1. Lecture 5b 3 Feb 2014 Atherosclerosis-Nutritional intervention- -emphasis should be on prevention-

2. Group activity A patient presents with severe atherosclerosis (severe stenosis and accompanying chest pains). From a clinical perspective is diet modification alone the best approach to reducing the risk of MI? Why or why not? If not then what are the other medical options available?

3. Eating well Canada’s food guide and exercise leads to reduced risk of atherosclerosis via good lipids and lipoprotein profiles (cholesterol, triglycerides, HDL, LDL, sd LDL) and platelet function resulting from good diet and exercise If one has disturbed lipid and lipoprotein and platelet function profiles then one needs the Therapeutic lifestyle change (TLC) diet

7. TLC diet addresses blood levels of concern: -Elevated Cholesterol -addressed when LDL is addressed via TLC diet -Elevated Triglycerides- -TLC diet helps and 2 servings per week of oily fish also helps But diet does not help with Lp(a)- diet does not alter Lp(a) due to very tight genetic control of Lp(a) levels

8. TLC diet addresses blood levels of concern Triglycerides and small dense LDL As plasma triglyceride levels fall there is a smaller percentage of small dense LDL -reduce triglycerides as above Triglycerides and low HDLc -this is due to low LPL activity -reduce triglycerides as above

9. Macrophages Increase dietary  -carotene, vitamin E and C-jury is still out on these issues?

10. Platelets Platelet membrane fatty acid composition- affected by diet- review dietary sources of arachidonic, gamma-linolenic, alpha-linolenic. eicosapentaenoic acid and docosahexaenoic acid

11. Platelets Platelet membrane fluidity-reduce saturated fat and dietary cholesterol since they both decrease membrane fluidity -TLC diet helps here

12. Platelets- Interaction with lipoproteins HDL-lowers aggregation-no observed impact of nutrition (no studies done) here LDL-elevates aggregation-no observed impact of nutrition (no studies done) here Lp (a)-depresses platelet aggregation though also thought to inhibit plasminogen activation no observed impact of nutrition (no studies done) here

13. Blood pressure Reduce saturated fats and dietary cholesterol and increase pufa to improve artery patency-TLC diet helps -remember that plaque formation ’ s sequelae include calcium deposition that further reduces artery patency

14. Obesity and diet -diets high in oleic acid (18:1 n-9) MAY result in weight loss Renal Disease and diet -see blood pressure- if reduce blood pressure reduce renal disease risk Various Pathogens and diet Adequate nutrient intake is critical to maintaining immune response

15. Nitric oxide -vasodilation, antiplatelet effects, also important in immune response -high salt intake in salt sensitive individuals reduces NO production and may explain increased blood pressure due to NO factor -MUFA increases nitric oxide production -may also explain why MUFA lowers blood pressure -increased blood pressure can result in increased platelet reactivity

16. Nitric oxide decreased NO production can result in decreased immune response (pathogen impact)

17. Diet drug interactions Cholestyramine-lowers cholesterol by acting as a bile acid sequestrant -nausea, GI distress and constipation and can lead to fat soluble vitamin deficiencies Colestipol -lowers cholesterol by acting as a bile acid sequestrant is less likely than cholestyramine to cause the above problems but it can give constipation

18. Diet drug interactions Gemfibrozil - speeds up LPL action on VLDL and hence reduces triglycerides-can lead to nausea and GI distress Statins (cholesterol lowering HMG-CoA synthase inhibitors)-lovastatin, pravastatin, simvastin) should not be given with grapefruit juice

19. Diet drug interactions Anticoagulants (eg aspirin) and -hyper doses of vitamin E (> 2000 IU/day) should be limited -coincidental high intakes of fish -to be avoided Aspirin can lead to folate and vitamin C deficiencies (potential heart disease)