Post on 22-May-2020
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
Zanoli L et al. J Hypertens 2016
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
Data of patients with CD and UC were analyzed as a whole group
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
Data of patients with CD and UC were analyzed as a whole group
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, control subjects
UC, ulcerative colitis
Ctrl
Zanoli L et al. Eur J Intern Med. 2018
UC, ulcerative colitis
Ctrl, control subjects
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. J Hypertens 2012
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
Zanoli L et al. J Hypertens 2016
Maintenance therapy with salicylates is associated
with aortic stiffening in patients with IBDA meta-regression analysis of cross-sectional studies
Zanoli L et al. J Hypertens 2017
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 …
Inflammation and aortic pulse wave velocity A multicentre longitudinal study in patients with IBD
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
*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
Inflammation and aortic pulse wave velocity A multicentre longitudinal study in patients with IBD
*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
Inflammation and aortic pulse wave velocity A multicentre longitudinal study in patients with IBD
*z-score was calculated in each centre at baseline
in patients with IBD
Zanoli L et al. JAHA 2018. DOI:10.1161/JAHA.118.010942
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: luca.zanoli@unict.it