Rheumatology 2012;51:2215–2223

RHEUMATOLOGY doi:10.1093/rheumatology/kes213
Advance Access publication 25 August 2012

Original article
Increase in ventricular–arterial stiffness in patients
with psoriatic arthritis
Qing Shang1, Lai-Shan Tam2, John E. Sanderson1, Jing-Ping Sun1, Edmund
Kwok-Ming Li2 and Cheuk-Man Yu1

Abstract
Objectives. Ventricular and arterial stiffness is an accepted cause of myocardial diastolic dysfunction.
The aim of this study is to determine whether there is increased ventricular and arterial stiffness in patients

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with PsA and any relationship with disease-related risk factors.
Methods. Seventy-three patients with PsA were divided into two subgroups based on the absence or
presence of hypertension and/or left ventricular (LV) hypertrophy. Fifty healthy controls were enrolled for
comparison. All participants underwent non-invasive assessments including conventional echocardiog-
raphy with tissue Doppler imaging and pulse wave analysis. Ventricular stiffness was measured by ven-
tricular end-systolic and diastolic elastance, whereas arterial stiffness was measured by total arterial
compliance and aortic augmentation index.
Results. There was significantly increased ventricular and arterial stiffness in patients with PsA (P < 0.001),
even in those without hypertension and/or LV hypertrophy. Based on the cut-off points derived from the
controls, 38.4% of PsA patients had increased LV stiffness including 31.5% in diastole and 17.8% in
systole, and 15.1% had increased arterial stiffness. Multivariable logistic regression analysis showed that
long PsA disease duration (>10 years) (odds ratio = 6.55, P = 0.001) was an independent risk factor for
increased LV diastolic elastance after adjusting for age, gender and hypertension.
Conclusion. Patients with PsA may have increased ventricular and arterial stiffness even without evidence
of LV remodelling, and those with long disease duration may be at a higher risk. Therefore, prolonged

CLINICAL
SCIENCE
inflammatory burden may be an important cause of early cardiovascular disease in patients with PsA.
Key words: stiffness, ventricular remodelling, PsA.

Introduction increased death [2]. However, the mechanism of CVD has

PsA is an autoimmune inflammatory disease, which is
associated with an increased prevalence of hypertension,
ischaemic heart disease, congestive heart failure, periph-
eral vascular disease, cerebrovascular disease and type II
diabetes [1]. A mortality study showed that cardiovascular
diseases (CVD) are the leading cause of death in patients
with PsA compared with controls with a 1.3-fold risk of
1
Division of Cardiology and 2Divsion of Rheumatology, Department of
Medicine and Therapeutics, Institute of Vascular Medicine, The
Chinese University of Hong Kong, Prince of Wales Hospital, Hong
Kong, China.
Submitted 13 December 2012; revised version accepted
29 June 2012.
Correspondence to: Cheuk-Man Yu, Division of Cardiology,
Department of Medicine and Therapeutics, The Chinese University of
Hong Kong, 9/F Clinical Sciences Building, Prince of Wales Hospital,
Shatin, NT, Hong Kong, China. E-mail: cmyu@cuhk.edu.hk
not been fully elucidated in these patients. Recently, ven-
tricular and arterial stiffness has been identified as an im-
portant pathophysiological determinant of CVD [3] and
has been studied in different populations including the
elderly, patients with cardiovascular risk factors, hyper-
tension, diabetes mellitus, end-stage renal disease and
obstructive sleep apnoea [4–9]. Nevertheless, no pub-
lished study has focused on the early detection of ven-
tricular and arterial stiffness in patients with PsA.
With tissue Doppler imaging subclinical myocardial dis-
ease, not detectable by conventional echocardiography,
can be recognized [10–13]. In addition, ventricular and
arterial stiffness can be derived from echocardiographic
measurements [14]. Furthermore, non-invasive pulse
wave analysis (PWA) has recently gained recognition as
a measure of subclinical vascular disease, using applana-
tion tonometry, which records a peripheral arterial

! The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com
Qing Shang et al.
waveform. A derived central aortic waveform can be
obtained by applying a generalized transfer function. The
aortic augmentation index provided by PWA can indirectly
evaluate arterial stiffness. Using these non-invasive tech-
niques, we sought to test the hypothesis that patients with
PsA might have a high propensity to experience increased
ventricular and arterial stiffness independent from stand-
ard risk factors and which may be associated with some
disease-related risk factors.
Methods
Study population
Ninety-five patients were screened, and 73 of them fulfill-
ing the classification of PsA criteria [15] were recruited
consecutively from the rheumatology clinic of a university
affiliated teaching hospital. Exclusion criteria included
pregnancy, hypothyroidism, clinically significant renal dis-
ease (serum creatinine level 5 270 mmol/l), diabetes melli-
tus, those with history of angina, stable coronary artery
disease, previous acute coronary syndromes, coronary
revascularization, bundle-branch block, second-degree
or higher atrioventricular block, atrial fibrillation, valvular
stenosis or at least moderate valvular regurgitation, valvu-
lar replacement or repair or mitral annular calcification.
Patients were divided into two subgroups based on the
absence or presence of hypertension (defined as a sys-
tolic blood pressure 5140 mm Hg or a diastolic blood
pressure 590 mm Hg or the use of antihypertensive
agents) and/or left ventricular hypertrophy (LVH) evi-
denced by echocardiography. Fifty healthy control sub-
jects without a history of overt CVD were recruited from
the community through advertisement or from other
clinics. The control group was matched to the patient sub-
group without hypertension or LVH for age, gender, BMI
and blood pressure. The Ethics Committee of our institu-
tion (Ethics Committee of The Chinese University of Hong
Kong and the Hong Kong Hospital Authority) approved the
study that was conducted in compliance with the
Declaration of Helsinki (2000) of the World Medical
Association. All participants provided written informed
consent.
PsA clinical assessment
Disease patterns
PsA patients with predominant peripheral arthritis were
included in the category of peripheral arthritis, and those
with predominant inflammatory arthritis of the back were
included in the category of spondyloarthritis.
Disease activity and severity
Pain, physician’s and patient’s global assessments, was
assessed using a 10-point visual analogue scale (0 = ex-
cellent well-being; 10 = feeling extremely unwell). Physical
examination recorded the number of tender and swollen
joints using the 68 tender/66 swollen joint count, the pres-
ence of dactylitis and the number of permanently
deformed joints. Disease activity was assessed using
the disease activity score in 28 joints (DAS28) [16].
2216
Sign and symptoms of psoriasis
Skin abnormality and nail lesions were examined, and the
psoriasis area and severity index (PASI) was calculated to
evaluate the severity of psoriasis [17]. Radiographs (spine,
pelvis, feet and hands) were reviewed for the presence of
erosion at the time of the study.
Laboratory
ESR was measured using the Westergren method. The
high-sensitivity CRP level was measured using an immu-
noturbidimetric assay performed with Olympus OSR6185
(Olympus Diagnostics, Lismeehan, County Clare, Ireland).
Apolipoproteins A and B were tested by automated ana-
lyzer (Cobas-Mira Plus, Hoffman-La Roche Diagnostics,
Mannheim, Germany), using a turbidimetric assay.
Plasminogen activator inhibitor-1 was measured by
ELISA, using commercially available kits (Diagnostica
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Stago, Freres Chausson, France). Fibrinogen was mea-
sured using a modified clot-rate assay.
Echocardiography
Conventional echocardiography
A comprehensive echocardiography with Doppler studies
was performed by using Vivid 7 systems with a 3.5-MHz
probe (GE Medical Systems, Milwaukee, WI, USA).
Standard echocardiographic assessments included the
measurements of LV dimensions, wall thickness, LV
mass index, ejection fraction and colour Doppler imaging
of all valves were done according to the recommenda-
tions of American Society of Echocardiography [18].
LVH was considered present if the LV mass index to
body surface exceeded 95 g/m2 in women and 115 g/m2
in men. Relative wall thickness (RWT) was calculated
by the formula (2  LV end-diastolic posterior wall thick-
ness/LV end-diastolic internal dimension) to classify
LV remodelling as normal geometry (no LVH
and RWT 40.42), concentric remodelling (no LVH
but RWT > 0.42), eccentric hypertrophy (LVH with
RWT 40.42) or concentric hypertrophy (LVH with
RWT >0.42) [18]. The LV ejection fraction was evaluated
by modified biplane Simpson method.
Tissue Doppler imaging and subclinical LV dysfunction
Color tissue Doppler images in at least three consecutive
beats were acquired from apical 4-chamber, 2-chamber
and long-axis with a highest possible frame rate (>100
frames/s), and off-line analysis programs (EchoPac-PC
108.1.5, Horten, Norway) included peak systolic (Sm)
and peak early diastolic (Em) myocardial velocities of 12
LV segments. Real-time pulsed-wave tissue Doppler velo-
cities were recorded from the septal and lateral sites of
the mitral annulus in the apical 4-chamber view for meas-
urements of early peak (E0 ) diastolic velocity. In our labora-
tory, the intraobserver and interobserver variability for
tissue Doppler velocity data were 3% and 5%, respect-
ively, as previously reported [19]. Subclinical LV diastolic
dysfunction was identified by lateral E0 <11.5 cm/s and/or
the ratio of the mitral inflow early diastolic filling velocity (E)
to lateral E0 (E/E0 ) >10 [20–22]; subclinical LV systolic
www.rheumatology.oxfordjournals.org

dysfunction was defined by mean Sm from only six basal
LV segments <4.4 cm/s [10]. Subclinical LV dysfunction
included subclinical LV diastolic and/or systolic
dysfunction.
Non-invasive vascular assessment
Vascular ultrasound
Carotid intima–media thickness (IMT) was scanned by
using B-mode ultrasound with a 10-MHz linear vascular
probe (Vivid 7; GE Vingmed Ultrasound, Horten, Norway).
Minimal gain was adjusted to visualize the lumen–intimal
and medial–adventitial interfaces defining IMT in the far
wall. Digital images of three cardiac cycles were saved
with ECG signals. The IMT was measured in the distal
1 cm of common carotid artery, carotid bifurcation and
the initial 1 cm of internal carotid artery by using dedicated
software (Carotid Analyzer; Medical Imaging Applications,
Coralville, IA, USA). The cardiologist was blinded to all
clinical information when carrying out online and offline
analysis. The mean IMT was recorded, not including pla-
ques, for the following calculation. Plaque was defined as
a localized thickening >1.2 mm that did not uniformly in-
volve the whole artery.
PWA
The examination was performed as recommended [23].
PWA was performed using the SphygmoCor device
(SCOR 2000 v.7.01; AtCor. Medical Pty Ltd, Sydney,
Australia) with a tonometer probe at the right radial
artery. The central aortic arterial pulse wave was trans-
ferred from the peripheral arterial pulse wave, and the
aortic augmentation index was standardized to a heart
rate of 75 bpm to minimize the effect of heart rate auto-
matically [24]. The standardized aortic augmentation
index was used for the main analysis.
Definitions of ventricular and arterial stiffness
Ventricular stiffness was evaluated by LV end-systolic ela-
stance (0.9  systolic blood pressure/LV end-systolic
volume) and diastolic elastance [(lateral E/E0 )/LV stroke
volume] [14]. Arterial stiffness was estimated by effective
arterial elastance (0.9  systolic blood pressure/LV stroke
volume), total arterial compliance (LV stroke volume/pulse
pressure) and aortic augmentation index [14, 25, 26].
Vascular ventricular coupling was assessed by the
ratio of effective arterial elastance to LV end-systolic ela-
stance [14].
Statistical analysis
SPSS 17.0 (SPSS, Inc., Chicago, IL, USA) was used for
the analyses. Results are expressed as mean (S.D.) for
normally distributed data and the median [interquartile
range (IQR)] for non-normally distributed data.
Comparisons among groups were assessed using un-
paired t-test or analysis of variance test for continuous
variables and 2 test for categorical variables.
Mann–Whitney U test was used for continuous variables
that were skewed. Curve estimation and logistic regres-
sion analysis were performed to assess the relationship
www.rheumatology.oxfordjournals.org
Ventricular–arterial stiffness in PsA
between echocardiographic and clinical variables. Curve
estimation is a curve-fitting program that can be used to
compare and select suitable curve relationships (such as
linear, logarithmic, inverse, compound and so on) to illus-
trate the relationships between variables, which are illu-
strated in figures with r values. As for logistic regression,
all potential risk factors were included into univariable lo-
gistic regression analysis based on t-test results, then
those with P < 0.10 in univariable logistic regression ana-
lysis were selected for the multivariable logistic regression
analysis. The cut-off points of LV and arterial stiffness
were derived from control group by using mean +2 S.D.,
because 95% of all the data values in control group can
be found between the mean +2 S.D. and the mean 2 S.D.
All tests were 2-tailed and P-values <0.05 were con-
sidered statistically significant.
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Results
The mean age of these 73 PsA patients at diagnosis was
34 years, and the median disease duration of PsA was
10.7 (IQR: 6.3–18.0) years. Fifty-seven (78.1%) patients
had concurrent psoriasis, 47 (64.4%) had nail lesions
and 34 (46.6%) had erosions on radiography at the time
of assessment. Sixty-one (83.6%) patients had peripheral
arthritis and 12 (16.4%) had spondyloarthritis. Based on
the DAS28 score, 45 (61.6%) patients had active disease.
More than half of the patients had been on NSAIDs and
DMARDs (Table 1). Forty-three patients did not have
hypertension or LVH, whereas 30 patients had either
hypertension (n = 27, 37.0%) or LVH (n = 7, 9.6%).
Stiffness in patients with PsA
Compared with controls, patients with PsA demonstrated
an increase in ventricular and arterial stiffness and an early
impairment of LV longitudinal systolic and diastolic func-
tion (P < 0.001), even in those without hypertension or
LVH (Table 2). Based on the cut-off points deduced
from controls (mean +2 S.D.), 28 (38.4%) PsA patients
had increased LV stiffness including 23 (31.5%) in diastole
(diastolic elastance >0.17) and 13 (17.8%) in systole
(end-systolic elastance >5.6), and 11 (15.1%) had
increased arterial stiffness (arterial elastance >3.1).
Altogether, 31 (42.5%) patients had increased ventricular
and/or arterial stiffness, and 20 (27.4%) had only
increased LV stiffness. Furthermore, patients without
hypertension or LVH presented a higher prevalence of
increased ventricular and/or arterial stiffness (27.9% vs.
8.0%, P = 0.011) and LV stiffness (20.9% vs. 6.0%,
P = 0.032) compared with matched controls.
Relationship between disease duration and stiffness
Fig. 1 showed the positive correlation between LV dia-
stolic elastance and PsA disease duration (r = 0.472,
P < 0.001). Table 3 compared the remodelling and
PsA-related parameters between patients with normal
and increased LV diastolic stiffness (identified by diastolic
elastance >0.17). There was a higher proportion of
women, longer PsA disease duration and a higher
2217
Qing Shang et al.

TABLE 1 Disease-related characteristics in patients (Fig. 1). However, these correlations were not significant
with PsA after adjustment for age, gender and hypertension.

Parameter PsA, n = 73 Discussion

Age at psoriasis diagnosis, years
Age at PsA diagnosis, years
Psoriasis duration, median (IQR)
PsA duration, years; median (IQR)
Disease pattern, n (%)
Peripheral
Spondylarthritis
Disease activity, n (%)
Inactive (DAS28 4 3.2)
Moderately active (3.2 < DAS28 4 5.1) 29 (39.7)
Very active (DAS28 > 5.1)
PASI, median (IQR)
Physician’s global (VAS 0–10),
34 (15) This study has demonstrated that there is increased ven-
39 (12) tricular and arterial stiffness in PsA patients, even in those
10.7 (6.3–18.0) without hypertension and LVH, and this is significantly
8.2 (2.1–11.4) associated with disease duration.
61 (83.6) Stiffness and remodelling in patients with PsA
12 (16.4)
It has been observed that normal age-related vascular
28 (38.4)
stiffening was accompanied by comparable changes
in the LV stiffness and diastolic compliance [14].
16 (21.9) Furthermore, this combination concomitance of ventricu-
2.4 (1.0–8.0) lar and arterial stiffening seems to be common in patients
2.0 (0–3.0) with hypertension and heart failure with preserved ejection

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median (IQR) fraction [27, 28]. Similar changes were observed in our
Patient’s global (VAS 0–10) 4.5 (2.3) current study. Does cardiovascular involvement in PsA
Number of damaged joints, 1.0 (0–4.0)
median (IQR)
share the same mechanisms as the ageing process or
Erosion, n (%) 17 (39.5) hypertension? In our study, PsA patients without hyper-
HAQ, median (IQR) 0.4 (0–0.9) tension and/or LVH still had significantly increased LV
ESR, mm/h, median (IQR) 22.0 (10.0–37.0) elastance and decreased total arterial compliance when
hs-CRP, median (IQR) 4.2 (1.6–12.5) compared with the matched control group. In addition, the
Apo A-1, mg/dl 151.0 (32.0) prevalence of abnormal LV stiffness was significantly
Apo B, mg/dl 83.2 (15.9) higher than that in age, BMI and blood pressure matched
Fibrinogen, mg/l 4.1 (0.8) controls, whereas vascular ventricular coupling was not
PAI-1, median (IQR) ng/ml 24.0 (15.6–36.2)
different. In a recent study, Costa et al. [29] compared
White cell count, 109/l 6.8 (2.3)
Platelet count, 109/l 305.0 (69.9)
the arterial stiffness (identified by aortic pulse wave vel-
Serum creatinine, mmol/l 72.0 (15.1) ocity) between 20 PsA patients without known cardiovas-
Current NSAIDs, n (%) 47 (64.4) cular risk factors and 20 age, weight and height matched
Current DMARDs, n (%) 41 (56.2) healthy controls, and an increased arterial stiffness was
Corticosteroid ever, n (%) 6 (8.2) found in patient group after adjusting for age, weight,
Current anti-hypertensive therapy, n (%) 16 (21.9) height, heart rate and central mean pressure. Therefore,
CCB 8 (11.0) there might be other risk factors contributing to cardio-
ACEI/ARB 2 (2.7) vascular stiffness besides the traditional risk factors
b-Blocker 8 (11.0) (hypertension and LVH) and conventional mechanisms
(age and vascular ventricular coupling). Furthermore,
VAS: visual analogue scale; Apo A-1: apolipoprotein A-1; these changes of ventricular stiffness may have an import-
Apo B: apolipoprotein B; PAI-1: plasminogen activator inhi-
ant detrimental effect on LV mechanics especially on
bitor-1; hs-CRP: high-sensitivity CRP; CCB: calcium-channel
exercise and lead to significant exercise limitation and
blocker; ACEI: angiotensin-converting enzyme inhibitor;
ARB: angiotensin receptor blocker. Data are expressed as breathlessness [30].
mean (S.D.) unless specified otherwise. Ventricular remodelling generally includes cellular pro-
liferation, hyperplasia, necrosis or apoptosis and intersti-
tial fibrosis, which may cause hypertrophy, dilation and
stiffening and finally result in cardiovascular dysfunction.
prevalence of hypertension and remodelling (P < 0.10) in Pieretti et al. found increased LV mass and prevalence of
patients with increased LV diastolic stiffness. Multivariable LVH (16.9%) in patients with SLE compared with age and
logistic regression analysis showed that PsA disease dur- gender matched controls and disease-related inflamma-
ation was an independent explanatory variable of LV dia- tory markers related to LV mass index, which suggested
stolic stiffness [odds ratio (OR) = 1.12, P = 0.012], and long inflammation-related arterial stiffening may be the pos-
disease duration (>10 years) contributed more to LV dia- sible reason [31]. Such ventricular remodelling was also
stolic stiffness (OR = 6.55, P = 0.001) after adjusting for found in our study; however, the prevalence of LVH (9.6%)
age, gender and hypertension (Table 4). and concentric remodelling (11.0%) was relative low.
Similar analysis was repeated between PsA disease Furthermore, Gonzalez-Juanatey et al. investigated 50
duration and other stiffness parameters, showing positive PsA patients without clinically evident CVD or classic ath-
correlation with LV end-systolic elastance (r = 0.238, erosclerosis risk factors and found no significant differ-
P = 0.047) and natural logarithm of aortic augmentation ence of LV dimension and mass compared with
index (r = 0.259, P = 0.036) and a negative correlation matched controls [32]. In addition, Fukuhara et al. [33]
with total arterial compliance (r = 0.267, P = 0.025) and Eliakim-Raz et al. [34] ever reported a potential

2218 www.rheumatology.oxfordjournals.org
 Ventricular–arterial stiffness in PsA

TABLE 2 Comparisons of ventricular and arterial stiffness and remodelling between patients and control groups

Controls, PsA without PsA with

Parameter n = 50 HT or LVH, n = 43 HT or LVH, n = 30 ANOVA, P

Age, years 44 (14) 43 (12) 53 (10)*,y 0.001

Gender, female/male 22/28 20/23 16/14 0.717
BMI, kg/m2 22.8 (3.3) 24.2 (5.4) 26.6 (3.7)*,z 0.005
Systolic BP, mm Hg 120 (12) 119 (10) 138 (17)*,y <0.001
Diastolic BP, mm Hg 74 (9) 74 (7) 82 (11)*,y <0.001
Stiffness
LV end-systolic elastance, mm Hg/ml 3.86 (0.87) 4.31 (1.15) 4.70 (1.32)* 0.007
LV diastolic elastance 0.11 (0.03) 0.13 (0.04)** 0.20 (0.08)*,y <0.001
Effective arterial elastance, mm Hg/ml 2.22 (0.44) 2.32 (0.45) 2.78 (0.88)*,z <0.001
Effective arterial elastance to LV 0.51 (0.15) 0.56 (0.14) 0.60 (0.13)** 0.046
end-systolic elastance ratio
Total arterial compliance, ml/mm Hg 1.26 (0.37) 1.10 (0.31)** 0.92 (0.37)*,z 0.001
Aortic augmentation index, % 14.7 (8.8) 22.0 (15.5)** 29.1 (15.3)*,z 0.001

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Remodelling
Interventricular septum thickness, cm 0.82 (0.12) 0.87 (0.16) 0.94 (0.22)*,z 0.008
LV end-diastolic diameter, cm 4.68 (0.32) 4.63 (0.45) 4.77 (0.34) 0.274
Posterior wall thickness, cm 0.79 (0.12) 0.81 (0.12) 0.89 (0.15)*,y 0.003
LV mass index, g/m2 74.6 (12.7) 77.8 (15.5) 88.5 (21.1)*,z 0.001
RWT 0.34 (0.05) 0.35 (0.06) 0.37 (0.06)** 0.047
LV remodelling, n (%)
Normal geometry 46 (92.0) 38 (88.4) 20 (66.7)* <0.001
Concentric remodelling 4 (8.0) 5 (11.6) 3 (10.0)*
Eccentric LVH 0 0 4 (13.3)*
Concentric LVH 0 0 3 (10.0)*
Mean of IMTCCA, mm 0.62 (0.08) 0.69 (0.16)** 0.75 (0.13)* 0.002
Max of IMTCCA, mm 0.65 (0.09) 0.73 (0.17)** 0.82 (0.15)*,z <0.001
Cardiac function
Left ventricle
LV ejection fraction, % 65.1 (6.0) 64.4 (5.2) 63.3 (5.7) 0.410
Mean Sm of LV 12 segments, cm/s 5.8 (1.0) 4.5 (1.0)* 4.2 (1.1)* <0.001
Mean Em of LV 12 segments, cm/s 7.8 (1.9) 7.0 (2.0)** 5.5 (1.6)*,y <0.001
E/E0 ratio 5.8 (1.1) 6.1 (1.5) 9.3 (2.8)*,y <0.001
Subclinical LV dysfunction, n (%)
Normal 41 (82.0) 24 (55.8) 5 (16.7) <0.001
Only diastolic dysfunction 9 (18.0) 9 (20.9) 14 (46.7)
Only systolic dysfunction 0 4 (9.3) 0
Both 0 6 (14.0) 11 (36.7)
Right ventricle
PASP, mm Hg 15.2 (9.7) 22.6 (10.1)** 27.3 (13.5)** <0.001
S0 at tricuspid annulus, cm/s 13.8 (1.7) 12.8 (2.4) 11.7 (1.5)** 0.001
E0 at tricuspid annulus, cm/s 14.4 (2.7) 11.8 (3.2)* 9.7 (2.0)*,z <0.001

ANOVA: analysis of variance; HT: hypertension; BP: blood pressure; IMTCCA: IMT thickness of common carotid artery; PASP:
pulmonary arterial systolic pressure; S0 : peak systolic annulus velocity. Data are expressed as mean (S.D.) unless specified
otherwise. *P < 0.005 and **P < 0.05, compared with controls; yP < 0.05 and zP < 0.05, compared with PsA without HT or LVH.

relationship between PsA/psoriasis and dilated cardiomy-
opathy. All the above studies suggest that there is a di-
versity of remodelling in autoimmune inflammatory
diseases and that LVH may be a late manifestation of
cardiac involvement in PsA.
PsA disease duration: a surrogate long-term
inflammatory burden and a risk factor for stiffness
Many studies have verified that inflammation may accel-
erate cardiovascular damage by its involvement in athero-
sclerosis, contributing to cardiac fibrosis [35], and
accelerating necrosis and apoptosis. In general, inflam-
mation may lead to so-called functional stiffening of the
large arteries because of reduced nitric oxide bioavailabil-
ity and increased activity of opposing mediators such as
endothelin-1 [36, 37], and structural stiffening of the larger
vessels because of smooth muscle cell proliferation and
increased synthesis of structural proteins including colla-
gen [38]. Recent studies have found evidence of CVD in
SLE without any clinically obvious CVD, such as LVH,
subclinical myocardial dysfunction and increased arterial
stiffness, which were associated with disease duration,

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Qing Shang et al.

FIG. 1 Relationship between stiffness and PsA disease duration.

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PsA duration was positively correlated with LV diastolic elastance and negatively correlated with total arterial compliance.

TABLE 3 Comparison between patients with normal and increased LV diastolic stiffness

LV diastolic stiffness
Parameter
Normal, n = 50 Increased, n = 23 P

Age, years 46 (13) 50 (10) 0.140

Gender, male/female 30/20 7/16 0.019
HT, n (%) 14 (28.0) 13 (56.5) 0.019
LV ejection fraction, % 64.1 (5.4) 63.6 (5.6) 0.712
PASP, mm Hg 23.4 (11.0) 27.1 (13.3) 0.219
S0 at tricuspid annulus, cm/s 12.5 (2.0) 11.9 (2.2) 0.290
E0 at tricuspid annulus, cm/s 11.2 (2.9) 10.3 (3.0) 0.205
Remodelling
LV mass index, g/m2 83.1 (19.9) 80.6 (15.0) 0.597
RWT 0.37 (0.07) 0.35 (0.05) 0.190
LV remodelling, n (%)
Normal geometry 39 (78.0) 19 (82.6) 0.054
Concentric remodelling 8 (16.0) 0
LVH 3 (6.0) 4 (17.4)
Mean of IMTCCA, mm 0.71 (0.15) 0.72 (0.13) 0.877
Max of IMTCCA, mm 0.76 (0.17) 0.78 (0.15) 0.716
PsA-related parameters
Age at psoriasis diagnosis, years 35 (16) 33 (12) 0.864
Age at PsA diagnosis, years 38 (13) 39 (10) 0.853
Psoriasis duration, median (IQR), years 4.9 (1.2–9.3) 10.8 (9.4–13.4) 0.003
PsA duration, median (IQR), years 8.4 (4.0–15.3) 14.6 (10.1–25.3) 0.001
PsA duration >10 years, n (%) 11 (22.0) 15 (65.2) <0.001
Disease pattern, n (%)
Peripheral 44 (88.0) 17 (73.9) 0.131
Spondylarthritis 6 (12.0) 6 (26.1)
Disease activity, n (%)
Inactive (DAS28 4 3.2) 19 (38.0) 9 (39.1) 0.803
Moderately active (3.2 < DAS28 4 5.1) 19 (38.0) 10 (43.5)
Very active (DAS28 > 5.1) 12 (24.0) 4 (17.4)
PASI, median (IQR) 1.8 (0.8–7.7) 3.3 (1.8–8.8) 0.173
Apo A-1, mg/dl 153.9 (33.3) 146.1 (31.7) 0.441
Apo B, mg/dl 84.1 (17.5) 81.6 (13.1) 0.662
ESR, median (IQR) mm/h 16.0 (9.0–37.0) 26.0 (14.5–44.0) 0.296
hs-CRP, median (IQR) mg/l 4.0 (1.6–12.5) 4.3 (1.3–15.4) 1.000
Medical therapy, n (%)
Current NSAIDs 31 (62.0) 16 (69.6) 0.531
Current DMARDs 27 (54.0) 14 (60.9) 0.583
Current anti-hypertensive therapy 9 (18.0) 7 (30.4) 0.233

Data are expressed as mean (S.D.) unless specified otherwise. Apo A-1: apolipoprotein A-1; Apo B:
apolipoprotein B; HT: hypertension; PASP: pulmonary arterial systolic pressure.

2220 www.rheumatology.oxfordjournals.org
 Ventricular–arterial stiffness in PsA

severity and/or activity [31, 39, 40]. Similar findings were
also reported in RA [41]. Moreover, the disease-modifying
anti-rheumatic drugs could improve inflammation-
associated arterial stiffness [42]. All these studies not
only confirmed the role of inflammation in the pathogen-
esis of CVD but also demonstrated that patients with
autoimmune inflammatory diseases are vulnerable to de-
veloping CVD early.
PsA with long disease duration is characterized by a
remitting and relapsing disease course, that is to say,
long disease duration can be considered as a surrogate
of long-term inflammatory burden. This was borne out in
our current study as disease duration positively correlated
with ventricular and arterial elastance and negatively with
total arterial compliance. Also, disease duration was an
independent factor of LV diastolic stiffening after adjusting
for gender, hypertension and LV remodelling. In addition,
patients with long disease duration (>10 years) had a
higher risk of LV stiffening. This is similar to results from
the study by Costa et al. [29], where a positive relationship
was found between arterial stiffness and PsA duration
after adjusting for age, weight, height, heart rate and cen-
tral mean pressure. Although there was no correlation be-
tween stiffness and classic inflammatory markers, such as
ESR and high-sensitive CRP in either Costa et al. [29] or
our studies, the potential relationship between ventricular
stiffening and inflammatory burden remains highly likely.
Laboratory results just report the inflammatory status at
one time point, which could not reflect the totality of the
inflammatory burden since the onset of the disease. Fig. 2
summarized a possible relationship between inflammatory
burden and cardiovascular remodelling, stiffening and

Downloaded from http://rheumatology.oxfordjournals.org/ at Oakland University on April 6, 2015

dysfunction in patients with PsA. Finally, although there
was a significant difference in the duration of psoriasis
TABLE 4 Risk factors of increased LV diastolic stiffness between patients with normal and increased LV diastolic
stiffness, it was not included into the multi-regression ana-
lysis because psoriasis and PsA disease duration belong
Logistic regression analysis
Parameter to the same category, with both indirectly reflecting
Univariate Multivariate long-term inflammatory burdens.
OR (95% CI) OR (95% CI) In this current study, female gender was the other inde-
pendent risk factor for LV diastolic stiffness. A commu-
Age, years 1.03 (0.99, 1.08) –
nity-based study that investigated >2000 subjects also
Female gender 3.43 (1.20, 9.80) 3.12 (1.01, 9.57)
HT 3.34 (1.19, 9.36) – reported that female gender was associated with
LV remodelling 1.18 (0.55, 2.52) – increases in vascular and ventricular systolic and diastolic
PsA duration 1.12 (1.03, 1.22) 1.12 (1.02, 1.22) stiffness even in the absence of CVD [14]. The cause of
PsA duration 6.65 (2.24, 19.74) 6.55 (2.11, 20.32) gender differences in ventricular and arterial stiffening is
> 10 years unclear, although several studies suggested the effects

FIG. 2 Cardiovascular remodelling, stiffening and dysfunction in patients with PsA.

Here, the possible relationship between inflammatory burden and cardiovascular remodelling, stiffening and dysfunction
in patients with PsA is shown. In the early stage of cardiovascular involvement, long-term inflammatory burden may
contribute to increased cardiovascular stiffness and remodelling, which subsequently results in subclinical myocardial
dysfunction.

www.rheumatology.oxfordjournals.org 2221
Qing Shang et al.
of body size and vasculature length on arterial stiffness
[43, 44].
The obvious limitation of this study is the relatively the
small sample size and no intervention to improve those
with increased cardiovascular stiffness, but the results
seem clear even with this sample size. In conclusion,
this is the first case–control study to assess ventricular
and arterial stiffness in PsA, and an increase in cardiovas-
cular stiffness was found in patients with PsA, even in
those without hypertension and LVH; disease duration
as a long-term inflammatory surrogate may be an inde-
pendent risk factor.
Rheumatology key messages
. Ventricular and arterial stiffness is high in patients
with PsA.
. PsA itself contributes to cardiac involvement.
Disclosure statement: The authors have declared no
conflicts of interest.
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