Cardiovascular Disease:

Prevention and Treatment

Dietary Factors that
Affect Blood Lipids
Saturated Fatty Acids
 Elevate blood cholesterol in all lipoprotein
fractions (LDL and HDL) when substituted
for CHO or other fatty acids
 Dose-response between SFA and LDL-C
– For every 1% of energy intake increase in sfa,
plasma cholesterol increases 2.7%
 Most hypercholesterolemic sfas are lauric
(C12:0) myristic (C14:0) and palmitic
(C16:0) (palmitic is 60% of sfa intake)
 Stearic (C18:0) is neutral
Saturated Fatty Acids
 The most hypercholesterolemic fats
are palm kernel, coconut and palm
oils, lard, and butter
 SFAs also associated with CAD
progression: milk, cheese, butter,
lamb, bakery goods, fast foods, snacks
 Average American intake is 11% of
kcals
Polyunsaturated Fatty
Acids
 If CHO is replaced by linoleic acid
(C18:2) LDL-C ↓ and HDL-C ↑
 When SFA is replaced by PUFA in a
low fat diet, both LDL and HDL ↓
 Eliminating SFA is twice as effective in
lowering cholesterol as ↑ PUFA
 A 1% increase in PUFA ↓ TC by 1.4
mg/dl
Polyunsaturated Fatty
Acids
 Major source of omega-6 PUFAs are
vegetable oils, salad dressings, and
margarines made with the oil
 U.S. population intake 7% of calories
 Large amounts may increase LDL
oxidation
Omega-3 Polyunsaturated
Fatty Acids: EPA, DHA
 Found in fish oils, fish oil capsules, and
ocean fish (eicosapentaenoic and
docosahexaenoic acid)
 Do not affect TC; may ↑ LDL-C (5-10%) and
decrease TG (25-30%) especially in patients
with high TG
 Anticoagulant effect
 Decrease vasoconstriction
 Improve endothelial dysfunction
 Reduce inflammation
Omega-3 Fatty Acids: ALA

 Alpha-linolenic acid
 An essential fatty acid
 Shorter-chain found in various plant
sources such as flax, canola, walnuts,
and soy
 Benefits less clear; may protect
against CVD by reducing inflammation
Omega-3 Fatty Acids
 Consumption of fish and fish oils rich
in EPA, DHA will lower cholesterol,
LDL, and TG and reduce sudden
cardiac death
 One fatty fish meal/week resulted in
50% decrease in risk of cardiac arrest
 1 g supplement of omega-3 daily
reduced risk of CVD, nonfatal MI,
nonfatal stroke
Cis-Monounsaturated Fat

 Naturally occurring monounsaturated

fat
 Found in olive oil, canola oil, avocado,
olives, pecans, peanuts, and other
nuts
 Oleic acid is the most prevalent MFA in
the US diet
Cis-Monounsaturated Fat
 When fat is replaced by CHO, it lowers
HDL as well as LDL-C
 When sfa is replaced by mfa, lowers
LDL-C without lowering HDL-C
 When substituted for carbohydrate,
mfa reduces serum triglyceride levels
 Can recommend a higher fat diet if
much of the fat comes from mfa
Cis-Monounsaturated Fat
 Mediterranean diet: high in fat,
especially MFA (olive oil), fish, nuts,
low in red meat associated with ↓ risk
of CVD
 Emphasizes fruits, root vegetables, flax,
canola
 High fat diets should be used with
caution
Trans-Monounsaturated
Fats
 Produced in the hydrogenation process
 Commonly used in the food industry to
harden unsaturated oils and soft margarines
 50% of trans-fatty acids come from animal
foods (beef, butter, milk fats)
 Major foods sources in US are stick
margarine, shortening, commercial frying
fats, high fat baked goods
Trans Fatty Acids

 Elaidic acid (trans-isomer of oleic acid)

raises blood cholesterol compared with
PUFA
 Has less of a cholesterol raising effect
than sfa
 Lowers HDL
Margarine vs Butter
 The combined amount of saturated fat and
trans fat in butter is higher than that in
margarine
 Soft or liquid margarine is the preferred
spread
 Average intake of trans fats is 7-8% of total
fat intake
 Choose lowfat desserts, dairy products,
meats will lower trans fatty acid intakes
Fat Type Per Serving
Product Total Sfa g Trans Combi choles
fat g fat g ned terol
Butter 10.8 7.2 .3 7.5 31.1

Stick 11 2.1 2.8 4.9 0

marg
Spread 9.7 1.8 2.7 4.5 0
marg
Tub 6.7 1.2 .6 1.8 0
marg

Source: FDA http://www.cfsan.fda.gov/~dms/qatrans2.html

Total Fat Content of Diet
 High fat diets are associated with obesity,
which increases the risk of CHD
 Low fat diets (<25% of kcals from fat) raise
triglycerides and lower HDL; however these
changes are not associated with ↑ risk
 Low fat diets lower LDL only when they are
low in sfa
 AHA: total fat <30% of kcals
 ATP III: 25%-35% of kcals from fat
Dietary Cholesterol
 Dietary cholesterol raises total and LDL-
cholesterol, but less than sfa
 A 25 mg increase in dietary cholesterol
raises serum cholesterol 1 mg/dl
 At 500 mg intake, increments are even
less; appears to be a threshold for
response
 TLC guidelines: <200 mg/day
 AHA guidelines: <300 mg/day
Dietary Cholesterol
 Response to dietary cholesterol is
highly variable; hyper-responders may
have poor rates of conversion of
cholesterol to bile acids
 Dietary intakes of cholesterol have
been declining since the 1960s
 Intake acts synergistically with sfa;
positively related to CHD risk
Fiber

 Soluble fibers (pectins, gums,

mucilages, algal polysaccharides, some
hemicelluloses) in legumes, oats, fruit
and psyllium lower serum cholesterol
and LDL-C
 Quantity needed varies by food (more
legumes than pectins or gums)
Fiber

 Average decline in LDL-C is 14% for

hypercholesterolemics and 10% for
normocholesterolemics when soluble
fiber is added to a low fat diet
 Fiber may bind bile acids, which
lowers serum cholesterol to replete the
bile acid pool
Fiber
 Insoluble fibers have no effect
(celluloses and lignin)
 Of total fiber (25-30 grams) 6 to 10
grams should be from soluble fiber
 Can be achieved with 5 or more
servings of fruits or vegetables a day
and 6 or more servings of whole grains
and high-fiber cereals
Alcohol
 Affects total triglyceride and HDL-C
 Effects on TG are dose dependent and are
greater in persons with TG>150 mg/dl
 Moderate alcohol consumption has been
associated with decreased risk of MI and
CHD mortality in white men
 Alcohol raises both HDL2 and HDL3
subfractions
 Current intake in US is 2% of total kcals
 No increase is recommended to decrease
CHD risk
Coffee
 Mixed results in studies on effect of
coffee on lipids
 Heavy intake of regular coffee (720 ml)
causes minor increases in TC (9 mg/dl)
LDL-C (6 mg/dl) and HDL-C (4 mg/dl)
 Boiled coffee (European) produces
greater elevations than filtered coffee
Coffee

 Large population studies have failed to

find associations between coffee
consumption and CHD incidence or
mortality
 Coffee drinkers consume more
saturated fat and cholesterol, smoked
more cigarettes, and were less likely
to exercise
Antioxidants
 Antioxidants have been studied for possible
role in preventing oxidation of LDL-C
 Epidemiological studies suggest vitamin E
and carotenoids are inversely related to
CVD, but randomized trials have not
supported this
 Vitamin E: no primary or secondary
prevention trials show positive effect
 B-carotene supplements appear to have no
benefits
 Use food sources
Calcium

 Supplementation produces small

decreases in LDL-C in
hypercholesterolemic men
 May form insoluble soaps with fatty
acids
Soy Protein
 Substituting soy protein lowers TC (9%) and
LDL-C (13%) and TG (11%) with no effect
on HDL-C
 Effect in addition to a Step 1 diet; occurs
only in persons with hypercholesterolemia
 Dose response
 Daily intake of 25 g of soy will lower LDL-C
by 4 to 8% in hypercholesterolemic persons
Stanols/Sterols
 Isolated from soybean oils or pine tree
oil
 Lowers blood cholesterol
 Esterified and made into margarines
 Consuming 2-3 grams/day lowers
cholesterol by 9-20% in persons with
hypercholesterolemia
 Inhibits absorption of dietary cholesterol
Stanols/Sterols
Nuts
 Tree nuts can reduce risk of CHD via lipid-
lowering effects;
 Peanuts also cardioprotective
 Almonds, hazelnuts, pecans, pistachio nuts,
and walnuts modestly reduce serum
cholesterol
 Nuts are a rich source of fiber, vitamin E,
magnesium, and MUFA and PUFA
 ALA in walnuts, arginine, and antioxidant
and antithrombotic effects
 May reduce insulin resistance
Nuts

 Epidemiological evidence suggests an

inverse relationship between nut
consumption and CHD risk and type 2
diabetes
 Nurses’ Health Study: women who ate
5+ servings lowered risk of CHD by
45%
Nuts

 Recommend 1 to 2 ounces of nuts (1

to 2 large handfuls) in place of other
sources of energy
 Choose unsalted, roasted, or raw nuts
Garlic

 Anti cholesterolemic
 Lowers blood pressure
AHA 2006 Diet/Lifestyle
Recommendations for CVD Risk
Reduction
 These recommendations apply to the
general public for primary prevention
and can be used clinically
 New focus on weight management
 More focus on practical strategies for
implementation
AHA 2006 Diet/Lifestyle
Recommendations for CVD Risk
Reduction
 Balance calorie intake and physical
activity to achieve or maintain a
healthy body weight.
 Consume a diet rich in vegetables and
fruits
 Choose whole-grain, high-fiber foods
 Consume fish, especially oily fish, at
least twice a week
Circulation 2006;114:82-96
AHA 2006 Diet/Lifestyle
Recommendations for CVD Risk
Reduction
 Limit your intake of SFA to <7% of
energy, trans fat to <1% of energy,
cholesterol to <300 mg/day by
– Choosing lean meats and vegetable
alternatives
– Selecting fat-free (skim), 1%-fat, and
lowfat dairy products, and
– Minimizing intake of partially hydrogenated
fats
Circulation 2006;114:82-96
AHA 2006 Diet and Lifestyle
Recommendations for CVD Risk
Reduction
 Minimize your intake of beverages and foods
with added sugars
 Choose and prepare foods with little or no salt
 If you consume alcohol, do so in moderation
 When you eat food that is prepared outside of
the home, follow the AHA Diet and Lifestyle
Recommendations

Circulation 2006;114:82-96
Implementation 2006 AHA
Diet/Lifestyle Guidelines
 Know your calorie needs to achieve and
maintain a healthy weight
 Know the calorie content of the foods and
beverages you consume
 Track your weight, physical activity, and
calorie intake
 Prepare and eat smaller portions
 Track and, when possible, decrease screen
time

Circulation 2006;114:82-96
Implementation 2006 AHA
Diet/Lifestyle Guidelines
 Incorporate physical movement into
habitual activities
 Do not smoke or use tobacco products
 If you consume alcohol, do so in
moderation (1 drink/day in women, 2
in men)

Circulation 2006;114:82-96
Implementation 2006 AHA
Diet/Lifestyle Guidelines
 Use the nutrition facts panel and ingredients
list when choosing foods to buy
 Eat fresh, frozen, and canned vegetables
and fruits without high-calorie sauces and
added salt and sugars
 Replace high-calorie foods with fruits and
vegetables
 Increase fiber intake by eating beans, whole
grain products, fruits and vegetables

Circulation 2006;114:82-96
Implementation 2006 AHA
Diet/Lifestyle Guidelines
 Use liquid vegetable oils in place of solid
fats
 Limit beverages and foods high in added
sugars (fructose, sucrose, glucose, maltose,
dextrose, corn syrups, concentrated fruit
juice, and honey
 Choose foods made with whole grains
 Cut back on pastries and high-calorie bakery
products (e.g. muffins, doughnuts)

Circulation 2006;114:82-96
Implementation 2006 AHA
Diet/Lifestyle Guidelines
 Select milk and dairy products that are
either fat free or lowfat
 Reduce salt intake by
– Comparing the sodium content of similar
products and choosing those with less
– Choosing processed foods, including
cereals and baked goods that are reduced
in salt
– Limiting condiments, e.g. soy sauce,
catsup
Circulation 2006;114:82-96
Implementation 2006 AHA
Diet/Lifestyle Guidelines
 Use lean cuts of meat and remove skin from
poultry before eating
 Limit processed meats that are high in
saturated fat and sodium
 Grill, bake, or broil fish, meat and poultry
 Incorporate vegetable-based meat
substitutes into favorite recipes
 Encourage the consumption of whole
vegetables and fruits in place of juices

Circulation 2006;114:82-96
AHA on Antioxidant
Supplements
 Antioxidant vitamin supplements or other
antioxidants such are selenium are not
recommended
 Although observational studies suggest
that high intakes of antioxidant vitamins
from food and supplements are associated
with lower risk of CVD, intervention trials
have not confirmed this

Circulation 2006;114:82-96
Antioxidant Supplements
 Trials have documented potential harm, e.g.
higher risk of lung cancer with beta-
carotene supplements in smokers and
increased risk of heart failure and total
mortality from high dose vitamin E
supplements
 Although supplements are not
recommended, food sources of antioxidant
nutrients are
Circulation 2006;114:82-96
AHA on Soy Protein

 Evidence of a direct cardiovascular

health benefit from consuming soy
protein is minimal
 However, there may be some benefit if
soy protein is used to replace animal
and dairy products that contain SFA
and cholesterol

Circulation 2006;114:82-96
AHA on Folate and Other
B Vitamins
 Evidence is inadequate to recommend folate
and other B vitamins to reduce heart
disease risk
 Folate intake and B6 and B12 are inversely
associated with serum homocysteine levels,
which are associated with increased risk of
CVD
 Trials of homocysteine-reducing vitamin
therapy have been disappointing
Circulation 2006;114:82-96
AHA on Fish Oil
Supplements
 Fish intake is associated with decreased risk
of CVD
 Patients without documented CHD eat fish,
preferably oil fish, twice a week
 Patients with documented CVD should
consume ~1 gram of EPA + DHA per day,
preferably from oily fish, though
supplements can be considered with
physician input
Circulation 2006;114:82-96
Fish Oil Supplements

 For persons with hypertriglyceridemia,

2 to 4 g of EPA + DHA per day,
provided as capsules under a
physician’s care are recommended.

Circulation 2006;114:82-96
LDL-C Goals and Cutpoints for TLC
and Drug Therapy by Risk Categories
LDL Level to LDL Level at
LDL Goal Initiate Which
(mg/dL) Therapeutic to Consider
Lifestyle Changes Drug Therapy
Risk Category
(TLC) (mg/dL) (mg/dL)
CHD or CHD Risk <100 130
Equivalents
Optional Goal: 100 (100–129: drug
(10-year risk
< 70 mg/dl optional)
>20%)
10-year risk 10–
2+ Risk Factors 20%: 130
(10-year risk <130 130
20%) 10-year risk
<10%: 160
190
(160–189: LDL-
0–1 Risk Factor <160 160
lowering drug
optional)
Therapeutic Lifestyle Changes in
LDL-Lowering Therapy
 TLC Diet
– Reduced intake of cholesterol-raising nutrients
(same as previous Step II Diet)
 Saturated fats <7% of total calories
 Dietary cholesterol <200 mg per day
– LDL-lowering therapeutic options
 Plant stanols/sterols (2 g per day)
 Viscous (soluble) fiber (10–25 g per day)
 Weight reduction
 Increased physical activity
 Steps in
Therapeutic Lifestyle Changes
Visit 2 Visit 3
Evaluate LDL Evaluate LDL Visit N
Visit I 6 wks response 6 wks response Q 4-6 mo
Monitor
Begin If LDL goal not If LDL goal not Adherence
Lifestyle achieved, intensify achieved, to TLC
Therapies LDL-Lowering Tx consider
• Emphasize adding drug Tx
reduction in • Reinforce reduction
saturated fat &
in saturated fat and
cholesterol • Initiate Tx for
cholesterol
• Encourage Metabolic
• Consider adding Syndrome
moderate physical plant stanols/sterols
activity • Intensify weight
• Increase fiber intake mgt &
• Consider referral to
a dietitian
• Consider referral to physical activity
a dietitian • Consider referral
to a dietitian
The Metabolic Syndrome as a
Secondary Target of Therapy
 Abdominal obesity
 Atherogenic dyslipidemia
– Elevated triglycerides
– Small LDL particles
– Low HDL cholesterol
 Raised blood pressure
 Insulin resistance ( glucose intolerance)
 Prothrombotic state
 Proinflammatory state
Therapeutic Lifestyle
Changes (TLC)
 TLC Diet
– Saturated fat <7% of calories, cholesterol
<200 mg/dal
– Consider increased viscous (soluble) fiber
(10-25 g/day) and plant stanols/sterols
(2g/day)
 Weight management
 Increased physical activity
Nutrient Composition of TLC
Diet
Nutrient Recommended Intake
 Saturated fat Less than 7% of total calories
 Polyunsaturated fat Up to 10% of total calories
 Monounsaturated fat Up to 20% of total calories
 Total fat 25–35% of total calories
 Carbohydrate 50–60% of total calories
 Fiber 20–30 grams per day
 Protein Approximately 15% of total calories

 Cholesterol Less than 200 mg/day

 Total calories (energy) Balance energy intake and
expenditure to maintain desirable body weight
TLC Diet
Food Amount
Breads and cereals >6 servings (adjust to
meet energy needs)
Vegetables and 3-5 servings vegetables
fruits 2-4 servings fruits
Dairy products 2-3 servings
Eggs <2 yolks per week
Meat, fish, poultry <5 ounces per day
Fats and oils Adjust to caloric level
TLC: Healthy Cooking
 Bake, steam, roast, broil, stew or boil
instead of frying
 Remove poultry skin before eating
 Use a nonstick pan with cooking oil
spray or small amount of liquid
vegetable oil instead of lard, butter,
shortening, other solid fats
 Trim visible fat before you cook meats
 Chill meat and poultry broth until fat
becomes solid, remove
TLC Diet: Eat More
 Fresh, frozen, canned vegetables without added
fat, sauce, salt
 Fresh, frozen, canned or dried fruit
 Nonfat, ½%, and low-fat milk, buttermilk, yogurt,
cheese
 Unsaturated oils, soft or liquid margarines and
spreads, salad dressings, seeds and nuts
 Lean cuts of meat; extra lean hamburger, fish;
meat alternatives made with soy or TVP
 Whole grain breads and cereals, pasta, rice,
potatoes, dried beans and peas, lowfat crackers,
pretzels, cookies
TLC Diet: Eat Less
 High-fat bakery products (doughnuts,
biscuits, croissants, pies, cookies
 Chips, cheese puffs, snack mix,
regular crackers, buttered popcorn
 Whole and reduced-fat milk and dairy
products, ice cream, cream, half and
half, cream cheese, sour cream and
cheese
TLC Diet: Eat Less
 Whole eggs, yolks
 Fatty meat such as ribs, tbone steak,
regular hamburger, bacon, sausage,
salami, hot dogs, organ meats, liver,
brains, sweetbreads, fried meat,
poultry and fish
 Butter, shortening, stick margarine,
chocolate, tropical oils, coconut, palm
and palm kernel
Dealing with Problem
Foods
 Reduce the portion size
 Prepare the food more healthfully
 Reduce the frequency it is eaten
 Substitute a more healthful food for
the problem food
TLC: Healthy Shopping
 Choose chicken breast or drumstick
instead of wing and thigh
 Select skim milk or 1 percent instead
of 2 percent or whole milk
 Buy lean cuts of meat such as round,
sirloin, and loin
 Buy more vegetables, fruits and grains
 Read nutrition labels on food packages
TLC: Dining Out

 Choose restaurants that have low fat

options available
 Ask that sauces, gravies, and salad
dressings be served on the side
 Control portions by asking for an
appetizer serving or sharing with a
friend
TLC: Dining Out
 At fast food restaurants, go for salads,
grilled (not fried or breaded) skinless
chicken sandwiches, regular-sized
hamburgers, or roast beef sandwiches
 Avoid regular salad dressings and fatty
sauces. Limit jumbo or deluxe burgers,
sandwiches, french fries, and other foods.
 Lipid-Lowering Drugs
Added if Diets Are Not Successful

 After a 6-month trial on each diet, drugs are

added to the treatment.
 Types:
 Nicotinic acid and lovastatin
 Gemfibrozil, probucol, clofibrate—for high
TGs
 Cholestyramine and colestipol (bile acid
sequestrants)—to lower high cholesterol;
may increase TGs
HMG CoA Reductase Inhibitors
(Statins)
 Reduce LDL-C 18–55% & TG 7–
30%
 Raise HDL-C 5–15%
 Major side effects
– Myopathy
– Increased liver enzymes
 Contraindications
– Absolute: liver disease
– Relative: use with certain drugs
HMG CoA Reductase
Inhibitors (Statins)
Statin Dose Range
Lovastatin 20–80 mg
Pravastatin 20–40 mg
Simvastatin 20–80 mg
Fluvastatin 20–80 mg
Atorvastatin 10–80 mg
Cerivastatin 0.4–0.8 mg
Bile Acid Sequestrants
Major actions
– Reduce LDL-C 15–30%
– Raise HDL-C 3–5%
– May increase TG
 Side effects
– GI distress/constipation
– Decreased absorption of other drugs
 Contraindications
– Dysbetalipoproteinemia
– Raised TG (especially >400 mg/dL)
Bile Acid Sequestrants

Drug Dose
Range
Cholestyramine 4–16 g
Colestipol 5–20 g
Colesevelam 2.6–3.8
g
Nicotinic Acid
 Major actions
– Lowers LDL-C 5–25%
– Lowers TG 20–50%
– Raises HDL-C 15–35%
 Side effects: flushing, hyperglycemia,
hyperuricemia, upper GI distress,
hepatotoxicity
 Contraindications: liver disease, severe
gout, peptic ulcer
Nicotinic Acid
Drug Form Dose
Range

Immediate release 1.5–3 g

(crystalline)
Extended release 1–2 g
Sustained release 1–2 g
Fibric Acids
Major actions
– Lower LDL-C 5–20% (with normal TG)
– May raise LDL-C (with high TG)
– Lower TG 20–50%
– Raise HDL-C 10–20%
 Side effects: dyspepsia, gallstones,
myopathy
 Contraindications: Severe renal or
hepatic disease
Fibric Acids

Drug Dose
 Gemfibrozil 600 mg BID
 Fenofibrate 200 mg QD
 Clofibrate 1000 mg
BID
Secondary Prevention

Patients with established CHD have 5-7x

greater risk of subsequent MI
 Smoking cessation

 Reducing BP to <140/90 or 130/85

with CHF, renal insufficiency, DM
 Reduce LDL-C to <100 mg/dl; non-
HDL levels to <130 mg/dl
Secondary Prevention
(cont)
 Moderate physical activity for 30
minutes daily 3-4 days a week
 Weight management to attain BMI<25
 A1C<7%
 Use of 75 to 325 mg aspirin daily
unless contraindicated
 Use of ACE inhibitors and B-blockers
indefinitely