Archives of Dermatological Research

, 300:435

Increased frequency of pulmonary hypertension in psoriasis patients

Authors

    • Faculty of Medicine, Cardiology DepartmentYuzuncu Yil University
  • Mustafa Tuncer
    • Faculty of Medicine, Cardiology DepartmentYuzuncu Yil University
  • Omer Calka
    • Faculty of Medicine, Department of DermatologyYuzuncu Yil University
  • Unal Guntekin
    • Faculty of Medicine, Cardiology DepartmentYuzuncu Yil University
  • Necmettin Akdeniz
    • Faculty of Medicine, Cardiology DepartmentYuzuncu Yil University
  • Hakki Simsek
    • Faculty of Medicine, Cardiology DepartmentYuzuncu Yil University
  • Ilknur Yorgun Ozdemir
    • Faculty of Medicine, Cardiology DepartmentYuzuncu Yil University
Original Paper

DOI: 10.1007/s00403-008-0859-9

Cite this article as:
Gunes, Y., Tuncer, M., Calka, O. et al. Arch Dermatol Res (2008) 300: 435. doi:10.1007/s00403-008-0859-9

Abstract

Several reports have demonstrated an association between psoriasis and cardiovascular diseases such as hypertension, valvular disease and arrhythmia. However, the data is scarce. Forty-seven psoriasis patients and 20 healthy people underwent transthoracic echocardiographic examination including pulse- and tissue Doppler analysis and 24-h ambulatory electrocardiographic monitoring including heart rate variability (HRV) analysis. Patients having systemic hypertension, diabetes mellitus, history of structural or ischemic heart disease, chronic obstructive pulmonary disease and any associated systemic disease were excluded. Psoriasis Area and Severity Index (PASI) was calculated and severe psoriasis was defined in the case of history of hospitalizations for psoriasis and/or getting systemic therapy. Mean age of the patients was 35.7 ± 12.9 years and disease duration was 123.2 ± 84.3 (3–360) months. PASI ranged from 0.4 to 34.0 (mean ± SD: 7.1 ± 6.6) and 20 (42.6%) patients had severe psoriasis. There were no significant differences between psoriasis patients and control group with respect to mean values of blood pressure, body mass index, lipid profile and cardiac dimensions. However, frequency of being overweight was significantly higher in psoriasis patients (42.6 vs. 10.0%, P = 0.011). No patient had valvular disease. Mild pulmonary hypertension (PH) (30–40 mmHg) was significantly more frequent in psoriasis patients (31.9 vs. 0%, P = 0.003). Pulse wave mitral Doppler deceleration and isovolumetric relaxation times were significantly longer in psoriasis patients (195.9 ± 29.7 vs. 191.6 ± 14.7 ms, P = 0.002 and 91.6 ± 14.7 vs. 79.6 ± 10.5 ms, P = 0.001, respectively). However, frequency of diastolic dysfunction was not significantly different than the control group (8.5 vs. 0%, P = 0.309). HRV parameters and frequency of supraventricular and ventricular premature beats were not significantly different between the groups. No patient had ventricular tachycardia. Echocardiographic follow-up of psoriasis patients may be important due to possible association of PH. However, incidences of structural heart disease and arrythmia are not increased in psoriasis according to our results.

Keywords

PsoriasisPulmonary hypertensionDiastolic dysfunctionArrhythmia

Introduction

Psoriasis is a common inflammatory skin disorder clinically characterized by sharply demarcated chronic erythematous plaques covered by silvery-white scales, preferentially at the elbows, knees, scalp, umbilicus and lumbar area. Psoriasis is a chronic disease affecting 2–4% of the population [27]. Several reports have demonstrated an association between psoriasis and diabetes mellitus and cardiovascular diseases, including hypertension, myocardial infarction, heart failure, arrhythmia and valvular disease [1, 3, 9, 19, 21, 22, 26, 28].

The aim of this study was to evaluate structural heart disease, left ventricular systolic and diastolic functions, pulmonary pressure, arrhythmia and heart rate variability (HRV) in patients with psoriasis.

Methods

Fifty-seven consecutive outpatient psoriasis patients were evaluated. Diagnosis of psoriasis was confirmed by dermatologic examination and/or punch biopsy. Forty-seven psoriasis patients and 20 healthy people were examined by transthoracic echocardiography and 24-h ambulatory electrocardiographic monitoring.

Severity of the psoriasis was evaluated by Psoriasis Area and Severity Index (PASI) [7]. In addition, severe psoriasis was defined in the case of history of hospitalizations for psoriasis and/or getting systemic therapy including immunsupression, oral retinoids or psoralen plus ultraviolet A (PUVA).

Exclusion criteria were systemic hypertension, diabetes mellitus, history of structural or ischemic heart disease, chronic obstructive pulmonary disease and any associated systemic disease. Ten psoriasis patients: one having prosthetic mitral valve, seven having hypertension, one having diabetes and one having coronary artery disease were excluded from the study.

The study was approved by the Yuzuncu Yil University, Faculty of Medicine Ethics Committee in accordance with the Declaration of Helsinki. All participants were informed about the study and their consents were obtained.

Echocardiographic examination

The echocardiographic examination was performed at rest, with the patient at left lateral decubitis position, using a commercially available echocardiographic device (Vivid 3, General Electric) with a 3 MHz transducer, by two experienced echocardiographers who were blinded to the clinical data. Using M-mode echocardiography, long-axis measurements were obtained at the level distal to the mitral valve leaflets according to the current recommendations of the American Society of Echocardiography [14]. The pulsed Doppler sampling volume was placed between the tips of the mitral valve leaflets to obtain maximum filling velocities. Early diastolic flow (E), atrial contraction signal (A), E/A ratio and E deceleration time (DT) were measured. Isovolumetric relaxation time (IVRT) was determined as the interval between the end of the aortic outflow and the start of the mitral inflow signal. Pulmonary artery systolic pressure (PASP) was calculated from tricuspid insufficiency flow in the parasternal short axis and apical four-chamber view, and the highest tricuspid regurgitation velocity was taken as the study sample. Pulmonary hypertension (PH) was accepted as estimated PASP above 30 mmHg.

Tissue Doppler imaging (TDI) was acquired to assess diastolic function. The pulsed wave spectral mode was used for TDI. Filters and baselines were corrected when the velocity ranged between −20 and 20 cm/s. From the apical four-chamber view, a 5-mm sample volume was placed at the lateral corner of the mitral annulus. Early (Em) and late (Am) diastolic velocities were obtained. All values were measured on three separate beats and then averaged for all parameters.

Impaired left ventricular relaxation was defined as having an E/A ratio of <1 (<0.5 for >50 years), DT > 200 ms and IVRT > 100 ms (>105 ms for >50 years), all together and/or E/Em ratio of >10 and Ea < 10 cm/s in the presence of a preserved ejection fraction [23].

Heart rate variability analysis

Twenty-four-hour ambulatory electrocardiogram holter monitoring was performed using Aria digital holter recorder (Spacelabs healthcare). The recordings were analyzed with special computer software (Impresario Solo package). All recordings were visually examined and manually over read to verify beat classification by two experienced analyzers who were blinded to the clinical data. Only recordings with at least 20 h of data and 80% or more of quantified sinus beats were included in the analysis. Abnormal beats and areas of artifact were automatically and manually identified and excluded from the analysis. Also, the longest and shortest true normal-to-normal intervals were identified for each recording in order to exclude all beats outside this range from the HRV analysis. The following parameters were used in evaluation of HRV in time domain: (1) standard deviation (SD) of all normal-to-normal intervals [SDNN (milliseconds)]; (2) SD of mean of all normal-to-normal intervals in all consecutive 5-min segments of the entire recording [SDANN (milliseconds)]; (3) the root mean square of differences between adjacent normal-to-normal intervals [rMSSD (milliseconds)]; (4) percentage of R–R intervals with more than 50 ms variation (pNN50).

Statistics

Results are expressed as the mean ± SD. Using an SPSS package 10.0, data between the groups were compared with the Student’s t test for continuous variables and Chi-square test for qualitative variables and with Mann–Whitney’s U test for variables without normal distribution. Pearson correlation analysis was used to assess the correlation between variables. Multivariate linear regression analysis was used to analyze value of different variables as independent predictors of PH. A two-tailed P value <0.05 was considered significant.

Results

Mean disease duration was 123.2 ± 84.3 (range 3–360) months. PASI ranged from 0.4 to 34.0 (mean ± SD: 7.1 ± 6.6) (Table 1). There were no significant differences between psoriasis patients and control group in respect to blood pressure, body mass index (BMI), lipid profile and cardiac dimensions (Table 2). However, frequency of being overweight was significantly higher in psoriasis patients (42.6 vs. 10.0%, P = 0.011). Three patients had mild left ventricular hypertrophy (wall thickness of 12 mm). No patient had valvular pathology and all the regurgitations were slight being within physiological limits. Estimated PASP and frequency of PH was significantly higher among psoriasis patients. PH was mild in all patients (PASP = 30–40 mmHg). Presence of PH was significantly correlated with BMI (r = 0.256, P = 0.037) but not with age, smoking, disease duration and PASI. Regression analysis including age, gender, smoking, disease duration, severity of disease, PASI, BMI, treatment modalities, LVEF, DT and IVRT revealed that none of the parameters were significant independent predictors of PH. Mitral E/A ratio was <1 in 10 patients. Decelaration time and IVRT measures were significantly higher among psoriasis patients. After evaluation of all diastolic function parameters, diastolic dysfunction was defined in 4 (8.5%) psoriasis patients. Presence of diastolic dysfunction was correlated with age (r = 0.355, P = 0.003) but not with PASI and disease duration. HRV parameters and frequency of supraventricular premature beats (SVPB) and ventricular premature beats were not significantly different between groups (Table 3). One psoriasis patient had 740 SVPBs (670 single, 35 couplets) and two patients had four short supraventricular tachycardia attacks with the longest run being 7 beats. No patient had ventricular tachycardia.
Table 1

Characteristics of psoriasis patients

 

Psoriasis (n = 47)

Plaque type

41 (87.2%)

Pustular type

3 (6.4%)

Palmoplantar type

3 (6.4%)

PASI

7.1 ± 6.6

Severe psoriasis

18 (38.3%)

Family history of psoriasis

14 (29.8%)

Biopsy

41 (87.2%)

Steroid

39 (82.3%)

Retinoids

6 (12.7%)

Psoralen plus ultraviolet A

10 (21.3%)

Immunsupressive agent

14 (29.8%)

Etanercept

3 (6.3%)

Table 2

Comparison of age, gender, blood pressures and echocardiographic variables between psoriasis patients and healthy people

 

Psoriasis (n = 47)

Control (n = 20)

P value

Age (years)

35.7 ± 12.9

37.1 ± 10.4

0.675

Sex (male)

22 (46.8%)

13 (65.0%)

0.194

Smoking

12 (25.5%)

6 (30%)

0.767

BMI (kg/m2)

25.6 ± 5.9

23.1 ± 3.1

0.117

Overweight (BMI > 25 kg/m2)

20 (42.6%)

2 (10.0%)

0.011

Systolic BP (mmHg)

121.3 ± 12.9

121.0 ± 11.9

0.935

Diastolic BP (mmHg)

78.8 ± 9.1

76.5 ± 6.7

0.309

Total cholesterol (mg/dl)

167.7 ± 47.4

174.9 ± 38.1

0.549

LDL-cholesterol (mg/dl)

97.0 ± 35.5

103.7 ± 31.5

0.468

HDL-cholesterol (mg/dl)

45.8 ± 13.3

43.8 ± 10.1

0.543

Triglyceride (mg/dl)

152.6 ± 83.7

154.6 ± 85.5

0.928

LVDD (mm)

45.3 ± 3.4

46.6 ± 3.2

0.391

LVDS (mm)

30.3 ± 2.9

30.8 ± 3.9

0.613

LVEF (%)

61.8 ± 3.4

63.3 ± 2.3

0.081

IVS (mm)

78.8 ± 9.1

76.5 ± 6.7

0.196

PW (mm)

9.0 ± 1.2

9.1 ± 0.1

0.807

LA (mm)

33.2 ± 4.2

32.2 ± 2.7

0.330

Mitral regurgitation

6 (12.7%)

4 (20%)

0.470

Aortic regurgitation

2 (4.2%)

0

1.0

Tricuspid regurgitation

15 (31.9)

7 (35%)

1.0

Pulmonary hypertension

15 (31.9%)

0

0.003

Pulmonary artery pressure (mmHg)

20.7 ± 10.9

10.5 ± 4.0

<0.001

E (cm/s)

84.9 ± 13.1

86.7 ± 11.9

0.616

A (cm/s)

72.7 ± 17.4

67.1 ± 13.5

0.236

E/A

1.22 ± 0.30

1.32 ± 0.23

0.201

Em (cm/s)

15.5 ± 4.2

15.0 ± 2.3

0.636

Am (cm/s)

9.2 ± 2.2

9.2 ± 1.9

0.997

DT (ms)

195.9 ± 29.7

191.6 ± 14.7

0.002

IVRT (ms)

91.6 ± 14.7

79.6 ± 10.5

0.001

Diastolic dysfunction

4 (8.5%)

0 (0%)

0.309

BMI body mass index, LVDD left ventricular diastolic dimension, LVSD left ventricular systolic dimension, LVEF left ventricular ejection fraction, IVS interventricular septum thickness, PW posterior wall thickness, LA left atrium, DT deceleration time, IVRT isovolumetric relaxation time

Table 3

Results of 24-h electrocardiographic monitoring

 

Psoriasis (n = 47)

Control (n = 20)

P value

Heart rate (bpm)

  Mean

82.4 ± 8.5

84.5 ± 7.3

0.332

  Day

87.5 ± 10.6

90.0 ± 7.9

0.328

  Night

74.3 ± 10.1

73.8 ± 14.7

0.601

SDNN (ms)

  Mean

139.2 ± 35.3

143.4 ± 31..6

0.649

  Day

108.0 ± 28.3

112.0 ± 19.6

0.566

  Night

119.8 ± 39.5

137.6 ± 21.9

0.064

rMSSD (ms)

  Mean

44.5 ± 18.1

52.9 ± 35.8

0.207

  Day

40.5 ± 20.4

46.0 ± 31.3

0.395

  Night

50.8 ± 21.3

62.6 ± 42.7

0.134

PNN50 (%)

  Mean

11.5 ± 8.6

13.6 ± 12.0

0.773

  Day

8.5 ± 7.6

10.6 ± 10.4

0.362

  Night

18.3 ± 14.7

20.3 ± 17.8

0.631

SDANN

  Mean

131.7 ± 37.5

133.6 ± 41.6

0.860

  Day

96.1 ± 30.8

92.4 ± 32.0

0.658

  Night

96.5 ± 39.5

94.7 ± 44.3

0.867

 SVPB

23.6 ± 107.8

4.3 ± 5.6

0.686

 VPB

5.2 ± 20.8

0.35±1.3

0.145

SDNN standard deviation of all normal-to-normal intervals, rMSSD root mean square of differences between adjacent normal-to-normal intervals, PNN50 percentage of R–R intervals with more than 50 ms variation, SDANN standard deviation of mean of all normal-to-normal intervals, SVPB supraventricular premature beats, VPB ventricular premature beats

Discussion

Although atherosclerosis, heart valve abnormalities and arrhythmias have been reported in the course of psoriasis [1, 3, 9, 16, 19, 21, 22, 26, 28] specific cardiac involvement has not been reported and the data is limited. In the present study, we found that except for increased frequency of mild PH echocardiographic findings and 24-holter examinations of psoriasis patients were comparable to those of healthy subjects.

Inflammation is well known for its prevailing role in the initiation and progression of atherosclerosis [15]. The risk of atherosclerosis in psoriasis has been linked to low-grade inflammation, as evidenced by increased levels of acute-phase reactants and proinflammatory cytokines [4, 13, 16]. It has been proposed that inflammatory mechanisms could play a part in the genesis or progression of PH [6, 12]. PH is an increasingly recognized complication of rheumatic diseases, including rheumatoid arthritis and an inflammatory/autoimmune pathogenesis has been suggested [5, 18]. Similar mechanisms may be responsible for our finding of increased frequency of PH in psoriatic patients. Systemic nature of the inflammatory processes underlying the pathogenesis of psoriasis may potentially result in systemic involvement. Increased antigen presentation, increased cutaneous T lymphocyte activity, interleukins and tumor necrosis factor-α in the pathophysiology of psoriasis also cause endothelial dysfunction, an important mechanism in pathophysiology of PH [4, 10, 13, 27, 30]. Increased procoagulant activity and platelet activation in psoriasis are also potential mechanism for PH [17, 20]. We found a weak but significant correlation between PH and BMI. Elevated BMI may be a risk factor for both the development of psoriasis and PH [24, 25]. Several cytokines that have been identified as important mediators of psoriasis, such as interleukins-1, 4, 6, 8, 12 and tumor necrosis factor-α, have also been identified in metabolic syndrome, a chronic inflammatory state associated with obesity [27, 29]. Because PH may have an insidious onset and slow progression early recognition of symptoms of PH may be difficult and serial echocardiographic examination may be useful.

Biyik et al. [1] investigated 216 patients with psoriasis with echocardiography. Left ventricular hypertrophy, left ventricular diastolic dysfunction, left ventricular wall motion abnormalities and valvular pathologies, especially mitral and tricuspid valve prolapse, were significantly more frequent in patients with psoriasis than controls. Systolic and diastolic blood pressures were significantly higher in psoriasis patients. Significant correlations were found between disease duration and left ventricular diastolic dysfunction and systolic and diastolic blood pressures [1]. Consistent with our results, a recent study involving 50 patients with psoriatic arthritis and no cardiovascular disease risk factors or clinical disease found prevalences of valvular regurgitation, normal pulmonary artery pressures and abnormal diastolic relaxation comparable to those in 50 matched control subjects [11]. Mean PASP was 22.8 ± 3.4 mmHg in that study. However, frequency of patients having PASP > 30 mmHg was not given. Although mean PASP for psoriatic patients was 20.7 ± 10.9 mmHg in our study 31.9% of the patients had PASP above 30 mmHg.

There are scarce data in the literature on arrhythmia incidence in psoriatic patients. In the group of 22 patients with psoriatic arthritis, Carvalho et al. [2] reported a higher incidence of premature atrial beats. Markuszeski et al. [19] found higher heart rates both during the day and at night (P < 0.0001) and more frequent supraventricular beats (P < 0.0001) in 32 patients with psoriasis than in the control group. There was no correlation between psoriasis duration and arrhythmia incidence. However, a positive correlation between the increased heat rate and severity of the disease expressed as PASI was noted. They did not observe any statistically significant differences in the time domain HRV (SDNN and rMSSD). In our study, we did not find a significant difference between psoriasis patients and healthy people in respect to heart rate both during day and night and arrhythmia incidence was not significantly increased. Also we did not find a significant correlation between heart rate and PASI and disease duration. This difference may be due to relatively lower mean PASI level in our study compared to the study of Markuszeski et al. [19] (7.1 ± 6.6 vs. 13.4 ± 8.8).

Limitations

Small number of study patients is the major limitation. Despite differences between cases and controls for some variables many associations were found not significant and some differences may be, appeared significant, just by chance. Therefore, larger studies are needed to support our results. We did not have psoriatic patients having arthropathy in whom inflammation may be more severe.

Conclusions

Pulmonary artery pressure should be more carefully evaluated in psoriasis patients due to increased incidence of mild pulmonary hypertension. We did not find an increased frequency of structural heart disease and arrhythmia in psoriasis.

Copyright information

© Springer-Verlag Berlin Heidelberg 2008