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ORIGINAL ARTICLE
Year : 2022  |  Volume : 67  |  Issue : 4  |  Page : 328-333
A cross-sectional study to assess sub-clinical atherosclerosis in patients of psoriasis independent of metabolic syndrome


From the Department of Dermatology, Venerology and Leprosy, Dr. D. Y. Patil Medical College and Hospital and Research Centre, Pune, Maharashtra, India

Date of Web Publication2-Nov-2022

Correspondence Address:
Shreya Deoghare
Department of Dermatology, Venerology and Leprosy, Dr. D. Y. Patil Medical College and Hospital and Research Centre, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.ijd_1050_21

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   Abstract 


Background: A sustained inflammatory state of psoriasis causes comorbidities such as psoriatic arthritis, metabolic syndrome (MetS), and cardiovascular disease. Aims: To note the duration and severity of psoriasis, assess prevalence of MetS, and correlate these with indicators of sub-clinical atherosclerosis. Methodology: Thirty-two patients of chronic plaque psoriasis were enrolled in the study. Their demographic particulars, clinical details, results of investigations to assess MetS, and indicators of sub-clinical atherosclerosis, namely, carotid intimal media thickness (CIMT) measured using B-mode USG and epicardial fat thickness (EFT) using 2-D ECHO, were recorded. Results: The study participants were predominantly male (2.5:1); their mean age was 40.45 ± 12.42 years, the median disease duration (DD) was 2 years, and the mean psoriatic area severity index (PASI) score was 8.62 ± 7.49. Mild disease (PASI <5) was present in 12 participants (37.5%), and shorter DD (<5 years) was present in 16 (50%) participants. MetS, detected in 11 (37.5%) study participants, was not significantly associated with CIMT, EFT, DD, and PASI. CIMT and EFT too did not correlate significantly with DD, PASI, or measures of MetS. Neither did there exist any significant correlation between CIMT and EFT. Conclusion: Sub-clinical atherosclerosis in our study participants was not significantly associated with either measures of MetS or duration/severity of psoriasis.


Keywords: Chronic plaque psoriasis, metabolic syndrome, sub-clinical atherosclerosis


How to cite this article:
Deoghare S, Talanikar H, Deora MS, Kothari R, Sharma YK, Dalve K, Kapoor A, Patil A. A cross-sectional study to assess sub-clinical atherosclerosis in patients of psoriasis independent of metabolic syndrome. Indian J Dermatol 2022;67:328-33

How to cite this URL:
Deoghare S, Talanikar H, Deora MS, Kothari R, Sharma YK, Dalve K, Kapoor A, Patil A. A cross-sectional study to assess sub-clinical atherosclerosis in patients of psoriasis independent of metabolic syndrome. Indian J Dermatol [serial online] 2022 [cited 2022 Dec 4];67:328-33. Available from: https://www.e-ijd.org/text.asp?2022/67/4/328/360293





   Introduction Top


Psoriasis, a relapsing immunologically mediated inflammatory dermatosis, affects 2–3% of the population globally.[1] Sustained dysregulation of innate and adaptive immune responses, continuously simmering in genetically predisposed individuals, peaks on encountering factors such as stress, trauma, and infections, leading not only to this multifactorial disease but also to an array of comorbidities – metabolic, cardiovascular, arthritic, and psychological.[1],[2]

Components of metabolic syndrome (MetS) – abdominal obesity, insulin resistance, hypertension, and dyslipidaemia – may eventuate by progressive sub-endothelial accumulation of lipids in the arterioles into atherosclerosis, thereby increasing the risk of cardiovascular disease (CVD).[3],[4] Although significant association between psoriasis, MetS, and CVD[2] is well known, extension of this association to sub-clinical atherosclerosis remains ambiguous. The presence of such an association could provide insight not only into the role of psoriasis in the development of CVD but also subsequently guiding discussion about early management of this potential co-morbidity.[4]

With studies from India determining the association of sub-clinical atherosclerosis irrespective of MetS, duration, and severity of psoriasis being scarce, we were motivated to undertake this study.

The objectives of the study were to note the duration and severity of psoriasis, assess prevalence of MetS, and determine correlation thereof with indicators of sub-clinical atherosclerosis.


   Methodology Top


This cross-sectional observational study was conducted over a period of 2 years in our tertiary care hospital in western India after obtaining clearance of the institutional ethics committee.

Patients, ≥18 years of age, diagnosed to have chronic plaque psoriasis as per Delphi consensus of international experts' clinical examination-based diagnostic criteria[5] were enrolled in the study. Those with present or past history of psoriatic arthritis, chronic inflammatory or auto-immune disease(s), cardiovascular disease, or an abnormal electrocardiogram were excluded. After briefing about the purpose of the study, informed written consent was obtained from those willing to participate.

Waist circumference was taken at the mid-point of xiphisternum and pubic symphysis with a measuring tape. Blood pressure was measured with a sphygmomanometer at the right brachial artery in the supine position. Ten millilitre of venous blood was collected from the cubital vein for estimating fasting blood sugar (BSL-F) and the fasting lipid profile (FLP).

International Diabetes Federation (IDF) 2006 criteria (for Asian ethnicity)[3] were used to diagnose MetS, namely, waist circumference, ≥90 cm (males) and ≥80 cm (females), plus two or more of the following parameters; fasting blood sugar (BSL-F), ≥100 mg/dl; high-density cholesterol-C (HDL-C), <40 mg/dl (males) and <50 mg/dl (females); fasting triglyceride (F-TG), ≥150 mg/dl; and systolic blood pressure (SBP), ≥130 mm Hg or diastolic blood pressure (DBP), ≥85 mm Hg.

Carotid intimal media thickness (CIMT) was measured manually by recording the images [Figure 1] of right and left common carotid arteries using high-resolution B-mode ultrasound with a 7.5 MHz linear array transducer. After identifying a region one cm proximal to the carotid bifurcation, the distance between the luminal border of the intima and the outer border of the media wall represented by a double-line pattern[6] on still images was obtained ultrasonographically. The maximum values of the right common carotid artery (CIMT-r) and left common carotid artery (CIMT-l) were recorded, and their averages were calculated. The cut-off of CIMT was taken to be ≥1 mm.[6]
Figure 1: Measurement of CIMT using B-mode USG (A: Adventitia, CIMT: Carotid intimal media thickness, I: Intima, M: Media)

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A cardiologist assessed epicardial fat thickness (EFT) through transthoracic 2-D ECHO in the left lateral position using a parasternal long-axis view of the free wall of the right ventricle measured perpendicular to the thickness of this echo-free space in the pericardial layers at the end-systolic phase of the cardiac cycle[6] [Figure 2]. In order to prevent bias, the radiologists and cardiologists – although aware of the patients' disease – were kept oblivious of their clinical and laboratory data. There was no absolute cut-off value for EFT; higher its value, greater the chance of sub-clinical atherosclerosis.[6]
Figure 2: Measurement of EFT using 2-D ECHO (EFT: Epicardial fat thickness, LA: Left atrium, LV: Left ventricle, RA: Right atrium, RV: Right ventricle)

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The normality of data was assessed using Kolmogorov–Smirnov test. Categorical data were assessed using percentages; uniformly distributed quantitative data were assessed using mean and standard deviation, and non-uniformly distributed quantitative data were assessed using median and interquartile range. Student's t-test and the Mann-Whitney U-test were used to compare continuous variables and Pearson's or Spearman's correlation analyses for correlation.


   Results Top


The mean values of demographic characteristics, clinical and laboratory measures of MetS, disease duration (DD)/severity, and indicators of sub-clinical atherosclerosis of the study participants are shown in [Table 1].
Table 1: Demographic characteristics, measures of MetS, duration, and severity of psoriasis and indicators of sub-clinical atherosclerosis

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DD ranged from 1 to 5 years in 16 (50%); less than 1 year, in seven (21.87%); 5 to 10 years, in six (18.75%); and over 10 years, in three (9.37%) participants. In 12 (37.5%), the PASI score was <5 (mild disease), and in 10 (31.25%) participants each, ≥5 to <10 (moderate disease) and ≥10 (severe disease).

As regards de-ranged components of MetS, central obesity prevailed in 14 (43.75%), 10 males and 4 females; abnormal BSL-F, 11 (32.35%); abnormal FTG, nine (28.12%); low HDL-C, 11 (32.35%), eight males and three females; raised SBP, nine (28.12%); and raised DBP, seven (21.87%) participants. MetS was present in 12 (37.50%), eight (66.67%) males and four (33.33%) females. Of those without MetS, 15 (75%) were males and five (25%), females.

There was no statistically significant difference in the mean value of PASI score (11.13 ± 9.42 vs 7.64 ± 6.58; P value = 0.2947); indictors of sub-clinical atherosclerosis (CIMT, 0.68 ± 0.22 vs 0.75 ± 0.19; P value = 0.3241 and EFT, 7.70 ± 2.48 vs 7.22 ± 2.54; P value = 0.6282); and the mean value of measures of MetS in our study participants with DD either <5 years or ≥5 years.

None of the mean values of DD, CIMT (0.68 ± 0.21 vs 0.74 ± 0.21; P value = 0.5967), EFT (7.73 ± 2.68 vs 7.20 ± 1.99; P value = 0.5828), and measures of MetS showed any significance in our study participants with mild to moderate (PASI, <10) or severe (PASI, ≥10) disease.

Only three (9.37%) study participants, two males and one female, had sub-clinical atherosclerosis (CIMT ≥1 mm). There emerged no significant association of MetS with duration or severity of psoriasis and indicators of sub-clinical atherosclerosis [Table 2]. CIMT and EFT showed negligible to weak correlation with demographic characteristics, measures of MetS, DD, and severity of psoriasis [Table 3].
Table 2: Comparison of duration and severity of psoriasis and indicators of sub-clinical atherosclerosis in participants with and without MetS

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Table 3: Relationship of CIMT and EFT with demographic characteristics, measures of MetS, duration, and severity of psoriasis

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   Discussion Top


The average age at the time of study and the gender ratio of our study participants largely conformed to the usual age and sex ratio in many previous studies. However, the DD and severity of various studies might not be strictly comparable, dependent as it is on the patients' presentation to the out-patient department as also the varying inclusion and exclusion criteria of different studies.

A large number of earlier studies[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28] reported higher prevalence of MetS ranging from 30% to 60% and increased sub-clinical atherosclerosis in psoriatic patients compared to age- and sex-matched controls. However, the assessment of sub-clinical atherosclerosis has been done in a few studies in patients of psoriasis with and without MetS.[7],[8]

MetS was present in 37.5% of our study participants. Even though measures of MetS and radiological parameters were higher in those with longer DD and a severe PASI grade, none of the same was statistically significant. The mean PASI score was higher in those with longer DD (p value = 0.2947), and the mean DD was longer in the severe PASI grade (p value = 0.3917). The mean values of DD, PASI, CIMT, and EFT – although higher in study participants with MetS – were not statistically significant (p value = 0.05321, 0.0980, 0.1228, and 0.3624, respectively). Both CIMT and EFT showed a weak correlation with age, DD, disease severity, and measures of MetS. There was a weak correlation between CIMT and EFT (r = –0.0215, P = 0.9068).

In our study participants, central obesity prevailed in 43.75%; raised BSL-F, 32.35%; raised HDL–C, 32.3 5%; raised FTG, 28.12%; raised SBP, 28.12%; and raised DBP, 21.87%. A study conducted by Gangaiah et al.[9] also reported a high prevalence of raised BSL-F (32%), hypertriglyceridemia (34%), low HDL-C (50%), and hypertension (38%).

A large number of studies have demonstrated an increased prevalence of MetS in patients of psoriasis compared to matched controls.[9],[10],[11] The prevalence of our study, 12 (37.5%), falls well within the reported range (30% to 45%) in many previous studies.[8],[9],[11],[12],[13],[14],[15] However, lower (7% to 17%)[16],[17] as well as higher (58% to 70%)[8],[10],[18] prevalences have also been reported.

Our study participants with MetS had a significantly higher mean waist circumference (p value = 0.0001), BSL-F (p value = 0.0001), FTG (p value = 0.0101), and SBP and DBP (p value = 0.0031 and 0.0123, respectively). Although the mean HDL-C level was also higher in participants with MetS, the same was not significant (p value = 0.7004). Similar findings were reported by Aggarwal et al.[11]; their study participants with MetS had a significantly higher mean FTG (p value = 0.02), LDL cholesterol (p value = 0.004), BSL-F (p value = 0.000), systolic and diastolic BP (p value = 0.000 and 0.000, respectively), and waist circumference (p value = 0.000) but a significantly lower mean HDL-C (p value = 0.002). Obviously, such significant association resulted because of de-ranged parameters of those with MetS compared to those without.

Similar to some other studies[9],[10],[11],[12], our study revealed no significant association of MetS with DD (p value = 0.5321) or PASI (p value = 0.0980). Kothiwala et al.[13] found a linear increase in prevalence of MetS and its components with increased duration and severity of psoriasis. Contrary to our hospital-based study, the population-based study of Langan et al.[19] revealed increasing significant association of psoriasis with MetS with increasing disease severity. The difference could have been because of a large sample size and different inclusion and exclusion criteria of their study.

The association between psoriasis and atherosclerotic disease is ambiguous, whether higher prevalence of cardiovascular risk factors contributes to accelerated atherosclerosis or the systemic inflammation related to relentless release of pro-inflammatory cytokines does so.[6] Whatever be the aetiopathogenesis of atherosclerosis, an absolute CIMT difference of 0.1 mm increases the risk of myocardial infarction by 10–15% and the risk of stroke by 13–18%.[6] In our study, three (9.37%) participants, including two males and one female, had CIMT ≥1 mm, with the mean value of CIMT being 0.70 ± 0.21 mm. Many previous studies[6],[13],[16],[20],[21],[22] reported a similar range (0.61 mm to 0.84 mm) of values; some others, higher[23],[24],[25],[26] (0.9 mm to 1.03 mm) and still others,[18],[27] lower (0.5 mm).

The increased visceral fat deposit in the heart, EFT, is probably increased in psoriatic patients because of chronic immune-mediated systemic inflammation, more pro-inflammatory mediators such as interleukins, MCP-1, and TNF-alpha, possibly inducing mononuclear cell infiltration of vascular intima, an important step in the development of atherosclerosis.[28] A meta-analysis by Wang et al.[28] demonstrated increased EFT as an independent risk factor for psoriasis. The mean EFT in our study participants was 7.56 ± 2.46 mm, well within the range (6.4 mm to 7.6 mm) reported previously.[6],[14],[18],[26]

Our study revealed only a weak correlation between CIMT and DD (r = 0.2837, P = 0.1156) as also severity of psoriasis (r = –0.0815, P = 0.6574). Many previous studies[15],[17],[18],[20],[21],[26] too did not find any significant correlation between these parameters. However, a few others[14],[24],[25] did reveal a significant correlation of CIMT with DD and PASI score. The reason could be that unlike our exclusion of participants with psoriatic arthritis to nullify the effect of systemic inflammation, these studies had included such patients. Our study participants had milder psoriasis of shorter duration. Unlike our study, those receiving immuno-suppressive medications were excluded from these studies.

Similar to other studies,[14],[18] a weak correlation of EFT with DD (r = –0.1972, P = 0.2793) and PASI score (r = –0.2223, P = 0.2214) emerged in our study. However, in the study by Bulbul Sen et al.,[6] EFT was associated with DD but not with PASI score. They felt that in patients with longer DD, potential flares and the cumulative effect of chronic inflammation might be higher, thereby accentuating inflammatory damage and the risk of cardiovascular disease; they further remarked that one-time measurements of PASI, representing clinical severity of that one time only, may not be sufficient to predict the long-term prognosis and co-morbidities. Contrary to studies by Bulbul Sen et al.[6] and Girisha et al.,[18] our study showed no correlation between CIMT and EFT [Figure 3].
Figure 3: Graph showing no correlation between CIMT and EFT (r = –0.0215, P = 0.9068)

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Episodes of exacerbation and remission with a variable PASI score may or may not be related to the disease duration.[20] Neither our study nor the previous ones had a pre-decided range of disease duration or PASI score as inclusion criteria. This could account for the difference in observations, considerable variations in DD, and severity of psoriasis causing difficulty in their correlation with indicators of sub-clinical atherosclerosis. There was no statistically significant difference in CIMT (0.77 ± 0.22 vs 0.65 ± 0.19, P value = 0.1228) and EFT (8.08 ± 2.4 mm vs 7.25 ± 2.47, P value = 0.3624) in our study participants with or without MetS. Many other studies[7],[8],[14],[18] recorded similar findings. Thus, MetS does not appear to influence CIMT or EFT values in patients of psoriasis.

Our study had several limitations: first, a small sample size without age- and sex-matched controls because a large number of previous studies demonstrate association of various parameters in the psoriasis group versus the control group; second, ours was a cross-sectional type of observational study, although prospective studies are more likely to show de-ranged clinical, laboratory, and radiological parameters over the long duration of chronic diseases such as psoriasis; third, 2-D ECHO was used, being convenient and inexpensive, for assessing EFT despite being less accurate than the gold standard magnetic resonance imaging or computed tomography; and finally, the previous treatment and its duration were not taken into consideration; such treatment over long duration might have lessened the chances of systemic inflammation and, in turn, sub-clinical atherosclerosis.


   Conclusion Top


Psoriasis is a chronic immune-mediated inflammatory disease with periods of exacerbations and remissions. Metabolic syndrome, sub-clinical atherosclerosis, and psoriasis are independent risk factors for development of CVD. Several studies have reported greater chances of developing CVD because of sustained systemic inflammation of severe and prolonged psoriasis and of psoriatic arthritis. However, the indicators of sub-clinical atherosclerosis, namely, CIMT and EFT, showed no statistically significant correlation with MetS, duration, or severity of psoriasis in our study.

Patients may present to a dermatologist even with mild psoriasis and may not always be cognizant of treatments taken, duration, and episodes of relapse. Because of the lack of these data, the duration of disease might get misjudged. Our study suggests that all patients of psoriasis should be screened for sub-clinical atherosclerosis by simple non-invasive methods irrespective of MetS, duration, or severity of disease.


   Acknowledgements Top


We would like to thank all the faculties and residents of departments of radiology, cardiology, pathology, and community medicine of our hospital for helping us with investigations and statistics of our study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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   Methodology
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   Discussion
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   Acknowledgements
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