesterol: xanthomata pacesmrcpuk.blogspot.com www.wikipedia.com More findings… Eruptive Xanthomata Arcus senilis (juvenilis) www.nlm.nih.gov Augenheilkunde MediUni Graz Which of the following have high cholesterol? A B C D (After several Hours of standing) Duration of Fasting? chol Non-fasting Starvation Standing → lying down Standing → sitting down HDL LDL TG Pre-analytical Considerations Heart attack ↓LDL 10% up to 12 weeks Pregnancy ↑LDL, HDL, TG Major illness ↑ or ↓ up to 3 months Hypothyroid ↑LDL, TC Citrate, oxalate tubes – ↓10% Protocols What is the protocol? What is my risk? Who should be monitored? How often? BC Guidelines Currently draft form To be released within a few months BC Guidelines Goals • Prevent heart disease • Diet • Smoking • Exercise • Assess 10 year CHD risk • Tools for assessment Probably based on Canadian 2003 guidelines • Canadian Cardiovascular Society 2006 guidelines stricter, although not as commonly used. What is my risk? If diabetic use UKPDS calculator If not-diabetic use Framingham Risk What is Framingham? •Study started in 1948 •5209 men & women •Physical exams, lifestyle interviews •Patients reviewed every 2 years •Part 2 started in 1971 •5124 of the children •Part 3 just starting Risk calculator Formula used to calculate risk of having a heart attack in the next 10 years Add points # of points determines risk Risk calculator Age, years • • • • • • • • • • • Age 20-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 male -9 -4 0 3 6 8 10 11 12 13 female -7 -3 0 3 6 8 10 12 14 16 Risk calculator Smoker? • No: 0 points • Yes: • age • Male • Female 20-39 8 9 40-49 5 7 50-59 3 4 60-69 1 2 70-79 1 1 Risk calculator For males • • • • • • TC ≤4.14 4.15-5.19 5.20-6.19 6.20-7.20 ≥7.21 20-39 0 4 7 9 11 40-49 0 3 5 6 8 50-59 0 2 3 4 5 60-69 0 1 1 2 3 70-79 0 0 0 1 1 20-39 0 4 8 11 13 40-49 0 3 6 8 10 50-59 0 2 4 5 7 60-69 0 1 2 3 4 70-79 0 1 1 2 2 For females • • • • • • TC ≤4.14 4.15-5.19 5.20-6.19 6.20-7.20 ≥7.21 Risk calculator BP: untreated • • • • • • SBP <120 120-129 130-139 140-159 ≥160 male 0 0 1 1 2 female 0 1 2 3 4 male 0 1 2 3 3 female 0 3 4 5 6 BP: treated • • • • • • SBP <120 120-129 130-139 140-159 ≥160 Risk calculator HDL • • • • • HDL ≥1.55 1.30-1.54 1.04-1.29 <1.04 -1 0 1 2 What is my risk of a heart attack in the next 10 years? • • • • • • • • • • • • • • • • • • • Points 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 male 1% 1 1 1 1 2 2 3 4 5 6 8 10 12 16 20 25 >30 female 1% 1 1 1 1 1 1 1 1 1 1 1 1 2 2 3 4 5 points 18 19 20 21 22 23 24 ≥25 female 6% 8 11 14 17 22 27 >30 What do you do with that number? Risk ≥20% 10-19% <10% desirable LDL <2.5 <3.5 <4.5 TG optimal <1.5 mmol/L TC/HDL ratio <4.0 <5.0 <6.0 Treatment Are medications the only choice? Fats? Fibre? Diagnosis Fredrickson (WHO) classification • Phenotypic • Largely historic • Little clinical use Pattern as Aid to Diagnosis & Treatment HDL LDL TG Obesity, smoking, anabolic steroids, inactivity, Tangier’s, apo AI defic. Familial hyperlipidaemia, B100 Not fasting, obesity, alcohol, pregnancy, DM, beta-blockers, FCHL, CII-defic., FHTG, LPL defic., gout, kidney disease, steroids DM, hypothyroid, nephrotic, FCHL, diuretics Treatment options Diet saturated fatty acids mono-unsaturated polyunsaturated cholesterol fish oil Obesity Smoking Exercise Alcohol chol HDL LDL TG Fibre? Insoluble Fibre Wheat bran, whole grains, Fruit & vegetable skins Almost no effect on cholesterol Soluble Fibre Pectin, gums (guar etc.), oats, Legumes, brown rice, broccoli, Potatoes Cholesterol ↓0.04 mmol/L / g Drugs to Treat Class Statin Fibrates Niacin Sequest LDL ↓18-55% ↓5-20% ↓5-25% ↓15-30% HDL ↑5-15% ↑10-20% ↑15-35% ↑3-5% TG ↓7-30% ↓20-50% ↓20-50% 0% Children, Teens and cholesterol Familial conditions • Can see heart attacks starting at 4 years old • Rare outside of Quebec Routine screening • Not recommended Obesity Future Whats coming 5-10 years from now? Apo B Asterisked test Each particle of LDL has 1 apo B protein Number vs. size of LDL particles May replace LDL measurements Yusuf et al. 2004 Lancet 364: 912 Lp(a) Asterisked test Special form of LDL Absence not harmful Independent risk factor Non-standardized Variable reference range ? treatment No need to repeat measurement Wieringa 2000 Ann. Clin. Biochem. 37: 571 Bennet et al. 2008 Arch Intern Med 168(6): 598 LDL Calculated LDL = total cholesterol – HDL – TG*0.45 • Fasting • TG < 4.5 mmol/L • not high VLDL Direct measurement • At least 5 different methods on market now NMR • Proprietary technique New collection procedure Theory: most of the day isn’t fasting; therefore, non-fasting may better represent risk. Standardized “meal” and measurement at 2 hours Could be combined with OGTT No evidence Ridker 2008 Clin. Chem. 54: 11 Conclusions Cholesterol increases risk for atherosclerosis which increases risk of a heart attack LDL is “bad” cholesterol, HDL is “good” cholesterol Most people asymptomatic Diet & exercise help Treatment is “life-long”
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