Cholesterol, Heart Attack and Stroke. Dr Tai E Shyong Consultant Department of Endocrinology Singapore General Hospital

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1 Cholesterol, Heart Attack and Stroke Dr Tai E Shyong Consultant Department of Endocrinology Singapore General Hospital

2 Outline Why are we interested in cholesterol What is a heart attack and how does it happen? What are good and bad types of cholesterol What can we do in relation to cholesterol to prevent the heart attack How can we lower the levels of bad cholesterol and what is the effect of doing that? Are drugs the only way to achieve this?

3 Along the way Show you some nice pictures Give you an idea of how a heart attack occurs Try to show you how doctors think about heart disease and how we decide what types of treatment are important

4 Changes in the causes of death over time

5 Heart disease in Singapore age standardized mortality for Singaporeans aged Hughes et al. International Journal of Epidemiology, Vol 15, 44-50

6 Causes of death in Singapore Total No. of Deaths 15,367 15,820 16,033 % of Total Deaths 1. Cancer [ICD9 : ] Ischaemic Heart Disease [ICD9 : ] Pneumonia [ICD9 : ] Cerebrovascular Disease [ICD9 : ] Injuries [ICD9 : E800-E999] Other Heart Diseases [ICD9 : ,402, ] Chronic Obstructive Lung [ICD9 : , 496] Diabetes Mellitus [ICD9 : 250] Nephritis, Nephrotic Syndrome & Nephrosis [ICD9 : ] Chronic Liver Disease & Cirrhosis [ICD9 : 571]

7 Death from heart disease and stroke in Singapore Korea China (rural) Japan France Canada USA France Hong Kong IHD Hong Kong China (urban) Italy Greece Canada stroke Sweden Australia New Zealand UK Italy USA Japan Sweden Singapore Australia Greece Singapore UK New Zealand Korea China (rural) China (urban) World Health Organisation World Health Statistics Annual

8 Dietary fat and coronary heart disease-the seven countries study

9 Hypertension and Hyperlipidemia Are Major Risk Factors for CHD Framingham study (N=5209) CHD indications/ < >295 TC (mg/dl) in men Shurtleff D. 1974;US DHEW, Pub no (NIH) , sec 30; Castelli WP. Am J Med. 1984;76:4-12.

10 Nature is always hinting at us. It hints over and over again. And suddenly, we take the hint Robert Frost

11 The foolhardy acceptance of the dietary cholesterol-saturated fat hypothesis of atherosclerotic etiology... represents dangers to medicine and health that are far more serious than not accepting it. Altschule MD. Symposium on atherosclerosis. Med Clin North Am 1974; 58:

12 "It is probably of little value to reduce raised serum cholesterol concentrations in patients with overt [coronary heart disease ]" "reduction of raised serum cholesterol is a card of uncertain quality in the primary prevention of [coronary heart disease]" "reduction of raised serum cholesterol could lead to adverse biological changes" Michael Oliver Lancet May 11;1(8437):1087-9

4S: Total Mortality 1.00 Proportion alive 0.95 0.

0003 This improvement in survival is accounted for

0 1 2 3 4 5 Years since randomisation 6 The

13 4S: Total Mortality 1.00 Proportion alive simvastatin placebo Log rank p= This improvement in survival is accounted for by the 42% reduction in coronary death Years since randomisation 6 The Scandinavian Simvastatin Survival Study Group. Lancet 1994;344:

14 'When the facts change, I change my mind. What do you do?' Michael Oliver, 1996, Nobel Prize Anniversary Meeting

membrane Smooth muscle cell Elastic/collagen fibres External

15 Normal Arterial Wall Tunica adventitia Tunica media Tunica intima Endothelium Subendothelial connective tissue Internal elastic membrane Smooth muscle cell Elastic/collagen fibres External elastic membrane Adapted from Weissberg PL. Eur Heart J Supplements 1999:1:T13 18

16 Endothelial Dysfunction in Atherosclerosis Upregulation of endothelial adhesion molecules Leukocyte adhesion Increased endothelial permeability Migration of leukocytes into the artery wall Adapted from Ross R. N Engl J Med 1999;362:

17 Formation of the Complicated Atherosclerotic Plaque Formation of the fibrous cap Accumulation of macrophages Formation of necrotic core Adapted from Ross R. N Engl J Med 1999;362:

18 Chest pain and cardiovascular disease Netter FH, The Ciba Collection of Medical Illustrations, Vol. 5, Heart, CIBA, 1978, p. 223.

19 Why are we interested if high cholesterol? Many of us will develop and die of heart disease People with high cholesterol are more likely to develop heart disease But perhaps, most importantly, treatment to reduce cholesterol reduces that risk

20 What are bad and good cholesterol? Bad cholesterol Good cholesterol

21 This is cholesterol It is neutral, there is no good and bad

22 Structure of Lipoproteins Free cholesterol Phospholipid Triglyceride Apolipoprotein Cholesteryl ester

23 Lipoprotein Classes Chylomicrons, VLDL, and their catabolic remnants LDL HDL > 30 nm nm Atherogenic and proinflammatory 9 15 nm Antiatherogenic and antiinflammatory

24 Lipoproteins and Atherosclerosis Risk Factors Atherogenic Lipoproteins + LDL The bad cholesterol Protective Lipoproteins HDL The good cholesterol -

25 Lipoproteins and Atherosclerosis LDL HDL

26 Lipoproteins and Atherosclerosis LDL HDL

27 What can we do about out cholesterol levels Treatments which lower LDL cholesterol reduce the risk of heart disease Treatments which raise HDL cholesterol also reduce the risk of heart disease

29 Are Drugs the only way to go?

Lyon Diet Heart Study: Cumulative Survival without

30 Lyon Diet Heart Study: Cumulative Survival without Cardiac Death and Nonfatal MI 100 % Without Event Control P = Experimental Year de Lorgeril M et al. Circulation 1999;99: Lippincott Williams & Wilkins. Canola oil based margarine, fiber, low cholesterol, low saturated fat, fruits, vegetables

31 But dieting doesn t work High LDL-Cholesterol Diet 8-10% LDL-cholesterol lowering Drugs 20-55% LDL-cholesterol lowering Does not require you to see a doctor Minimal side effects More expensive Requires you to see a doctor Risk of side effects, especially at high doses

32 More intensive dietary changes Standard cholesterol lowering diet Added More soluble fibre Plant stanol esters Almonds More Soy Compared against drug treatment with lovastatin 20 mg per day

33 Sample menu-substitute, don t add Breakfast Bran flakes cereal Skim milk Blueberries Fat-free vanilla yogurt Double-fruit jam Breakfast Hot oat-bran cereal Soy beverage Blueberries Sugar and psyllium Oat-bran bread Test margarine Snack 1 Snack 1 Bran muffin Almonds Control light margarine Soy beverage Fresh fruit Fresh fruit

34 Comparing diet and drug treatment

35 What else can we do?

36 Fermented red yeast rice Effect of on LDL cholesterol after 6 weeks treatment baseline 6 weeks xuezhikang placebo

37 Effect of fermented red yeast rice on LDL cholesterol baseline 6 weeks xuezhikang placebo

38 Plant stanol esters N Engl J Med Nov 333(20):

39 Fish oils and lipids

40 Fish oils and sudden death Albert et al, NEJM 2002 April (15)

41 Allium sativum Linn Good for a little while Meta-analysis of 45 trials Arch Intern Med Mar 26;161(6):

42 .but smelly

43 Cafetiere vs filtered coffee BMJ 1996; 313: Coffee anybody?

44 May lower LDL- cholesterol by 10-20% Raises HDL - cholesterol by about 5-7%

45 Conclusions High levels of LDL-cholesterol and low levels of HDL-cholesterol can lead to heart disease Drugs are commonly used to lower LDLcholesterol and raise HDL-cholesterol However, lifestyle changes do work, and may be appropriate for people whose LDLcholesterol levels are not too high

46 Conclusions Multiple types of dietary interventions are better than any one change Some supplements have also been shown to have interesting effects Fermented red yeast rice Plant stanol esters Omega-3 fatty acids

47 Conclusions Even if you decide that you want to try dietary changes to lower your cholesterol, you should make sure that you consult your doctor and test your cholesterol to make sure that the treatment is working

CHOLESTEROL GUIDELINES

CHOLESTEROL GUIDELINES High cholesterol and lipid levels can significantly increase a person's risk of developing chest pain, heart attack, and stroke. Fortunately, a number of effective treatment options