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UNDERSTANDING ATHEROSCLEROSIS:

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UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D. TRADITIONAL RISK FACTORS Cholesterol-high LDL ... – PowerPoint PPT presentation

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Title: UNDERSTANDING ATHEROSCLEROSIS:


1
UNDERSTANDING ATHEROSCLEROSIS
  • THE NEW RISK FACTORS
  • June 10, 2008
  • Mordechai Litman, M.D.

2
TRADITIONAL RISK FACTORS
  • Cholesterol-high LDL
  • -low HDL
  • High Triglycerides
  • High Blood Pressure
  • Smoking
  • Obesity

3
ENHANCE Trial2008
  • Comparison of Simvistatin to Simvistatin plus
    Ezetimibe(different cholesterol-lowering drug)
  • Simvistatin lowered LDL cholesterol on average
    from 320 to 188
  • Combination drug lowered LDL to average of 134
  • But the significantly lower cholesterol had no
    further improvement in slowing carotid artery
    narrowing
  • Brought into question how significant is
    cholesterol level in itself in atherosclerosis

4
RISKS OF LOW CHOLESTEROL
  • Levels below 180 associated with increased risk
    of suicidal behaviour, depression, cancer, car
    accidents, hemorrhagic stroke
  • Cholesterol part of normal cell membrane
    function, cell receptors, and hormone production

5
NEW RISK FACTORS
  • CRPindicator of inflammation
  • Homocysteine
  • Lp(a)lipoprotein (a)
  • Ferritin
  • Oxidative Stressuncontrolled free radical damage
  • Fibrinogentendency to form clots
  • Transfats
  • Insulin Resistance
  • In general, these risk factors damage endothelium
    (lining of arteries) and promote inflammation

6
OLD THEORY
  • High cholesterol causes plaque by building up on
    wall of arteriestherefore, focus was on lowering
    cholesterol as much as possible
  • BUT.
  • 1) In 10 year study period on island of Crete,
    there were no recorded heart attacks despite high
    cholesterols
  • 2) French study showed reduced risk of second
    heart attack or cardiac-related death in those
    following the Mediterranean Diet compared to
    those on a low fat cardiac diet, despite
    similar cholesterol levels in both groups

7
NEW THEORY
  • Atherosclerosis is the result of damage to the
    endothelium (inner lining of arteries) and
    inflammation causing progressive damage
  • This then allows cholesterol (especially
    oxidized LDL) to enter the artery wall-causing
    more damage and reaction from the immune
    system-builds plaque
  • Creates cycle of inflammation and plaque
  • Progressively narrows the artery and it becomes
    stiffer, interfering with blood to vital organs

8
STABLE and UNSTABLE PLAQUE
  • Stable--strong seal or cap forms over the
    plaquestill interferes with blood flow, but less
    likely to cause sudden heart attacks
  • Unstablecontinuing inflammation starts to break
    down capplaque can rupturecause clot to form
    and completely block arteryresulting in heart
    attack or stroke

9
PREVENTING PLAQUE FORMATION and INSTABILITY
  • Stop active process of atherosclerosis
  • Reduce damage to endothelium
  • Reduce inflammation
  • Reduce tendency to clot

10
CRPC-Reactive Protein
  • Mediator of inflammation-normally rises
    transiently to help fight infection
  • Constant high levels reflect inappropriate
    inflammation
  • Abdominal fat can lead to increased levels of CRP
    (one of the ways that obesity increases risk)
  • High CRP statistically related to increased risk
    of heart attack and stroke

11
HOMOCYSTEINE
  • Amino acid (metabolite of important amino acid
    methionine)
  • Usually metabolized further to useful substances
  • Can build up if not processed properly
  • High homocysteine associated with increased
    atherosclerosis (and many other chronic diseases)
  • Causes damage in the arterial wall and oxidizes
    (damages) cholesterol and proteins

12
LIPOPROTEIN (a)Lp(a)
  • Functions normally in role of basic repair of
    damage in arterial wall
  • When in excess (usually in response to
    inflammation or insufficient amounts of Vitamin
    C), it becomes a more powerful promoter of plaque
    than LDL
  • In medical studies, there is a connection between
    high Lp(a) and poor outcomes of angioplasty or
    by-pass surgery

13
FERRITIN
  • Measurement of iron levels in the body
  • Too much iron can oxidize LDL, making it more
    likely to form plaque
  • Can damage endothelial cells
  • Can promote inflammation
  • Finnish Studymen aged 42-60 yrs with ferritin
    levels above 200 had 2x risk of heart attack. If
    combined with high LDL, then there was 5x risk.

14
OXIDATIVE STRESS
  • Free radical (positively-charged) atoms
  • Can damage DNA, proteins, mitochondria (cells
    main energy producers)
  • Can oxidize LDL, increasing plaque-forming
    tendency
  • Major factor in aging process in general
  • Free radicals produced as product of normal
    metabolism or taken into the body as toxins eg.
    smoking
  • Also generated by high refined sugar intake,
    heavy metals (eg lead, mercury), stress,
    radiation
  • Controlled by antioxidantsboth those produced in
    the body or taken in food or supplements
  • If insufficient antioxidants to control free
    radicals, then resulting damage known as
    oxidative stress

15
FIBRINOGEN
  • Factor in blood clotting--needed in normal
    process to stop bleeding
  • Too much can promote abnormal blood clots
  • High levels are a risk for heart attack, stroke,
    sudden death, and re-stenosis after angioplasty
  • Smoking raises fibrinogen
  • Low estrogen in women and low testosterone in
    both sexes raises fibrinogen

16
TRANSFATTY ACIDS
  • Artificially hydrogenated fatty acidsmade in
    order to prolong shelf life
  • Can also occur when heating many oils at high
    temperatures
  • Associated with-increased free radical damage to
    cell membranes
  • -increased
    inflammation
  • -raised Lp(a)
  • -promotion of LDL
    oxidation
  • -lowered HDL

17
INSULIN RESISTANCE
  • Combination of both high insulin and high blood
    sugar
  • The cells do not respond as well to insulinmore
    than normal amounts needed to get response
  • Both high insulin and high glucose can cause
    damage
  • Glycationglucose binds to and damages healthy
    proteins
  • Increase tendency of blood to clot
  • Increase tendency of blood vessels to constrict
  • Increase blood pressure
  • Probably result of prolonged high intake of
    refined sugars and starches requiring need for
    high output of insulin to deal with it

18
MANAGING THE RISKS
  • Diet--low in refined carbohydrates, hydrogenated
    fats, toxins
  • --high in fruits/vegetables with high
    antioxidant and high anti-inflammatory nutrients
  • Appropriate supplements
  • Physical activity
  • No smoking
  • Manage stress

19
SUPPLEMENTS
  • Vitamins, minerals, and food extracts can modify
    many risk factors
  • Usually need to be used in combinationsgenerally
    more effective than individual supplements
  • Some studies had negative results because they
    either used low doses, less effective forms of
    vitamins, or high doses of isolated vitamins
    without their needed partners

20
SUPPLEMENTS
  • Some related research
  • Vit C or E alone decreased 3 year carotid artery
    disease progression by 5. But together,
    progression is slowed by 45
  • Vit C, E, A, beta-carotine together improved
    post-MI recovery and decreased death rate by 1/3
    in the first month following heart attack
  • Combinations of anti-oxidants protect against
    arrhythmia and heart attack in bypass surgery
    patients

21
OMEGA-3 FATTY ACIDS (FISH OIL)
  • Decreases Lp(a)
  • Decreases triglycerides
  • Decreases blood pressure
  • Decreases inflammation in artery wall
  • Decreases clot formation
  • May help counteract arrhythmias
  • Large Italian study showed that supplementation
    with 850 mg of EPA/DHA reduced the risk of sudden
    cardiac death and all causes of death by 30 over
    a 1 year period

22
MAGNESIUM
  • Deficiency now common due to lower levels in many
    foods than in the past
  • Magnesium necessary for many biochemical
    processes in the body
  • Helps
  • Stabilize plaque
  • Decrease arrhythmias
  • Dilate coronary arteriesdecrease angina
  • Lower blood pressure
  • Improve energy production in heart muscle

23
MAGNESIUM--Studies
  • AmJCard 2003 study from Israel, U.S.,Austria.
    Magnesium improved exercise tolerance and
    quality of life in heart patients
  • Honolulu Heart Program 7000 patients followed
    for over 30 years. Those with low magnesium
    intake had almost 2x risk of heart attack
    compared to those with high intake
  • CurrOpinLipidol 2008 Role of dietary magnesium
    in cardiovascular disease, prevention, insulin
    sensitivity and diabetes
  • -lowers inflammation
  • -decreases oxidative stress
  • -decreases endothelial dysfunction
  • -reduces platelet aggregation (helps
    prevent clots)

24
MAGNESIUM- Studies
  • IntJCardiol 2008 Magnesium orotate in severe
    congestive heart failure
  • Double-blind trial of patients receiving
    optimal cardiovascular medication
    with either magnesium or a placebo.
  • Only 52 of medication-only group alive
    after 1 year.
  • 76 of magnesium group alive after 1
    year.
  • Conclusion in study adding magnesium improved
    survival and lessened symptoms.

25
VITAMIN C
  • For people with atherosclerosis, Vit C can
    decrease heart attacks and deaths by 40-60
  • Decreases the need for repeat angioplasty by 57
  • Improves endothelial function
  • Lowers CRP
  • Decreases harmful effects of Lp(a) and
    Homocysteine
  • An analysis of 9 major studies showed that those
    who take more than 700 mg of Vit C per day had
    30 less CVD mortality compared to non-users

26
VITAMIN C--Study
  • 2002 Italian study followed 1000 patients for
    over 10 years1/2 received 1000 mg Vit C per day
  • -those with mild atherosclerosis at beginning
    showed significant progression of disease in 13
    without Vit C supplement compared to 3 with Vit
    C
  • -those with moderate plaque at beginning
    showed deterioration in 38 without Vit C and 8
    with Vit C
  • -those with more severe plaque at beginning
    showed deterioration in 66 without Vit C and 21
    with added Vit C

27
NIACIN-Vitamin B3
  • Lowers LDL
  • Lowers triglycerides
  • Lowers Lp(a)
  • Raises HDL
  • Improves almost all of the lipid disorders
    associated with atherosclerosis
  • Many studies done over many years have shown that
    niacin reduces progression of atherosclerosis and
    mortality from heart disease
  • Main problem in past with niacin use was the
    niacin flushmainly when first starting niacin
    at high doses.
  • --can avoid it with use of new
    no-flush niacin, but may need higher to get
    same results

28
B VITAMINS HOMOCYSTEINE
  • The enzymes needed to metabolize Homocysteine
    require sufficient amounts of vitamins B6, B12,
    Folic acidor the homocysteine levels can rise to
    dangerous levels
  • JAMA 2002-study of patients after angioplasty
  • -1/2 of group was given added
    B6, B12, Folic acid and ½ given placebo
  • -in group given B vitamins,
    19 showed re-narrowing of arteries after 6
    months
  • -in placebo group, 38 showed
    re-narrowing
  • Some studies indicated that those already with
    severe disease, treatment of homocysteine may not
    be very effective or it may need even greater
    lowering of the levels than was accomplished in
    those studies

29
VITAMIN E
  • Complex of 8 different molecules (most commercial
    supplements contain only 1 component)
  • Conclusions of some medical studies
  • 1) decreased by 50 the 2 year heart attack
    rate in newly diagnosed CVD patients
  • 2) decreased disease progression following
    by-pass surgery
  • 3) decreased by an additional 50 the
    incidents of strokes when added to ASA as
    prevention
  • There have been recent controversies from some
    negative studies. There are problems with
    results if only testing 1 of 8 components rather
    than a normal physiological blend. Also problems
    when not combining with other antioxidants that
    normally work as a team with Vit E

30
VITAMIN K2
  • Vitamin K needed to make clotting factors
  • Newer research looking into the effects on bone
    density and health of blood vessels
  • Helps to reduce calcium in plaque (which is
    related to the severity of atherosclerosis) and
    increases calcium in bone eg. puts calcium where
    it is needed and removes it from where it is
    harmful
  • ( caution when using it along with Coumadin, a
    blood thinnerneed to monitor closely)

31
VITAMIN D
  • Low levels are associated with increased
    cardiovascular disease, high blood pressure,
    stroke (and many other diseases)
  • Deficiency is now commoneven taking the old
    RDAs was insufficient to maintain normal blood
    levelsrecommended intakes are continually
    increasingold concerns about toxicity have been
    shown to have been greatly exaggerated when using
    Vit D3(natural vit D)
  • Can now follow by measuring blood levels

32
CO-ENZYME Q10 (CoQ10)
  • Produced in all cells in the body
  • Powerful antioxidant
  • Involved in energy production in cells
  • Highest levels normally in heart muscleuses the
    highest amount of energy
  • Protects endothelium from free-radical damage (
    especially when combined with other antioxidants
    )
  • Can help lower blood pressure
  • Heart failure correlated to low CoQ10 levels
  • Studies show significant benefit for heart
    failure and improving results of by-pass surgery
  • (CoQ10 levels are significantly lowered by statin
    usesame enzyme involved in cholesterol
    production also used in CoQ10 production)

33
POMEGRANATE JUICE
  • Research study in ClinNutr 2004
  • Title Pomegranate juice consumption for 3 years
    by patients with carotid artery stenosis reduces
    common carotid intima thickness, blood pressure
    and LDL oxidation
  • Patients with severe carotid artery stenosis
    (narrowing) treated with drugs (statins and blood
    pressure drugs) or the same drugs plus
    pomegranate juice.
  • Results-drugs only group showed 9 increase in
    intima thickness (worsening) after 1 year
  • -pomegranate plus drugs showed a 35
    decrease (improvement) in thickness and a 44
    increase in carotid blood flow after 1 year

34
HORMONES AND THE HEART--TESTOSTERONE
  • Higher physiological levels associated with lower
    cardiovascular disease
  • Decreases clotting tendency
  • Decreases fibrinogen
  • Decreases Lp(a)
  • Decreases triglycerides
  • Decreases blood pressure
  • Decreases abdominal fat
  • Increases HDL
  • Improves blood sugar control
  • Used in Europe for many years in management of
    heart disease (if levels low on testing)

35
HORMONES AND THE HEART--ESTROGEN
  • Inhibits vasoconstriction
  • Lowers fibrinogen
  • Decreases LDL, increases HDL
  • Improves insulin sensitivity
  • Lowers Lp(a)
  • Meta-analysis of HRT and Heart Disease Risk
  • JGenIntMed 2007
  • Results 32 reduction in coronary heart disease
    events (eg heart attack) for women who start
    treatment in their 50s (soon after menopause)
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