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Presentation on theme: "UNDERSTANDING ATHEROSCLEROSIS: THE NEW RISK FACTORS June 10, 2008 Mordechai Litman, M.D."— Presentation transcript:


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

3 ENHANCE Trial 2008 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 rupture cause 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 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 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

20 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

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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