Aristotele
Università degli Studi di Catanzaro Magna Græcia
IGaleno
Università degli Studi di Catanzaro Magna Græcia
Università degli Studi di Catanzaro Magna Græcia
VASCULAR REMODELING
Active process of structural alteration
that involves
cell growth
cell death
cell migration
production and degradation of EM
Università degli Studi di Catanzaro Magna Græcia
VASCULAR REMODELING
Dynamic interaction between locally
generated
growth factors
vasoactive substances
hemodynamic stimuli
Università degli Studi di Catanzaro Magna Græcia
VASCULAR REMODELING
Is usually an adaptive process that occurs in
response to long-term changes in hemodynamic
conditions, but it may subsequently contribute
to the pathophysiology of vascular diseases and
circulatory disorders
Università degli Studi di Catanzaro Magna Græcia
VASCULAR REMODELING
SENSORS
TRANSDUCERS
STRUCTURAL
CHANGES
MEDIATORS
Università degli Studi di Catanzaro Magna Græcia
SIGNALS
SENSORS
MEDIATORS
Università degli Studi di Catanzaro Magna Græcia
VSMC–inflammatory cell interactions in atherosclerosis
MMPs secreted by
macrophages degrade the
extracellular matrix
TNF-a
Macrophage
PDGF
IL-1
T-lymphocyte
IFN-g
Macrophages secrete growth factors that
promote VSMC recruitment and proliferation
Macrophages
induce
VSMC
apoptosis
Fibrous
cap
Inflammatory
cytokines
inhibit matrix
protein
production
by VSMCs
Università degli Studi di Catanzaro Magna Græcia
THE SPECTRUM OF VASCULAR REMODELING
pressure
flow
injury
Università degli Studi di Catanzaro Magna Græcia
Università degli Studi di Catanzaro Magna Græcia
avventizia
c
media
b
a
intima
Università degli Studi di Catanzaro Magna Græcia
Università degli Studi di Catanzaro Magna Græcia
Fluctuations in Amplitude of Flow, Pressure,
and Diameter in a Large Artery
Flow
Pressure
300%
60%
Diameter
10%
Università degli Studi di Catanzaro Magna Græcia
Pressure mmHg
Changes in the Contour and Amplitude
of the Pressure and Flow Waves in Arteries
100
80
60
Asc.
aorta
Aorta
arch
Abd
aorta
Fem.
artery
Sap.
artery
Flow cm/s
140
100
60
20
0
-20
Università degli Studi di Catanzaro Magna Græcia
Representative Radial arterial
Waveform in Different Age Groups
Age 25 years
Age 47 years
Age 80 years
McVeigh GE et al. Hypertension 1999; 33:1392-1398
Università degli Studi di Catanzaro Magna Græcia
Alterazioni Carotidee ed Eventi Cardiovascolari
Area mio-intimale
Spessore mio-intimale
1,1
22
mm
mm2
0,9
18
0,7
14
0,5
10
NG
RC
IE
IC
NG
IE
IC
%
Eventi CV
%
Placche
RC
50
30
MJ Koren et al
Ann Intern Med
1991
20
30
MJ Roman et al
JACC 1996
10
10
0
NG
RC
IE
IC
NG
RC
IE
IC
Università degli Studi di Catanzaro Magna Græcia
Fatal CV Events (x 100 pts-years)
Progressive Increase in CV Mortality
According to Tertiles of the Distribution of PP
1,4
1,2
1
0,8
0,6
0,4
0,2
0
<50 51-65 >65
cPP, mmHg
<45 46-53 >53
aPP, mmHg
Verdecchia P et al. Hypertension 1998; 32:983-988
Università degli Studi di Catanzaro Magna Græcia
Total CV Events (x 100 pts-years)
Progressive Increase in CV Morbidity
According to Tertiles of the Distribution of PP
5
4,5
4
3,5
3
2,5
2
1,5
1
0,5
0
<50 51-65 >65
cPP, mmHg
<45 46-53 >53
aPP, mmHg
Verdecchia P et al. Hypertension 1998; 32:983-988
Università degli Studi di Catanzaro Magna Græcia
6
5
4
3
2
1
<50
51-65
>65
0
Total CV Events (x 100 pts-years)
Relationship Between Tertiles of PP and Total CV Events
clinic PP, mmHg
Verdecchia P et al. Hypertension 1998; 32:983-988
Università degli Studi di Catanzaro Magna Græcia
Comparison of LVM and RWT
and Tertile of Arterial Stiffness Index
250
0,45
p=NS
p<0.001
150
RWT
LVM (g)
200
100
0,35
50
0,25
0
First
Second
Thrid
Tertiles of Stiffness Index
First
Second
Thrid
Tertiles of Stiffness Index
Roman MJ et al. Hypertension 2000; 36:489-494
Università degli Studi di Catanzaro Magna Græcia
Carotid Arterial Stiffness as a Predictor
of Cardiovascular and All-Cause
Mortality in End-Stage Renal Disease
Jacques Blacher, Bruno Pannier, Alain P. Guerin,
Sylvain J. Marchais, Michel E. Safar, Gérad M. London
Hypertension, 1998;32:570-74
Università degli Studi di Catanzaro Magna Græcia
Probabilities of Overall Survival and Event-free Survival
According to Level of PWV Divided Into Tertiles
Probability of Overall Survival
Probability of Event-free Survival
Blacher J et al. Circulation 1999; 99:2434-2439
Università degli Studi di Catanzaro Magna Græcia
Survival by Quartiles of Pulse Pressure Adjusted
for Age and EF in Patients with LV Dysfunction
Survival (%)
100
Quartile
Quartile
Quartile
Quartile
80
60
365
730
1095
2
1
3
4
1460
Follow-up time (days)
Domanski et al. JACC 1999; 33:951-8
Università degli Studi di Catanzaro Magna Græcia
Relative Risk for Total CV Mortality
According to PP and Gender and Presence of Hypertension
NT Women
NT Men
HT Women
HT Men
0.4 0.6
0.8 1.0 1.2
RR
1.4 1.6
1.8
2.0
Chen et al. JACC 1998; 32:1221-7
Università degli Studi di Catanzaro Magna Græcia
Predict Event Rates for Stroke and Coronary Events
Rate
15
Coronary events
10
Stroke
5
0
50
60
70
80
90
100
110
120
DBP (mmHg)
Millar JA et al. Hypertension 2000; 36:907-911
Università degli Studi di Catanzaro Magna Græcia
Empiric Models of RR Index for Stroke and Coronary Events
when Predicted by Mean BP and PP
Risk
Risk
1.80
1.80
Stroke risk
1.50
1.50
1.20
1.20
0.90
0.90
0.60
0.60
50
70
90
110
130
MI risk
50
70
90
110
130
DBP (mmHg)
Millar JA et al. Hypertension 2000; 36:907-911
Università degli Studi di Catanzaro Magna Græcia
Pulse Wave Velocity
Systole
Università degli Studi di Catanzaro Magna Græcia
COMPLIANCE
Absolute change in volume following changes in pressure
Distensibility
Relative volume or diameter change for a given pressure
Pulse Wave Velocity
Speed of travel of the pulse along an arterial segment distance
Università degli Studi di Catanzaro Magna Græcia
Università degli Studi di Catanzaro Magna Græcia
Università degli Studi di Catanzaro Magna Græcia
ARTERIES – from heart
capillaries
VEINS – to heart
Università degli Studi di Catanzaro Magna Græcia
Peak Percent Increase in FBF After Acetylcholine
(ACh) Infusion Versus LVMI in Hypertensives
Peak Response to ACh
(% of increase)
800
r = -0.554
p < 0.00001
600
400
200
0
50
100
150
LVMI (g/m2)
200
250
F Perticone et al., Circulation 1999
Università degli Studi di Catanzaro Magna Græcia
Ipertensione Arteriosa e Danno d’Organo
Università degli Studi di Catanzaro Magna Græcia