PowerPoint PresentationTHANK YOU DR. OZ
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Inflamation
CD40L=CD40 ligand; TNF-α=tumor necrosis factor-alpha; IL=interleukin; VCAM=vascular cell adhesion molecule;
ICAM=intercellular adhesion molecule.
Cockerill GW et al. Arterioscler Thromb Vasc Biol. 1995;15:1987-1994; Andre P et al. Circulation. 2002;106:896-899; Libby
P. Circulation. 2001;104:365-372; Libby P et al. Circulation. 2002;105:1135-1143; Ross R. N Engl J Med. 1999;340:115-126.
Vessel lumen Monocyte
(a) the lipid theory
cardiovascular risk factors are known
a. Fibrinogen
b. TMAO
c. Homocysteine
d. Lp(a)
Eugene Braunwald Professor of Medicine Brigham and Women’s Hospital,
Harvard Medical School, Boston MA, USA
Ridker ACC 2017
Additional LDL Reduction
IMPROVE-IT : Ezetimibe 6% RRR FOURIER/SPIRE: PCSK9 Inhibition q2 weeks 15% RRR
Additional Inflammation Reduction
Known Cardiovascular Disease LDL 150 mg/dL (3.8 mmol/L)
hsCRP 4.5mg/L
Ridker ESC 2017
“Residual Inflammatory Risk”
RESIDUAL INFLAMMATORY RISK: Addressing the Obverse Side of the Atherosclerosis Prevention Coin
Ridker PM. Eur Heart J 2016;37:1720-22
CAN INFLAMMATION REDUCTION
REDUCE CARDIOVASCULAR EVENT
Ridker PM. Circ Res 2016;118:145-156.
FROM CRP TO IL-6 TO IL-1: MOVING UPSTREAM TO IDENTIFY NOVEL TARGETS FOR ATHEROPROTECTION
Ridker ESC 2017
bind to human IL-1b and functionally
neutralize the bioactivity of this pro-
inflammatory cytokine
reduction for up to 3 months
Ridker ESC 2017
Stable CAD (post MI)
Persistent Elevation
Nonfatal Stroke, Cardiovascular
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h a
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Placebo SC q 3 mth
Canakinumab 50mg SC q 3 mth
Canakinumab 150mg SC q 3 mth Canakinumab 300mg SC q 3 mth
0.5 1.0 Canakinumab
CONCLUSIONS:
1. CANTOS was designed to directly test the inflammatory hypothesis of atherothrombosis.
2. As shown in these data, inhibition of IL-1 with SC canakinumab given once every three months among patients with a prior myocardial infarction substantially lowered the inflammatory biomarkers hsCRP and IL-6 while having no beneficial impact on atherogenic lipids.
3. The 150mg group met all pre-specified multiplicity adjusted thresholds for statistical significance for both the primary and secondary cardiovascular outcomes.
Ridker ESC 2017
CONCLUSIONS: THE CANAKINUMAB ANTI-INFLAMMATORY THROMBOSIS OUTCOMES STUDY (CANTOS)
In conclusion, these randomized placebo- controlled trial data demonstrate that targeting the IL-1 to IL-6 pathway of innate immunity with canakinumab reduces cardiovascular event rates. These data provide proof that inflammation inhibition, in the absence of lipid lowering, can improve atherothrombotic outcomes
Ridker ESC 2017
INFLAMMATION AND MEAT
WITH BIOMARKERS OF INFLAMMATION
• PLANT-BASED INVERSELY ASSOCIATED WITH
BIOMARKERS OF INFLAMMATION
Barbaresko J, et al. Dietary pattern analysis and biomarkers of low-grade inflammation: A systematic literature review. Nutr Rev. 2013;71:511–527. Lev SH, et al. Associations between red meat intake and biomarkers of inflammation and glucose metabolism in women. Am J Clin Nutr. 2010:99:352–360.
RED MEAT ALLERGY
AND HEART DISEASE
RED MEAT ALLERGY AND HEART DISEASE
RED MEAT ALLERGY AND HEART DISEASE
RED MEAT ALLERGY AND HEART DISEASE
Wilson JM et al. Arterioscler Thromb Vasc Biol. 2018 Jun 14. pii:
ATVBAHA.118.311222
Associated With Increased Atheroma Volume and Plaques With Unstable
SENSITIVITY, COMPARED
WITH CONVENTIONAL
DIABETES DIET.
• ↑ VISCERAL FAT → ↑
INSULIN RESISTANCE
Kahleova H, et al. Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with type 2 diabetes. Diabet Med. 2011;28:549-559. Hamdy O, et al. Metabolic obesity: The paradox between visceral and subcutaneous fat. Curr Diabetes Rev. 2006;2:367–373.
ORNISH LIFESTYLE PROGRAM: INFLAMMATION
BASED VEGAN DIET VS THE AMERICAN HEART
ASSOCIATION - RECOMMENDED DIET IN PATIENTS WITH
CORONARY ARTERY DISEASE:
Binita Shah et al
Wei et al., 2008; Cheng et al., 2014)
Eating Less, Living More
FMD in Humans: “The stomach receives food, while the metabolism fasts’
• Consists of soups, bars, teas, drinks, and snacks
• Five consecutive days/month, up to 12 times/year,
• Demonstrated to rejuvenate the body, induce fast fat loss
without decreasing muscle or bone mass, and prevent (and
potentially reverses) age-related metabolic changes
“The stomach receives food, while the metabolism fasts’
• Consists of soups, bars, teas, drinks, and snacks
• Five consecutive days/month, up to 12 times/year,
• Demonstrated to rejuvenate the body, induce fast fat loss
without decreasing muscle or bone mass, and prevent (and
potentially reverses) age-related metabolic changes
FMD: WFPB-ISH
Wei et al., Sci. Transl. Med. 9, 15 February 2017
SPICES
STEP 1: ELIMINATE ALL TYPES OF MEAT LIKE BEEF, PORK, LAMB, FISH,
CHICKEN, EGGS AND DAIRY PRODUCTS.
STEP 2: ELIMINATE ADDED OILS
STEP 3: ELIMINATE PROCESSED FOODS
STEP 4: ADDED IN LARGE AMOUNTS OF RAW FRUITS, VEGETABLES,
GREENS, SEEDS NUTS
STEP 5: ADD IN HYDRATION FROM PURE WATER
STEP 6: ADD IN OMEGA-3 WITH AT LEAST A ¼ CUP OF CHIA AND
FLAX SEEDS DAILY
COMPLEX THAT DETECTS PATHOGENIC MICROORGANISMS
AND STERILE STRESSORS, AND THAT ACTIVATES THE HIGHLY
PRO-INFLAMMATORY CYTOKINES INTERLEUKIN-1B (IL-1B)
NUMBER OF AUTOINFLAMMATORY SYNDROMES AND
AUTOIMMUNE DISEASES.
NLRP3 INFLAMMASONE
IMPORTANTLY ALSO THE MOST CLINICALLY
IMPLICATED INFLAMMASOME.
REDUCED RISK OF EARLY DEATH
• 68,273 SWEDISH MEN AND WOMEN AGED 45 TO 83 YEARS WHO
WERE FOLLOWED FOR 16 YEARS
• PARTICIPANTS WHO MOST CLOSELY FOLLOWED AN ANTI- INFLAMMATORY DIET HAD AN 18% LOWER RISK OF ALL-CAUSE
MORTALITY, A 20% LOWER RISK OF CARDIOVASCULAR MORTALITY, AND A 13% LOWER RISK OF CANCER MORTALITY
• SMOKERS WHO FOLLOWED THE DIET EXPERIENCED EVEN GREATER
BENEFITS WHEN COMPARED WITH SMOKERS WHO DID NOT FOLLOW THE
AND VEGETABLES, TEA, COFFEE, WHOLE GRAIN
BREAD, BREAKFAST CEREAL, OLIVE OIL AND CANOLA
OIL, NUTS, CHOCOLATE, AND MODERATE AMOUNTS
OF RED WINE AND BEER.
• PRO-INFLAMMATORY FOODS INCLUDE UNPROCESSED
AND SOFT-DRINK BEVERAGES.