Upload
fiorella-torre
View
230
Download
7
Embed Size (px)
Citation preview
Università Magna Græcia di CatanzaroUniversità Magna Græcia di CatanzaroDipartimento di Medicina Sperimentale e ClinicaDipartimento di Medicina Sperimentale e Clinica
Cattedra di Medicina InternaScuola di Specializzazione in Geriatria
U.O. Malattie Cardiovascolari GeriatricheProf. Francesco Perticone
Cattedra di Medicina InternaScuola di Specializzazione in Geriatria
U.O. Malattie Cardiovascolari GeriatricheProf. Francesco Perticone
Sindrome Sindrome Infiammatoria Infiammatoria
Sistemica e Sistemica e Rischio CVRischio CV
Association Between Airflow Obstruction, CRP and AMI
Ukena C et al. Int J Cardiol 2010
Inflammatory Events in Complex Inflammatory Events in Complex ComorbiditiesComorbidities
Ukena C et al. Int J Cardiol 2010
Cardiopulmonary ContinuumCardiopulmonary ContinuumConcept of systemic inflammatory processes as underlying
pathophysiological relationship between COPD and CAD
Ukena C et al. Int J Cardiol 2010
Low-Dose Aspirin Reduces Low-Dose Aspirin Reduces Thromboxane BThromboxane B22 but not but not
CRPCRP
Seru
m C
RP
(% o
f B
ase
line)
140
100
60
20
Placebo(n=11)
Feldman M et al. J Am Coll Cardiol 2001;37:2036-2041
140
100
60
20Seru
m T
hro
mb
oxane
(% o
f B
ase
line)
ASA 81 mg qd(n=13)
Placebo(n=11)
ASA 81 mg qd(n=13)
28 Days31 Days
* p<0.001
* *
0
1
2
3R
isch
io r
ela
tivo d
i u
n e
vento
Infiammazione Assente
Infiammazione Presente( PCR e SAA)
P trend=0.005
Ridker et al: Circulation 1998;98:839–844
PP=0.007=0.007
CARE: La Pravastatina Riduce il Rischio CARE: La Pravastatina Riduce il Rischio Rappresentato dall’InfiammazioneRappresentato dall’Infiammazione
PravastatinaPravastatinaPlaceboPlaceboPravastatinaPravastatinaPlaceboPlacebo
Seru
m L
-ascorb
ic a
cid
, m
ol/
L
Serum CRP, mg/L
Tzoulaky I et al., Circulation 2005
Seru
m L
-ascorb
ic a
cid
,
Controls PAD
L-ascorbic Acid Depletion in Spiked Sera L-ascorbic Acid Depletion in Spiked Sera from Nonsmoking Men (10 control subjects, from Nonsmoking Men (10 control subjects, 15 PAD patients), Stratified for Serum CRP 15 PAD patients), Stratified for Serum CRP
(5.0 mg/L)(5.0 mg/L)Correlation Between Serum L-ascorbic Acid Correlation Between Serum L-ascorbic Acid
and CRP Concentrations in PAD Patientsand CRP Concentrations in PAD Patients
r= -0.72P< .001
Cangemi R et al, Eur Heart J 2008;29:54–62
Oxidative Stress and AtorvastatinOxidative Stress and Atorvastatin
Perticone F et al, Clin J Am Soc Nephrol, accepted
Vascular Function According to Median Vascular Function According to Median of Hbof Hb
Baseline 0 30 60 90 120
SBP
DBP
HR
Hemodynamics and FlowHemodynamics and FlowBefore and After SmokingBefore and After Smoking
60
80
100
120
140H
R (
b/m
) and B
P
(mm
Hg)
FBF
100
120
140
160
180
FBF
(ml/m
in)
J Lekakis et al, Am J Cardiol 1998;81:1225-28
min
Flow-mediated Dilation of the Brachial Artery Flow-mediated Dilation of the Brachial Artery after Smoking, Sham Smoking and after after Smoking, Sham Smoking and after
Smoking a Second CigaretteSmoking a Second Cigarette
0
2
4
6
8
10
12
0 30 60 90 120Time, min
J Lekakis et al, Am J Cardiol 1998
FM
D (
%)
sham1st cigarette2nd cigarette
Relationship Between Relationship Between Smoking and Flow Smoking and Flow Mediated DilationMediated Dilation
FM
D %
10
5
0
Celermajer et al, N Engl J Med 1996
None
1 - 4
5 - 9
10 - 19
> 20
P < .01< .01
P < .001
0
5
10
15
20
Controls Passive Active smokers smokers
FMD
%P < .001 P = NS
Celermajer et al, N Engl J Med 1996
Relationship Between Relationship Between Passive Smoking and Flow Passive Smoking and Flow
Mediated DilationMediated Dilation
O2
O-2
e-
NADH/NA DPHOxidase
NO
OONO-
L-arginina
NO-
citrullina
e-NOS
Maximal vasodilatory response to ACh (%)Maximal vasodilatory response to ACh (%)
5.6
-years
esti
mate
d
5.6
-years
esti
mate
d
pro
bab
ilit
y o
f d
iab
ete
s (
%)
pro
bab
ilit
y o
f d
iab
ete
s (
%)
10008006004002000
80
60
40
20
0
Exponential fittingr=0.85P<0.001
Endothelial Dysfunction and C-Reactive Protein Are Risk Factors for Diabetes in Essential Hypertension
Perticone F et al, Diabetes 2008Perticone F et al, Diabetes 2008
0 1 2 3 4 50
2
4
6
8
C-r
eact
ive
Pro
tein
(m
g/L)
Number of Components of the Metabolic Syndrome
Ridker PM, et al. Circulation. 2003;107:391-397.
Sindrome Metabolica e Sindrome Metabolica e LLivelli di PCRivelli di PCR
Coronary Heart Disease Mortality
0 2 4 6 8 10 12
0
5
10
15
20
RR (95% CI), 3.77 (1.74-8.17)
Follow-up, Y
Cu
mu
lati
ve H
azar
d (
%)
Yes
No
866
288
852
279
834
234
292
100
Unadjusted Kaplan-Meier CurvesUnadjusted Kaplan-Meier Curves
No. at RiskMetabolic Syndrome
YesMetabolic Syndrome:
0 2 4 6 8 10 12
0
5
10
15
20
RR (95% CI), 3.55 (1.96-6.43)
Follow-up, Y
866
288
852
279
834
234
292
100
0 2 4 6 8 10 12
0
5
10
15
20
RR (95% CI), 2.43 (1.64-3.61)
Follow-up, Y
866
288
852
279
834
234
292
100
Cardiovascular Disease Mortality
All Cause Mortality
Lakka H-M, et al. JAMA. 2002;288:2709-2716.
No
Relationship between metabolic Relationship between metabolic syndrome, lung dysfunction and CV syndrome, lung dysfunction and CV
diseasedisease
IL-6IL-6
TNF-TNF-ααIL-1IL-1ββ
un solido indicatore di rischio CV
CRPCRP1rst 2nd 3rd 4th
CRP quartiles PREVEND study, Kidney Int 63:654, 2003
Creatinine Cl(ml/min/1.73m2)100
95
90
The 3 years risk for CV events in the women health studyRidker NEJM 2000; 342:836
8
6
4
2
0
4.44.4
FBF, % increase
0
400
800
0,4 0,6 0,8 1
r = 0.587
P < 0.0001
ADMA mol/L
Perticone F et al, J Am Coll Cardiol, 2005;46:518-23
ADMA and Endothelial Vasodilation in ADMA and Endothelial Vasodilation in HypertensionHypertension
-30 0 30 60 min
SVR(change)
400
200
0
-200
MBP(change)
5
0
-5
ADMA
Achan V & Vallance P. ATVB 2003Achan V & Vallance P. ATVB 2003
Perticone F et al, Int J Cardiol 2009
Sciacqua A et al, NMCD 2010
Fasting Insulin and Left Ventricular Mass Fasting Insulin and Left Ventricular Mass
G Sesti, F Perticone et al, J Hypertens 2007
LV
MI,
g/m
2
70
120
170
220
0 10 20 30Insulin, U/mL
r = 0.636p< 0.0001
F Perticone et al, J Clin Endocrinol Metab 2001
Signaling Pathways Used by Bone Morphometric Proteins in Osteoblasts
Signaling Determining Mesenchimal-Cell Differentiation toward Osteoblasts and Signals Acting on Mature Osteoblasts to Enhance Bone Formation
Takimoto E , Kass DA, Hypertension 2007Takimoto E , Kass DA, Hypertension 2007
Molecular signaling pathways Molecular signaling pathways linking ROS to cardiac hypertrophy linking ROS to cardiac hypertrophy
and remodelingand remodeling
Perticone F et al, J Am Coll Cardiol 1997;29:365-9Perticone F et al, J Am Coll Cardiol 1997;29:365-9
Deletion Polymorphism of ACE-Deletion Polymorphism of ACE-Gene and Left Ventricular Gene and Left Ventricular
HypertrophyHypertrophy
Scieffer B et al, Circulation, 2000;101:1372-78
Effect of Fructose on Various Organ Systems
Johnson RJ et al, Endocrine Reviews 2009;30:96–116
0
0,4
0,8
1,2
1,6
2
0 100 200 300 400 500 600 700 800 900
0.001
0.012
0.3400.7990.3550.1920.124
0.0900.071
HR
(p
lus u
ric a
cid
1 g
/dL
incre
ase)
ACh % of increase
Acido Urico, Funzione Endoteliale e Diabete
Perticone F et al, submitted
Perticone F et al, Circulation 2010
Endothelial Dysfunction and Endothelial Dysfunction and e-GFR Declinee-GFR Decline
Effects of LDL Particles on the Wessel Wall
Rocha VZ and Libby P, Nat Rev Cardiol 2009;6:399-409
Effects of FFA on Various Organs
INSULIN RESISTANCEINSULIN RESISTANCE ENDOTHELIAL DYSFUNCTION
HYPERTENSIONHYPERTENSION
DIABETESDIABETES
TARGET ORGAN TARGET ORGAN DAMAGEDAMAGE
AMIAMI STROSTROKEKE
HEART HEART FAILUREFAILURE
SUDDEN SUDDEN DEATHDEATH
INFLAMMATIOINFLAMMATIONN