Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins...

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Dr. S. Nishan Silva (MBBS)

Transcript of Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins...

Page 1: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Dr. S. Nishan Silva

(MBBS)

Page 2: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Atherosclerosis

Page 3: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Functions of the Plasma Lipoproteins

• Chylomicron—Transport of dietary triglyceride

• VLDL—Transport of endogenous triglyceride

• IDL—LDL precursor• LDL—Major cholesterol transport

lipoprotein• HDL—Reverse cholesterol transport

Page 4: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

HyperlipidemiasHyperlipidemias• Elevated blood triglycerides and/or

cholesterol• Lipoproteins found in blood

Chylomicrons = postprandial dietary fat Very-low-density lipoproteins (VLDL) = lipid being

transported from liver to peripheral tissue Low-density lipoproteins (LDL) = transport of

cholesterol High-density lipoproteins (HDL) = reverse

transport of cholesterol, tissues to liver• Type of hyperlipidemia depends upon

portion of particles present

• Elevated blood triglycerides and/or cholesterol

• Lipoproteins found in blood Chylomicrons = postprandial dietary fat Very-low-density lipoproteins (VLDL) = lipid being

transported from liver to peripheral tissue Low-density lipoproteins (LDL) = transport of

cholesterol High-density lipoproteins (HDL) = reverse

transport of cholesterol, tissues to liver• Type of hyperlipidemia depends upon

portion of particles present

Page 5: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

ATP III Classifications/GuidelinesATP III Classifications/Guidelines

TestTest LevelLevel Health ImpressionHealth Impression

Total Total

CholesterolCholesterol

<200 mg/dl<200 mg/dl200-239 mg/dl

>240 mg/dl

DesirableDesirableBorderline High

High

LDLLDL

CholesterolCholesterol

<100 mg/dl<100 mg/dl

100-129 mg/dl100-129 mg/dl130-159 mg/dl160-189 mg/dl

>190 mg/dl

OptimalOptimal

Near OptimalNear OptimalBorderline High

HighVery High

HDLHDL

CholesterolCholesterol<40 mg/dl

>60 mg/dl>60 mg/dlLow

HighHigh

TriglyceridesTriglycerides

<150 mg/dl<150 mg/dl150-199 mg/dl200-499 mg/dl

>500 mg/dl

NormalNormalBorderline High

HighVery High

Blood PressureBlood Pressure≥ 140 mm Hg (systolic BP)≥ 90 mm Hg (diastolic BP)

High High

Page 6: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

CARDIOVASCULAR DISEASE ~ TREATMENT

– Primary ~ preventivemajor disease reduction benefit occurs at this stage ~BUT~ only if therapy implemented

– Secondarymorbidity and mortality benefits from therapy is well below that of primary prevention

Page 7: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Cardiovascular Risk Factors• Category I—cigarette smoking, LDL

cholesterol, high-fat diet, hypertension• Category II—diabetes mellitus, physical

inactivity, HDL cholesterol, TG, obesity• Category III—psychosocial factors,

lipoprotein a, homocysteine• Category IV—age, male gender, low

socioeconomic status, family history

Page 8: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

CVD ~ Endothelial Dysfunction

• Critical elements include:–Genotype ~ –Intrauterine & perinatal nutrition &

growth–Dyslipidemia ~ –Insulin Resistance and obesity–Diet–Exercise ~ Sedentary lifestyle vs

regular exercise–Smoking & environmental pollutants

Page 9: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

CardioVascular Diease:

TREATMENT • Focus of primary and secondary preventive therapy is to:

– Reduce cholesterol levels ~• Statins ~ PLUS ~ diet

– Reduce platelet activity• Aspirin ~ PLUS ~ Omega-3-Essential fatty Acids

– Reduce Inflammation ~• Statins + aspirin – diet?

– Improve Endothelial Dysfunction• Statins – diet?

– Control blood pressure• ACE inhibitors, ACE receptor inhibitors - Diet

• chlorthiazides, calcium-channel blockers

What about improving cardiac & vascular cell

metabolism?

Page 10: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Key Emphasis Components of a Heart - Healthy Diet

Division of Lung DiseasesNHLBI, NIH

Limit salt (sodium) Limit salt (sodium) Limit CholesterolLimit Cholesterol

Regular Physical Regular Physical ActivityActivity

Limit Saturated FatLimit Saturated Fat

Moderation, Variety & Nutrient AdequacyModeration, Variety & Nutrient Adequacy

Calories to Achieve/Maintain Healthy Weight

Page 11: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

““The Steps”The Steps” For a Heart Healthy LifestyleFor a Heart Healthy Lifestyle

1.1. Eat lessEat less • Cholesterol• Saturated fat• Trans fat• Sodium

2.2. Eat moreEat more• Fiber• Soy-based products

Page 12: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

““The Steps”The Steps” For a Heart Healthy LifestyleFor a Heart Healthy Lifestyle

3.3. Reduce your weightReduce your weight

4.4. Increase physical Increase physical activity levelactivity level

5.5. Learn toLearn to

• Shop smart• Cook smart• Dine out more

healthy

Page 13: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Step # 1Step # 1“Lowering Cholesterol & LDL Levels”“Lowering Cholesterol & LDL Levels”

• Eat less fat.Eat less fat.– Avoid fried foods, fatty meats,

& whole milk products.

• Eat less cholesterol.Eat less cholesterol. – Cholesterol is found in foods

from animals (foods from plants generally contain no cholesterol).

Page 14: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Step # 1Step # 1““Lowering Cholesterol & LDL levels”Lowering Cholesterol & LDL levels”

• Eat less saturated fat.Eat less saturated fat.– Saturated fats are usuallyusually

found in animal products.– However you should minimizeshould minimize

coconut, palm, and palm coconut, palm, and palm kernel oilkernel oil as they are high in saturated fat.

– Coconut oil – later

• Use lessUse less hydrogenated or hydrogenated or partially hydrogenated fats.partially hydrogenated fats.

Page 15: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.
Page 16: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Step # 1Step # 1““Lowering Trigylcerides”Lowering Trigylcerides”

• Avoid Alcohol.Avoid Alcohol.– Beer, wine, or hard liquor.

• Avoid Sugar.Avoid Sugar. – Candy & regular soda.

• Eat Fewer Carbohydrates.Eat Fewer Carbohydrates.– Breads, cereals, rice, pasta, fruits, &

dairy products.

Page 17: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

What is Trans Fat?What is Trans Fat?• Also known as Trans fatty acids.Trans fatty acids.

• Type of fat formed when liquid oils are made into solid fats (process called hydrogenationhydrogenation).– Shortening– Hard margarine

• Trans fat can be found naturally,can be found naturally, in small amounts, in some animal-based foods.

• Trans fats are in packaged cookies, crackers, packaged cookies, crackers, other baked goods, commercially prepared other baked goods, commercially prepared fried foods, chips, doughnuts, some fried foods, chips, doughnuts, some margarines & most short-eatsmargarines & most short-eats

Page 18: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Why is it BadWhy is it Bad??

• Trans fat is as badis as bad for you as saturated fat.saturated fat.

• It has been shown to– raiseraise LDL levelsLDL levels – lowerlower HDL levels HDL levels– increaseincrease your risk for

heart disease

Page 19: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.
Page 20: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Step # 1Step # 1““Lowering Trans Fat”Lowering Trans Fat”

1. Choose liquid or soft margarines & use in moderation.

• 1 gm saturate fat/serving• First ingredient should read “liquid

vegetable oil”

2. Use olive or sunflower oil (natural, un-hydrogenated oils).

3. Look for processed foods that use un-hydrogenated oils.

4. Limit intake of foods high in trans-fat

Page 21: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Step # 1Step # 1““Decrease Sodium (Salt) Intake”Decrease Sodium (Salt) Intake”

• Eating a diet high in sodium (salt) can increaseincrease blood pressure.

– Canned foods, dried meats or fish, packaged foods, frozen meals, lunch meats, salad dressings, marinades, and any salted food item

• Having a normal blood pressure reduces the riskreduces the risk of heart disease.

Page 22: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.
Page 23: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Step # 2Step # 2““Increase Soluble Fiber Intake”Increase Soluble Fiber Intake”

• The type of fiber found in oats, barley, dry beans & oats, barley, dry beans & peas, fruits & vegetablespeas, fruits & vegetables may help to lowerlower cholesterol levels.

– Choose 5 or more servings of vegetables & fruits/day.

– Choose 6 or more servings of whole grain breads, cereals, pasta, rice, & dry beans/day.

Page 24: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Step # 2Step # 2““Increase Soy Intake”Increase Soy Intake”

• Soy protein has been shown to reducereduce the risk of heart disease.

• Add soy to your diet.– Tofu, soynuts, soymilk, or

other whole soy products.

– Don’t count on powdered soy drinks as a good source of soy protein.

Page 25: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Fish oils

Page 26: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

CVD Therapy: omega-3-Fatty Acids

• Omega-3-EFAs 1000mg/day is also very effective

– Omega-3-EFA therapy significantly prevents:• cardiac arrhythmia• Thrombotic disorders

Page 27: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Coconut Oil???• Contain Saturated fats – But

medium chain fatty acids – lauric acid

• Medium chain FA – can be easily used by tissues

• Research done on hydorgenated coconut oils – not on pure oil.

• Recommendations– Generally take low– Better than hydrogenated oils or

other saturated oils– Better for deep frying than

unsaturated oils – like even sunflower oil

Page 28: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.
Page 29: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Benefits Vs Risks• Proven

– Wine reduces CVD– But Wine has flavinoids too!!

– One to Two drinks per day – reduces CVD, death

• Risks proven– Large mounts increases

– CVD, Obesity, Atherosclerosis– Chronic Liver diseases– Cancers

• Recommended• Men should drink no more than 21 units of alcohol per week

(and no more than four units in any one day).• Women should drink no more than 14 units of alcohol per

week (and no more than three units in any one day)• One unit of alcohol is 10 ml (1 cl) by volume, or 8 g by

weight, of pure alcohol. For example:

Page 30: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Recommendation

Page 31: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Combination therapy proven with research..

• Statin + omega-3FAs

• Statin & Niacin

Page 32: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Important Nutirents

• Arginine – Produces NO in vascular endothelial cells

• Vitamin C – Reduces development of CVD• Vitamin E – protects endothelium

• Selenium - works synergistically with Vit E

• Antioxidents – Flavanoids, • Vitamins B6, Folate, B12 & Betaine - reduce

serum homocysteine level • Garlic – Reduces progression of CVD

Page 33: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Evidence-based Best Practice Guideline,

New Zealand Guidelines Group, December 2003.1) Enjoy three meals a day, selecting from dishes that encourage you to eat

plant foods and fish, with little or no dairy fat, meat fat or deep fried foods2) Choose fruits and/or vegetables at every meal and most snacks.3) Select whole grains, whole grain breads, or high fibre breakfast cereals in

place of white bread and low fibre varieties at most meals and snacks4) Include fish, or dried peas, beans and soy products, or a small serving of

lean meat or skinned poultry, at one or two meals each day5) Choose low fat milk, low fat milk products, soy or legume products every

day 6) Use small amounts of oil, margarine, nuts or seeds7) Drink plenty of fluids each day, particularly water, and limit sugar-

sweetened drinks and alcohol8) Use only small amounts of total fats and oils, sugar and salt when

cooking and preparing meals, snacks, or drinks. Choose ready-prepared foods low in these ingredients

9) Mostly avoid or rarely include butter, deep-fried and fatty foods, and only occasionally choose sweet bakery products

Page 34: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Diet Therapy for High Blood Cholesterol

Diet Therapy for High Blood Cholesterol

(Data from National Cholesterol Education Program [NCEP]. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel II]. NIH Publication N. 93-3095. Bethesda, MD; National Institutes of Health. National Heart, Lung, and Blood Institute, 1993.) * Calories from alcohol not included.

Page 35: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Endothelial Dysfunction: Diet

Page 36: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Genes, Diet and Disease

Genomic research has identified multiple gene-regulated transcription binding proteins that are: a) responsive to dietary lipid and CHO intake and b) propel metabolism towards common disease phenotypes CHD, Hypertension, Insulin Resistance, Diabetes etc.

Individual gene variants have also been identified that affecta) disease development and b) response to nutritional and pharmacological therapy

Page 37: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

• Normal Plasma K+ concentration 3.5 - 5mmol/L

• Major source of excretion-renal• Major intracellular cation• K+ in the ECF <2% of the total

body content• K+ intake-40-120

mmol/day,90% of which is absorbed by the GI tract.

Page 38: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Increased potassium release from cells• Pseudohyperkalemia• Metabolic acidosis• Insulin deficiency, hyperglycemia, and hyperosmolality• Increased tissue catabolism• β-adrenergic blockade• Digitalis overdose

Reduced urinary potassium excretion• Hypoaldosteronism• Renal failure• Effective circulating volume depletion• Hyperkalemic type 4 renal tubular acidosis

Hyperkalemia Causes

Page 39: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Hyperkalemia

• Identify condition that predisposes to hyperkalemia.

• Asymptomatic

• Generalised fatigue

• Paralysis

• Palpitations

Page 40: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

• Severe Hyperkalemia-

Absence of P waves

Intraventricular blocks,BBB,

Progressive widening of QRS complex

Sine wave pattern ventricular fibrillation,asystole

Page 41: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.
Page 42: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

Treatment

• Drug therapy

• Diet therapy– Can prevent as well

• Hemodialysis– When urgernt – end stage ECG changes,

Serum K is high

Page 43: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.
Page 44: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.

To avoid / limit

Page 45: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.
Page 46: Dr. S. Nishan Silva (MBBS). Atherosclerosis Functions of the Plasma Lipoproteins Chylomicron—Transport of dietary triglyceride VLDL—Transport of endogenous.