Herbs and Arterial Compliance - Dick Middleton

8/14/2019 Herbs and Arterial Compliance - Dick Middleton

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Herbs and arterialcompliance

Dr Dick Middleton

Lichtwer Pharma UK Ltd &

Medic Herb UK Ltd


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Aortic Elasticity (Compliance)

Pulse Wave Velocity (PWV)

Clinical Significance


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AORTIC ELASTICITY (STIFFNESS)

Reduced aortic elasticity effectively means a

reduced Windkessel function of the aorta.

Factors affecting aortic elasticity include:

AgeHypertensionGenderVascular diseases

atherosclerosisdiabetes mellitusfamilial hypercholesterolemia

Belz 1995 Cardiovascular Drugs and Therapy, 9, 73-83


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THE WINDKESSEL FUNCTION

A Windkessel is an air- (top) and water-

(bottom) filled reservoir similar to the pump of

an old fashioned fire hose - its purpose is to

transform the rhythmic water output of the

plunger strokes into an almost continuous

waterjet.

Belz 1995 Cardiovascular Drugs and Therapy, 9, 73-83


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Left ventricle Aortic valve (open) Aorta walls expand

SYSTOLE

DIASTOLE

Aortic valve (closed) Aorta walls contract

AORTIC WINDKESSEL FUNCTION


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During systole, the left ventricle ejects the stroke volume (100%)

into the aorta. Around 50% of the volume is forwarded into the peripheral

circulation. The other 50% leads to an extension of the

aortic wall and is stored (storage volume).

AORTIC WINDKESSEL FUNCTION cont

In diastole, the aorta

wall passivelycontracts due to its

elastic properties.

Utilising the energy

stored during systole,

the other

50% of the stroke

volume is forwarded

into the peripheral

circulation - including

the coronary

circulation system


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Aortic pressure wave

P1, first systolic peak; P2 second systolic peak; IP, inflection point

Ag, augmentation; PP pulse pressure; Tr, time to wave reflection


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Waveform in the carotid artery:diastolic Bp 75, systolic 142 mm Hg


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What happens? What if ?

WindkesselAorta

VariablerWiderstandkleine Arterien undArteriolen

VariablePumpleistungHerzkammern

AustauscherKapillaren und Venolen

With

windkesselfunction

heart: normal heart

work

vessels: compensation of

variations ofpressurecaused by

heartbeat no harmfulpressure peaks

continuousblood supply

normal bloodpressure

Without

windkesselfunction

heart:

more heart work

vessels:

variations ofpressurecaused byheartbeat

harmful pressurepeaks

irregular blood

supply raised blood

pressureResult: weakening ofwindkessel function increasesthe cardiovascular risk- Higherrisk for heart and vessels

increased mortality risk

Windkesselaorta

Variable pumping

performance

ventricles

Variable resistanceSmall arteries and

arterioles

Exchanger

capillaries and venules


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Scale for windkessel function

WindkesselAorta

VariablerWiderstandkleine Arterien undArteriolen

VariablePumpleistungHerzkammern

AustauscherKapillaren und Venolen

Facts Every heartbeat

produces a pulse wavewhich proceeds muchfaster than the blood

stream The stiffer the

response, the lesselastic the aorta, thehigher the pulse wave

velocityMeasurement The measurement of

pulse wave velocity ismade viasimultaneouslyregistered pulse curves

windkessel

aorta

Variable pumping

performance

ventricles

Windkessel

aorta

Variable resistance

Small arteries and

arterioles

Exchanger

capillaries and venules


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Pulse Wave Velocity (PWV)

Carotid and femoral artery pressure pulse wavesrecorded simultaneously using non invasive

techniques

PWV (m/s) calculated from the time delay in

pulse pressure waves from the carotid to thefemoral artery divided by the length of the arterial

segment.

Average of three readings used

Breithaupt et al., 1992 Clin. Physiol. Biochem., 9, 18-25

PWV increases as aortic elasticity is reduced


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Flow velocity waveforms in two arteries

x= time delay of pulse wave


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Elastic Vascular Resistance (EVR)

EVR is a pressure standardised index of aortic elasticity

EVR = (PWV) *

MAP

MAP (mean arterial blood pressure) =

DBP+0.43 (SBP-DBP) **

* Breithaupt-Grgler et al., 1996 Cardiovasc. Drugs Ther., 10, 49-57

** Wezler et al., 1939 Ergebn Physiol, 41, 291


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CLINICAL RELEVANCE OF REDUCED AORTIC

WINDKESSEL FUNCTION CAUSED BY REDUCED

AORTIC ELASTICITY

Increase in systolic blood pressure and an

increase in left ventricular afterload1

Reduced relaxation of the left ventricle2

Reduced coronary blood flow3

Increased peripheral vascular damage and

arteriosclerosis 4

1 Simon et al., 1991 Cor. Art. Dis., 2, 1111-1120

2 Ochi et al., 1991 Am. J. Noninvas. Cardiol., 5, 149-154

3 Watanabe et al., 1993 J. Am. Coll. Cardiol., 21, 1497-1506

4 ORourke et al., 1990 Hypertension, 15, 339-347


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modified from Schimmler 1965 Arch Kreislaufforsch;47:188-233

Pulse Wave Velocity (PWV) & Bp

means of age groups, n=1442 male volunteers

5

6

7

8

9

10

11

12

80 90 100 110 120 130 140 150 160 170

mean (arterial) blood pressure (mmHg)

25 45 54 63 73 years

PWV(m

/s)

fast

slow

stiffened

elastic


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Type 2 Diabetes

Population-based study 261 normal glucose metabolism 170 impaired glucose metabolism 188 type 2 diabetes

Measurement of arterial stiffness

Conclusion: Impaired glucose metabolism and Type 2diabetes were both associated with a significant increase

in arterial stiffness, which is more pronounced in Type 2diabetes. This may partly explain why both disease states

are associated with increased cardiovascular risk.

Mullan et al. 2004 Hypertension, 43(2), 176-181


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Reuter 1995 Phytomedicine, 2(1), 73-91

Garlic - medicinal properties

plasma lipids & lipid metabolism

anti-hypertensive

platelet adhesion & aggregation

free radical scavenging properties

hypoglycaemic activity anti-bacterial

anti-fungal

anti-viral anti-tumour


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RECENT KEY PUBLICATIONS:

Breithaupt-Grgleret al., 1997 Protective effect ofchronic garlic intake on elastic properties of aorta in

the elderly. Circulation, 96 (7), 2649-2655

Orekhovet al., 1997 Effects of garlic onatherosclerosis. Nutrition, 13 (7/8), 656-661

Adleret al., 1997 Effect of garlic and fish-oilsupplementation on serum lipid and lipoprotein

concentrations in hypercholesterolaemic men. Am. J.Clin. Nutr., 65, 445-450,.


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Breithaupt-Grgleret al., 1997

Garlic Study

Exclusion criteria: Regular drug treatment affecting aortic

elasticity

- ACE inhibitors

- Direct acting vaso-dilating drugs

- Lipid lowering drugs

Regular nutritional garlic ingestion


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Study design

matched pairs technique (n=202)

Garlic tablet users

n=101 healthy subjects(52 female, 49 male)

standardized garlic (LI111) intake (300-900 mg

daily) for at least 2

(median 5.7) years

no regular treatment withmedications

influencing aortic elastic

properties

Controls

n = 101 healthy controls(52 female, 49 male)

no high nutritional garlic intake no regular medication

Matched for:

sex

age (+/- 5 years)

body weight (+/- 10 %)

geographic region

non-smokers


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** p


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PWV of Garlic tablet users & Controls:

The elasticity benefits of Garlic tablets

evident at rest and under stress

6

7

8

9

10

11

12

13

14

15

Garlicusers Controls Garlic users Controls

PWV(m/s)

p=0.0001

p=0.0001

Rest Standardized stress

stiffened

elastic


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Garlic tablet users compared to controls

Differences () in PWV become more distinct in older age

-3

-2.5

-2

-1.5

-1

-0.5

05059 6069 7080

Age (years)

PWV(m/s)

p=0.06

p=0.0001

p=0.0016

The older a person, the greater the benefit of garlic tablets (elasticity)


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-3

-2.5

-2

-1.5

-1

-0.5

0134 135149 150

Systolic blood pressure (mmHg)

PWV(m/s)

p=0.22

p=0.0005

p=0.0001

The higher the blood pressure is, the greater the benefit of garlic tablets (elasticity)

Garlic tablet users compared to controls

Differences () in PWV become more distinct with higher blood pressure


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Garlic Study: Key Results

Pulse Wave Velocity Measurements (PWV)

Elastic Vascular Resistance (EVR)

Significantly lower in garlic group

Greater difference in the older age groups

Age and PWV correlated well in both groups

Systolic blood pressure and PWV correlated

well in both groups

Breithaupt-Grogleret al., 1997


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Micronutrients & other herbs

and aortic elasticity


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Ascorbic Acid

30 subjects with Type 2 diabetesdouble-blind, placebo-controlled

randomised parallel group design

average age 59

500mg ascorbic acid or placebo daily for 4 weeks

Conclusion: ascorbic acid reduced blood pressure andarterial stiffness in patients with Type 2 diabetes. As strict

control of blood pressure reduces cardiovascular risk in

diabetes, ascorbic acid supplementation may potentially bea useful and adjunctive therapy.

Mullan et al. 2002 Hypertension, 40(6), 804-809


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Vitamin E

Study design20 post-menopausal women

double-blind

placebo-controlled

crossover design:

no washout

average age 55

400iu synthetic vitamin E/d x

10 weeks or placebo

Outcome measuresBPPWV (arterial stiffness)

plasma vitamin E

Rasool et al. 2003 Int J Clin Pharmacol Ther, 41 (12), 587-592

ResultsSupplementary vitamin E

for 10 weeks at

400iu daily

has no effect on arterial

stiffness in healthy

post-menopausal women


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Caffeine

20 healthy subjects

double-blind

placebo-controlled

crossover design

average age 50

250mg caffeine or placebo

single dose

Conclusion: Caffeine increases aortic stiffness.

Vlachopoulos et al. 2003

Journal of Hypertension, 21(3), 563-570


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Isoflavones

80 healthy subjects 34F/46M

double-blindplacebo-controlled, crossover design

average age 54

80mg isoflavones (Novogen) or placebo daily

6 weeks (one week wash out)

Conclusion: Red Clover isoflavones reduced arterialstiffness & total vascular resistance but had no effect

on blood pressure. These effects may partly explainthe lower cardiovascular risk in populations eating

isoflavone-rich diets.

Teede et al. 2003 Aterioscler. Thromb. Vasc. Biol., 23,1066-1071


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Conclusion Several studies indicate that garlic reduces age-

related aortic stiffness. This was particularly evidentin the large study discussed in this talk, of people who

had been taking a standardized garlic powder

preparation for > 2 years. These observations support

the hypothesis that garlic intake is protective of age-related aortic elasticity

Vitamin C and isolated isoflavones from red clover

reduce aortic stiffness: caffeine in its isolated form

increases it, while vitamin E has shown no effect Decreased Aortic Elasticity (Compliance) & Increased

Pulse Wave Velocity (PWV) are inter-related risk

factors for CVD worthy of consideration in patient care

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Herbs and Arterial Compliance - Dick Middleton