Cardiovascular Health And Complementary Medicine Oumitana Kajkenova, MD April 11, 2006.

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