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Mædica - a Journal of Clinical Medicine ORIGIN AL PAPERSORIGIN AL PAPERS

19Maedica A Journal of Clinical Medicine, Volume 9 No.1 2014

MAEDICA – a Journal of Clinical Medicine 2014; 9(1): 19-24

Cardiovascular Risk in Psoriatic Arthritis – A Cross-Sectional Study

Claudiu POPESCUa,b; Ana Maria PINTILIEb; Violeta BOJINCAa,b; Andra BALANESCUa,b; Ruxandra IONESCUa,b

a„Sfanta Maria” Clinical Hospital, Bucharest, Romania bDepartment of Rheumatology and Internal Medicine, „Carol Davila” University of

Medicine and Pharmacy, Bucharest, Romania

Address for correspondence: Claudiu Popescu, „Sfânta Maria” Clinical Hospital, 37-39 Ion Mihalache Boulevard, 011192, 1st District, Bucharest, Romania. E-mail: [email protected].

Article received on the 20th of September 2013. Article accepted on the 25th of February 2014.

ABSTRACT Objectives: The present study aims to estimate long term cardiovascular risk in psoriatic arthritis

(PsA) patients and to identify clinical and/or laboratory features which influence this risk. Materials and methods: cross-sectional design; sample: 103 in-patients known with psoriatic ar-

thritis (PsA) and 56 normal age-matched female in-patients; cardiovascular variables recorded: age, gender, arterial hypertension (AHT), ischemic heart disease (IHD), dyslipidemia (lipid profile), type II diabetes mellitus (DM; fasting plasma glucose - FPG), obesity (body mass index - BMI), smoking, car- diovascular 10-year risk (SCORE high risk charts); PsA variables recorded: age at onset, inflammation markers; phenotype (peripheral/axial disease); type of treatment.

Outcomes: The PsA group included 44 males and 59 females (p = 0.167) with an average age of 52 years (23-80). SCORE was significantly correlated with age of onset, BMI, triglycerides, FPG. Among these patients, males, smokers, those with axial involvement, with IHT, with AHT and those not treated with glucocorticoids had a significantly higher SCORE. The subgroup of 56 PsA women, age-matched with 56 normal women, had a significantly higher SCORE, even after controlling for covariates.

Conclusions: Cardiovascular risk of PsA patients estimated on SCORE charts correlates with meta- bolic clinical and laboratory features and is associated with classical cardiovascular risk factors. The axial involvement in PsA is associated with a higher cardiovascular risk when compared to non-axial PsA. Women with PsA have a higher cardiovascular risk than normal women, which sustains the opin- ion that PsA may be considered an independent cardiovascular risk factor.

Keywords: psoriatic arthritis, cardiovascular risk, SCORE

INTRODUCTION

P soriatic arthritis (PsA) is an auto-im- mune chronic inflammatory disease associated with psoriasis and the lack of rheumatoid factor in most patients (1). It has been classified as

a spondylarthritis (2), since it shares some clini- cal elements with this nosological group, name-

ly sacroiliitis, dactylitis, enthesitis and uveitis. Compared with the general population, PsA patients have higher morbidity and mortality rates (3,4) and a higher cardiovascular risk (5). In fact, more than a third of PsA patients’ deaths are caused by cardiovascular factors (3,6,7). This excess in cardiovascular mortality can be explained by the association of PsA with ath- erosclerosis (8), as a recent meta-analysis also

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demonstrates (9). Thus, compared to normal individuals, PsA patients have a higher preva- lence of ischemic heart disease (IHD),(3) arte- rial hypertension (AHT) (3,10), angina and myo cardial infarction (11), heart failure and vas cular disease (9), obesity and metabolic syn- drome (12), type II diabetes mellitus (DM) and hyperglycemia (8,13,14), dyslipidemia (3,8) and inflammation (8). It has been established that PsA is equivalent to rheumatoid arthritis and DM regarding its cardiovascular risk (15,16). There are several tools used to esti- mate long term cardiovascular risk, such as SCORE charts (Systematic Coronary Risk Evalu- ation), published by the European Society of Cardiology (17). Good clinical practice requires an approximation of PsA cardiovascular risk since this disease can be considered an inde- pendent cardiovascular risk factor (7), which indicates an early detection and therapeutic management of these patients (18,19). There is insufficient and contradictory data regarding the decrease of cardiovascular risk of PsA pa- tients using disease modifying anti-rheumatic drugs (DMARDs) (9). For example, some au- thors observed that methotrexate does not de- crease the risk of hospitalization for IHD (20) and others showed that TNF blockers are not cardio-protective in PsA patients (21). In this context, the present study aims to estimate long term cardiovascular risk in PsA patients and to identify clinical and/or laboratory fea- tures which influence this risk. 

MATERIALS AND METHODS

The population sample was studied in a cross-sectional design and it comprised two groups of in-patients, randomly admitted to the hospital from 2012 to 2013. The first group in- cluded 103 patients known with PsA, who ful- filled the disease classification criteria (CASPAR 2006) (22). The second group included 56 nor- mal female patients, matched with an equal number of PsA women by age, ethnicity and geographical area. Each participant in the study gave informed consent, and the study was ap- proved by the local ethics committee.

AHT was defined as: systolic blood pres- sure ≥140 mmHg or diastolic blood pressure ≥90 mmHg (mechanical sphygmomanometer; 5 mmHg error) or anti-hypertensive drug the- rapy (23). IHD was defined if the patient had suggestive electrocardiographic modifications

or a history of acute coronary syndromes, an- gina, rhythm or conduction abnormalities, ischemic heart failure (24). Dyslipidemia was defined as triglycerides >150 mg/dL or total cholesterol >200 mg/dL or treatment with statins/fibrates (25). Type II DM was defined if the patient had fasting plasma glucose level (FPG) >126 mg/dL on two occasions or plasma glucose level ≥200 on one occasion or treat- ment with insulin/oral hypoglycemic drugs (26). Obesity was defined by a body mass in- dex (BMI) ≥30 kg/m2 (wall stadiometer, 0.5 cm error; mechanical scale, 100 mg error). Cardio- vascular risk was estimated using high risk SCORE charts, adequate for the Romanian population (17).

Normally distributed data were reported as “mean (standard deviation; interval)”, while non-normally distributed data were reported as “median (interval)”. Differences were evaluat- ed using non-parametric tests: 2 test (with Fisher’s correction were appropriate) for nomi- nal variables; Mann-Whitney U test for scale variables. Spearman correlation coefficients were computed. Since most variables were non-normally distributed, linear regression and parametric covariance analysis could not be done. So, for testing the significance of SCORE differences between normal and PsA patients controlling for confounding variables (age, BMI etc.) the following algorithm was used: SCORE and its covariates were ranked; the ranks of SCORE were linearly regressed on the ranks of covariates, saving un-standardized residuals; a one-way analysis of variance war run on these residuals with the diagnostic grouping variable (normal/PsA) (27). All tests were two-sided, were considered significant if p ≤0.05 and were computed using SPSS Statistics v.17.0.1 for Windows (SPSS Inc., Chicago, S.U.A., 2008). 

OUTCOMES

1. General characteristics. Table 1 summa- rizes the general characteristics of the PsA group. Overweight, hyperglycemia, dyslipid- emia, inflammatory syndrome, peripheral di- sease pattern, smoking and IHD predominated in this group.

2. Cardiovascular risk. The SCORE value correlated significantly with age (a variable in- cluded in SCORE), age of PsA onset, triglycer- ides, FPG and BMI (Table 2). On average, the

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following subgroups had a significantly higher SCORE compared to the respective subgroup: men, smokers, patients with IHD and AHT, pa- tients with axial PsA (Figure 1A) and patients who did not receive glucocorticoids (GCs; see Table 3). Compared to patients without anti- TNF, PsA patients receiving this biologic treat- ment had a significantly higher median disease duration (120 months compared to 48 months, p = 0.001) and a lower mean SCORE-estimat- ed cardiovascular risk (1.35% compared to 2.52%, p = 0.077), which failed to reach statis- tical significance in this group. There were no significant differences between these two sub- groups regarding the frequency of cardiovascu- lar disease (p > 0.05).

3. Comparison of a PsA subgroup with nor- mal individuals. The subgroup of 56 PsA wom- en, age-matched with 56 normal women, had significantly lower rates of AHT and dyslipid- emia, but significantly higher inflammation markers (Table 4). Compared to normal wom- en, PsA had a significantly higher SCORE (Fig. 1B), even after controlling for the covariates recorded by the study (smoking, DM, IHD, AHT, dyslipidemia, cholesterol, triglycerides, FPG, ESR, CRP). 

DISCUSSION

The present study reports a mean SCORE of 2.3% in 103 PsA patients. The main cardio- vascular risk factors observed had the following prevalence in the PsA group: smoking: 23.3%

(24/103); type II DM: 11.6% (12/103); AHT: 42.7% (44/103); IHD: 22.3% (23/103); obesi- ty: 34.9% (36/103); dyslipidemia: 33.9% (35/103). The observed cardiovascular risk fac- tors had a marked tendency to cluster. For e xample, patients with AHT, compared with non-AHT patients, had significantly higher age, BMI, triglycerides, FPG and significantly higher frequencies of obesity, type II DM and dyslipi- demia (p <0.05). The same was true for any of these variables.

FIGURE 1A. Distribution of SCORE values among PsA subgroups with axial disease (n = 46; average 2.9%) and without axial disease (n = 57; average 1.7%; p = 0.022). B. Distribution of SCORE values in the normal female group (n = 56; average 1.79%) compared to 56 PsA female patients (average 3.02%; p = 0.010).

TABLE 1. PsA group’s general characteristics (n = 103). * 32 patients (31.1%) were on statins; 12 patients (11.7%) were on fibrates

PsA – psoriatic arthritis; PAD – peripheral (periph.) and axial disease (dis.); NSAID – non-steroidal anti- inflammatory drugs; GCs - glucocorticoids; DMARD – disease modifying anti-rheumatic drugs; biologics – TNF blockers; DM – diabetes mellitus; AHT – arterial hypertension; IHD – ischemic heart disease; BMI – body mass index; TC – total cholesterol; TG – triglycerides; FPG – fasting plasma glucose; ESR – erythrocyte sedimentation rate; CRP - C-reactive protein; SBP – systolic blood pressure.

variable present absent p variable value

males 44 (42.7%) 59 (57.3%) 0.167 age (years) 52.3 (12.7; 23 - 80) smokers 24 (23.3%) 79 (76.7%) < 0.001 age onset (years) 45.8 (14.1; 17 - 80) periph. dis. 99 (96.1%) 4 (3.90%) < 0.001 dis. duration (mo) 53 (1 - 360) axial dis. 46 (44.7%) 57 (55.3%) 0.324 BMI (kg/m2) 27.9 (5.6; 15.1 - 44.5) PAD 42 (40.8%) 61 (59.2%) 0.076 TC (mg/dL) 198 (102 - 305) NSAID 68 (66.1%) 35 (33.9%) 0.001 TG (mg/dL) 114 (37 - 677) GCs 21 (20.4%) 81 (79.6%) < 0.001 FPG (mg/dL) 106.1 (40.6; 66 - 428) DMARD 78 (75.7%) 25 (24.3%) < 0.001 ESR (mm/1h) 37.2 (2 - 124) biologics 20 (19.4%) 83 (80.6%) < 0.001 CRP (mg/L) 9.43 (0.14 - 139.4) type II DM 12 (11.6%) 92 (89.3%) < 0.001 SBP (mmHg) 130.6 (12; 110 - 150) AHT 44 (42.7%) 59 (57.3%) 0.167 SCORE (%) 1 (0 - 12) IHD 23 (22.3%) 80 (77.7%) < 0.001 obesity 36 (34.9%) 67 (65.1%) 0.003 dyslipidemia* 35 (33.9%) 68 (66.1%) < 0.001 statins 32 (31.1%) 71 (68.9%) < 0.001

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The SEPHAR study data offer an adequate comparison regarding the cardiovascular risk and its factors, since this study was carried out on a representative sample of the normal Ro- manian population. Thus, the average cardio- vascular risk of the SEPHAR sample, estimated using the same high risk SCORE charts, was 3.5% (range: 0-35%) (28), higher than the aver- age of our 103 PsA patients. This difference probably originates from the type of patients included in the two studies: most of the SEP- HAR subjects were not on record for cardiovas- cular risk factors and thus they did not benefit from medical strategies aimed to reduce their risk, while our PsA patients, due to the nature

of their chronic disease, were regularly reevalu- ated by their physicians and were receiving ad- equate medical therapies (blood pressure and lipid lowering drugs, aspirin etc.) and lifestyle modification advice. The prevalence of AHT (42.7%) and smoking (23.3%) in our PsA group did not differ significantly from the respective frequencies in the SEPHAR sample (44.9%; 906/2017; p=0.661; respectively 27%; 545/2017; p=0.407) (28,29). Compared to the data from the PRESENT study (another epi- de miologic study conducted on a representa- tive sample for the normal Romanian popula- tion) (30), our PsA group had significantly lower prevalence of type II DM (11.6% compared to 20%; 159/796; p=0.043) and dyslipidemia (33.9% compared to 47%; 374/796; p=0.013), and a significantly higher prevalence of IHD (22.3% compared to 13%; 104/796; p=0.011), with no significant differences in obesity preva- lence (34.9% compared to 33%; 263/796; p=0.698). The differences regarding the preva- lence of DM and dyslipidemia can be ex- plained by the fact that PRESENT investigators recorded these diagnoses anamnestically, while our study, besides anamnesis (which includes questions regarding drug therapies) was de- signed to objectively measure of FPG and lipid profile.

It is interesting to note that SCORE corre- lated in our PsA group with two elements of the metabolic syndrome (FPG, BMI) (31,32), which indicates a common physiopathological pro- cess responsible for metabolic and cardiovas- cular modifications. The fact that SCORE was significantly higher in men, smokers, patients with AHT and IHD from our sample strength- ens this assertion.

Regarding the differences of SCORE be- tween PsA subgroups, two aspects deserve dis- cussion. The first aspect refers to the unusual behavior of the PsA subgroup which was on GCs at the time of inclusion in the study. The expected therapeutic effect of GCs in PsA is their anti-inflammatory function, but our GCs- treated PsA patients had significantly higher ESR than those not treated with GCs. Some of the most important side effects of GCs are the metabolic modifications (dyslipidemia, obesi- ty), but our GCs-treated PsA patients had a sig- nificantly lower average BMI and dyslipidemia prevalence than those not receiving GCs. Al- though they did not differ from any other point of view, GCs-treated PsA patients had a signifi- cantly lower SCORE than those not receiving

TABLE 2. Spearman correlations of SCORE with continuous variables in the PsA groups (n = 103). PsA – psoriatic arthritis; BMI – body mass index; TC – total cholesterol; TG – triglycerides; FPG – fasting plasma glucose; ESR – erythrocyte sedimentation rate; CRP – C-reactive protein; SBP – systolic blood pressure

SCORE SCORE

variable rho p variable rho p age 0.815 < 0.001 BMI 0.239 0.015 age at onset 0.766 < 0.001 TC 0.118 0.235 disease duration - 0.137 0.168 TG 0.223 0.023 ESR 0.148 0.136 FPG 0.432 < 0.001 CRP 0.163 0.100 SBP 0.141 0.154

TABLE 3. Spearman correlations of SCORE with continuous variables in the PsA groups (n = 103). & SCORE percentages represent the mean of the certain PsA subgroup

PsA – psoriatic arthritis; PAD – peripheral (periph.) and axial disease (dis.); NSAID – non-steroidal anti-inflammatory drugs; GCs – glucocorticoids; DMARD – disease modifying anti-rheumatic drugs; biologics – TNF blockers; DM – diabetes mellitus; AHT – arterial hypertension; IHD – ischemic heart disease.

subgroup p

SC O

R E

v al

u e

males (n = 44): 3.5% females (n = 59) 1.3% < 0.001 with periph. dis. (n = 99):

1.0% without periph. dis. (n =

4): 3.0% 0.146

with axial dis. (n = 46): 2.9%

without axial dis. (n = 57): 1.7%

0.022

with PAD (n = 42): 2.8% without PAD (n = 61):

1.9% 0.080

with NSAID (n = 68): 2.5%

without NSAID (n = 35): 2.2%

0.551

with GCs (n = 21): 1.5% without GCs (n = 81):

2.5% 0.041

with DMARD (n = 78): 2.2%

without DMARD (n = 25): 2.6%

0.551

with biologics (n = 20): 1.4%

without biologics (n = 83): 2.5%

0.065

smokers (n = 24): 3.7% nonsmokers (n = 79): 1.9% 0.021

with AHT (n = 44): 3.6% without AHT (n = 59):

1.4% < 0.001

with IHD (n = 23): 3.7% without IHT (n = 80):

1.8% < 0.001

with DM (n = 11): 4.0% without DM (n = 92): 2.1% 0.064 obese (n = 36): 2.5% non-obese (n = 67): 2.2% 0.416

with dyslipidemia (n = 35): 2.6%

without dyslipidemia (n = 68): 2.1%

0.154

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GCs. These observations point out either a cardio-protective role of GCs either the prefer- ence of rheumatologist to prescribe GC to pa- tients with a better cardiovascular risk factor profile and active disease. Testing these hy- potheses requires a prospective study design, which must record the duration and dose of GCs therapy. The fact that anti-TNF treated patients had a significantly longer disease dura- tion reflects the algorithm by which patients end up receiving biologic drugs, in the sense that their disease activity has to be insufficiently controlled by DMARD therapy first. In spite of this difference, knowing that a longer disease duration is associated with a more adverse car- diovascular profile, our PsA treated with bio- logics tended to have a lower SCORE, which is in accordance with the general view on cardio- vascular risk reduction potential of biologics.

The second aspect refers to the cardiovas- cular risk of PsA with axial involvement, which was significantly higher in our group compared with non-axial disease. There are many studies which demonstrate on one hand that PsA pa- tients have a higher cardiovascular risk than the general population and on the other hand that spondylarthritis is associated with such an ele- vated risk (33,34), but to our knowledge, no other author reported a higher cardiovascular risk in PsA with axial involvement.

The limits of the study include: its cross- sectional design, which did not allow following the patients and recording their cardiovascular events/diagnoses; the relatively small sample size, which did not produce normally distrib- uted variables; the lack of normal age-matched male subjects (cardiovascular risk profiles in men and women evolve quite differently so, even in the availability of a normal male group, the statistical analysis would have been more appropriately done for each sex subgroup in- dependently); the absence of such variables as cholesterol fractions (HDL, LDL) and abdomi- nal circumference, which would have allowed the diagnosis of the metabolic syndrome. 

CONCLUSIONS

Cardiovascular risk of PsA patients estimated on SCORE charts correlates with metabolic clinical and laboratory features (BMI, triglycer- ides, FPG) and is associated with classical car- diovascular risk factors (male gender, smoking, IHD, AHT). These cardiovascular risk factors have a strong tendency to aggregate in the same patient. The axial involvement in PsA is associated with a higher cardiovascular risk when compared to non-axial PsA. Women with PsA have a higher cardiovascular risk than normal women, which sustains the opinion that PsA may be considered an independent cardiovascular risk factor. The cardiovascular risk of PsA patients receiving classical DMARDs was similar with that of PsA patients without this treatment, but it was significantly lower in PsA patients on GCs when compared to those without GCs. Prospective studies are needed to asses the true value of disease modifying thera- py in PsA regarding cardiovascular risk reduc- tion.

Conflicts of interests: none declared. Financial support: none declared. Acknowledgments: The authors would like

to thank the rheumatologists of “Sfanta Maria” Clinical Hospital of Bucharest for providing pa- tients.

TABLE 4. The comparison between a subgroup of PsA women and an age-matched normal women group. * SCORE difference remains significant after controlling with any of the listed variables

PsA – psoriatic arthritis; DM – diabetes mellitus; AHT – arterial hypertension; IHD – ischemic heart disease; BMI – body mass index; TC – total cholesterol; TG – triglycerides; FPG – fasting plasma glucose; ESR – erythrocyte sedimentation rate; CRP – C-reactive protein

variable PsA (n = 56) normal (n = 56) p female 56 (100%) 56 (100%) 0.000 smokers 17 (30.3%) 13 (23.2%) 0.393 type II DM 9 (16.1%) 10 (17.8%) 0.801 AHT 27 (48.2%) 39 (69.6%) 0.021 IHD 17 (30.6%) 17 (30.6%) 1,000 dyslipidemia 21 (37.05%) 34 (60.7%) 0.014 obesity 22 (39.3%) 17 (30.6%) 0.321 age (years) 56.89 (9.41) 56.95 (9.27) 0.968 BMI (kg/m2) 28.9 (5.9) 29.7 (5.2) 0.383 TC (mg/dL) 207 (125-302) 211 (132-333) 0.481 TG (mg/dL) 125.5 (54-667) 110 (43-843) 0.076 FPG (mg/dL) 99 (79-428) 104 (80-210) 0.238 ESR (mm/dL) 32.5 (2-112) 21 (5-133) 0.013 CRP (mg/L) 9.78 (1.3-139) 4 (0.1-155) < 0.001

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