الفهرس 
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Abstract
Psoriasis, an immune-mediated inflammatory disease that primarily contributes to chronic cutaneous inflammation, has been found to be associated in nearly 30% of cases with a chronic inflammatory seronegative arthropathy named psoriatic arthritis (PsA) that may present with peripheral arthritis, axial joint involvement, dactylitis, and/or enthesitis.
Psoriasis and PsA may have a negative influence on the quality of life and also may account for an increased risk of developing several comorbid diseases such as diabetes, depression, malignancy and cardiovascular diseases.
In patients with psoriatic disease, cardiovascular involvement is a prominent comorbidity, which may be owing to the highly prevalent conventional cardiovascular risk factors and the persistent inflammatory state associated with this disease. Therefore, the early detection of preclinical cardiovascular affection in these patients could guide early treatment and careful disease follow up with subsequent betterment of their cardiovascular outcome. For this reason, identifying appropriate methods such as laboratory biomarkers or imaging techniques that could detect the cardiovascular disease at its initial stages and stratify the cardiovascular risk in a proper manner is increasingly required for these patients.
The endothelial biomarkers appear to be important tools and promising alternatives to conventional methods for the early diagnosis of cardiovascular diseases. One of such biomarkers is endothelial cell specific molecule-1 (endocan). Endocan, a soluble proteoglycan mediator secreted by the vascular endothelium, is found to play a role in endothelial-dependent pathological disorders such as various inflammatory and vascular diseases. Thereby, it is greatly recognized to be a potential indicator for endothelial cell dysfunction and cardiovascular diseases. To the best of our knowledge, the serum levels of endocan and their relation to cardiovascular involvement have not been yet assessed in PsA patients.
The use of combined methods strategy in the assessment of endothelial cell function could stratify the cardiovascular risk in a more powerful way. In addition to endocan, endothelial dysfunction (an early stage of atherosclerosis) could be evaluated by measuring brachial artery flow-mediated vasodilatation (FMD), which represents a noninvasive ultrasonographic tool and the most widely utilized technique to evaluate the endothelial cell function. Moreover, subclinical atherosclerosis could be assessed noninvasively by echocardiographic measurement of epicardial fat tissue (EFT) thickness, which is the visceral fat surrounding the heart.
Tissue Doppler echocardiographic imaging (TDI) is a noninvasive and relatively load independent echocardiographic method, measuring the velocities of myocardial tissue directly rather than identifying the changes that occur in blood flow dynamics. Thus, it seems to have a higher sensitivity than standard echocardiography in detecting subclinical myocardial dysfunction.
This study aimed to measure serum endothelial cell specific molecule-1 (endocan) level in order to detect its potential role in subclinical cardiovascular involvement and to document the use of FMD, EFT thickness and TDI as objective tools for the early diagnosis of subclinical cardiovascular involvement in psoriatic patients with or without arthritis.
We carried out this study on 28 psoriatic patients that were divided into 14 PsA patients (group A) and 14 psoriatic patients with only skin manifestations (PsO patients) (group B). In addition, 14 healthy subjects were enrolled into this work as controls (group C). The patients had been matched with the controls regarding age, body mass index (BMI) and sex.
All subjects underwent detailed history taking and thorough clinical examination with particular emphasis on general, cardiac, skin, nail, and joint examination. Moreover, they were subjected to serum endocan level measurement, assessment for subclinical atherosclerosis using FMD and echocardiographic measurement of EFT thickness, and echocardiographic examination including standard echocardiography and TDI.
Our results showed that:
There was a highly statistically significant increase in the serum level of endocan in group (A) as compared to group (B), in group (A) as compared to group (C), and in group (B) as compared to group (C).
FMD% showed a highly statistically significant decrease in group (A) when compared to group (C) and was statistically significantly lower in group (B) than group (C), whereas the difference as regards FMD% was statistically nonsignificant between groups (A&B). FMD abnormality (subclinical atherosclerosis) was detected in 4 (28.6%) PsA patients and 1 (7.1%) patient with PsO, while it was absent among the controls. EFT thickness was statistically significantly greater in group (A) than group (C) and in group (B) than group (C), while it was similar between groups (A&B).
Standard echocardiographic examination revealed that isovolu¬mic relaxation time (IVRT) was statistically significantly prolonged in group (A) in comparison to group (C), whereas it was comparable between groups (A&B) as well as groups (B&C). The differences among the studied groups concerning the other standard echocardiographic parameters were statistically nonsignificant.
TDI examination demonstrated that group (A) had a highly statistically significant decrease in early diastolic mitral annular velocity (E’) as compared to group (C). E’ was found to be significantly lower in group (A) than group (B) and in group (B) than group (C). E’ abnormality (diastolic dysfunction) detected only in 5 (35.7%) PsA patients was grade one. In addition, early diastolic peak velocity of mitral inflow (E)/E’ ratio showed a highly statistically significant elevation in group (A) when compared to group (C) and was statistically significantly higher in group (A) than group (B), while it differed nonsignificantly between groups (B&C). As regards late diastolic mitral annular velocity (A’), there was no statistically significant difference among the studied groups. No mitral annular systolic motion velocity (Sm) abnormality, systolic dysfunction, was diagnosed among all participants.
In PsA group, the serum level of endocan showed a highly statistically significant increase in patients with E’ abnormality compared to those without, while it was statistically significantly elevated in patients with FMD abnormality compared to those without.
PsO group demonstrated that there was a highly statistically significant elevation of serum endocan level in one patient with FMD abnormality in comparison to those without.
In each of the psoriatic groups, serum endocan level had a highly statistically significant positive correlation with disease duration, while it showed statistically nonsignificant correlations with age, psoriasis area severity index (PASI) and nail psoriasis severity index (NAPSI). PsA patients showed that there was a highly statistically significant positive correlation between serum endocan level and Leeds enthesitis index (LEI).
Serum endocan level had a statistically significant negative correlation in PsA patients and a highly statistically significant negative correlation in PsO patients with FMD%, whereas it showed no significant correlation with EFT thickness in each of the psoriatic groups.
There were no statistically significant correlations of the serum level of endocan with systolic function parameters assessed by standard echocardiography in each psoriatic group. Serum endocan level and Sm had a highly statistically significant negative correlation in PsA patients, while both correlated nonsignificantly in PsO patients.
Regarding diastolic function assessed by standard echocardiography, serum endocan level showed a statistically significant negative correlation with early/late diastolic peak velocities of mitral inflow (E/A) and a highly statistically significant negative correlation with E wave in PsA group, while it had no statistically significant correlations with them in PsO group. There were no statistically significant correlations between the serum level of endocan and the other diastolic function parameters in each of the psoriatic groups.
E’ had a highly statistically significant negative correlation with serum endocan level in each psoriatic group. Serum endocan level showed a highly statistically significant positive correlation in PsA patients and a statistically significant positive correlation in PsO patients with E/E’, while it revealed no statistically significant correlation with A’ in each of the psoriatic groups.
In psoriatic patients with or without arthritis, serum endocan could detect FMD and E’ abnormalities at cut off levels of ≥681 ng/L and ≥705 ng/L, respectively with a sensitivity of 100% and 100%, specificity of 91.3% and 95.7%, negative predictive value of 100% and 100%, positive predictive value of 71.4% and 83.3%, and diagnostic accuracy of 92.9% and 96.4%, respectively.
In conclusion, psoriatic patients had subclinical cardiovascular involvement, which was more evident in those with arthritis. Additionally, serum endocan was associated with preclinical cardiac dysfunction and early stages of subclinical atherosclerosis in patients with psoriatic disease and, therefore, serum endocan may be a promising endothelial biomarker for the detection of subclinical cardiovascular involvement in these patients. FMD, echocardiographic measurement of EFT thickness and TDI are objective tools that could be used for the early diagnosis of comorbid cardiovascular disease in psoriatic patients.