cardiovascular health and complementary medicine oumitana kajkenova, md april 11, 2006
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Cardiovascular Health And Complementary Medicine
Oumitana Kajkenova, MD
April 11, 2006
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 200:2:88
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; 280:1569
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
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.
Prevalence of hypertension
Incidence of atherothrombotic stroke per 100 subjects per year
Incidence of coronary artery disease
Lakatta E.G; Circulation, 2003
Yuchiro Miura, 70 years old- the oldest person ever to summit Everest
Hutchinson-Gilford Progeria Syndrome- advanced AVD at 10-13 years of age
Endothelial Physiology
Function is to maintain the vessel in dilated stateIn response to shear stress- flow-mediated vasodilation (FMD) occursIt is regulated by by release of nitric oxide (NO) from the endotheliumNO is synthesized from L-arginine by endothelial NO synthase (eNOS)FMD response is abolished by eNOS inhibitor
Factors that lead to endothelial dysfunction and
activation
Liao, J. Clin Chemistry 1998; 44:1799-1808
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
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
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
L-arginine and clinical trials
http://www.clinicaltrials.gov/ct/screen/AdvancedSearch;jsessionid=055BC8606C0D5471D91F88CDEFEB86EA
L- arginine
Nonessential amino acid, produced in the body from glutamic acid
Primary function- detoxification of urea
L-Arginine and diet
Average daily intake in US 1-4 grams (meat and fish). Goal 6-9 grams, requires supplement
Caution: herpes simplex
Antioxidants for CVD
Vit E does not appear efficacious
Vit C- no benefit
Beta carotene may be dangerous and should be discouraged
Vit E – potential benefits
Protects human LDL against oxidationReverses endothelial dysfunction or prevents its developmentInhibits platelet aggregation and prevents intraarterial thrombus formationDecreases monocyte-endothelial cell adhesion
Vit E and CVD
Clinical benefit Lancet.1996;347:781
No clinical benefit Lancet 1999; 354:154; N Eng J Med 2000; 342:154
Meta-analysis of 7 randomized trials showed: Data this time do not support the routine use of vit E supplements for CVD.Lancet. 2003; 361:2017
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 durationLack of benefit of vit E in preventing CV eventsConcern about an increased risk of heart failure related to vit E
JAMA 2005; 293:1338-1347
Few thoughts on antioxidants
High levels ROS are toxicLow levels ROS-important regulators of signaling pathways and gene expression in vasculatureAntioxidant supplementation can suppress redox-mediated signaling and increase vulnerability of the blood vessel to oxidative injury
More thoughts on antioxidants
Antioxidants are given in constant amounts and dosing intervals
Oxidative stress is not a continuous, uniform process
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
Alpha and gamma tocopherol
Gamma-tocopherol
Represents 70% of vit E in our diet
Sources: vegetable oils (corn, soybean, and sesame), nuts (walnuts, pecans, peanuts)
www.clinicaltrials.gov
ClinicalTrials.gov - Information on Clinical Trials and Human Research Studies: Focused Search
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-oxidantCoQ10 peaks in early 20s and gradually decreases with age
Coenzyme Q10
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
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-carnitine+coenzyme Q10+magnesium
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
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; 928:274-280
Garlic
Reduces plasma cholesterol by 8-10% Warshafsky, 1995)
Minor blood pressure-lowering effect (Sillagy, 1995)
Antioxidant
Increases NO production
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
Red Yeast Rice
Fermented rice product
Active substance- monacolins (HMG CoA reductase inhibitor)
Effectively lowers cholesterol and LDL
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
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
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
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
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.
Chelation Therapy
Lack of evidence800,000 procedures in 1997NIH (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;
Thermal Therapy
60 degrees C dry heat sauna bath x 15 min, then kept in bed covered with blankets x 30min qd x 2 wksImproved endothelial function in patients with CAD risk factorsImproved 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 2001:38:1083Kihara T, et al. Repeated sauna treatment improves vascular endothelial and cardiac function in patients with CHF. J Am Coll Cardiol 2002;39:754
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
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
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
Eastern exercise
Yoga and Tai Chi
Mechanism is similar to meditation
Trials are small, not randomized but benefit without controversy
RESPeRATE
-FDA approved medical device (2002)-lowers BP by an average 14/9-mmHg -
Useful Links
http://www.consumerlab.com/
http://www.clinicaltrials.gov/
http://holisticmedicine.com/
Useful websites
http://www.consumerlab.com
http://ods.od.nih.gov/news/conferences_and_workshops.aspx
http://www.biomedcentral.com/bmccomplementalternmed/
http://grande.nal.usda.gov/ibids/index.php
http://cards-pws.od.nih.gov/cards/ProxyServlet?objectHandle=Search&actionHandle=getSearchFields&nextPage=jsp/search/searchMain.jsp
Useful websites
http://www.holisticmedicine.org/
http://www.nlm.nih.gov/medlineplus/druginfo/herb_All.html#A
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed
http://www.worldhealth.net/p/longevity-and-age-management.html