Università Magna Græcia di Catanzaro
Dipartimento di Medicina Sperimentale e Clinica
Cattedra di Medicina Interna
Scuola di Specializzazione in Geriatria
U.O. Malattie Cardiovascolari Geriatriche
Prof. Francesco Perticone
Sindrome
Infiammatoria
Sistemica e Rischio CV
Association Between Airflow
Obstruction, CRP and AMI
Ukena C et al. Int J Cardiol 2010
Inflammatory Events in Complex Comorbidities
Ukena C et al. Int J Cardiol 2010
Cardiopulmonary Continuum
Concept of systemic inflammatory processes as underlying
pathophysiological relationship between COPD and CAD
Ukena C et al. Int J Cardiol 2010
Low-Dose Aspirin Reduces
Thromboxane B2 but not CRP
140
Serum Thromboxane
(% of Baseline)
Serum CRP
(% of Baseline)
140
100
60
20
Placebo
(n=11)
ASA 81 mg qd
(n=13)
28 Days
31 Days
100
60
* p<0.001
20
* *
Placebo
(n=11)
ASA 81 mg qd
(n=13)
Feldman M et al. J Am Coll Cardiol 2001;37:2036-2041
CARE: La Pravastatina Riduce il Rischio
Rappresentato dall’Infiammazione
P trend=0.005
Rischio relativo di un evento
3
P=0.007
2
1
0
Pravastatina
Placebo
Pravastatina
Placebo
Infiammazione Assente Infiammazione Presente
( PCR e SAA)
Ridker et al: Circulation 1998;98:839–844
L-ascorbic Acid Depletion in Spiked Sera from
Nonsmoking Men (10 control subjects, 15 PAD
patients), Stratified for Serum CRP (5.0 mg/L)
r= -0.72
P< .001
Serum CRP, mg/L
Serum L-ascorbic acid, %
Serum L-ascorbic acid, mmol/L
Correlation Between Serum L-ascorbic Acid and
CRP Concentrations in PAD Patients
Controls
PAD
Tzoulaky I et al., Circulation 2005
Oxidative Stress and Atorvastatin
Cangemi R et al, Eur Heart J 2008;29:54–62
Vascular Function According to Median of Hb
Perticone F et al, Clin J Am Soc Nephrol, accepted
140
FBF
180
SBP
120
160
100
140
DBP
80
120
FBF (ml/min)
HR (b/m) and BP (mmHg)
Hemodynamics and Flow
Before and After Smoking
HR
60
100
J Lekakis et al, Am J Cardiol 1998;81:1225-28
Flow-mediated Dilation of the Brachial Artery after Smoking,
Sham Smoking and after Smoking a Second Cigarette
12
sham
1st cigarette
2nd cigarette
FMD (%)
10
8
6
4
2
0
0
30
60
90 120
Time, min
J Lekakis et al, Am J Cardiol 1998
Relationship Between Smoking and
Flow Mediated Dilation
FMD %
10
P < .01
5
0
None
1-4
5-9
10 - 19
> 20
Celermajer et al, N Engl J Med 1996
Relationship Between Passive
Smoking and Flow Mediated Dilation
P < .001
20
P < .001
P = NS
FMD %
15
10
5
0
Controls
Passive
smokers
Active
smokers
Celermajer et al, N Engl J Med 1996
NADH/NA DPH
Oxidase
e-NOS
L-arginina
O2
citrullina
NO-
eO-2 NO
OONO-
Endothelial Dysfunction and C-Reactive Protein Are Risk
Factors for Diabetes in Essential Hypertension
5.6-years estimated
probability of diabetes (%)
80
Exponential fitting
r=0.85
P<0.001
60
40
20
0
0
200
400
600
800
1000
Maximal vasodilatory response to ACh (%)
Perticone F et al, Diabetes 2008
Sindrome Metabolica e Livelli di PCR
C-reactive Protein (mg/L)
8
6
4
2
0
0
1
2
3
4
5
Number of Components of the Metabolic Syndrome
Ridker PM, et al. Circulation. 2003;107:391-397.
Unadjusted Kaplan-Meier Curves
Cardiovascular Disease
Mortality
Coronary Heart Disease Mortality
20
20
All Cause Mortality
Cumulative Hazard (%)
20
15
15
15
RR (95% CI), 3.55 (1.96-6.43)
RR (95% CI), 3.77 (1.74-8.17)
10
10
5
5
0
0
2
0
4
No. at Risk
Metabolic Syndrome
Yes
No
866
288
852
279
8
10
6
Follow-up, Y
12
834
234
292
100
Metabolic Syndrome:
RR (95% CI), 2.43 (1.64-3.61)
10
5
0
0
2
866
288
8
6
4
Follow-up, Y
852
279
Yes
834
234
10
12
0
2
4
6
8
10
12
Follow-up, Y
292
100
866
288
852
279
834
234
292
100
No
Lakka H-M, et al. JAMA. 2002;288:2709-2716.
Relationship between metabolic syndrome,
lung dysfunction and CV disease
TNF-α
IL-1β
The 3 years risk for CV events in the women health study
Ridker NEJM 2000; 342:836
8
6
IL-6
4.4
4
2
0
Creatinine Cl
(ml/min/1.73m2)
100
CRP
un solido indicatore di rischio CV
95
90
1rst
2nd
3rd
4th
CRP quartiles
PREVEND study, Kidney Int 63:654, 2003
ADMA and Endothelial Vasodilation in Hypertension
Achan V & Vallance P. ATVB 2003
FBF, % increase
Perticone F et al, J Am Coll Cardiol, 2005;46:518-23
800
ADMA
r = 0.587
P < 0.0001
MBP
(change)
5
400
0
-5
SVR
(change)
400
200
0
-30
-200
0
30
60 min
0
0,4
0,6
0,8
ADMA mmol/L
Perticone F et al, Int J Cardiol 2009
1
Sciacqua A et al, NMCD 2010
Fasting Insulin and Left Ventricular Mass
r = 0.636
p< 0.0001
LVMI, g/m2
220
170
120
70
0
10
20
Insulin, mU/mL
30
F Perticone et al, J Clin Endocrinol Metab 2001
G Sesti, F Perticone et al, J Hypertens 2007
Signaling Determining Mesenchimal-Cell Differentiation
toward Osteoblasts and Signals Acting on Mature
Osteoblasts to Enhance Bone Formation
Signaling Pathways Used by Bone Morphometric
Proteins in Osteoblasts
Molecular signaling pathways linking ROS to
cardiac hypertrophy and remodeling
Deletion Polymorphism of ACE-Gene
and Left Ventricular Hypertrophy
Takimoto E , Kass DA, Hypertension 2007
Perticone F et al, J Am Coll Cardiol 1997;29:365-9
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
HR (plus uric acid 1 g/dL
increase)
Acido Urico, Funzione Endoteliale
e Diabete
0.001
2
0.012
1,6
0.340
1,2
0.799
0.355 0.192
0.124
0.090 0.071
0,8
0,4
0
0
100 200 300 400 500 600 700 800 900
ACh % of increase
Perticone F et al, submitted
Endothelial Dysfunction and
e-GFR Decline
Perticone F et al, Circulation 2010
Effects of FFA on Various Organs
Effects of LDL Particles on the Wessel Wall
Rocha VZ and Libby P, Nat Rev Cardiol 2009;6:399-409
INFLAMMATION
INSULIN RESISTANCE
ENDOTHELIAL DYSFUNCTION
HYPERTENSION
DIABETES
TARGET ORGAN DAMAGE
AMI
STROKE
HEART FAILURE
SUDDEN DEATH