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