Carotid Intima-Media Thickness in Patients with Psoriasis

1. INTRODUCTION

Psoriasis is a chronic inflammatory disease with the prevalence in the general population ranging from 0.51% to 11.43% in adults and 0% to 1.37% in children [1]. The progress of this disease is unpredictable, showing a persistent or recurrent course; no cure is currently available. Psoriasis may seriously affect patients’ quality of life and cause negative psychological issues, such as depression, emotional disorders, and suicidal thoughts. Moreover, many comorbidities are associated with psoriasis, including psoriatic arthritis, Crohn's disease, psychological or psychiatric disorders, and metabolic syndrome. Even though the cutaneous manifestations may ameliorate with routine treatments, the systemic involvements may progress chronically.

Psoriasis is a systemic inflammatory disorder that may be associated with atherosclerosis and cardiovascular comorbidities [2]. This theory was supported by the “psoriatic march,” in which the systemic inflammation causes insulin resistance, resulting in endothelial cell dysfunctions. Atherosclerosis increases the risk of fatal complications, such as myocardial infarction, ischemic stroke, and arterial embolism. Therefore, preclinical atherosclerotic screening is beneficial for the early perception of atherosclerosis progression. The rise in the Carotid Intima-Media Thickness (CIMT) is not only a surrogate marker of atherosclerotic damage, but also an independent predictor of myocardial infarction and stroke. Every 0.1 mm increase in the CIMT increases the risk of myocardial infarction by 10% to 15% and of stroke by 13% to 18% [3]. Atherosclerotic complications are typically present abruptly; however, the disease itself may have persisted asymptomatically for a long time. Currently, several methods are used for determining the carotid artery thickness, such as ultrasound, computed tomography, magnetic resonance angiography, and thoracic angiography. Among these, ultrasound is inexpensive, non-invasive, and extremely affordable. Furthermore, ultrasound machine is easily available without any health-related risks. Therefore, the CIMT measured using ultrasound has been readily used for the detection of atherosclerosis and its progression.

The CIMT cut-off value plays a vital role in the accurate assessment of cardiovascular risk in asymptomatic patients and early detection of coronary artery disease; this increases the efficacy of treatment and reduces mortality. Several studies have demonstrated an increase in the CIMT in patients with psoriasis and suggested the implementation of this measure to determine the cardiovascular risks in patients with psoriasis. Furthermore, Akdogan et al. recently reported that every 0.1 unit increase in the CIMT rose the risk of psoriasis 1.51-fold [4]. However, no study in Vietnam has investigated the association between CIMT and psoriasis. Therefore, this study aimed to investigate the CIMT and other corresponding factors, such as the clinical manifestations and risk factors for CIMT increase in patients with psoriasis. The findings of this study may contribute to the early detection of atherosclerotic plaques and cardiovascular events in psoriasis patients and provide physicians with a proper treatment plan.

2. MATERIALS AND METHODS

3. RESULTS

3.2. Ultrasonographic Characteristics

The magnitude of CIMT change in the CCA, ICA, and ECA was measured both in patients and in healthy volunteers. The CIMT value of the CCA in psoriatic patients [0.59 mm (0.53 - 0.71)] was statistically higher than that of controls [0.54 mm (0.52 - 0.62), p = 0.036]. Similarly, the ECA was thicker in psoriasis patients than in controls [0.62 mm (0.55 - 0.70 vs. 0.56 mm (0.50-0.67), respectively, p = 0.046]. The diameter of the atherosclerotic plaques in psoriasis patients was 0.27 ± 0.68 mm and was statistically greater than that of controls (0.03 ± 0.17 mm) (p = 0.035) (Fig. 1a, b and c). However, no statistically significant difference was observed in the ICA diameter between the two groups [0.64 mm (0.56 - 0.72) vs. 0.61 mm (0.53 - 0.66), respectively, p = 0.134] (Table 2).

Table 2.

Characteristics	Psoriasis Group	Normal Group	p-value(*)
	Median (25%, 75%)	Median (25%, 75%)
CCA (mm)	0.59 (0.53, 0.71)	0.54 (0.52, 0.62)	0.036
Max	1.2	0.86	-
Min	0.42	0.44	-
ICA (mm)	0.64 (0.56, 0.72)	0.61 (0.53, 0.66)	0.134
Max	1.3	0.85	-
Min	0.44	0.45	-
ECA (mm)	0.62 (0.55, 0.7)	0.56 (0.50. 0.67)	0.046
Max	1.3	0.75	-
Min	0.44	0.46	-
Atherosclerosis plaque	-	-	0.035
Max	0.27 ± 0.68	0.03 ± 0.17	-
Min	3	1	-
-	0	0	-

CCA: Common Carotid Artery, ICA: Internal Carotid Artery, ECA: External Carotid Artery, CIMT: Carotid Intima-Media Thickness
(*) Mann-Whitney U test

4. DISCUSSION

We found that the CIMT value in the psoriasis group was higher than that in controls (p < 0.05), and this difference was statistically significant. This result was concurrent with that of a study by Balci et al. in which the CIMT values at the left, right, and mean positions were higher in the psoriasis group than in the healthy group (0.607 ± 0.44 mm vs. 0.532 ± 0.01 mm, 0.611 ± 0.157 mm vs. 0.521 ± 0.17 mm, and 0.609 ± 0.16 mm vs. 0.526 ± 0.14 mm, respectively, p < 0.01) [6]. Similar findings (statistically higher CIMT values in the psoriasis group than in the control group) were observed in studies by Troitzsch et al. [7], Enany et al. and Yiu et al. (0.73 ± 0.11 mm vs. 0.67 ± 0.08 mm, respectively, p<0.01), and Antonucci et al. (Italy) (1.465 ± 0.53 mm vs. 0.89 ± 0.27, respectively, p < 0.001) [8-10]. Di Minno et al. conducted a literature review including 12 studies which revealed that the CIMT value was statistically higher in 759 patients with psoriatic arthritis than in 937 healthy controls (p < 0.001) [11]. A similar result was observed in the study by Dünya et al. in 2015, which compared the CIMT in 42 patients with psoriatic arthritis and 30 healthy individuals (0.76 ± 0.15 mm vs. 0.57 ± 0.12 mm, respectively, p < 0.001) [12]. A Malaysian study by Mazlan et al. involving 63 patients with psoriatic arthritis concluded that 16% of the patients had a mean CIMT of 0.725 ± 0.260 mm [13]. The difference between the two groups with respect to the corresponding CIMT factors such as age (p = 0.005), waist circumference (p = 0.001), hypertension (p = 0.007), diabetes (p = 0.002), and metabolic syndrome (p = 0.001) was also statistically significant [14]. In contrast, Kim et al. evaluated the CIMT and stiffness of the artery in 54 patients and 60 age- and sex-matched healthy controls and reported that although the CIMT value in the psoriasis group was higher than that in controls, this difference was not statistically significant (p = 0.076). However, this study found that only the stiffness of the artery was statistically correlated to age, systolic pressure, and disease severity [15]. According to a cross-sectional study enrolling 62 patients with plaque-type psoriasis and 31 age- and sex-matched controls, CIMT was considered an independent risk factor for psoriasis [4]. In summary, most studies showed that the CIMT value was higher in psoriatic patients compared with controls.

Atherosclerosis, a critical process in cardiovascular disease, is inflammatory in origin. Psoriasis is a systemic inflammatory disease that is presented with an increase in the conventional inflammatory cytokines and adipokines, such as resistin and leptin. Adipokines in the serum of psoriasis patients are similar to those seen in prediabetic patients and are strong predictors of an insulin-resistant condition. In addition to insulin resistance, excessive adipokines may result in atherosclerosis through immune regulatory mechanisms, such as improved endothelial cell linkage. At the level of the endothelial cells, insulin resistance causes endothelial cell dysfunction, consequently making the arteries stiffer. This cascade results in an increase in the CIMT and calcification of the carotid artery, thus increasing the risk of severe cardiovascular comorbidities, such as myocardial infarction and stroke [16]. Moreover, proinflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α) and interferon found in psoriasis, play a vital role in endothelial dysfunction and atherosclerotic plaque formation [17].

Age, sex, smoking, alcohol use, BMI, and obesity are known to increase the CIMT. However, we observed that only a history of smoking showed a significant association; smokers exhibited a significantly higher CIMT value (0.68 mm) than non-smokers (0.56 mm, p = 0.009). In smokers, either the inflammatory process or reduced internal fibrinolysis was suggested to correlate with atherosclerotic pathology [18]. We found that CIMT had a positive correlation with age (r = 0.63, p < 0.001) and the PASI (r = 0.38, p = 0.002). This correlation between the CIMT and PASI was not only due to the chronic inflammation but was also related to artery growth factors, such as the Vascular Endothelial Growth Factor (VEGF). VEGFs are produced by the keratinocytes in psoriatic lesions and are strongly related to the disease severity and an increase in the IMT [7]. Several studies have exhibited a decrease in the CIMT after psoriasis treatment. A decrease in the CIMT (p = 0.010) was observed in a 2-year follow-up study by Tam et al. in patients with psoriatic arthritis who were treated with monoclonal antibodies against TNF-α [19]. A similar result was obtained in a study by Jókai et al. (p = 0.0002) [20]. In 2018, Martinez-Lopez et al. demonstrated that CIMT tended to decrease with biological treatments, particularly with anti-IL-12/23 agents and methotrexate in patients suffering from moderate and severe psoriasis [21]. However, additional larger studies are needed to fully confirm the association between psoriasis treatment and CIMT decrease.

The number of atherosclerotic plaques in psoriasis group patients was statistically higher than that in healthy controls, which was in accordance with the results of the study by Di Minno et al. [11]. Inflammation, triggered by the autoimmune response to plaque antigens, such as oxygenated LDL and heat shock protein, is thought to induce the formation and development of atherosclerotic plaques. The promotion of self-activating T helper type 1 (Th1) cells and a decrease in moderator T cells induces the release of proinflammatory cytokines, such as TNFα, interleukin (IL)-1β, and IL-6; these are the common pathways among the genetic predisposition, leading to atherosclerosis, arthritis, and psoriasis [22]. The presence of atherosclerotic plaques is considered a more credible prognosticator of cardiovascular accidents than the CIMT [23].

This was a case-control study that allowed us to evaluate the significant difference between the CIMT value of psoriatic patients and healthy volunteers. This result supports the measurement of CIMT through ultrasound in clinical practice to help identify patients at high cardiovascular risks. However, our research had some limitations. First of all, our sample size was still modest. Secondly, we did not follow up with the patients to determine the effects of treatment on the CIMT. Thus, more comprehensive researches are warranted with a larger sample size to identify the CIMT cut-off value in psoriasis patients. Furthermore, the correlations between the change of CIMT value and clinical manifestations in psoriasis patients before and after systemic treatments remain to be elucidated in the near future.

CONCLUSION

The CIMT value in the psoriatic group was higher than that in healthy controls. Although no correlation was found between the CIMT and serum lipid levels, a positive relationship between the CIMT and age, as well as PASI (p < 0.0001), was observed. The number of atherosclerotic plaques in the psoriasis group was significantly higher than that in the control group. From these results, we concluded that ultrasound is a simple, non-invasive technique for evaluating the CIMT and the number of atherosclerosis plaques. This will assist in the diagnosis of preclinical atherosclerosis and will screen individuals at high risk of cardiovascular events. Elderly patients with severe psoriasis should be evaluated carefully with regard to the CIMT, and atherosclerotic plaques as these signs are representative of increased cardiovascular events.

REFERENCES