Post on 13-Jan-2016
Cardiovascular Disease [70-80%]
atherosclerosis [the disease of the arteries]
endothelial dysfunction
Laszlo G. MeszarosDept. Animal PhysiologyUniv. of Kaposvar, HungaryLife Science FoundationAugusta, GA, USA
- A novel diagnostic method- Nutraceutical therapy
“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
LDL ↑(ApoB/ApoA ↑
Lp-PLA2 ↑)
HDL ↓CRP ↑
MetabolicdiseaseBPsys ↑
Obesity ↑Homo-Cystein ↑
Diabetes
LDL ↑(ApoB/ApoA ↑
Lp-PLA2 ↑)
HDL ↓CRP ↑
MetabolicdiseaseBPsys ↑
Obesity ↑Homo-Cystein ↑
Diabetes
AHA - 2012Diet & Physical Inactivity – 74%
SmokingAlcoholGenetics
(Air) Pollution
AHA - 2012Diet & Physical Inactivity – 74%
SmokingAlcoholGenetics
(Air) Pollution
AS is a degenerative (chronic) disease
Age
Putative causes:error accumulationepigenetics
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 Waymethod to assess endothelial function in the arteries
HU (P1000657) and US (US 61483768) patents
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 I.
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)
Techniques to assess arterial health II.
Blacher, J.: Impact of Aortic Stiffness on Survival…,Circulation 99:2434 (1999)
Aorta-Femoral
For instance, very good correlation between B-A PWVand coronary calcification:Liu, C-S.: Arterial Stiffness is Highly Correlatedwith Coronary Atherosclerosis, J. Athero. Thromb.18:online (2011)
Localized or not?No, it is not!
Localized or not?No, it is not!
Techniques to assess arterial health III.
FMD (Flow-Mediated Dilation with ultrasound) – the first sign, but…
Bots, ML.et al.: Assessmentof flow-mediated vasodilatation(FMD) of the brachial artery,Eur. Heart J., 26:363 (2004)
Localized or not?No, it is most likely not!
Localized or not?No, it is most likely not!
Techniques to assess arterial health IV.
Wang, K-L. et al.: Wave Reflection and ArterialStiffness…, Hypertension, 55:799 (2010)
AixSphygmoCorArteriografArcSolverCVprofiler…
SI and RI:Pulse TracerBioClip
Millaseau, SC. et al.: Determination of age-related increases in large artery stiffness by digital pulsecontour analysis, Clin. Sci., 103:371 (2002)
According to the theory behind them:evolution is STUPID.
Pulse Contour Analysis (PCA) – less costly
Some problems with PCA
2. Math:Without curve fitting?Pulse contour types
1. The model:“wave reflection”
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 lengthand heightMax. rate of rise (rsys) computed fromnormalized records by taking thetime-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 theelderly
Vasography = FMD differently and better
NG = nitroglycerin, an NO donor
The rate difference between PP and VPdecreases after NG in the elderly
(Max. rate in PP is not altered by NG)
Thus, max. rate in VP measuresendothelial function (just like FMDwith ultrasound, but without the snags)
Vasography = FMD differently and better
A: R = 0.783; P < 0.001B: Difference is significant (P < 0.05)
Vasography = FMD differently and better
The exponential curve is NOT a surprise
Tone + Pulsation (PWV)vs.
Pulsation (rsys)
Vasography = Pulsating FMD (PFMD)
Thanks for listening…