Cardiovascular Health And Complementary Medicine

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Cardiovascular Health And Complementary Medicine

• Oumitana Kajkenova, MD
• April 11, 2006

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Complementary and Alternative Medicine (CAM)

• Complementary and Alternative Medicine is often
  defined as therapies that are neither taught
  widely in medical school nor generally available
  in hospitals.
• JAMDA 200288

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                        Estimated annual
out-of-pocket expenditures for alternative
therapies vs conventional medical services,
United States, 1997. Data are from the Health
Care Financing Administration, United States.
RBRVS indicates Resource-Based Relative Value
Scale. JAMA, 1998 2801569
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                        Trends in annual visits
to practitioners of alternative therapies vs
visits to primary care physicians, United
States, 1997 vs 1990. Data are from the National
Ambulatory Medical Care Survey from 1996 and
1990. From   Eisenberg JAMA, Volume
280(18).November 11, 1998.1569-1575
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The demographic imperative

Number of persons 65 years of age and older
(light bars) and 85 years of age and older in the
United States from 1900 through 2030. Data taken
form the US Census Bureau data with projections
for 2030.
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Prevalence of hypertension
Incidence of atherothrombotic stroke per
100 subjects per year
Incidence of coronary artery disease
Lakatta E.G Circulation, 2003
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Yuchiro Miura, 70 years old- the oldest person
ever to summit Everest
Hutchinson-Gilford Progeria Syndrome- advanced
AVD at 10-13 years of age
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Endothelial Physiology

• Function is to maintain the vessel in dilated
  state
• In response to shear stress- flow-mediated
  vasodilation (FMD) occurs
• It is regulated by by release of nitric oxide
  (NO) from the endothelium
• NO is synthesized from L-arginine by endothelial
  NO synthase (eNOS)
• FMD response is abolished by eNOS inhibitor

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Factors that lead to endothelial dysfunction and
activation

Liao, J. Clin Chemistry 1998 441799-1808
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L-Arginine- potential benefits

• Precursor of Nitric Oxide- Increases NO
  availability and activity
• Decreases plasma endothelin concentration
• Increases apoptosis of vascular cells in intimal
  lesions, leading to regression of atherosclerosis
  and decreased symptoms
• Prevents formation of atherosclerotic plaques

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L-ARGININE

• Trials are small and conflicting ( 2/9 trials
  showed no benefit for CAD)
• 7/9 trials showed benefit
• -Improves blood flow through in AVD arteries
• - Improves functional status in CHF
• - Increases exercise performance
• - Reduces symptoms in PVD

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L- arginine therapy in Acute Myocardial
Infarction (VINTAGE_MI)

• L-arginine does not improve vascular stiffness
  measurements or ejection fraction and may be
  associated with higher postinfarction mortality
• JAMA 2006 295 58-64

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L-arginine and clinical trials

• http//www.clinicaltrials.gov/ct/screen/AdvancedSe
  archjsessionid055BC8606C0D5471D91F88CDEFEB86EA

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L- arginine

• Nonessential amino acid, produced in the body
  from glutamic acid
• Primary function- detoxification of urea

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L-Arginine and diet

• Average daily intake in US 1-4 grams (meat and
  fish). Goal 6-9 grams, requires supplement
• Caution herpes simplex

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Antioxidants for CVD

• Vit E does not appear efficacious
• Vit C- no benefit
• Beta carotene may be dangerous and should be
  discouraged

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Vit E potential benefits

• Protects human LDL against oxidation
• Reverses endothelial dysfunction or prevents its
  development
• Inhibits platelet aggregation and prevents
  intraarterial thrombus formation
• Decreases monocyte-endothelial cell adhesion

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Vit E and CVD

• Clinical benefit Lancet.1996347781
• No clinical benefit Lancet 1999 354154 N Eng J
  Med 2000 342154
• Meta-analysis of 7 randomized trials showed Data
  this time do not support the routine use of vit E
  supplements for CVD.
• Lancet. 2003 3612017

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Heart Outcomes Prevention Evaluation ( HOPE and
HOPE-TOO (The Ongoing Outcomes))

• Ramipiril vs placebo vit E 400IU vs placebo
  (9541 patients at risk for CV events)- 7.2 years
  duration
• Lack of benefit of vit E in preventing CV events
• Concern about an increased risk of heart failure
  related to vit E
• JAMA 2005 2931338-1347

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Few thoughts on antioxidants

• High levels ROS are toxic
• Low levels ROS-important regulators of signaling
  pathways and gene expression in vasculature
• Antioxidant supplementation can suppress
  redox-mediated signaling and increase
  vulnerability of the blood vessel to oxidative
  injury

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More thoughts on antioxidants

• Antioxidants are given in constant amounts and
  dosing intervals
• Oxidative stress is not a continuous, uniform
  process

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And more thoughts

• Vit E has eight diasteereoisomers
• -many clinical studies do not specify which
  isomer was administered
• -studies with dietary sources of vit E are more
  encouraging than studies using a single isomer

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Alpha and gamma tocopherol

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Gamma-tocopherol

• Represents 70 of vit E in our diet
• Sources vegetable oils (corn, soybean, and
  sesame), nuts (walnuts, pecans, peanuts)

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www.clinicaltrials.gov

• ClinicalTrials.gov - Information on Clinical
  Trials and Human Research Studies Focused Search

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Coenzyme q10 (ubiquinone)

• Found in food and is synthesized in all tissues
  (highest concentrations in heart, brain, skeletal
  muscle and liver)
• Two major functions it is an integral component
  of the ATP production and it is a lipid-soluble
  anti-oxidant
• CoQ10 peaks in early 20s and gradually decreases
  with age

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Coenzyme Q10
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Co Q10 effects

• Lowers BP (Burke, 2001)
• Decreases HgbA1C
• Improves endothelial dysfunction of the brachial
  artery in diabetics
• Improvement in CHF symptoms (controversial)
• Reversal of statin-related myopathy

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Metabolic cardiology

• Human heart contains 700 mg of ATP, enough for
  10 heartbeats
• One needs 6 grams
• ATP- adenine D-ribose 3 phos groups
• D-ribose L-carnitinecoenzyme Q10magnesium

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Green tea

• Dutch study of 3,400 people without CVD found
  drinking 1-2 cups tea/day led to 46 lower risk
  of developing severe atherosclerosis. Arch
  Internal Medicine, 1999
• Japanese study of 393 people found 70 lower risk
  of atherosclerosis 42 less likely to have heart
  attack. Am J Card, 2002

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Green tea

• Effect of green tea on mean age of death from all
  causes (11-year follow up study 1,109 subjects)
• Sueoka N.et al. Annals New York Academy of
  Sciences 2001 928274-280

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Garlic

• Reduces plasma cholesterol by 8-10 Warshafsky,
  1995)
• Minor blood pressure-lowering effect (Sillagy,
  1995)
• Antioxidant
• Increases NO production

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Garlic- current trials

• Comparing Effects of 3 Sources of Garlic
  on Cholesterol Levels
• - funded by NCCAM (NIH)
• - 220 patients
• Stanford Center for Research in Disease
  Prevention
• Garlic in hyperlipidemia caused by HAART
• -funded by NCAAM (NIH)
• -146 patients with HIV
• -Bastyr University Center for Natural Health,
  Seattle, Washington

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Red Yeast Rice

• Fermented rice product
• Active substance- monacolins (HMG CoA reductase
  inhibitor)
• Effectively lowers cholesterol and LDL

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Omega-3 fatty acids

• Sources fatty fish (salmon), flaxseed and
  flaxseed oil, canola oil, soybean oil, and nuts
• Decrease serum triglycerides (15g/day lowers by
  50)
• Decrease thrombotic tendency
• Improve endothelial function

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Omega-3 fatty acids

• AHA recommendations at least two servings of
  fish per week to confer cardioprotective effect
• Supplementation for patients with
  hypertriglyceridemia
• Side effects GI, fall in circulating levels of
  vit E (vit E 200 IU can restore the levels),
  might worsen the glycemic control

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Omega-3 fatty acids- current trials

• Safety and Effectiveness of Flaxseed for
  Reducing High Cholesterol
• - funded by NCCAM (NIH)
• 60 patients age 45-75 years
• 40 grams of flax seed in baked products
• 10 weeks
• Univ of Pensilvania

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Omega-3 fatty acids- current trials

• Macrobiotic Diet and Flax Seed Effects on
  Estrogens, Phytoestrogens and Fibrinolytic
  Factors
• funded by NCCAM
• AHA step1 diet vs AHA step2 diet 10 g/day flax
  seed vs macrobiotic diet
• Outcomes include endothelial function and levels
  of antioxidants
• -Columbia University

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Chelation Therapy

• Introduced in 1955 as a treatment of AVD
• repeated administration of EDTA (I/v infusion
  over the 4 hours, several times per week up to 20
  infusions)
• Rationale EDTA has high affinity for divalent
  ions (calcium), reduces oxidation of lipoproteins
  (by removal of copper), increases the dilating
  capacity of arteries.

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Chelation Therapy

• Lack of evidence
• 800,000 procedures in 1997
• NIH (NCCAM and NHLBI) funds phase III trial
• Trial To Assess Chelation Therapy (TACT)
• - 2,300 patients with previous MI at more 100
  research centers in US over 5 years
• - 30 weekly EDTA infusions followed by 10
  bimonthly
• - 30 million

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Thermal Therapy

• 60 degrees C dry heat sauna bath x 15 min, then
  kept in bed covered with blankets x 30min qd x 2
  wks
• Improved endothelial function in patients with
  CAD risk factors
• Improved clinical symptoms in pts with CHF NYHA
  II or III, with significant improvement in
  endothelial function as well as decrease in brain
  natriuretic peptide Imamura m, et al. Repeated
  thermal therapy improves impaired vascular
  endothelial function in patients with coronary
  risk factors. J Am Coll Cardiol 2001381083
• Kihara T, et al. Repeated sauna treatment
  improves vascular endothelial and cardiac
  function in patients with CHF. J Am Coll Cardiol
  200239754

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Meditation

• Cognitive tool used to develop focused attention
  through concentration on specified thought or
  object
• Dampens sympathetic response and decreases
  respiration and heart rate, plasma cortisol and
  blood pressure

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Meditation-current trials

• Effects of Meditation on Mechanism of
  Coronary Heart Disease
• - primary outcomes arterial vasomotor
  dysfunction (brachial artery response), autonomic
  nervous system imbalances (heart rate
  variability), transient myocardial ischemia
• secondary psychological stress and quality of
  life
• Preventive and Rehabilitative Cardiac Center, LA,
  CA

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Meditation-current trials

• Basic Mechanisms of Mediation and
  Cardiovascular Disease in Older Blacks
• - funded by NCCAM, NIA and NHLBI
• - similar outcomes
• - age 65 and older
• - Maharishi Univ of Management Center for Health
  and Aging Studies, Fairfield, Iowa

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Eastern exercise

• Yoga and Tai Chi
• Mechanism is similar to meditation
• Trials are small, not randomized but benefit
  without controversy

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RESPeRATE
-FDA approved medical device (2002) -lowers BP by
an average 14/9-mmHg -
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Useful Links

• http//www.consumerlab.com/
• http//www.clinicaltrials.gov/
• http//holisticmedicine.com/

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Useful websites

• http//www.consumerlab.com
• http//ods.od.nih.gov/news/conferences_and_worksho
  ps.aspx
• http//www.biomedcentral.com/bmccomplementalternme
  d/
• http//grande.nal.usda.gov/ibids/index.php
• http//cards-pws.od.nih.gov/cards/ProxyServlet?obj
  ectHandleSearchactionHandlegetSearchFieldsnext
  Pagejsp/search/searchMain.jsp

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Useful websites

• http//www.holisticmedicine.org/
• http//www.nlm.nih.gov/medlineplus/druginfo/herb_A
  ll.htmlA
• http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?DBp
  ubmed
• http//www.worldhealth.net/p/longevity-and-age-man
  agement.html