BRIEF REPORT

Psoriatic arthritis is associated with increased arterialstiffness in the absence of known cardiovascularrisk factors: a case control study

Luisa Costa & Francesco Caso & Lanfranco D’Elia & Mariangela Atteno &

Rosario Peluso & Antonio Del Puente & Pasquale Strazzullo & Raffaele Scarpa

Received: 28 October 2011 /Accepted: 1 November 2011 /Published online: 24 November 2011# Clinical Rheumatology 2011

Abstract The objective of the study was the evaluation ofarterial stiffness, a cardiovascular risk factor, in patients withpsoriatic arthritis (PsA). Twenty PsA patients classified on thebasis of the CASPAR criteria (M/W, 14/6; mean age,38.6 years; range, 22–53), attending our out-patient clinic,and 20 healthy control subjects (M/W, 14/6; mean age,38.7 years; range, 22–53) matched for age, weight, heightand with similar cardiometabolic profile entered the study. Anexclusion criterion was the presence of known cardiovascularrisk factors. Central hemodynamic parameters and aortic pulsewave velocity (aPWV) were assessed non-invasively by aSphygmoCor device. A significantly higher aPWV wasrecorded in PsA patients when compared to controls. Thedifference remained statistically significant after adjustmentfor age, weight, height, heart rate (HR) and central meanpressure (mean±SE; PsA, 8.3±0.2 versus control, 6.8±0.2 m/s;p<0.0001). Among PsA patients, aPWV was related toknown duration of disease (r=0.63; p=0.003). This resultwas confirmed after adjustment for the main confounders (β=0.011; p=0.013). These results support the concept ofpsoriatic disease as a systemic condition involving not onlythe skin, joints and gastrointestinal tract but also arterialvessels. The involvement of the vascular system indicates the

presence of pathogenetic mechanisms that could accelerate theatherosclerotic process in this condition.

Keywords Arterial stiffness . Psoriatic arthritis . Psoriaticdisease . Pulse wave velocity

Introduction

Psoriatic arthritis (PsA) is a chronic inflammatory arthritisassociated with psoriasis and belonging to the spondyloar-thritic area [1]. Articular manifestations of PsA are part of acomplex disease involving not only the joints and the skinbut also other sites such as the bowel [2]. This point hasrecently lead to the novel concept of psoriatic disease(PsoD), a systemic condition characterised by the involve-ment of different organs [3]. Recent evidences suggest thatPsoD is also associated with an increased cardiovascularrisk [4, 5] similar to other rheumatic conditions such asrheumatoid arthritis and systemic lupus erythematosus, inboth of which accelerated atherosclerosis and increasedcardiovascular risk have been described [6, 7].

Endothelial inflammation and dysfunction have beenrecognised as early events in the development of athero-sclerosis. Endothelium activation leads to altered arterialwall permeability, increased leukocyte adhesion and cyto-kine release, thus sustaining inflammation and the forma-tion of atherosclerotic plaque formation [8]. One of themajor factors involved in these processes is tumour necrosisfactor alpha (TNFα), a proinflammatory agent [9] inducingneutrophil chemotaxis, macrophage activation and super-oxide anion production [10–12].

In addition to the traditional cardiovascular risk factors,arterial stiffness has been recently recognised as anindependent predictor of cardiovascular risk [13, 14], being

L. Costa and F. Caso contributed equally to this study.

L. Costa : F. Caso :M. Atteno : R. Peluso :A. Del Puente :R. Scarpa (*)Rheumatology Research Unit, Department of Clinical andExperimental Medicine, University Federico II,Via Sergio Pansini n. 5,80131 Naples, Italye-mail: rscarpa@unina.it

L. D’Elia : P. StrazzulloExcellence Center of Hypertension, Department of Clinical andExperimental Medicine, University Federico II,Naples, Italy

Clin Rheumatol (2012) 31:711–715DOI 10.1007/s10067-011-1892-1

an expression of arterial distensibility and arterial compli-ance and thus of the elastic properties of large and medium-sized vessels [15]. Few studies have shown increasedarterial stiffness and evidence of atherosclerosis in patientswith classical psoriasis [16, 17]. To our knowledge,however, no studies have been performed in the peculiargroup of patients with PsA and the aim of this study wasthus the evaluation of arterial stiffness in PsA patients freeof other known cardiovascular risk factors.

Patients and methods

Study population

In an 8-month period, 20 patients with established PsAclassified on the basis of the CASPAR criteria [18],attending our out-patient clinic (M/W, 14/6; mean age,38.6 years; range, 22–53) and 20 healthy control subjects(M/W, 14/6; mean age, 38.7 years; range, 22–53) matchedfor age, height, weight and with a similar cardiovascularprofile were enrolled in this study. An exclusion criterion wasthe presence of known cardiovascular risk factors. Inparticular, none of them presented with BMI ≥25 kg/m2,systolic pressure ≥140 mmHg, diastolic pressure ≥90 mmHg,diabetes mellitus, hyperlipidemia, history of cardiovascularand cerebrovascular events, arrhythmia, smoking habits,renal failure, endocrine abnormalities, haemorrhagic orthrombotic disorders and/or hormone replacement therapy.

The following data were collected for each PsA patient:family and personal history, physical examination, record-ing of vital signs, joint counts (tender, swollen), PsoriasisArea and Severity Index (PASI), Health AssessmentQuestionnaire (HAQ), Disease Activity Score of 28 joints(DAS 28), fasting lipid profile, blood glucose and inflam-matory indices measurement. Fourteen PsA patients wereon traditional DMARDs (disease-modifying anti-rheumaticdrugs) while the remaining 6 did not follow any regulartherapy.

Brachial blood pressure was measured at the non-dominantarm with an automated digital oscillometric sphygmomanom-eter (OMRON 705-CP, Omron Corp, Japan). Three measure-ments were performed at 3-min interval and the mean of thelast two measurements was used for the analysis.

Central hemodynamic parameters and arterial stiffness,assessed in PsA patients and control subjects, wereevaluated by a high-fidelity applanation tonometer (Millar,SPT-301, Houston, TX, USA) and analysed by theSphygmoCor device (version 8.0, Atcor Medical, Sydney,Australia). The measurements were performed in a quietand controlled temperature room, after 10 min in the supineposition, with the subject fasting and refraining fromalcohol use for at least the previous 10 h.

All measurements were made in duplicate by a singletrained operator according to the international recommen-dations [19] and the mean of the two values was used in theanalysis. Central arterial waveforms and pressures, obtainedat the radial artery, were calibrated using systolic anddiastolic pressure values from conventional measurement.From 20 sequential radial pressure waveforms, an averageradial pressure waveform was generated. A correspondingaverage central pressure waveform was produced using avalidated mathematical transfer function [20], and fromthis, we evaluated the aortic pulse wave velocity (aPWV)considered the gold standard measurement of arterialstiffness [14]. Aortic PWV was calculated as the differencein travel time of the pulse wave between two differentrecording sites (carotid and femoral) and the heart, dividedby the travel distance of the pulse waveform. Pressurewaves were recorded sequentially from the sites, and transittime was calculated using registration with a simultaneouslyrecorded ECG. The initial part of the pressure waveform wasused as a reference point. All patients gave their writteninformed consent.

Statistical analysis

Statistical analysis was performed using the SPSS software,version 13 (SPSS Inc, Chicago, IL, USA). All variableswere normally distributed. Analysis of variance was used toassess differences between group means. Bivariate relation-ships between the main features of the PsA and arterialdistensibility values were evaluated by Pearson correlationanalysis. Furthermore, we performed multiple linear regres-sion analysis, to determine the independent effect of PsA onarterial stiffness, controlling for the main confounders.

It was estimated that 20 subjects were required in each armto detect a true difference of 1.0 m/s in PWV and to provide80% power at 5% probability level (two sided). Continuousvalues were reported as mean±SD. Two-sided p values lessthan 0.05 were considered statistically significant.

Results

Characteristics

Demographic and anthropometric characteristics of PsApatients and healthy controls included in the study arereported in Table 1. Patients and controls did not differ forage, sex, BMI, weight and height (p = n.s.).

In PsA patients, the mean values and range wereobtained for the following variables: TJC, 3.7 (7–14);SJC, 0.25 (0–3); DAS28, 2.8 (1.5–5.1); HAQ, 0.59 (0–1.7);PASI, 2.9 (0–39.6); PsA duration, 68.4 months (8–157);psoriasis duration, 99.7 months (9–231); duration of PsA

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treatment (only 14 subjects), 21.5 months (range, 0–96).Erythrocyte sedimentation rate, C-reactive protein, fibrino-gen and fasting serum total cholesterol, HDL cholesterol,triglycerides and glucose levels were all in the normalrange.

Hemodynamic variables

Hemodynamic parameters and arterial stiffness are reportedin Table 2. A significantly higher aPWV was found in PsApatients as compared to controls (mean±SD, 8.2±0.8versus 6.8±1.0 m/s; p<0.0001) (Fig.1).

In a multiple linear regression analysis, aPWV remainedsignificantly higher in PsA patients when compared to thecontrol group, after adjustment for age, weight, height,heart rate and central mean pressure (8.3±0.2 versus 6.8±0.2 m/s; p<0.0001; R2=31%).

Relation between aPWV and disease-related variablesin PsA patients

Among PsA patients, aPWV was also positively related toknown duration of the disease (r=0.63; p=0.003) (Fig. 2).This result was confirmed after adjustment for confounders(age, weight, height, heart rate and central mean pressure)(β=0.011; p=0.013; R2=35%). We did not find significant

correlation between aPWV and ESR or DAS28 or psoriasisduration.

Discussion

For a long time, PsA has been considered a disease with alow clinical and inflammatory profile. However, recentepidemiological and outcome data provided increasingevidence on the severe and multisystemic impact of thiscondition [4]. The results of present study are in keepingwith this view and show that PsA patients without knowncardiovascular risk factors have a higher arterial stiffnesswhen compared with the healthy controls. In addition, inPsA patients, the increased arterial stiffness was directlyassociated with the duration of articular involvement ratherthan with the duration of psoriasis per se.

Table 1 Demographics and anthropometric variables in psoriaticarthritis (PsA) patients and control subjects

Variable PsA Control subjects

Patients (number) 20 20

Men/women 14/6 14/6

Age (years) 38.6±9.7 38.7±9.8

Weight (kg) 74.4±11.1 73.9±11.3

Height (cm) 173.3±8.7 172.7±8.4

Body mass index (kg/m2) 24.5±2.2 24.6±2.3

Data expressed as mean±SD

Table 2 Hemodynamic data in psoriatic arthritis (PsA) patients andcontrol subjects

Variable PsA Control subjects

SBPp (mmHg) 129.5±8.2 129.6±8.7

DBPp (mmHg) 76.7±7.2 76.4±8.1

HR (beats/min) 70.6±6.8 66.7±5.7

aPWV (m/s) 8.2±0.8* 6.8±1.0

Data expressed as mean±SD

SBPp peripheral systolic blood pressure, DBPp peripheral diastolicblood pressure, HR heart rate, aPWV aortic pulse wave velocity

*p<0.0001 vs. controls

Aor

tic P

ulse

Wav

e V

eloc

ity (m

/s)

Control PsA

Fig. 1 Box plot of aortic PWV (median and interquartile range) inpsoriatic arthritis (PsA) patients and control subjects (mean±SD: PsA=8.2±0.8 versus control subjects 6.8±1.0 m/s; p<0.0001)

Aor

tic P

ulse

Wav

e V

eloc

ity (m

/s)

Duration of Arthritis (months)

Fig. 2 Aortic PWV directly correlated to duration of arthritis diseasein PsA patients (r=0.63; p=0.003)

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The mechanism of the arterial impairment is not clearbut the possible involvement of inflammatory cytokines isan intriguing hypothesis. In particular, TNFα has beenrecognised as a major factor in the complex pathogenesis ofpsoriasis and PsA and could be a pivotal factor linking thedifferent expressions of PsoD, including vessels involve-ment [21]. TNFα induces neutrophil chemotaxis, macro-phage activation and superoxide production. These actionsare involved in the pathogenesis of endothelial inflamma-tion and dysfunction which may participate in the develop-ment of arterial damage [22]. Further support to a possiblerole of this cytokine comes from preliminary evidence thatTNFα blockers, while reducing disease activity andinflammation, also improve endothelial function and lipo-protein pattern [23]. Moreover, TNFα blocking therapy hasbeen shown to reduce the incidence of cardiovascularevents in psoriasis and PsA [24, 25].

The strengths of our study are the careful matching ofPsA patients and controls and the exclusion of patients withknown conventional cardiovascular risk factors, making theassociation between PsA and arterial stiffness unconfound-ed by other relevant causal factors. Weaknesses orlimitations are: the relatively small sample size (justifiedat present by the difficulty to find a careful matching ofPsA patients and controls), the cross-sectional design andthe lacking of data on biochemical markers of inflammationhypothetically involved in the pathogenesis of the arterialdamage.

In conclusion, our study shows that in the PsA patientsthere is an increase of aortic stiffness. This result couldsupport the hypothesis that the PsA is a systemic conditionalso associated with an increased cardiovascular risk.

Disclosures None.

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