understanding atherosclerosis: the new risk factors june 10, 2008 mordechai litman, m.d
TRANSCRIPT
![Page 1: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/1.jpg)
UNDERSTANDING ATHEROSCLEROSIS:
THE “NEW” RISK FACTORS
June 10, 2008Mordechai Litman, M.D.
![Page 2: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/2.jpg)
TRADITIONAL RISK FACTORS
Cholesterol-high LDL
-low HDL High Triglycerides High Blood Pressure Smoking Obesity
![Page 3: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/3.jpg)
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
![Page 4: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/4.jpg)
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
![Page 5: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/5.jpg)
“NEW RISK FACTORS”
• CRP—indicator of inflammation• Homocysteine• Lp(a)—lipoprotein (a)• Ferritin• Oxidative Stress—uncontrolled free radical damage• Fibrinogen—tendency to form clots• Transfats• Insulin ResistanceIn general, these risk factors damage endothelium (lining of
arteries) and promote inflammation
![Page 6: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/6.jpg)
“OLD THEORY”
High cholesterol causes plaque by building up on wall of arteries—therefore, 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
![Page 7: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/7.jpg)
“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
![Page 8: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/8.jpg)
STABLE and UNSTABLE PLAQUE
Stable--strong “seal” or cap forms over the plaque—still interferes with blood flow, but less likely to cause sudden heart attacks
Unstable—continuing inflammation starts to break down cap—plaque can rupture—cause clot to form and completely block artery—resulting in heart attack or stroke
![Page 9: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/9.jpg)
PREVENTING PLAQUE FORMATION and INSTABILITY
Stop active process of atherosclerosis: Reduce damage to endothelium Reduce inflammation Reduce tendency to clot
![Page 10: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/10.jpg)
CRP—C-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
![Page 11: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/11.jpg)
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
![Page 12: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/12.jpg)
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
![Page 13: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/13.jpg)
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 inflammationFinnish Study—men 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.
![Page 14: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/14.jpg)
OXIDATIVE STRESS Free radical (positively-charged) atoms Can damage DNA, proteins, mitochondria (cell’s 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 antioxidants—both 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
![Page 15: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/15.jpg)
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
![Page 16: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/16.jpg)
TRANSFATTY ACIDS
Artificially hydrogenated fatty acids—made 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
![Page 17: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/17.jpg)
INSULIN RESISTANCE Combination of both high insulin and high blood sugar The cells do not respond as well to insulin—more than
normal amounts needed to get response Both high insulin and high glucose can cause damage Glycation—glucose 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
![Page 18: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/18.jpg)
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 activityNo smokingManage stress
![Page 19: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/19.jpg)
SUPPLEMENTS
Vitamins, minerals, and food extracts can modify many risk factors
Usually need to be used in combinations—generally 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”
![Page 20: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/20.jpg)
SUPPLEMENTS
Some related research:1) Vit C or E alone decreased 3 year carotid
artery disease progression by 5%. But together, progression is slowed by 45%
2) 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
3) Combinations of anti-oxidants protect against arrhythmia and heart attack in bypass surgery patients
![Page 21: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/21.jpg)
OMEGA-3 FATTY ACIDS (FISH OIL)
Decreases Lp(a)Decreases triglyceridesDecreases blood pressureDecreases inflammation in artery wallDecreases clot formationMay help counteract arrhythmiasLarge 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
![Page 22: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/22.jpg)
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 plaqueDecrease arrhythmiasDilate coronary arteries—decrease anginaLower blood pressure Improve energy production in heart muscle
![Page 23: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/23.jpg)
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)
![Page 24: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/24.jpg)
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.
![Page 25: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/25.jpg)
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 functionLowers CRPDecreases harmful effects of Lp(a) and
HomocysteineAn 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
![Page 26: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/26.jpg)
VITAMIN C--Study
2002 Italian study: followed 1000 patients for over 10 years—1/2 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
![Page 27: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/27.jpg)
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 flush”—mainly 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
![Page 28: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/28.jpg)
B VITAMINS & HOMOCYSTEINE
The enzymes needed to metabolize Homocysteine require sufficient amounts of vitamins B6, B12, Folic acid—or 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
![Page 29: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/29.jpg)
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 preventionThere 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
![Page 30: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/30.jpg)
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 thinner”—need to monitor closely)
![Page 31: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/31.jpg)
VITAMIN D
Low levels are associated with increased cardiovascular disease, high blood pressure, stroke (and many other diseases)
Deficiency is now common—even taking the old RDA’s was insufficient to maintain normal blood levels—recommended intakes are continually increasing—old 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
![Page 32: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/32.jpg)
CO-ENZYME Q10 (CoQ10) Produced in all cells in the body Powerful antioxidant Involved in energy production in cells Highest levels normally in heart muscle—uses 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 use—same enzyme
involved in cholesterol production also used in CoQ10 production)
![Page 33: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/33.jpg)
POMEGRANATE JUICE
Research study in: ClinNutr 2004Title: 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
![Page 34: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/34.jpg)
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 controlUsed in Europe for many years in management of heart
disease (if levels low on testing)
![Page 35: UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D](https://reader035.vdocument.in/reader035/viewer/2022070305/5513df3c5503463a298b57ba/html5/thumbnails/35.jpg)
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 RiskJGenIntMed 2007Results: 32% reduction in coronary heart disease
events (eg heart attack) for women who start treatment in their 50’s (soon after menopause)