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Nutrition Medicine in CARDIOVASCULAR DISEASE

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Nutrition Medicine in CARDIOVASCULAR DISEASE Dr. Melvyn A Sydney-Smith. KGSJ. Adjunct Professor (Nutrition Medicine) RMIT University. Melbourne. Cardiovascular ... – PowerPoint PPT presentation

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Title: Nutrition Medicine in CARDIOVASCULAR DISEASE


1
Nutrition Medicine in CARDIOVASCULAR DISEASE
  • Dr. Melvyn A Sydney-Smith. KGSJ.
  • Adjunct Professor (Nutrition Medicine)
  • RMIT University. Melbourne.

2
Cardiovascular Disease Prevalence in 2004-05
  • In 2004-2005 18 (3.5 million) of Australians
    reported having a long-term cardiovascular
    condition.
  • hypertension 11 (2.1 million)
  • heart, stroke or vascular conditions 3.8
  • 28 reported angina,
  • 20 another ischaemic heart disease,
  • 12 a cerebrovascular disease,
  • 35 oedema and heart failure and
  • 27 reported an arterial disease capillaries
  • The number of Australians with cardiovascular
    disease declined from 4.3 in 2001, to 3.8 in
    2004-05

3
Age-related prevalence of cardiovascular
conditions 2004-05
Age group (years) Source ABS, National Health
Survey Summary of Results, Australia, 2004-05
cat. no 4364.0
4
Reported prevalence of cardiovascular conditions,
2004-05
Source ABS, National Aboriginal and Torres
Strait Islander Health Survey, 2004-05, cat. no.
4715.0
5
Cardiovascular Disease mortality rate
Australian CVD mortality rates remain high
110/1000 though lower than USA, New Zealand and
the UK. Australian Bureau Statistics. 2004
6
SELECTED CAUSES OF DEATH 197072 AND 200204
                                               
               
7
Cardiovascular Disease mortality rates
8
  • CARDIOVASCULAR DISEASE
  • PATHOGENESIS

9
Cardiovascular Disease pathophysiology
  • Atherothrombosis
  • most common trigger factor of a CVD event
  • Atheromatous plaque erosion or rupture ?
  • Formation of a platelet-rich thrombus ?
  • Partial or complete vascular occlusion ?
  • Tissue ischaemia, damage and necrosis
  • Chapman MJ, Pharmacol Therapeut. 2007.
    113(184-96)
  • 3 Major atherogenic mechanisms are
  • Dyslipidemia Apo-lipoprotein balance
  • Endothelial dysfunction
  • Inflammation

10
ATHEROMA PLAQUE DEVELOPMENT
  • Key players in all stages of atherothrombosis
    are
  • Vascular endothelial cells
  • Prostacyclin production from PGH2 by
    prostacyclin synthase
  • Nitric Oxide synthesis from Arginine by eNOS3
  • Blood Platelets
  • Atherogenesis
  • Plaque progression inflammation
  • Thrombosis
  • Leukocytes monocytes neutrophils
    lymphocytes
  • Inflammatory cascade production of cytokines,
    free radicals and proinflammatory eicosanoids
  • Fibroblasts myoblasts
  • cellular proliferation and intercellular matrix
    changes

11
(No Transcript)
12
Cardiovascular Disease atherogenesis
  • Pathophysiological mechanisms involved
  • Endothelial dysfunction
  • Inflammation
  • Oxidative stress
  • Cholesterol accumulation
  • Cellular apoptosis
  • Extracellular matrix degeneration
  • Accelerated by major risk factors
  • Dyslipidemia
  • Hypertension
  • Smoking
  • Insulin resistance ?? obesity
  • Chapman MJ, Pharmacol Therapeut. 2007. 113(184-96)

13
Cardiovascular Disease atherogenesis
  • Multiple mechanisms contribute synergistically to
    atheromatous plaque development cascading
    towards the disease phenotype
  • Chapman MJ, Pharmacol Therapeut. 2007. 113(184-96)

14
CARDIOVASCULAR DISEASE TREATMENT
  • Primary preventive major disease reduction
    benefit occurs at this stage BUT only if
    therapy implemented
  • Secondary morbidity and mortality benefits from
    therapy is well below that of primary prevention

15
CardioVascular Diease TREATMENT
  • Focus of primary and secondary preventive therapy
    is to
  • Reduce cholesterol levels
  • Statins PLUS Mediterranean diet
  • Reduce platelet activity
  • Aspirin PLUS Omega-3-Essential fatty Acids
  • Reduce Inflammation
  • Statins aspirin
  • Improve Endothelial Dysfunction
  • Statins
  • Control blood pressure
  • ACE inhibitors, ACE receptor inhibitors
  • chlorthiazides, calcium-channel blockers

What about improving cardiac vascular cell
metabolism?
16
Cardiovascular Disease Dyslipidemia is a major
risk factor, related to CHD risk
17
  • Cardiovascular Disease Dyslipidemia
  • LDL cholesterol reduction reportedly decreases
  • CVD events including myocardial infarction and
    stroke
  • CVD mortality by about 30-40
  • Clinical Significance of Statin Pleiotropic
    Effects Hypotheses Versus Evidence. Davidson
    MH. Circulation 20051112280-2281

18
Primary prevention statin therapy
  • Baigent C, Keech A, et al. 2005. Lancet
    366(9493). "Efficacy and safety of
    cholesterol-lowering treatment prospective
    meta-analysis of data from 90,056 participants in
    14 randomised trials of statins."
  • The meta-analysis reported
  • 12 proportional reduction in all-cause mortality
    per 1 mmol/L reduction in LDL cholesterol
  • RR 0.88, 95 CI 0.84-0.91 plt0.0001)
  • 19 reduction in coronary mortality
  • RR 0.81, CI 0.76-0.85 plt0.0001), and
  • non-significant reductions in
  • non-coronary vascular mortality
  • RR 0.93, 0.83-1.03 p0.2
  • non-vascular mortality
  • RR 0.95, 0.90-1.01 p0.1

19
Primary prevention statin therapy
  • Thavendiranathan P. Bagai A, et al. 2006. Arch
    Intern Med. 166(21)2307.
  • Primary Prevention of Cardiovascular Diseases
    With Statin Therapy A Meta-analysis of
    Randomized Controlled Trials.
  • 7 trials 42 848 patients, 90 no CVD history,
    Mean follow-up 4.3 yrs
  • Statin therapy reduced the RR of
  • major coronary events, by 29.2
  • (95 CI, 16.7-39.8) (Plt0.001)
  • major cerebro-vascular events, 14.4
  • (95 CI, 2.8-24.6) (P0.02)
  • revascularizations 33.8
  • (95 CI, 19.6-45.5) (Plt0.001)
  • Statin therapy produced non-significant
    reductions in
  • CHD mortality of 22.6
  • (95 CI, 0.56-1.08) (P0.13)
  • Overall mortality 8
  • (95 CI, 0.84-1.01) (P0.09)

20
Secondary prevention statin therapy
  • Maycock A, Muhlestein CA et al. 2002. J Am Coll
    Cardiol 40(10) 1777.
  • Statin therapy is associated with reduced
    mortality across all age groups of individuals
    with significant coronary disease, including very
    elderly patients.
  • Mortality was decreased among statin users vs
    non-users in all age groups
  • gt80 yrs 29.5 non-users vs 8.5 users HR 0.50,
    p 0.036
  • 65-79 yrs 18.7 non-users vs. 6.0 users HR
    0.56, plt0.001
  • lt65 yrs 8.9 non-users vs. 3.1 users HR 0.70,
    p 0.097
  • NB the Hazard Ratio for those lt65 yrs age was
    actually NOT significant contrary to the
    authors stated conclusions.

21
CVD Therapy omega-3-Fatty Acids
  • Omega-3-EFAs 1000mg/day is also very effective
  • Gizzi Prevenzione Trial reported
  • 20 reduction in overall mortality
  • 30 reduction in cardiovascular deaths and
  • 45 reduction in sudden death
  • Stone NJ. GISSI-Prevenzione Trial. Curr Cardiol
    Rep 2000 2(5)445-451
  • Omega-3-EFA therapy significantly prevents
  • cardiac arrhythmia and
  • Thrombotic disorders
  • Von Schacky C. The role of omega-3 fatty acids in
    cardiovascular disease. Curr Atheroscler Rep
    2003 5(2)139-145
  • Nambi V and Ballantyne CM. 2006). "Combination
    therapy with statins and omega-3 fatty acids. Am
    J Cardiol 200698 341-381

22
Dyslipidemia and Antilipidemic Therapy Studer,
M., M. Briel, et al. (2005). "Effect of Different
Antilipidemic Agents and Diets on Mortality A
Systematic Review." Arch Intern Med. 165(7)
725-30.
  • Compared with control groups, risk ratios for
    overall mortality were
  • 0.77 for n-3 fatty acids (95 CI, 0.63-0.94)
  • 0.87 for statins (95 CI, 0.81-0.94)
  • 0.84 for resins (95 CI, 0.66-1.08)
  • 0.96 for niacin (95 CI, 0.86-1.08)
  • 0.97 for diet (95 CI, 0.91-1.04).
  • 1.00 for fibrates (95 CI, 0.91-1.11)

23
CVD Omega-3-FAs Statins Nambi, V. and C. M.
Ballantyne (2006). "Combination therapy with
statins and omega-3 fatty acids. Am J Cardiol
200698 341-381.
  • statin monotherapy is commonly insufficient to
    reduce
  • Non-HDL cholesterol to recommended goals
  • Triglyceride levels
  • Statin omega-3FAs consistently shown to be
  • effective, safe, and well-tolerated treatment
  • provide additional lipid improvement without
    requiring additional laboratory tests
  • do not increase risk for adverse muscle or liver
    effects.
  • Patients with recent myocardial infarction may
    also benefit from this combination.

24
Dyslipidemia Statin Niacin
  • Nicotinic acid is a more potent agent than
    fibrates for raising HDL-C, by up to 29 at
    recommended doses.
  • It also substantially reduces triglycerides and
    LDL-C, and
  • promotes a shift from small, dense LDL to larger,
    more buoyant LDL particles.
  • nicotinic acid with a statin will produce a
    greater reduction in cardiovascular risk in
    patients with diabetes and metabolic syndrome
    than statin monotherapy alone.
  • Nicotinic acid is safe for use in patients with
    diabetes, with no evidence of clinically relevant
    deterioration in glycaemic control at recommended
    doses ( 2g/day).
  • Chapman, M. J., G. Assmann, et al. (2004).
    "Raising high-density lipoprotein cholesterol
    with reduction of cardiovascular risk the role
    of nicotinic acid a position paper developed by
    the European Consensus Panel on HDL-C." Current
    Medical Research and Opinion 20 1253.

25
Dyslipidemia Statin Niacin
  • Simvastatin (mean daily dose 13 6 mg) and
    nicotinic acid (mean daily dose (2.4 2.0 g) led
    to
  • 26 increase in HDL-C, 38 reduction in
    triglycerides and 42 reduction in LDL-C.
  • associated with a 90 fall in the frequency of
    major coronary events compared with placebo (p
    0.03) in patients with CHD,
  • significant angiographic regression of stenosis
    by 0.4 on average, compared with progression of
    3.9 on placebo (p lt 0.001).
  • Brown BG, Zhao XQ, Chait A, et al. Simvastatin
    and niacin, antioxidant vitamins, or the
    combination for the prevention of coronary
    disease. N Engl J Med 20013451583-92
  • Taylor, A. J., L. E. Sullenberger, et al. (2004).
    "Arterial Biology for the Investigation of the
    Treatment Effects of Reducing Cholesterol
    (ARBITER) 2 A Double-Blind, Placebo-Controlled
    Study of Extended-Release Niacin on
    Atherosclerosis Progression in Secondary
    Prevention Patients Treated With Statins."
    Circulation 110(23) 3512-7.

26
Secondary prevention Multiple Risk Factor
Intervention
  • Multiple risk factor intervention trials show
    little overall benefit statins, hypertensive
    agents, lifestyle counselling, AHA diet
  • these interventions may have small effects on
    levels of the major risk factors but very
    limited, impact on reducing mortality and
    morbidity.
  • the pooled odds ratios for total and CHD
    mortality were
  • 0.96 (95 CI 0.92 to 1.01) for total mortality
    and
  • 0.96 (95 CI 0.89 to 1.04) for CHD mortality
  • Net changes in systolic and diastolic blood
    pressure, were (weighted mean differences) -3.6
    mmHg (95 CI -3.9 to -3.3 mmHg), -2.8 mmHg (95
    CI -2.9 to -2.6 mmHg) and and blood cholesterol
    -0.07 mMol/l (95 CI -0.8 to -0.06 mMol/l)
    respectively.
  • Multiple risk factor interventions for primary
    prevention of coronary heart disease. Ebrahim S
    et al. Cochrane Database of Systematic Reviews
    Reviews 2006 Issue 4

27
Dyslipidemia Red Yeast Rice A Natural Statin
Journoud, M. and P. J. H. Jones (2004). "Red
yeast rice a new hypolipidemic drug. Life
Sciences 74(22) 2675.
  • Evidence shows that fermented red yeast rice
  • lowers cholesterol levels moderately compared to
    other statin drugs,
  • but with
  • the added advantage of causing less adverse
    effects.
  • A review of the body of evidence surrounding the
  • properties of red yeast rice underscores its
    potential as a new alternative to lipid level
    control.

28
Dyslipidemia A Natural Statin Zhao, S.-P., L.
Liu, et al. (2003). "Effect of xuezhikang, a
cholestin extract, on reflecting postprandial
triglyceridemia after a high-fat meal in patients
with coronary heart disease." Atherosclerosis.
168(2) 375.
  • Xuezhikang (cholestin) significantly reduced
  • fasting serum total cholesterol (TC) by 20
  • low-density lipoprotein cholesterol (LDL-C) by
    34
  • Triglycerides (TG) by 32 and
  • ApoB by 27) levels
  • Significantly (plt0.001) elevated
  • high-density lipoprotein cholesterol (HDL-C) by
    18
  • apoA-I levels by 13

29
  • CARDIOVASCULAR DISEASE
  • INFLAMMATION

30
CVD Inflammation Gerard C Rollins BJ. 2001.
Chemokines and disease. Nature Immunology
2108-15 Moutsopoulos, N. M. and P. N. Madianos
(2006). "Low-Grade Inflammation in Chronic
Infectious Diseases Paradigm of Periodontal
Infections." Ann NY Acad Sci 1088(1) 251-64
  • Chronic inflammation is positively linked to CVD
  • Elevated hs-CRP, proinflammatory cytokines IL-6
    and TNF-alpha and chemokines
  • Increased incidence of CVD in those with
  • Overt inflammatory conditions
  • Autoimmune disease, renal disease, allergic
    disease, coeliac disease, periodontal disease and
    inflammatory bowel disease
  • Fatty infiltration of liver
  • Persistent elevated GGT is predictive of
    metabolic syndrome
  • insulin resistance ?? obesity
  • Adipocyte production of cytokines and chemokines.

31
CVD Inflammation
  • Recommended treatment is Aspirin therapy
  • Downregulates platelet activation by selectively
    inhibiting COX-1 activity ?
  • Reduces platelet TXA2 synthesis and decreases
  • Thrombogenesis
  • Cytokine chemokine release
  • Pro-Inflammatory eicosanoid production
  • Adverse effects of aspirin therapy are
  • Increased intestinal mucosal permeability
  • Increased gastro-duodenal ulceration and bleeding
  • Increased risk of haemorrhagic stroke

32
CVD Inflammation aspirin therapy Njaman W,
Miyauchi K, et al. (2006). "Impact of Aspirin
Treatment on Long-Term Outcome (Over 10Years)
After Percutaneous Coronary Intervention." Int
Heart J 47(1) 37-45
  • Aspirin therapy following PCI reportedly reduced
  • all cause mortality (10 versus 16.4 P 0.01)
    and
  • cardiac death (3.7 versus 8.0 P 0.02)
    compared to other antiplatelet drugs.
  • The hazard ratio (HR) was
  • all cause mortality (HR, 0.49 95CI 0.29-0.80,
    P 0.005) and
  • cardiac mortality (HR, 0.32 95CI 0.14-0.72, P
    0.006)
  • .

33
CVD Inflammation aspirin therapy Aspirin for
the Primary Prevention of Cardiovascular Events
in Women and Men A Sex-Specific Meta-analysis of
Randomized Controlled Trials. Berger JS,
Roncaglioni MC et al. 2006 JAMA 295(3) 306-13.
  • Among 51 342 women, aspirin therapy was
    associated with
  • 12 reduction in CV events, OR 0.88 95 CI,
    0.79-0.99 P 0.03
  • 17 reduction in stroke, OR 0.83 95 CI,
    0.70-0.97 P 0.02)
  • reflecting lower ischemic stroke (OR, 0.76 95
    CI, 0.63-0.93 P0.008)
  • No significant effect on MI or cardiovascular
    mortality.
  • Among 44 114 men, aspirin therapy was associated
    with
  • 14 reduction in CV events (OR, 0.86 95 CI,
    0.78-0.94 P 0.01)
  • 32 reduction in MI (OR, 0.68 95 CI, 0.54-0.86
    P 0.001)
  • No significant effect on stroke or cardiovascular
    mortality
  • Aspirin Rx increased risk of bleeding
  • In women (OR, 1.68 95 CI, 1.13-2.52 P .01)
    and
  • in men (OR, 1.72 95 CI, 1.35-2.20 Plt.001).

34
CVD Inflammation combined therapy
Hippisley-Cox J. Copland C. 2005. "Effect of
combinations of drugs on all cause mortality in
patients with ischaemic heart disease nested
case-control analysis." BMJ 330(7499)1059-63.
  • Drug combinations apparently exhibit synergistic
    effects
  • greatest reduction in all cause mortality were
  • statins, aspirin, and beta-blockers 83
    reduction (77 - 88 CI)
  • statins, aspirin, B-blockers, and ACE inhibitors
    (75 reduction, 65 - 82 CI)
  • statins, aspirin, and ACE inhibitors (71
    reduction, 59 - 79)

What about Niacin and omega-3-EFAs?
35
Enter THE POLYPILL Wald NJ and Law MR. 2003. A
strategy to reduce cardiovascular disease by
more than 80. BMJ. 326(7404) 1419.
  • One statin drug
  • (atorvastatin 10 mg/d or simvastatin 40 mg/d)
  • Three antihypertensive drugs
  • thiazide, beta blocker, ACE inhibitor
  • (at half standard dose)
  • Folic acid (0.8 mg/d)
  • Aspirin (75 mg/d)
  • Estimated to reduce CHD events by 88 and stroke
    by 80
  • 30 people above age 55 would gain 11 years,
    event-free
  • 8 15 would suffer medication adverse events

36
CVD Inflammation periodontal
therapy Moutsopoulos, N. M. and P. N. Madianos
(2006). "Low-Grade Inflammation in Chronic
Infectious Diseases Paradigm of Periodontal
Infections." Ann NY Acad Sci 1088(1) 251-64.
  • Periodontitis appears to be a primary risk factor
    for cardiovascular disease
  • contributes to generation of a systemic
    inflammatory phenotype
  • Elevated systemic inflammation markers
  • C-reactive protein, interleukin 6, haptoglobin
    fibrinogen
  • These markers are higher in periodontal patients
    with acute myocardial infarction (AMI) than in
    patients with AMI alone
  • Intervention trials indicate periodontal therapy
  • improves endothelial function
  • Reduces inflammatory markers

37
CVD Inflammation periodontal therapy Gebaraa
EC, Pustiglioni AN et al. 2003. Propolis extract
as an adjuvant to periodontal treatment. Oral
Health Prev Dent..1(1)29-35.
  • Post-scaling subgingival propolis irrigation was
    more effective than conventional treatment by
    both clinical and microbiological parameters
  • Decreased anaerobic bacteria (p0.007)
  • Increased sites with low level P. gingivalis
    (p0.005)
  • Decreased sites with detectable yeasts (p0.000)
  • No increase in coagulase positive Staphylococci
    and Pseudomonas spp.
  • Increased sites with probing depth (PD) lt or 3
    mm

38
CVD Inflammation periodontal therapy English,
H. K., A. R. Pack, et al. (2004). "The effects of
manuka honey on plaque and gingivitis a pilot
study." J Int Acad Periodontol 6(2) 63-7.
  • Compared to the control group, manuka honey
    significantly reduced
  • mean dental plaque scores (0.99 down to 0.65
    p0.001),
  • percentage of bleeding sites (48 down to 17
    p0.001),
  • Conclusion These results indicate potential
    therapeutic role for manuka honey in the
    treatment of gingivitis and periodontal disease

39
  • ENDOTHELIAL
  • DYSFUNCTION
  • Probably the most important factor in the
    promotion of cardiovascular disease
  • Drexler, H. and B. Hornig (1999). "Endothelial
    Dysfunction in Human Disease. J Molec Cell
    Cardiol. 31 51.

40
CVD Endothelial Dysfunction Napoli, C., W. C.
Stanley, et al. (2007). Nutrition and
cardiovascular disease Putting a pathogenic
framework into focus. Cardiovascular Research.
73(2) 253.
  • Critical elements include
  • Genotype
  • multiple polymorphic genes interact adversely
    with environment
  • affecting lipid glucose metabolism, cytokine
    eicosanoid synthesis production
  • Intrauterine perinatal nutrition growth
  • Dyslipidemia
  • particularly LDL/HDL ratio oxidised LDL
  • Insulin Resistance and obesity
  • Diet
  • Many have been chosen but few are effective
  • Mediterranean diet most researched
  • Lyon Heart Study, GISSI Preventiozone, DASH
  • Exercise Sedentary lifestyle vs regular
    exercise
  • Smoking environmental pollutants

41
CVD Genotypic disease
  • Multiple polymorphic genes interact adversely
    with environment
  • affecting lipid glucose metabolism, cytokine
    eicosanoid synthesis production

42
CVD Genotypic disease
  • The human genome is comprised of 46 chromosomes
  • 22 autosomal pairs plus 2 sex chromosomes
  • The 3 billion base pairs of DNA contain about
    30,000 - 40,000 protein-coding genes.
  • a much smaller number than predicted
  • only twice as many as in the worm or fly
  • The coding regions are less than 5 of the genome
  • function of the remaining DNA is not clear
  • some chromosomes have a higher gene density than
    others.
  • Understanding Genetics available from
    http//www.geneticalliance.org/ksc_assets/pdfs/man
    ual
  • Accessed 12th July 2006.

43
Gene Polymorphism
  • Single nucleotide polymorphisms
  • Single base-pair DNA differences observed between
    people
  • simplest and most common form of DNA polymorphism
  • frequency about of 1/1,000 base pairs
  • In any individual, gene polymorphism is estimated
    to affect about 10 of the genome
  • SNPs may cause disease if they affect expression
    of an enzyme-coding gene
  • About 1000 monogenic diseases due to SNPs have
    been identified
  • Jimenez-Sanchez G et al. 2001. Nature. 409853-55

44
Gene Polymorphism
  • Each gene is composed of 2 alleles which may be
  • the same homozygous AA or aa
  • or
  • different heterozygous Aa
  • However, there may be more than 2 allele variants
    polymorphisms
  • e.g APO E2, APO E3, APO E4
  • Thus a persons APO E genotype may be
  • E2/E2, E2/E3, E2/E4
  • E3/E3, E3/E4, E4/E4
  • NB 6 different genotypes

45
Gene Polymorphism and Disease
  • Incidence of specific allele variants between
    populations often varies
  • Thus the APO E4 gene
  • Caucasian population
  • mean frequency 15
  • North-South variance 23 in Finland and 20
    in Sweden down to 8 in Italy
  • Non-Caucasian populations
  • About 30 in Africans (Nigeria)
  • 35 in Papua New Guinea
  • 5 in China

46
Multi-Genetic Disease
  • Moreover, multiple polymorphisms interact to
  • modify nutrient demand and metabolism
  • affect enzyme production and efficiency
  • alter epigenetic regulatory mechanisms
  • cytokines, hormones, sensor molecules and
    transcription factors
  • Ppars, MAP kinases, NF-Kappa-B
  • modulate expression of other genes
  • further alters metabolism and regulatory
    elements
  • change responses to environmental factors
  • nutrition, exercise, xenobiotics

Leads to development of disease
phenotype Hypertension, coronary heart disease,
Type 2 diabetes
47
Multigenic disease arteriosclerosis
  • Multiple polymorphisms that regulate expression
    and activity of genes involved in blood lipid
    regulation are common
  • Occur in 7 16 of population
  • Apolipoproteins Apo A-IV, Apo A, Apo B, Apo E
  • Lipoprotein lipase
  • Cholesterol ester transfer protein
  • Affect cholesterol binding and clearance
  • Promote hyperlipidaemia, arteriosclerotic
    disease and dementia
  • Alter responses to cholesterol reducing
    interventions
  • Both dietary pharmacological
  • Confound epidemiological interventional
    research
  • Knoblauch H, Bauerfeind A et al. Hum Molec Genet,
    2002 11(12)147785.

48
  • Other links have been identified
  • Peroxisome proliferator activated receptor
  • Regulates genes coding for inflammatory
    mediators, lipogenesis and glucose metabolism
  • Gene variants contribute to cholesterol
    metabolism, insulin resistance obesity
  • Sterol regulatory element-binding protein 1c
    (SREBP-1c)
  • activates insulin-dependent increase in lipogenic
    gene expression
  • Carbohydrate Response element Binding Protein
    (ChREBP)
  • Glucose sensor that regulates glyco-lipid
    metabolism

49
  • Carbohydrate Response-Element Binding Protein
    (ChREBP) major gene-metabolic molecule
  • Transcription factor coded for by a polymorphic
    gene
  • Upregulates genes that code for lipogenesis
  • Downregulates genes that code for glucose and
    lipid oxidation
  • Activated by dietary carbohydrate (glucose
    sucrose) and insulin
  • ChREBP activity inhibited/normalised by
    omega-3-EFA
  • Uyeda et al, 2002

50
Gene-Nutrients-Lifestyle
  • Genotype is NOT an immutable prescription for
    disease
  • Multiple dietary, nutritional lifestyle factors
    strongly influence
  • Nuclear mitochondrial gene expression
  • Promoter suppressor codon activity
  • Transcription factor production activity
  • Modulatory epigenetic molecules
  • Nutritional lifestyle modification can counter
    a disease promoting genome
  • Kaput Rodriguez, 2004

51
Endothelial Dysfunction Foetal Perinatal
Nutrition Atul Singhal. 2005. Endothelial
dysfunction role in obesity-related disorders
and the early origins of CVD. Proceedings of the
Nutrition Society (2005), 64, 1522.
  • Intrauterine growth retardation impairs vascular
    function programming.
  • Vascular function is impaired in infants born
    small-for-gestational age, but not in those of
    low birth weight due to prematurity
  • Singhal A et al. 2001. Preterm birth, vascular
    function and risk factors for atherosclerosis.
    Lancet 358, 11591160
  • Cheung YF et al. 2004. Relation of arterial
    stiffness with gestational age and birth weight.
    Archives of Disease in Childhood 89, 217221
  • Vascular function is programmed in both preterm
    and full-term infants and the effects appear to
    be independent of size at birth.
  • Faster postnatal growth has a detrimental
    programming effect on long-term vascular
    function.

52
Endothelial Dysfunction Environmental Pollution
Bhatnagar, A. (2006). "Environmental
Cardiology Studying Mechanistic Links Between
Pollution and Heart Disease." Circ Res 99(7)
692-705.
  • Many studies report that air pollution is
    associated with increased cardiovascular
    mortality
  • significant relationships between particulate
    air pollution and ischemic heart disease,
    arrhythmias, and heart failure have been reported
  • Exposures to arsenic, lead, cadmium, pollutant
    gases, solvents, and pesticides are also linked
    to increased incidence of cardiovascular disease.
  • Urban diesel exhaust impairs vascular function
    and fibrinolysis
  • Mills NL, Tornqvist H., et al. 2005. Diesel
    Exhaust Inhalation Causes Vascular Dysfunction
    and Impaired Endogenous Fibrinolysis. Circulation
    112(25) 3930-6.

53
  • However, The major influence
  • on genomic an cardiovascular disease is probably
  • the gross discrepancy
  • between our human ancestral genome
  • and the modern consumer-age diet

54
  • The human genome evolved under harsh selection
    conditions over a period of 3.5 million years
  • The spontaneous mutation rate for nuclear DNA is
    estimated at about 0.5 per million years
  • Over the past 10,000 years, the human genome is
    calculated to have changed only 0.05 from our
    paleolithic ancestors
  • The human genome is now struggling to cope with
    the vastly different diet and lifestyle of the
    modern era
  • Eaton SB. 2006. Proc Nutrit Soc. 65(1)1-6

55
The modern Homo sapiens genome evolved in
northeast Africa about 200,000 years ago then
migrated throughout the rest of the world The
first migration occurred following hominid
decimation about 70,000 years ago ?
hunter-gatherer societies of the Middle East,
Asia and Australia
56
  • Following the last Ice-Age 12,000 years ago, the
    birth of agriculture 10,000 years ago ? Settled
    lifestyle and increased population density
  • increased demand for intensive farming animal
    husbandry which occurred about 8,000 years ago
  • greater starch-yielding grain crops
  • increased gluten content in grains
  • altered fat content in animals from
    supplemental feeding
  • Industrial revolution altered food supply even
    further
  • farming monoculture developed
  • increased dependence on grains
  • refined sugars became more accessible
  • increased fat and trans-fat intake
  • increased omega-6/omega-3 EFA ratio
  • Bradshaw Foundation. www.bradshawfoundation.com/st
    ephenoppenheimer

57
Paleolithic diet
Modern Diet Protein
30-40 10-20 Carbohydrates
35 60-70 sugars
2-3 15 Fats
30-35 30-35 Saturated fats
7.5 15-30 Trans-fat lt 1 5-10
of fats Omega-6/omega-3 21 10-201
58
  • Before European contact, hunter-gatherer
    population diets approximated the Paleolithic
    Diet
  • Australian Aborigines migrated 50,000 yrs ago
    and isolated until 1778
  • Diet based on wild game, seafood, nuts, seeds,
    yams greens
  • Pacific Islands Fiji 1500 BC, Samoa Cook
    Islands 200 BC, Hawaii 600 AD,
  • New Zealand about 1250 AD
  • Diet was based on seafood, poultry, pig taro,
    cassava, various greens, tropical fruits, nuts,
    seeds and coconut

59
Hunter-gatherer diets. Analysis of dietary
intake of 229 Hunter-Gatherer populations around
the world showed median animal food intakes of 66
75 and plant food intakes 26 35 of total
energy. Cordain L, Eaton SB et al. 2002.
EJCN.56,Suppl 1S42S52.
60
  • Traditional diet improves chronic disease
  • In full-blood Aborigines with CHD, diabetes and
    hypertension, reversion for 7 weeks to a
    traditional diet resulted in
  • mean wt loss of 8kg over 7 weeks
  • reduced blood pressure
  • reduced fasting insulin glucose
  • improved glucose and insulin responses on GTT
  • reduced triglyceride and VLDL levels
  • reduction or cessation of medication
  • The traditional diet consisted of
  • 64 protein,
  • 13 fat and
  • 23 low-GI/GL CHOs 1200 Cal/person/day
  • K O'Dea. 1984. Diabetes, 33(6) 596-603.

61
Genes, Diet and Disease
  • Summary
  • The broad perspective of human metabolic and
    archeological data suggests that human genes are
    adapted to a nutrient intake that approximates
    that of the Paleolithic Diet
  • Genomic research has identified multiple
    gene-regulated transcription binding proteins
    that are a) responsive to dietary lipid and CHO
    intake and b) propel metabolism towards common
    disease phenotypes
  • CHD, Hypertension, Insulin Resistance,
    Diabetes etc.
  • Individual gene variants have also been
    identified that affect
  • disease development and
  • response to nutritional and pharmacological
    therapy

62
DIET, Insulin Resistance Obesity Napoli, C.,
W. C. Stanley, et al. (2007). Nutrition and
cardiovascular disease Putting a pathogenic
framework into focus. Cardiovascular Research.
73(2) 253.
  • Improper diet and lack of exercise are the major
    contributory factors in development of obesity
  • Obesity promotes atherogenesis via two related
    pathways
  • insulin resistance
  • ? hyperinsulinaemia and elevated blood glucose
  • ? endothelial dysfunction
  • Promotes low-grade chronic inflammation
  • ? elevated TNF-alpha and other cytokines
  • IL6, PAF and various chemokines

63
Endothelial Dysfunction Obesity Hotamisligil
GS. 2006. Inflammation and metabolic disorders.
NATURE. 444(14)860-67.
  • Metabolic and immune response pathways have been
    evolutionarily conserved throughout the species
  • Immune activity and metabolic regulation are
    highly integrated and interdependent
  • This interface acts as a central homeostatic
    mechanism
  • Dysfunction promotes obesity and leads to a
    cluster of chronic metabolic disorders

64
Atherogenesis Endothelial Dysfunction Diet
  • Multiple dietary factors and nutrient balances
    reportedly affect endothelial function,
    inflammation and blood lipids
  • Saturate fat vs unsaturated fat intake
  • Omega-6 vs omega-3 unsaturated fat intake
  • Dietary carbohydrate load
  • Carbohydrate vs fat intake
  • Dietary antioxidant and polyphenol intake
  • Dietary fibre intake
  • Dietary fat vs polyphenol vs carbohydrate intake
  • Cordain, L., S. B. Eaton, et al. (2005). "Origins
    and evolution of the Western diet health
    implications for the 21st century." Am J Clin
    Nutr. 81(2) 341-54.
  • Giugliano, D., A. Ceriello, et al. (2006). "The
    Effects of Diet on Inflammation Emphasis on the
    Metabolic Syndrome." J Am Coll Cardiol. 48(4)
    677.
  • Kopp, W. (2006). The atherogenic potential of
    dietary carbohydrate. Preventive Medicine. 42(5)
    336.

65
The Assessment and Management of Cardiovascular
Risk. Evidence-based Best Practice Guideline,
New Zealand Guidelines Group, December 2003.
  • 1) Enjoy three meals a day, selecting from dishes
    that encourage you to eat plant foods and fish,
    with little or no dairy fat, meat fat or deep
    fried foods
  • 2) Choose fruits and/or vegetables at every meal
    and most snacks.
  • 3) Select whole grains, whole grain breads, or
    high fibre breakfast cereals in place of white
    bread and low fibre varieties at most meals and
    snacks
  • 4) Include fish, or dried peas, beans and soy
    products, or a small serving of lean meat or
    skinned poultry, at one or two meals each day
  • 5) Choose low fat milk, low fat milk products,
    soy or legume products every day
  • 6) Use small amounts of oil, margarine, nuts or
    seeds
  • 7) Drink plenty of fluids each day, particularly
    water, and limit sugar-sweetened drinks and
    alcohol
  • 8) Use only small amounts of total fats and oils,
    sugar and salt when cooking and preparing meals,
    snacks, or drinks. Choose ready-prepared foods
    low in these ingredients
  • 9) Mostly avoid or rarely include butter,
    deep-fried and fatty foods, and only occasionally
    choose sweet bakery products

66
Atherogenesis Endothelial Dysfunction Diet
Parikh P, McDaniel MC et al. 2005. Diets and
Cardiovascular Disease. J Am Coll Cardiol
200545137987
  • Low-Fat diet
  • Difficult to achieve
  • Promotes Insulin Resistance
  • No impact on mortality
  • Very-Low-Fat Diet
  • May decrease cardiac events
  • Concern about applicability and sustainability
  • Low Glycemic Index Diet
  • Unproven effects on CVD
  • Initiate reduced intake of energy-dense CHOs and
  • initiate weight loss
  • Low-Carbohydrate Diet
  • Short-term weight loss
  • Long-term effects on CVD unknown
  • Initiate decreased energy intake weight loss
  • Mediterranean Diet
  • Secondary prevention
  • Prevention of sudden cardiac death
  • Healthy overall approach to dieting
  • Long-term sustainability
  • DASH
  • Decreased hypertension by 5.5/3.3mm
  • Similar to Mediterranean Diet

67
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68
  • Low GI or GL diets inconclusive. Parikh P et al.
    J Am Coll Cardiol 200545137987

69
CHD Risk DIET Mediterranean Diet
70
Endothelial Dysfunction Optimal Diet
  • What is the optimal diet?
  • Maintain low-moderate Glycemic Index and Glycemic
    Load
  • Optimise Antioxidant fibre intake fruit
    vegetables
  • Increase Essential Fatty Acid intake
    omega-3/omega-6 balance
  • Maintain protein intake fish, nuts/seeds, lean
    meat, cheese, legumes wholegrains
  • Reduce saturated fat trans-fat intake
  • Reduce calorie intake ? 20-30 reduction
    promotes antiaging effect

71
Endothelial Dysfunction Diet
72
Enter THE POLYMEAL
73
  • SPECIFIC NUTRIENTS
  • IN
  • CARDIOVASCULAR
  • DISEASE

74
Cardiovascular Disease Endothelial
Dysfunction, Nitric Oxide and Arginine Wu G and
Meininger CJ. 2000. Arginine Nutrition and
Cardiovascular Function. J. Nutr. 130
26262629, 2000
  • Nitric Oxide is a major mediator in endothelial
    function
  • Produced in vascular endothelial cells by
    NO-synthetase from arginine
  • NO is a vital anti-atherogenic molecule that
  • Inhibits atherogenesis
  • Enhances vasodilator activity
  • Reduced NO production
  • is a measure of impaired endothelial health and
  • directly facilitates development of
    atherosclerosis
  • eNOS activity NO production can be increased
    by
  • High antioxidant intake particularly ascorbate
  • Arginine therapy
  • Statin therapy

75
Cardiovascular Disease Arginine, NO and
endothelial dysfunction
  • Compelling evidence shows that Arginine
  • reverses endothelial dysfunction associated with
    major cardiovascular risk factors
  • hypercholesterolemia, smoking, hypertension,
    diabetes, obesity/insulin resistance and aging
  • ameliorates many common cardiovascular disorders
  • coronary and peripheral arterial disease, heart
    failure, and ischemia/reperfusion injury
  • Increasing dietary arginine ascorbate intake
    increases endothelial NO production
  • Wu G and Meininger CJ. Arginine Nutrition and
    Cardiovascular Function. J. Nutr. 130 26262629,
    2000

76
Cardiovascular Disease Arginine and
endothelial dysfunction
77
CVD Therapy Antioxidants Vitamin C
  • Vitamin C
  • Epidemiological study reported development of CHD
    in males correlated inversely with Vit C status
  • Nyyssonen K, Parviainen MT et al. Vitamin C
    deficiency and risk of myocardial infarction
    BMJ 1997 314(7081)634-638.
  • Vit C was not useful in secondary prevention of
    CHD
  • MRC/BHF Heart Protection Study of antioxidant
    vitamin supplementation in 20,536 high-risk
    individuals Lancet 2002 360(9326)23-33
  • Nurses Health Study showed significantly reduced
    CHD event risk with ascorbate supplement use
  • Osganian SK, Stampfer MJ et al. Vitamin C and
    risk of coronary heart disease in women. J Am
    Coll Cardiol 2003 42(2)246-252

78
CVD Therapy Antioxidants Vitamin E
  • Vitamin E
  • Regulates endothelial cell proliferation
  • Inhibits platelet adhesion activation
  • Protects against oxidation particularly LDL
  • BUT must be natural mixed tocopherols and high
    dose gt 400 800 IU/day
  • ?-tocopherol markedly reduces ?-tocopherol level
  • ?-tocopherol is the more effective endovascular
    protective agent
  • reduces LDL cholesterol
  • Neutralises peroxynitrite damage
  • Singh, I., A. H. Turner, et al. (2005). Effects
    of gamma-tocopherol supplementation on thrombotic
    risk factors and measures of oxidative stress.
    Asia Pacific J Clin Nutri.14 S48.
  • Dietrich, M., M. G. Traber, et al. (2006). Does
    Gamma-tocopherol play a role in the primary
    prevention of heart disease and cancer? A review.
    JACN. 25(4) 292.

79
CVD Therapy Antioxidants Vitamin E
  • Contemporary studies indicate Vit E therapy
  • Has no impact on CVD occurrence or outcome OR
  • May promote CCF occurrence and mortality
  • Lonn E, Bosch J, et al. (2005). "Effects of
    long-term vitamin E supplementation on
    cardiovascular events and cancer a randomized
    controlled trial." JAMA. 293(11) 1338.
  • Most Vit E studies are heavily flawed
  • No monitoring of oxidative stress and markers of
    vascular response,
  • No monitoring of vitamin E levels.
  • Short duration and suboptimal dosages of vitamin
    E,
  • Suppression of gamma-tocopherol by
    alpha-tocopherol,
  • Unbalanced Vitamin E supplementation
  • Inappropriate administration relative to meal
    ingestion,
  • Robinson, I., D. G. de Serna, et al. (2006).
    "Vitamin E in humans an explanation of clinical
    trial failure. Endocrine Practice. 12(5) 576-82 .

80
CVD Therapy Antioxidants Selenium
  • Useful antioxidants
  • Selenium works synergistically with Vit E
  • protects cell membrane from oxidative damage
  • Selenium concentrations were inversely associated
    with coronary heart disease risk in observational
    studies
  • Flores-Mateo, G., A. Navas-Acien, et al. (2006).
    Selenium and coronary heart disease a
    meta-analysis. Am J Clin Nutr 84(4) 762-73.
  • Women living in the community who have higher
    serum selenium are at a lower risk of death HR
    0.71, 95 CI 0.56-0.90.
  • Ray AL, Semba RD, et al. 2006. Low serum
    selenium and total carotenoids predict mortality
    among older women living in the community the
    women's health and aging studies. J Nutr 136(1)
    172-6.

81
CVD Therapy Antioxidants Flavonoids
  • Bioflavonoids (quercetin hesperidin) and
    polyphenols)
  • increase tissue antioxidant capacity
  • increase anti-inflammatory activity
  • decrease platelet activation and
  • enhance vascular endothelial function
  • intake inversely associated with cardiovascular
    disease
  • Bucki R, Pastore JJ, et al. 2003. Flavonoid
    inhibition of platelet procoagulant activity and
    phosphoinositide synthesis. J Thromb Haemost
    1(8) 1820-8.
  • Geleijnse, J. M., L. J. Launer, et al. (2002).
    "Inverse association of tea and flavonoid intakes
    with incident myocardial infarction the
    Rotterdam Study." Am J Clin Nutr 75(5) 880-6.
  • Perez-Vizcaino, F., J. Duarte, et al. (2006).
    "Endothelial function and cardiovascular disease
    effects of quercetin and wine polyphenols." Free
    Radic Res 40(10) 1054-65.

82
CVD Therapy Antioxidants Cocoa Chocolate
  • Engler, M. B. and M. M. Engler (2006). "The
    emerging role of flavonoid-rich cocoa and
    chocolate in cardiovascular health and disease."
    Nutr Rev 64(3) 109-18.
  • Cocoa and chocolate are rich sources of
    antioxidant flavonoids with beneficial
    cardiovascular properties.
  • Favorable physiological effects include
  • antioxidant activity,
  • Vasodilation blood pressure reduction,
  • reduced platelet activity
  • Increased anti-inflammatory activity
  • Improved isulin sensitivity
  • Increasing evidence, experimental clinical,
    suggest an important role for these
    high-flavanol-containing foods in heart and
    vascular protection.

83
CVD Treatment Coenzyme Q10 Tran MT, Mitchell
TM, et al. 2001. Role of coenzyme Q10 in chronic
heart failure, angina, and hypertension.
Pharmacotherapy 21(7) 797-806.
  • CoQ10 is an essential lipid-soluble element of
    the Electron-Transport Chain
  • Mitochondrial antioxidant electron transfer
    molecule
  • Essential to mitochondrial oxidative activity
    and
  • myocardial contractility
  • Improves outcomes in cardiomyopathy CCF
  • Increases ejection fraction, stroke volume,
    cardiac output and exercise tolerance
  • Co-Q10 level is reduced by statin therapy
  • Sander S, Coleman CI, et al. 2006. The impact of
    coenzyme Q10 on systolic function in patients
    with chronic heart failure. J Card Fail 12(6)
    464-72.
  • Chew GT. and Watts GF. 2004. Coenzyme Q10 and
    diabetic endotheliopathy oxidative stress and
    the 'recoupling hypothesis'. Quart J Med. 97(8)
    537-48.

84
CVD Treatment alpha-Lipoic acid Jones W, Li X,
et al. 2002. Uptake, recycling, and antioxidant
actions of alpha-lipoic acid in endothelial
cells. Free Radic Biol Med 33(1) 83-93
  • Lipoic acid sulphur-containing antioxidant
  • Essential to cell membrane integrity function
  • particularly electrical conductance
  • Stimulates glutathione synthesis
  • enhances endothelial antioxidant defence and
    function
  • recycles dehydroascorbic acid to ascorbate,
  • decreases ROS generated by redox cycling
  • generates nitric oxide
  • restores mitochondrial aldehyde dehydrogenase
    activity thereby improving nitrate tolerance
  • Wenzel P, Hink U, et al. 2007. Role of reduced
    lipoic acid in the redox regulation of
    mitochondrial aldehyde dehydrogenase (ALDH-2)
    activity. Implications for mitochondrial
    oxidative stress and nitrate tolerance. J Biol
    Chem 282(1)792-9.

85
CVD Treatment alpha-Lipoic acid Sethumadhavan,
S. and P. Chinnakannu (2006). "L-carnitine and
alpha-lipoic acid improve age-associated decline
in mitochondrial respiratory chain activity of
rat heart muscle." J Gerontol A Biol Sci Med Sci
61(7) 650-9.
  • Progressive mitochondrial structural damage and
    loss of integrity occurs with aging ?
  • impairs cellular energy genesis, reducing
    activity of
  • TCA cycle enzymes and
  • electron transport chain complexes
  • Combined carnitine/lipoic acid treatment
  • raises mitochondrial energy producing capacity
  • reverses age-related mitochondrial enzyme decline
  • protects mitochondria from aging

86
CVD Treatment Garlic Rahman K. and Lowe GM.
2006. Garlic and cardiovascular disease a
critical review. J Nutr 136(3 Suppl) 736S-40S.
  • Epidemiologic studies show an inverse correlation
    between garlic consumption and progression of
    cardiovascular disease.
  • Numerous in vitro studies report that garlic
  • inhibits enzymes involved in lipid synthesis,
  • decreases platelet aggregation,
  • prevents lipid peroxidation of oxidized
    erythrocytes and LDL,
  • increases antioxidant status,
  • inhibits angiotension-converting enzyme.
  • 44 of clinical studies report positive effects
    from garlic
  • reduces cholesterol,
  • inhibits platelet aggregation,
  • reduces blood pressure,
  • increases antioxidant status.

87
CVD Treatment Garlic Borek C. 2006. Garlic
reduces dementia and heart-disease risk. J Nutr
136(3 Suppl) 810S-2S.
  • Aged Garlic Extract (AGE) reportedly
  • scavenges oxidants,
  • increases superoxide dismutase, catalase,
    glutathione peroxidase, and glutathione levels,
  • inhibits lipid peroxidation and inflammatory
    prostaglandins.
  • reduces cholesterol synthesis
  • by inhibiting 3-hydroxy-3-methylglutaryl-CoA
    reductase
  • effect is additive with statins in its action.

88
CVD Treatment Garlic Rahman K. and Lowe GM.
2006. Garlic and cardiovascular disease a
critical review. J Nutr 136(3 Suppl) 736S-40S.
  • Over 50 of clinical trials report negative
    results, possibly due to
  • usage of different garlic preparations,
  • unknown active constituents and their
    bioavalability,
  • inadequate randomization,
  • selection of inappropriate subjects,
  • short duration of trials.

89
CVD Therapy Vitamins B6, Folate, B12 Betaine
  • These nutrients reduce serum homocysteine level
  • Homocysteine gt 12mm/L is an independent risk
    factor for vascular disease smoking high
    lipids.
  • Graham IM, Daly LE et al. Plasma homocysteine as
    a risk factor for vascular disease. JAMA 1997
    277(22)1775-1781.
  • Elevated homocysteine impairs endothelial
    function
  • Endothelial dysfunction responds to folate
    therapy independent of homocysteine level
  • ? By maintaining tetrahydrobiopterin activity
  • Vit B6 insufficiency impairs endothelial function
  • Moat SJ, Lang D et al. Folate, homocysteine,
    endothelial function and cardiovascular
    disease. J Nutr Biochem 2004 15(2)64-79

90
CVD Therapy Niacin Elam MB, Humminghake DB et
al. ADMIT study. JAMA. 2000. 2841263-70
  • Niacin therapy
  • Increased HDL cholesterol by 29
  • Reduced triglycerides by about 25 and
  • Reduced LDL cholesterol by about 9
  • was safe for use in patients with diabetes
  • Use the Inositol Hexaniacinate form
  • Minimises risk of niacin reaction
  • With phosphatidylcholine, hexaniacinate can
    optimise bile-salt production cholesterol
    excretion
  • Goldberg AC. 2004. A meta-analysis of randomized
    controlled studies on the effects of
    Extended-Release niacin in women. Am J Cardiol.
    94(1)121.

91
Nutrient Therapy in Vascular Disease
  • Mineral therapy
  • Magnesium Potassium
  • improve myocardial metabolism and inhibits
    arrhythmia and lowers blood pressure
  • Calcium essential for myocardial contraction
    and assists in regulating BP
  • Zinc essential for mitochondrial function and
    DNA/RNA repair
  • Chromium essential for Glucose Tolerance Factor
    activity
  • Vanadium Stabilises blood sugar reduces blood
    lipids

92
Nutrient Therapy in Vascular Disease
  • Cardiovascular disease arises as a result of the
    interaction between multiple related causal
    factors
  • Good research into the role of many of these
    factors and the management thereof remains
    woefully inadequate
  • broad spectrum pharmacotherapy is NOT a good
    option particularly for primary prevention
  • Good management should seek to remediate all
    causal factors identified in the patient,
    utilising an integrated regimen of
  • Diet
  • Exercise
  • Nutrient supplementation
  • Targeted pharmacotherapy

93
Nutrient Therapy in Vascular Disease
  • Effective management needs to be systematic
    our protocol is to assess and optimise
  • Digestion
  • Diet
  • Antioxidant capacity
  • Essential Fatty Acid balance
  • Bowel dysbiosis
  • Specific therapy
  • Neurotransmitter balance
  • Hepatic detoxification
  • Hormonal balance

94
  • Thank you for your attention
  • and
  • Please feel free to speak to me
  • during the breaks
  • AND

95
Dont forget enjoy your daily Polymeal
  • Grilled salmon with onion garlic
  • Served with sauce of tomato paste, garlic,
    coriander
  • Salad lettuce, purslane, celery, cucumber,
    tomato, capsicum, mushroom, avocado, tofu
    almonds
  • Dressing olive oil, garlic vinegar
  • Green tea served before the meal
  • Dessert blueberries, strawberries with chocolate
    sauce (made with soy-milk dark chocolate)
  • After-dinner drinks Cabernet sauvignon 1glass
  • Plus 1 Poly-nutrient pill
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