Cardiovascular Disease [70-80%]
atherosclerosis
[the disease of the arteries]
endothelial dysfunction
- A novel diagnostic method
- Nutraceutical therapy
Laszlo G. Meszaros
Dept. Animal Physiology
Univ. of Kaposvar, Hungary
Life Science Foundation
Augusta, GA, USA
“You’re as old as your arteries…”
Some Cardiovascular Disease (CVD) Statistics
Atherosclerosis (AS)
Some more AS statistics – WHO 2008
The most “deadliest” risk factors all relate to AS…
“As old as your arteries…”
Non-optimal circulation: in essence, every organ, tissue affected
AS risk factors and markers
AHA - 2012
LDL ↑
Diet & Physical Inactivity – 74%
(ApoB/ApoA ↑
Lp-PLA2 ↑)
Smoking
Alcohol
Genetics
(Air) Pollution
HDL ↓
CRP ↑
Metabolic
disease
BPsys ↑
Obesity ↑
Homo-Cystein ↑
Diabetes
Frequency
AS is a degenerative (chronic) disease
Putative causes:
error accumulation
epigenetics
Age
Anatomy of arteries
Function of arterial cells – Vasodilation 1
Endothelial cell layer (largest endocrine organ):
• regulates smooth muscle constriction/dilation
• thereby, sets vessel diameter (and?)
• (permeability, blood cell – vessel wall interact.)
Vasodilators:
• synth.: EDHF (C-natriuretic peptide?), NO
• mediates: shear stress, bradykinin, ANP*, VIP*,
prostagladines, prostacyclin…
Vasoconstrictors:
• synthesize: endothelins
• mediates: adrenerg-, muscarinic agonists,
vasopressin, thromboxane, hypox.
*Atrial Natriuretic Peptide, Vasoactive Intestinal Peptide
Function of arterial cells – Vasodilation 2
AS ̶ initiation and progression of the disease
AS Stages:
1. Endothelial dysfunction (ED) – NO  (aging, free radicals, ADMA)
(Flow-mediated dilation )
endothelial activation (early inflammation?)
LDL-cholesterol oxidation (free radicals?) – fatty streaks
NON-LOCALIZED
Years
2. Recruitment of immune cells, collagen synthesis, calcification,
endothelial permeability, apoptosis, SM proliferation – plaques
LOCALIZED and/or NON-LOCALIZED
3. Thrombocyte activation, thrombus formation
mosly LOCALIZED
Techniques to assess arterial health must consider LOCALITY/NON-LOCALITY.
Vasography: Flow-Mediated Dilation Another Way
method to assess endothelial function in the arteries
HU (P1000657) and US (US 61483768) patents
Techniques to assess arterial health I.
Sorting them out…
- invasive vs. non-invasive
- early vs. late
- expensive vs. less expensive
- usable for screening vs. …
- locality vs. non-locality
- simple to use vs. …(requirement of clinical setting)
- grading, staging
Costly, clinical setting required:
Angiography – invasive, local
Stress test (ECG) – indirect
Calcium “scoring” (CT) – late stage
Ultrasound – seems user-dependent, local?
Intravascular ultrasound – invasive, local (advantage?)
Techniques to assess arterial health II.
Pulse Wave Velocity (much less costly)
- narrower the artery faster the pulse travels (Bernoulli)
- detection of pulse appearance at two locations
with different distances from the heart
Arterial Stiffness (m/s)
Localized or not?
No, it is not!
Aorta-Femoral
For instance, very good correlation between B-A PWV
and coronary calcification:
Liu, C-S.: Arterial Stiffness is Highly Correlated
with Coronary Atherosclerosis, J. Athero. Thromb.
18:online (2011)
Blacher, J.: Impact of Aortic Stiffness on Survival…,
Circulation 99:2434 (1999)
Techniques to assess arterial health III.
FMD (Flow-Mediated Dilation with ultrasound) – the first sign, but…
Localized or not?
No, it is most likely not!
Bots, ML.et al.: Assessment
of flow-mediated vasodilatation
(FMD) of the brachial artery,
Eur. Heart J., 26:363 (2004)
Techniques to assess arterial health IV.
Pulse Contour Analysis (PCA) – less costly
Millaseau, SC. et al.: Determination of age-related
increases in large artery stiffness by digital pulse
contour analysis, Clin. Sci., 103:371 (2002)
Aix
SphygmoCor
Arteriograf
ArcSolver
CVprofiler…
SI and RI:
Pulse Tracer
BioClip
According to the theory behind them:
evolution is STUPID.
Wang, K-L. et al.: Wave Reflection and Arterial
Stiffness…, Hypertension, 55:799 (2010)
Some problems with PCA
1. The model:
“wave reflection”
2. Math:
Without curve fitting?
Pulse contour types
Vasography = FMD differently and better
Reminder:
shear stress ↑, then Ca ↑, which makes NO ↑
resulting in vasodilation.
Vasography = FMD differently and better
Methods:
- Pressure pulse (PP) recorded by using
piezoelectric sensor (UFI, USA)
- Volume pulse recorded near-infrared
plethysmographic sensor (Norelco, USA)
SIMULTANEOUSLY
Data fed into a 12 bit A/D converter
Pulses averaged, then normalized in length
and height
Max. rate of rise (rsys) computed from
normalized records by taking the
time-derivative
Significance by ANOVA
Vasography = FMD differently and better
Development of VP is delayed (relative to PP)
The delay is larger, max. rate is slower in the
elderly
Vasography = FMD differently and better
NG = nitroglycerin, an NO donor
The rate difference between PP and VP
decreases after NG in the elderly
(Max. rate in PP is not altered by NG)
Thus, max. rate in VP measures
endothelial function (just like FMD
with ultrasound, but without the snags)
Vasography = FMD differently and better
A: R = 0.783; P < 0.001
B: Difference is significant (P < 0.05)
Vasography = FMD differently and better
Tone + Pulsation (PWV)
vs.
Pulsation (rsys)
The exponential curve is NOT a surprise
Vasography = Pulsating FMD (PFMD)
Thanks for listening…