inflammation and aortic pulse wave velocity. a multicentre ... · inflammation and aortic pulse...

a University of Catania, Catania, Italy; b Gulhane School of Medicine, Ankara, Turkey; c University of Palermo, Palermo, Italy; d University of Campania “Luigi Vanvitelli”, Naples, Italy; e HEGP, AP-HP, INSERM U970, Paris, France.

Inflammation and aortic pulse wave velocity.

A multicentre longitudinal study in patients

with inflammatory bowel disease

Luca Zanoli,a Kadir Ozturk,b Maria Cappello,c Gaetano Inserra,a

Giulio Geraci,c Antonio Tuttolomondo,c Daniele Torres,c Antonio Pinto,c Andrea Duminuco,a Gaia Riguccio,a Musa B Aykan,b

Giuseppe Mulé,c Santina Cottone,c Alessandra F Perna,d

Stephane Laurent,e Pasquale Fatuzzo,a Pietro Castellino,a

Pierre Boutouyrie.e

Cardiovascular risk in patients with

inflammatory bowel disease(Crohn’s disease and ulcerative colitis)

ECCO Guideline/Consensus Paper

The First European Evidence-based Consensus on Extra-intestinal Manifestations in Inflammatory Bowel Disease

J Crohns Colitis 2016

IBD vs. Gen pop

Cholesterol ▼

Obesity▼

Diabetes▼General

pop.

IBD

Cardiovascular Risk

Zanoli L et al. Trends Cardiovasc Med. 2015

Infiammation

Arterial stiffness

Cardiovascular

Risk

Aortic

PWV

Potential mechanisms by which inflammation can lead to

functional and structural arterial stiffening

eNOS: Endothelial nitric oxide synthase; H2O2: Hydrogen peroxide; IL-1: Interleukin-1; MMPs: Matrix

metalloproteinases; NO: Nitric oxide; O2-: Superoxide; ROS: Reactive oxygen species; TIMP: Tissue inhibitor of

matrix metalloproteinases; TNF-α: Tumor necrosis factor alpha.

Zanoli L et al. World J Gastroenterol 2015

Endothelial function and IMT in IBDA meta-analysis of cross-sectional studies

Wu G et al. Angiology 2016

flow-mediated dilation Intima-media thickness

Data of patients with CD and UC were analyzed as a whole group

Arterial stiffness is increased in IBD

a cross-sectional studies

For a comparable central MBP, elastic and muscular artery stiffenessare increased in IBD

Zanoli L et al. J Hypertens 2012


1.08 (0.55–1.61) P<0.0001 1.34 (0.71–1.97) P<0.0001

Aortic PWV is increased in IBD

A systematic review and meta-analysis

of cross-sectional studies

Wu G et al. Angiology 2016

Aortic PWV is increased in IBD

A systematic review and meta-analysis

of cross-sectional studies


Aortic PWV is increased in IBDAn individual participant data meta-analysis

of 4 cross-sectional studies

Zanoli L et al. JAHA 2017

Augmentation index is increased in IBDA meta-analysis of cross-sectional studies

Zanoli L et al. Eur J Intern Med. 2016


Early vascular aging in IBDIncreased elastic artery stiffness

Aortic PWV

Zanoli L et al. JAHA 2017 Zanoli L et al. Eur J Intern Med. 2018

UC, CKD

Ctrl

UC, CD

CD, Crohn’s disease

Ctrl, control subjects

UC, ulcerative colitis

CKD, chronic kidney disease



Ctrl

Zanoli L et al. Eur J Intern Med. 2018



CKD, chronic kidney disease

Carotid-radial (brachial) PWV Aortic/brachial PWV ratio

UC

UC

Ctrl

CKD

Ctrl

CKD

Early vascular aging in IBDIncreased muscular artery stiffness

Arterial stiffness and disease duration

in cross-sectional studies


Zanoli L et al. Atherosclerosis 2014

Korkmaz H et al. Eur J

Gastroenterol Hepatol. 2014

Ozturk K et al.

Inflamm Bowel Dis 2015

Arterial stiffness and inflammation in IBDAn individual participant data meta-analysis

of 4 cross-sectional studies

Zanoli L et al. JAHA 2017

Disease duration White blood cells

Aortic PWV is reduced by anti-TNF therapy in IBD A pilot longitudinal study

Follow-up: 3.4 years

n=30 n=14 n=11 n=7

Zanoli L et al. Atherosclerosis 2014

Aortic PWV is lower in IBD patients

treated with anti-TNF therapyA meta-regression analysis of cross-sectional studies

β= -2.6 m/s; 95% CI -4.9 to -0.2 m/s; p=0.03


Maintenance therapy with salicylates is associated

with aortic stiffening in patients with IBDA meta-regression analysis of cross-sectional studies


Zanoli L et al. JAHA 2018. DOI:10.1161/JAHA.118.010942

Inflammation and aortic pulse wave velocity A multicentre longitudinal study in patients with IBD

Aims

To test the hypothesis that chronic inflammation leads to aortic stiffening and

that anti-TNF therapy reduce aortic stiffness in patients with IBD

Methods

Sample size: 167 IBD and 167 controls matched for age, sex and mean BP

Study design: multicentre (n=3), open-label longitudinal prospective study

Follow-up: 4 years

Outcome: Aortic pulse wave velocity (measured with SphygmoCor in 2

centres and Arteriograph in 1 centre; arteriograph PWV was converted in

SphygmoCor PWV according to Ring et al. Hypertens Res 2014)

Inclusion criteria

Sequential patients with an established clinical and endoscopic diagnosis of

IBD; healthy volunteers matched for age, sex and MBP (ratio 1:1)

Exclusion criteria

Coronary heart disease, stroke, transient ischaemic attack, diabetes, chronic

kidney disease, infectious, inflammatory disorders other than IBD, subjects

on treatment for hypertension or dyslipidaemia.

UC

(n=82)

CD

(n=85)

Controls

(n=167)

P-value Group’s

comparison

Group A B C

Age, years 37 (11) 39 (13) 38 (12) 0.56

Male sex, % 55 61 57 0.71

Mean BP, mm Hg 87 (11) 89 (11) 87 (11) 0.39

Systolic BP, mm Hg 117 (20) 120 (14) 118 (13) 0.43

Diastolic BP, mm Hg 72 (10) 73 (12) 71 (11) 0.32

Heart rate, b/min 72 (13) 72 (13) 68 (11) 0.01 A≠C; B≠C

aPWV, m/s 7.8 (2.0) 7.9 (2.0) 7.1 (1.4) <0.001 A≠C; B≠C

hsCRP, log(mg/l) 0.96 (1.88) 1.03 (1.75) 0.48 (1.34) 0.02 B≠C

BMI, kg/m2 24 (5) 24 (4) 25 (5) 0.03

TC, mmol/l 4.08 (0.88) 4.47 (0.95) 4.56 (0.74) <0.001 A≠B; A≠C

HDL, mmol/l 1.24 (0.40) 1.28 (0.40) 1.30 (0.26) 0.45

TG, mmol/l 1.15 (0.70) 1.44 (0.69) 1.34 (0.85) 0.047

Active disease, % 28 33 … 0.49

Therapy <0.001

Salicylates, % 49 79 …

Anti-TNFα, % 27 8 …

Other therapy, % 24 13 …




*Data of patients with CD and UC were analyzed as a whole group

CD, Crohn’s disease

UC, ulcerative colitisZanoli L et al. JAHA 2018. DOI:10.1161/JAHA.118.010942

Independent variable Multivariate analysis

Beta

(z-score*)

P-value

Baseline measures

Baseline aPWV, z-score -0.31 0.003

Active disease, y/n 0.73 <0.001

Disease duration, 5 years 0.36 <0.001

Immunosuppressive therapy

Salycilates 0

Others -0.33 0.02

Anti-TNFα -0.45 0.02

Follow-up measures

ΔHeart rate, b/min 0.06 <0.001

ΔActive disease, y/n 1.49 0.004

Annual progression of aortic PWV in patients with IBDMultivariate generalized estimating equations


*z-score was calculated in each centre at baseline

in patients with IBD


Conclusions

In patients with IBD:

• Aortic PWV increase in those with longer

disease duration and a more severe disease

• Long-term (4 years) anti-TNFα therapy reduce

aortic PWV, an established surrogate measure

of cardiovascular risk

• This suggests that effective control of

inflammation may reduce cardiovascular risk

in these patients

Thank you!

Etna in eruption

Catania

For questions and collaborations

email: [email protected]

inflammation and aortic pulse wave velocity. a multicentre ... · inflammation and aortic pulse...

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