Similarities in Coronary Function and Myocardial Deformation Between Psoriasis and Coronary Artery Disease: The Role of Oxidative Stress and Inflammation

doi:10.1016/j.cjca.2014.11.002

Canadian Journal of Cardiology

Volume 31, Issue 3, March 2015, Pages 287-295

https://doi.org/10.1016/j.cjca.2014.11.002 Get rights and content

Abstract

Background

Psoriasis has been associated with increased risk for coronary artery disease (CAD). We investigated the presence of vascular and subclinical left ventricular (LV) dysfunction in patients with psoriasis compared with patients with CAD.

Methods

We compared 59 patients with psoriasis without evidence of CAD (psoriasis area and severity index [PASI], 11.5 ± 8) with 59 patients with angiographically documented CAD and 40 controls. We measured (1) the carotid-femoral pulse wave velocity (PWVc) and central augmentation index (CAI), (2) coronary flow reserve (CFR) by Doppler echocardiography, (3) flow-mediated dilation (FMD) of the brachial artery and carotid intima media thickness (IMT), (4) LV global longitudinal strain (GLS) and GLS rate (GLSR) using speckle tracking echocardiography, and (5) malondialdehyde (MDA) and interleukin-6 (IL-6) levels.

Results

Patients with psoriasis had higher PWVc, CAI, IMT, MDA, and IL-6 levels and lower FMD, CFR, GLS, and GLSR than did controls (P < 0.05), but they had values of these markers that were similar to those of patients with CAD (P > 0.05) after adjustment for atherosclerotic risk factors: (PWVc [m/s], 10.4 ± 1.8 vs 8.6 ± 1.5 vs 10.3 ± 2, respectively; CFR, 2.4 ± 0.1 vs 3.4 ± 0.6 vs 2.6 ± 0.6, respectively; GLS [%], −16.2 ± 4 vs −21.9 ± 1.6 vs −16.6 ± 4.5, respectively; GLSR [L/sec], −0.85 ± 0.2 vs −1.2 ± 0.12 vs −0.9 ± 0.4, respectively; MDA [nM/L], 1.68 vs 1.76 vs 1.01, respectively; IL-6 [pg/mL], 2.26 vs 2.2 vs 1.7, respectively; P < 0.05 for all comparisons). PASI was related to IMT (r = 0.67; P < 0.01). Decreased GLS was associated with increased MDA, IL-6, PWVc, CAI, and reduced CFR (P < 0.05).

Conclusions

Psoriasis and CAD present similar vascular and LV myocardial dysfunction, possibly because of similar underlying inflammatory and oxidative stress processes. Vascular dysfunction in psoriasis is linked to abnormal LV myocardial deformation.

Résumé

Introduction

Le psoriasis est associé à l’augmentation du risque de coronaropathie (CP). Nous avons étudié la présence de la dysfonction vasculaire et de la dysfonction ventriculaire gauche (VG) infraclinique chez les patients souffrant de psoriasis par rapport aux patients souffrant de CP.

Méthodes

Nous avons comparé 59 patients souffrant de psoriasis sans signe de CP (indice d’étendue et de gravité du psoriasis [PASI : psoriasis area and severity index], 11,5 ± 8) à 59 patients souffrant de CP démontrée par angiographie et à 40 témoins. Nous avons mesuré : 1) la vitesse de l’onde de pouls carotido-fémorale (VOPcf) et l’indice d’augmentation de la pression centrale (IApc); 2) la réserve coronarienne (RC) par échocardiographie Doppler; 3) la dilatation de l’artère brachiale induite par le flux (DIF) et l’épaisseur de l’intima-média de la carotide (EIMc); 4) la déformation longitudinale globale (DLG) du VG et le taux de déformation longitudinale globale (TDLG) par échocardiographie Speckle Tracking (suivi de pixel); 5) les concentrations de malondialdéhyde (MDA) et d’interleukine 6 (IL-6).

Résultats

Les patients souffrant de psoriasis avaient des VOPcf, IApc, EIMc, et des concentrations de MDA et de IL-6 plus élevés et des DIF, RC, DLG et TDLG plus faibles que les témoins (P < 0,05), mais les valeurs de ces marqueurs étaient similaires à celles des patients souffrant de CP (P > 0,05) après l’ajustement des facteurs de risque d’athérosclérose : (VOPcf [m/s], 10,4 ± 1,8 vs 8,6 ± 1,5 vs 10,3 ± 2, respectivement; RC, 2,4 ± 0,1 vs 3,4 ± 0,6 vs 2,6 ± 0,6, respectivement; DLG [%], –16,2 ± 4 vs –21,9 ± 1,6 vs –16,6 ± 4,5, respectivement; TDLG [l/sec], –0,85 ± 0,2 vs –1,2 ± 0,12 vs –0,9 ± 0,4, respectivement; MDA [nM/l], 1,68 vs 1,76 vs 1,01, respectivement; IL-6 [pg/ml], 2,26 vs 2,2 vs 1,7, respectivement; P < 0,05 pour toutes les comparaisons). Le PASI était associé à la EIMc (r = 0,67; P < 0,01). La diminution de la DLG était associée à l’augmentation du MDA, de la IL-6, de la VOPcf, du IApc, et à la réduction de la RC (P < 0,05).

Conclusions

Le psoriasis et la CP présentent des dysfonctions vasculaire et myocardique ventriculaire gauche similaires, possiblement en raison des processus de stress inflammatoire et oxydatif sous-jacents similaires. La dysfonction vasculaire lors de psoriasis est liée à la déformation anormale du myocarde VG.

Section snippets

Study population

We studied 59 patients with psoriasis matched by age and sex with 59 patients with angiographically documented CAD (≥ 70% luminal diameter stenosis) and preserved ejection fraction (EF) > 50%.

Forty participants with age, sex, and atherosclerotic risk factors similar to those of the patients with psoriasis—with normal electrocardiograms, echocardiograms, treadmill test results, and stress echocardiograms—were selected as a control group with low risk for obstructive CAD from participants

Baseline characteristics of the study population

Patients' clinical characteristics are shown in Table 1. Thirty-three patients with CAD (56%) had multivessel disease. Echocardiographic parameters were similar between the 3 study groups (P > 0.05) (Table 2) after adjustment for age, sex, hypertension, hyperlipidemia, smoking, systolic or diastolic blood pressure, β-blocker use, and statin use.

Markers of arterial stiffness and subclinical atherosclerosis

ANOVA showed significant differences in PWV, central aortic systolic pressure and pulse pressure, augmentation index, and carotid IMT among the 3 study

Discussion

In the present study, we have shown that markers of (1) vascular integrity and function (namely, carotid IMT, PWV, central aortic systolic blood pressure, augmentation index), (2) FMD of the brachial artery and CFR of the left anterior descending artery, (3) LV longitudinal deformation (namely, LV longitudinal strain and strain rate), and (4) inflammation and oxidative stress (namely, MDA and IL-6 levels) were similar among patients with psoriasis and those with CAD after adjustment for

Conclusions

In the present study, we found that patients with psoriasis and those with CAD share similar arterial wall abnormalities, coronary microcirculatory dysfunction, and LV myocardial deformation impairment because of a similarly increased inflammatory and oxidative stress burden when compared with controls. Increased oxidative and inflammatory burden, vascular dysfunction, and impaired coronary microcirculation were interrelated and linked with abnormal LV myocardial deformation in patients with

Funding Sources

This research was funded by the Hellenic Cardiac Society.

Disclosures

The authors have no conflicts of interest to disclose.

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Citation Excerpt :
The study protocol was approved by the Institute’s Ethics Committee, and written informed consents were obtained from all patients. Carotid-to-femoral PWV was measured using a previously published methodology (Complior; Alam Medical, Vincennes, France).5,20 Studies were performed using a VividE95 system (GE Medical Systems, Horten, Norway).
Interleukin (IL)-17A activity is implicated in psoriasis. We investigated the effects of IL-17A inhibition on vascular and left ventricular (LV) function in patients with psoriasis.
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Compared with cyclosporine and methotrexate, anti-IL-17A treatment resulted in a greater increase in GLS at 4 and 12 months after treatment (10% and 14% with anti-IL-17A vs 2% and 2% with cyclosporine vs 4% and 4% with methotrexate, respectively), GLSR, GLSR at early diastole (45% and 41% vs 5% and 4% vs 7% and 9%, respectively), and LV twisting (32% and 28% vs 6% and 8% vs 7% and 6%, respectively) (P < 0.05). Anti-IL-17A treatment resulted in greater improvement of CFR and PWV than cyclosporine or methotrexate (P < 0.05). PWV increased after cyclosporine treatment (+11% at 4 and +14% and 12 months) (P < 0.05). Markers of oxidative stress were reduced only after anti-IL-17A treatment (P < 0.05). Changes of myocardial deformation markers and CFR after anti-IL-17A treatment correlated with a concomitant reduction of oxidative stress.
In psoriasis, inhibition of IL-17A results in a greater improvement of vascular and myocardial function compared with cyclosporine or methotrexate treatment, indicating a beneficial effect on overall cardiovascular function.
L’activité de l’interleukine (IL)-17A intervient dans le psoriasis. Nous avons examiné les effets de l’inhibition de l’IL-17A sur la fonction vasculaire et ventriculaire gauche chez des patients atteints de psoriasis.
Au total, 150 patients atteints de psoriasis ont reçu un traitement par un agent anti-IL-17A (sécukinumab, n = 50), la cyclosporine (n = 50) ou le méthotrexate (n = 50). Nous avons mesuré, au départ et après 4 et 12 mois, 1) la déformation longitudinale globale du ventricule gauche, la vitesse de déformation longitudinale globale, la vitesse de déformation longitudinale globale au début de la diastole, la torsion et la détorsion du ventricule gauche; 2) la réserve coronarienne; 3) la vitesse des ondes pulsatiles et 4) la concentration du malondialdéhyde et de la protéine carbonyle comme marqueurs du stress oxydatif.
Comparativement à la cyclosporine et au méthotrexate, le traitement par un anti-IL-17A a été associé à une augmentation plus marquée de la déformation longitudinale globale après 4 et 12 mois de traitement (10 % et 14 % avec l’anti-IL-17A par rapport à 2 % et 2 % avec la cyclosporine et à 4 % et 4 % avec le méthotrexate, respectivement), de la vitesse de déformation longitudinale globale, de la vitesse de déformation longitudinale globale au début de la diastole (45 % et 41 % par rapport à 5 % et à 4 % et à 7 % et à 9 %, respectivement) et de la torsion du ventricule gauche (32 % et 28 % par rapport à 6 % et à 8 % et à 7 % et à 6 %, respectivement) (p < 0,05). Le traitement par un anti-IL-17A a été lié à une amélioration plus importante de la réserve coronarienne et de la vitesse des ondes pulsatiles que la cyclosporine ou le méthotrexate (p < 0,05). La vitesse des ondes pulsatiles s’est accélérée après le traitement par la cyclosporine (+ 11 % après 4 mois et + 14 % après 12 mois) (p < 0,05). Une réduction des marqueurs du stress oxydatif n’a été observée qu’après le traitement par un anti-IL-17A (p < 0,05). Les changements relatifs aux marqueurs de la déformation myocardique et à la réserve coronarienne étaient en corrélation avec la réduction concomitante du stress oxydatif.
En présence de psoriasis, l’inhibition de l’IL-17A a été associée à une amélioration accrue de la fonction vasculaire et myocardique comparativement au traitement par la cyclosporine ou le méthotrexate, indiquant un effet bénéfique sur la fonction cardiovasculaire globale.

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: See editorial by Mancini, pages 242-243 of this issue.

: See page 293 for disclosure information.

^∗: These authors contributed equally to this work.

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Clinical ResearchSimilarities in Coronary Function and Myocardial Deformation Between Psoriasis and Coronary Artery Disease: The Role of Oxidative Stress and Inflammation

Abstract

Background

Methods

Results

Conclusions

Résumé

Introduction

Méthodes

Résultats

Conclusions

Section snippets

Study population

Baseline characteristics of the study population

Markers of arterial stiffness and subclinical atherosclerosis

Discussion

Conclusions

Funding Sources

Disclosures

Atherosclerosis

Atherosclerosis

J Am Coll Cardiol

J Am Acad Dermatol

Int J Cardiol

Am J Cardiol

Atherosclerosis

Can J Cardiol

J Am Coll Cardiol

Am J Cardiol

Can J Cardiol

Can J Cardiol

Prevalence and treatment of psoriasis in the United Kingdom: a population-based study

Arch Dermatol

Cardiovascular disease and risk factors among psoriasis patients in two US healthcare databases, 2001-2002

Dermatology

Psoriasis and cardiovascular disease

Dermatol Ther

Expert consensus document on arterial stiffness: methodological issues and clinical applications

Eur Heart J

Aortic PWV and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function?

Circulation

Chronic plaque psoriasis is associated with increased arterial stiffness

Dermatology

Association of abnormal coronary microcirculatory function with impaired response of longitudinal left ventricular function during adenosine stress echocardiography in untreated hypertensive patients

Eur Heart J Cardiovasc Imaging

Incremental value of pulse wave velocity in the determination of coronary microcirculatory dysfunction in never-treated patients with essential hypertension

Am J Hypertens

Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation

European J Cardiovasc Prev Rehabil

Clinical Research
Similarities in Coronary Function and Myocardial Deformation Between Psoriasis and Coronary Artery Disease: The Role of Oxidative Stress and Inflammation