Lecture 5b 7 Feb 2011 Atherosclerosis-Nutritional intervention- -emphasis should be on prevention-

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?

Lipids LCAT preference for GLA > LA > OA > AA> DHA LPL-preferences increase activity-no reports found CETP-preferences increase activity-no reports found

Blood Levels of concern- new ATP-NCEP guidelines issued 2004-diet approaches are constantly changing   HDL Addressed when triglycerides are addressed LDL including oxidized LDL Table 6, Fig 1,2 ATP main target of diet

Blood Levels of concern Lp(a)- diet does not alter (very tight genetic control)   Cholesterol -addressed when LDL is addressed Triglycerides- Fasting plasma-fish is an option, reduction in saturated fat-frequently dietary recommendations for LDL also take care of triglycerides

Blood Levels of concern Triglycerides -post-prandial-fish is an option –what does this say about LPL?   HDLc: LDLc ratio of < 0.2 – again emphasis is on LDL first

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

Macrophages Increase B-carotene, vitamin E and C-jury is still out on these issues?

Platelets Platelet membrane fatty acid composition Phospholipase A2 and Cyclooxygenase  

Platelets Platelet membrane fluidity-reduce saturated fat and dietary cholesterol since they both decrease membrane fluidity  

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

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

-diets high in oleic acid (18:1 n-9) MAY result in weight loss Obesity -diets high in oleic acid (18:1 n-9) MAY result in weight loss   Renal Disease -see blood pressure Various Pathogens Adequate nutrient intake is critical to maintaining immune response

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 -may also explain why MUFA lowers blood pressure -increased blood pressure can result in increased platelet reactivity

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

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

Diet drug interactions Gemfibrozil - speeds up LPL action of 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 Limit alcohol content

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 inhibits platelet function by inhibiting cyclooxygenase Aspirin can lead to folate and vitamin C deficiencies (potential heart disease consequences?)