Herbs and Arterial Compliance - Dick Middleton
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Transcript of 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