cardiovascular disease and inflammation - simon mills

8/14/2019 Cardiovascular Disease and Inflammation - Simon Mills

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Inflammation - a newer,

potent risk factor for cardiovascular disease

Simon Mills - Herbal practitioner

Teaching Fellow in Integrated Healthcare

Peninsula Medical School

Universities of Exeter and Plymouth, UK

Chairman, British Herbal Medicine Association

Secretary, European Scientific Cooperative on Phytotherapy (ESCOP)

Director, Masters Program in Botanical Healing, Tai Sophia Institute

Laurel, Maryland USA

www.phytotherapy.info



Inflammation and cardiovascularInflammation and cardiovascular

diseasedisease A growing body of evidence, from population,A growing body of evidence, from population,

clinical and laboratory studies, suggests thatclinical and laboratory studies, suggests that

inflammation is an important factor ininflammation is an important factor in

atherosclerosis.atherosclerosis.




diseasedisease Established “risk factors” such asEstablished “risk factors” such as

hypercholesterolaemia, hypertension,hypercholesterolaemia, hypertension,

smoking, and obesity are not fully predictivesmoking, and obesity are not fully predictive

of heart disease. Half of USA heart attack of heart disease. Half of USA heart attack

victims have acceptable cholesterol and 25%victims have acceptable cholesterol and 25%

have no risk factors.have no risk factors. ..




diseasediseaseCurrent views of arterial diseaseCurrent views of arterial disease

atherosclerosis involves the activation of the acuteatherosclerosis involves the activation of the acute phase inflammatory response. phase inflammatory response.

signalled by interleukin-6, producing proteinssignalled by interleukin-6, producing proteins((fibrinogenfibrinogen,, C-reactive proteinC-reactive protein (CRP),(CRP), serum amyloidserum amyloidA, adhesion moleculesA, adhesion molecules) that lead to inflammatory) that lead to inflammatoryreactions.reactions.

localized inflammatory responses in the intimal layer localized inflammatory responses in the intimal layer of the arterial wall have been shown to be responsibleof the arterial wall have been shown to be responsiblefor many of the aspects of intimal thickening andfor many of the aspects of intimal thickening and

plaque disruption. plaque disruption.



C-reactive proteinC-reactive protein

An acute phase protein expressed by tissuesAn acute phase protein expressed by tissues

involved in inflammatory reactions.involved in inflammatory reactions.

Levels increase during systemic inflammation,Levels increase during systemic inflammation,immune disease and infections.immune disease and infections.




Laboratory studies suggest that high levels of CRPLaboratory studies suggest that high levels of CRPexpression from arterial walls is associated withexpression from arterial walls is associated withhigher levels of arterial wall cell surface protein, thehigher levels of arterial wall cell surface protein, theangiotensin I receptor, and subsequently with larger angiotensin I receptor, and subsequently with larger

plaques of artheroma. plaques of artheroma.

Ex vivo Ex vivo studies show an effect of CRP on endothelialstudies show an effect of CRP on endothelial

progenitor cells progenitor cells

Clinical studies suggest an association with higher Clinical studies suggest an association with higher levels of coronary calcium which is another marker levels of coronary calcium which is another marker

for the extent of atheroma.for the extent of atheroma.




A high sensitivity assay (hs-CRP) is now available.A high sensitivity assay (hs-CRP) is now available.

Range of CRP valuesRange of CRP values

<1.0 mg/L (low risk)<1.0 mg/L (low risk) 1.0 –3.0 mg/L (medium risk)1.0 –3.0 mg/L (medium risk)

>3.0 mg/L (high risk)>3.0 mg/L (high risk)

can exceed 10.0 mg/L in some infectionscan exceed 10.0 mg/L in some infections




US Centers for Disease Control andUS Centers for Disease Control and

Prevention have recently issued a jointPrevention have recently issued a joint

scientific statement reviewing the use of scientific statement reviewing the use of

inflammatory markers (mainly CRP) andinflammatory markers (mainly CRP) and

cardiovascular disease -cardiovascular disease -




High levels of hs-CRPHigh levels of hs-CRP consistently predict new coronary events in patients withconsistently predict new coronary events in patients with

unstable angina and acute myocardial infarction (x2unstable angina and acute myocardial infarction (x2 between highest and lowest quartiles) between highest and lowest quartiles)

correlate with low survival rate in this groupcorrelate with low survival rate in this group

may increase the risk of arterial reclosure after angioplastymay increase the risk of arterial reclosure after angioplasty

associated with increased recurrent events after stroke andassociated with increased recurrent events after stroke and peripheral arterial disease. peripheral arterial disease.



C-reactive protein - the debateC-reactive protein - the debate

““Combined with cholesterol levels seen to have aCombined with cholesterol levels seen to have acorrelation with the incidence of cardiovascular correlation with the incidence of cardiovascular

events”events”Ridker PM et al (2002)Ridker PM et al (2002) New Engl J Med New Engl J Med 347 (20) 1557-1565347 (20) 1557-1565

““relatively moderate predictor” on the incidence of relatively moderate predictor” on the incidence of

Coronary Heart Disease in relation to cholesterolCoronary Heart Disease in relation to cholesterollevels and cigarette smokinglevels and cigarette smoking

Danesh J et al (2004)Danesh J et al (2004) New Engl J Med New Engl J Med 350 (14) 1387-1397350 (14) 1387-1397




High levels associated with particular High levels associated with particular

infections:infections: CytomegalovirusCytomegalovirus

Chlamydia pneumoniaeChlamydia pneumoniae

Helicobacter pylori Helicobacter pylori

Herpes simplex Herpes simplex



Other causes of raised CRPOther causes of raised CRP

Gum disease?Gum disease? patients with periodontal disease (85% among heart patients with periodontal disease (85% among heart

attack patients - 30% among a matched population)attack patients - 30% among a matched population)have higher levels of CRP in direct relation to thehave higher levels of CRP in direct relation to theseverity of the diseaseseverity of the disease

a particularly dramatic increase in CRP levels amonga particularly dramatic increase in CRP levels among

heart attack sufferers with periodontal diseaseheart attack sufferers with periodontal diseasecompared with levels among sufferers without thecompared with levels among sufferers without thedisease.disease.




Tuberculosis?Tuberculosis? old physicians often saw a causative relationship betweenold physicians often saw a causative relationship between

mycobacterial and heart diseasemycobacterial and heart disease

mycobacterium is only micro-organism to depend onmycobacterium is only micro-organism to depend oncholesterol for its pathogenesischolesterol for its pathogenesis

US CDC maps for CV disease show close similarity to thoseUS CDC maps for CV disease show close similarity to thoseof State and regional TB casesof State and regional TB cases

proteins of mycobacterial origin lead to experimental proteins of mycobacterial origin lead to experimentalatherogenesis in animalsatherogenesis in animals

TB leads to raised CRP, homocysteine and interleukin-6TB leads to raised CRP, homocysteine and interleukin-6




DiabetesDiabetes

Both increased atherosclerosis and CRP levelsBoth increased atherosclerosis and CRP levels

among newly diagnosed diabetic men areamong newly diagnosed diabetic men are

maintained throughout the conditionmaintained throughout the condition




DepressionDepression

Extent of depression measured by Zung Self-ratingExtent of depression measured by Zung Self-rating

Depression Scale correlates with CRP levels,Depression Scale correlates with CRP levels,homocysteine, coagulation factors in cardiovascular-homocysteine, coagulation factors in cardiovascular-

free subjectsfree subjects



Treatments for inflammatory CVTreatments for inflammatory CV

diseasedisease

aspirinaspirin

angiotensin I blockers?angiotensin I blockers?

HMG-CoA reductase inhibitors (statins)HMG-CoA reductase inhibitors (statins) lower CRP levels as well as cholesterollower CRP levels as well as cholesterol

note lovostatin in red yeast ricenote lovostatin in red yeast rice




diseasedisease

Vitamin EVitamin E reduces CRP levels in smokers with coronary diseasereduces CRP levels in smokers with coronary disease

significantly lowers CRP levels in diabetics and non-significantly lowers CRP levels in diabetics and non-diabeticsdiabetics

minimises other aspects of the acute phase response andminimises other aspects of the acute phase response and

inflammatory damageinflammatory damage

Patrick L, Uzick M. (2001) Cardiovascular disease: C-reactive protein and thePatrick L, Uzick M. (2001) Cardiovascular disease: C-reactive protein and theinflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol,inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol,

red yeast rice, and olive oil polyphenols. A review of the literature. Altern Med Rev.red yeast rice, and olive oil polyphenols. A review of the literature. Altern Med Rev.

6(3): 248-71.6(3): 248-71.




diseasedisease

Fruit and vegetable intakeFruit and vegetable intake reduces CRP and homocysteine levels in elderlyreduces CRP and homocysteine levels in elderly

populations populations




diseasedisease

tomatoestomatoes reduction of low-density lipoprotein (LDL)reduction of low-density lipoprotein (LDL)

cholesterol, homocysteine, platelet aggregationcholesterol, homocysteine, platelet aggregationWillcox JK et al (2003) Tomatoes and cardiovascular health. Crit Rev Food SciWillcox JK et al (2003) Tomatoes and cardiovascular health. Crit Rev Food Sci

Nutr. 43(1): 1-18 Nutr. 43(1): 1-18




diseasedisease

soyasoya reduces homocysteine levels in premenopausalreduces homocysteine levels in premenopausal

women in spite of antioestrogenic effects of women in spite of antioestrogenic effects of isoflavonesisoflavones

Nagata C et al (2003) Soy product intake is inversely associated with serum Nagata C et al (2003) Soy product intake is inversely associated with serum

homocysteine level in premenopausal Japanese women. J Nutr. 133(3): 797-homocysteine level in premenopausal Japanese women. J Nutr. 133(3): 797-

800800




diseasedisease

flavonolsflavonols

red wine and beer red wine and beer Gaytan RJ, Prisant LM. (2001) Oral nutritional supplements and heart disease:Gaytan RJ, Prisant LM. (2001) Oral nutritional supplements and heart disease:

a review. Am J Ther. 8(4): 255-74.a review. Am J Ther. 8(4): 255-74.




diseasedisease

Exercise regimesExercise regimes significantly reduces CRP levels among coronarysignificantly reduces CRP levels among coronary

heart disease patientsheart disease patients




diseasedisease

PolyphenolsPolyphenols in black tea and coffee (notably chlorogenic acid) can actin black tea and coffee (notably chlorogenic acid) can act

as acceptors of methyl groups during the metabolism of as acceptors of methyl groups during the metabolism of

methionine to homocysteinemethionine to homocysteine

Hodgson JM et al (2003) Can black tea influence plasma total homocysteineHodgson JM et al (2003) Can black tea influence plasma total homocysteine

concentrations? Am J Clin Nutr. 77(4): 907-11concentrations? Am J Clin Nutr. 77(4): 907-11

may exacerbate through raising homocysteine levelsmay exacerbate through raising homocysteine levels

Olthof MR, et al. (2001) Consumption of high doses of chlorogenic acid,Olthof MR, et al. (2001) Consumption of high doses of chlorogenic acid,

present in coffee, or of black tea increases plasma total homocysteine present in coffee, or of black tea increases plasma total homocysteine

concentrations in humans. Am J Clin Nutr. 73(3):532-8concentrations in humans. Am J Clin Nutr. 73(3):532-8




diseasedisease

PolyphenolsPolyphenols However, polyphenolic compounds present inHowever, polyphenolic compounds present in

virgin olive oil also have anti-inflammatory andvirgin olive oil also have anti-inflammatory andantioxidative effects in cardiovascular disease.antioxidative effects in cardiovascular disease.They may explain some of the protective effectsThey may explain some of the protective effectsfound in epidemiological studies.found in epidemiological studies.Patrick L, Uzick M. (2001) Cardiovascular disease: C-reactive protein and thePatrick L, Uzick M. (2001) Cardiovascular disease: C-reactive protein and the

inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature.tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature.Altern Med Rev. 6(3): 248-71.Altern Med Rev. 6(3): 248-71.



What herbs may weWhat herbs may we

use?use?



Allium sativum L.



Herbs with potential benefits

for inflammatory CV disease

garlic hyperlipidaemia, vasculoactive





garlic hyperlipidaemia , vasculoactiveginkgo anti-PAF, anti-inflammatory



Ginkgo biloba L.



EGb 761

(Schwabe)



Ginkgolides

O H

R2

O

O

CH3

R1

H

H

H

But

R3H

O

O

O

O

HO H

H

Ginkgolide A OH H H

R1 R2 R3

Ginkgolide B OH OH H

Ginkgolide C OH OH OH





garlic hyperlipidaemia, vasculoactiveginkgo anti-PAF, anti-inflammatoryginger anti-inflammatory, vasoactive



Zingiber

officinale L.






cayenne anti-inflammatory, vasoactive



Capsicum spp.



Acrid, pungent constituents

Commonsources

Subjective impactand

traditional use

Confirmedpharmacological activity

cayenne, ginger,peppers

hot, heating, increasing warmthto diseased tissues, preventingfood poisoning in hot climates,sustaining febrile response infever management, topical to

arthritis and other subdermalinflammations

thermogenic and metabolicstimulant (involvingcatecholamine release andpossibly reflex irritation eg. fromvanilloid receptors on C-fibres),

increased gastric secretions,propylactic against some foodpoisoning, topical pain relief,increase in absorption of other nutrients and agents



OH

O

N

H

H3CO

Capsaicin



O OH

H3

CO

OH

Gingerols

n

6-gingerol 48-gingerol 6

10-gingerol 8

(CH2)nCH3



O

O

N

O

Piperine






cayenne anti-inflammatory, vasoactivefeverfew vascular activity



Tanacetum parthenium (L.) Schulz-Bip






cayenne anti-inflammatory, vasoactivefeverfew vascular activity

hawthorn vasoactive, procyanidins,



Crataegus spp.





garlic hyperlipidaemia, vasculoactive

ginkgo anti-PAF, anti-inflammatoryginger anti-inflammatory, vasoactivecayenne anti-inflammatory, vasoactive

feverfew vascular activity

hawthorn vasoactive, procyanidins,

turmeric anti-inflammatory prospects

T f i fl CV




diseasedisease

curcumincurcumin reduces CRP levels in laboratory animalsreduces CRP levels in laboratory animals

Banerjee M et al (2003) Modulation of inflammatory mediators by ibuprofenBanerjee M et al (2003) Modulation of inflammatory mediators by ibuprofenand curcumin treatment during chronic inflammation in rat. Immunopharmacoland curcumin treatment during chronic inflammation in rat. Immunopharmacol

Immunotoxicol. 25(2): 213-24Immunotoxicol. 25(2): 213-24

cardiovascular disease and inflammation - simon mills

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