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|Aortic stiffness in hidradenitis suppurativa: A case-control study
Emine Tugba Alatas1, Murat Biteker2, Omer Dogan Alatas3
1 Department of Dermatology, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla, Turkey
2 Department of Cardiology, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla, Turkey
3 Department of Emergency Medicine, Training and Research Hospital, Muğla Sıtkı Koçman University, Muğla, Turkey
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|Date of Submission||21-Jun-2020|
|Date of Decision||16-Aug-2021|
|Date of Acceptance||22-Sep-2021|
|Date of Web Publication||16-Nov-2021|
Background: Although increased aortic stiffness has been observed in chronic inflammatory skin diseases, it has not been examined in patients with hidradenitis suppurativa (HS). Objectives: This study aimed to compare aortic stiffness among HS patients and non-HS controls and to investigate the relation between aortic stiffness and disease severity in HS. Methods: Thirty-eight HS patients, and 76 age- and sex-matched controls were studied. Patients who had diabetes, cardiovascular diseases, chronic kidney disease, or other inflammatory conditions were excluded. Aortic stiffness was measured by transthoracic echocardiography. Disease severity and activity were assessed using Hurley stage, and physician global assessment (PGA) score, respectively. Severe disease was defined as Hurley stage III, or PGA scores ≥3. Results: The patients with HS had increased aortic stiffness determined by decreased strain and distensibility compared to control group patients. A significant negative correlation was found between aortic stiffness indices and high-sensitivity C-reactive protein, duration of the disease, Hurley stage, and PGA score. Multivariate analysis revealed the aortic strain and aortic distensibility were predictors of severe disease for Hurley stage III. Conclusion: Aortic stiffness is increased and associated with the severity of the disease in patients with HS.
Keywords: Aortic stiffness, hidradenitis suppurativa, transthoracic echocardiography
| Introduction|| |
Since coronary artery disease is a disease of chronic inflammation, chronic inflammatory skin diseases (CISDs), such as psoriasis, and atopic dermatitis have been associated with an increased risk of cardiovascular diseases (CVDs)., Although the exact pathogenesis of hidradenitis suppurativa (HS) remains uncertain, current knowledge has suggested that immune dysregulation leading to chronic inflammation plays a major role in its pathogenesis., Recent studies have also shown that several conditions, which predispose to the development of CVD such as diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome are more common in patients with HS.,, Not unexpectedly, observational and large cohort studies have revealed that HS patients have a higher risk of stroke and acute CVDs compared with controls. However, it is not clear whether the risk of cardiovascular events is increased due to the higher burden of comorbid diseases in HS patients, or HS itself is an independent risk factor for atherosclerotic adverse events.
Increased arterial stiffness is a risk factor for adverse cardiovascular and renal events and mortality in patients with diabetes mellitus, acute ischemic stroke, and coronary artery disease. Therefore, the measurement of arterial stiffness has gained importance in recent years for the evaluation of vascular risk. Consequently, studies investigating the association between arterial stiffness and CISD have shown that atopic dermatitis, and psoriasis are associated with increased aortic stiffness. However, no studies have been performed to investigate the relationship between arterial stiffness among HS patients and non-HS controls. Hence, the present study aimed to examine the association between arterial stiffness and HS, and it also aimed to find out the relation between disease activity and increased arterial stiffness in HS.
| Methods|| |
All patients aged ≥18 years with a diagnosis of HS admitted to Mugla Sıtkı Kocman University Training and Research Hospital (a tertiary hospital in Mugla, Turkey) dermatology outpatient clinic and emergency clinic between May 2019 and July 2019 was enrolled in this cross-sectional case–control study. The control group consisted of age- and gender-matched subjects admitted to the dermatology outpatient clinic during the study period due to skin disorders other than HS. The exclusion criteria for the HS and control groups were; (a) age <18 years; (b) history of coronary artery disease, chronic renal diseases, or liver diseases; (c) diabetes mellitus; (d) other concomitant inflammatory cutaneous and systemic conditions. The final study population included 38 h patients and 76 controls. The study protocol was approved by Mugla Sıtkı Kocman University Ethics Committee (14/VII, Oct. 17th, 2019) and all the participants provided informed written consent.
Baseline demographic and clinical data were noted. The routine laboratory data including high-sensitivity C-reactive protein (hs-CRP) concentrations were obtained in all HS patients and controls at enrollment. The variables associated with HS such as the duration of the disease, association with a pilonidal cyst and the number of involved areas were recorded. The severity of HS was assessed by the physician global assessment (PGA) tool, which includes 6 stages (scale 0–5); moderate-severe-very severe: PGA score ≥3, and minimal-mild HS: PGA <3. The severity of HS was also assessed by the Hurley staging. Patients with an HS-PGA score ≥3 and Hurley III stage were defined as severe HS.
Aortic stiffness was calculated by transthoracic echocardiography (Vivid 3 pro, GE Vingmed, Milwaukee, USA) in all HS patients and controls using the previously described formulas. The formulae used in the calculation of aortic distensibility and aortic were as follows: Aortic strain (%) = (aortic systolic diameter − diastolic diameter) ×100/diastolic diameter, Aortic distensibility (cm2/dyn) = (2 × aortic strain)/(systolic pressure − diastolic pressure).
All analyses were performed using SPSS Statistics version 23.0 for Windows (SPSS Inc., Chicago, IL, USA). Quantitative variables were compared by the Student's t-test or Mann–Whitney U-tests, and qualitative variables were compared by the Pearson's Chi-square test or Fisher exact tests. Correlation analyses were performed in HS patients and controls using Pearson correlation coefficient or Spearman rho when appropriate. Univariate and multivariate logistic regression analyses were applied to determine the relationship between disease severity, and aortic stiffness indices.
| Results|| |
Comparison of hidradenitis suppurativa and control groups
Baseline demographic, laboratory, and echocardiographic characteristics of the study patients and the control group are presented in [Table 1]. Thirty-eight HS patients (mean age 42.6 ± 11.2 years; 57.9% males) and 76 controls (mean age 43.2 ± 12.8 years; 56.6% males) were enrolled in the study. The patient and control groups were age- and gender-matched. There were also no significant differences in the prevalence of comorbid diseases, smoking status, and body mass indexes between the two groups. HS patients had significantly higher hsCRP levels compared to the control group. Compared with controls, the HS patients had reduced distensibility and strain in the ascending aorta.
The mean age of onset was 23.7 years, and the mean duration of the disease was 9.6 years. Of 38 patients, the distribution of Hurley classification was; 22 (57.9%) Hurley stage II, 12 (31.6%) Hurley III, and 4 (10.5%) Hurley I. Mean number of affected sites was 3.7, and the groin (18 patients) and the axilla (20 patients) were the most commonly involved sites. Eighteen patients had perineal region involvement, 9 patients had buttocks and abdominal involvement, 8 patients had breast involvement.
Correlation between aortic stiffness and the severity of the disease
Correlation between aortic stiffness indices (aortic strain and aortic distensibility) and clinical, laboratory variables are presented in [Figure 1]. There was a negative correlation between aortic stiffness indices and three variables: PGA score, hs-CRP, and disease duration (r: −0.324, P = 0.012, r: −0.187, P < 0.001, r: −0.504, P < 0.001, respectively).
|Figure 1: Scatter plots showing the correlation between aortic strain and high-sensitivity C-reactive protein, duration of the disease, and physician global assessment score.|
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Predictors of severe disease
Severe disease was defined as Hurley stage III. To identify the predictors of severe disease, multivariate analysis was performed for patients with Hurley stage III HS [Table 2]. Logistic regression models revealed the aortic strain and aortic distensibility were predictors of severe disease Hurley stage III.
|Table 2: Multivariate regression analysis for the prediction of disease severity according to Hurley Stage III|
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| Discussion|| |
Our study provides the first evidence that aortic stiffness is increased in HS, and it is associated with the severity of the disease. As far as we know, there is no study about aortic stiffness in HS. This is the first study to show the correlation of aortic stiffness in HS. Our results are in line with the previous survey showing epicardial fat tissue (EFT), which is associated with metabolic syndrome and coronary artery disease is significantly higher in HS patients.
CISDs, particularly psoriasis, have been found to be associated with increased risk for CVDs. Recent studies have suggested that other CISDs are also associated with increased risk for CVD. Although the pathophysiology of the CVD-CISD relationship is not clear, shared risk factors, increased activity of immune cells, and chronic inflammation are all thought to play a critical role., One possible mechanism that provides a linkage between CVD and CISD may be vascular inflammation and vascular aging. The observation that arterial stiffness is increased in patients with atopic dermatitis and psoriasis compared with controls strengthened this hypothesis. Increased aortic stiffness implies a worse prognosis in various cardiovascular and rheumatic diseases,, and even in the normal population. Although, the prognostic significance of aortic stiffness in has not been studied in HS before, recently published three studies showed an association between subclinical atherosclerosis, detected by carotid ultrasound, and HS.,, In the first cross-sectional, case–control study, 68 h patients, and 136 controls were analyzed. Carotid intima-media thickness and carotid plaques were measured by carotid ultrasonography. This study showed that HS patients had greater carotid intima-media thickness and more frequent carotid plaques than the controls. In the second prospective, and observational study 62 h patients, and 62 controls were enrolled to assess subclinical atherosclerosis which was defined as increased carotid intima-media thickness or the presence of carotid plaques. The results of this study showed that the prevalence of subclinical atherosclerosis was higher in HS patients than the patients in the control group (30.6% vs. 16.1%, respectively). The last study compared carotid ultrasound findings with the Framingham risk score for 60 patients with HS. The authors revealed that 32.6% of the patients in the Framingham risk score-based low and intermediate-risk categories had carotid plaques, and were reclassified into a high-risk category. The authors concluded that cardiovascular risk in HS patients might be underestimated by using the Framingham risk score. In the other study EFT which is adipose tissue and produces several inflammatory and atherogenic cytokines, is significantly higher in HS patients. It was found that hs-CRP and EFT were significantly higher in HS patients compared to controls.
These results support the hypothesis and findings of our study that HS is a systemic disease involving not only the skin but also the vascular system.
This is a single-center study, carried out in a tertiary university hospital in Turkey and patients with a history of coronary artery disease, chronic renal/liver diseases, CISDs, and diabetes mellitus were excluded. Thus, the results of our study cannot be directly applied to all patients with HS. The prognostic value of serial changes in aortic stiffness measurements could not be assessed.
| Conclusions|| |
Arterial stiffness is found to be significantly increased in HS patients compared to the control population. Those with higher disease activity and more severe disease had indices elevated over those of well-controlled cases. Thus, HS is a proinflammatory state with accelerated atherosclerosis and arterial stiffness indices can be used to predict cardiovascular adverse events, and various lifestyle and pharmacologic treatments can be advised early in the disease to reduce it.
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Conflicts of interest
There are no conflicts of interest.
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Emine Tugba Alatas,
Department of Dermatology, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla 48000
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]
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