Ankylosing spondylitis (AS) is increasingly reported to be at higher risk for cardiovascular morbidity, particularly represented as aortitis and aortic root dilation. However, the determinants of aortic root size in this population have not been fully investigated. To address the clinical and demographic factors underlying increased aortic root diameter (ARD) in patients with AS. The study enrolled 31 patients with AS. Echocardiography (ECG) was performed to measure the ARD. Demographic data, disease characteristics, cardiac functional status, disease duration, and medication history were collected. Data were analysed to identify independent predictors of ARD. This study enrolled 31 patients with ankylosing spondylitis, predominantly male (n=25, 80.6%), aged 37.3±11.2 years. The ECG findings demonstrated a high frequency of subclinical cardiac involvement, mild aortic valve regurgitation (29.0%), aortic root dilation (22.6%), and, less frequently, including diastolic impairment (16.1%), mild left ventricular systolic dysfunction (9.7%), and cardiac chamber abnormalities (9.7%). The most frequent associated dysfunction was aortic regurgitation, affecting five patients (71%). Diastolic dysfunction was noted in three patients (43%). ARD demonstrated a moderate positive correlation with patient age (r=+0.46, p=0.01) and a modest positive correlation with disease duration (r=+0.39, p=0.03). Aortic root dilation is present in AS patients and is unconventionally linked to male gender, disease chronicity, and inflammation. These outcomes imply that chronic control of inflammation and regular ECG monitoring, particularly in male patients with chronic disease, may be indicated to detect early aortic pathology.
Introduction
Ankylosing spondylitis (AS) has been described as a chronic inflammatory arthritis primarily affecting the sacroiliac joints and spine (Baronio et al., 2020; Ebrahimiadib et al., 2021; Bate et al., 2023; Nagdalian et al., 2024). However, the clinical findings of this ailment also involve the non-axial skeleton, as demonstrated by a range of extra-articular manifestations, including cardiovascular manifestations that carry a notable prognostic importance (Moutsopoulos & Zampeli, 2021; Assadiasl & Soleimanifar, 2022; Mehrzad et al., 2022; Del Vescovo et al., 2023; Venerito et al., 2023). The most important characteristic is a contribution to the proximal aorta, where inflammation can lead to root dilation and valvular deficits (Willerson & Buja, 2020; Sen et al., 2021; Huyen et al., 2023; Sakhnenkova et al., 2023). This process is subclinical and can silently proceed for years, only manifesting as a late-onset murmur of aortic regurgitation or as an acute aortic syndrome (Klingberg et al., 2015; Bozkurt et al., 2016; Chetrit et al., 2020; Shoghi & Kian, 2022; Petronis et al., 2023).
The clinical challenge is linked to detecting the aorta before extensive damage occurs (Chetrit et al., 2020; Ebrahimiadib et al., 2021). The etiology is multifaceted, involving continuous systemic inflammation, biomechanical pressure, and genetic deficits (Hwang et al., 2021; Efremov, 2023; Cantile et al., 2024). A model that measures the contribution of specific factors, such as disease type, past medical history, smoking status, and genetic markers, is lacking.
With advances in the management of AS, the control of musculoskeletal symptoms with new medications has proportionally increased the significance of extra-articular risks, including aortitis, a silent but overwhelming inflammation of the aortic root that can result in progressive dilation and, hence, aortic deficits. While ECG diagnosis is recommended, the criteria for which patients require screening remain obscure and constitute a rich area of research (Nguyen & Hoang, 2022; Efremov, 2023). This uncertainty pertained to the partial interpretation of the influences of aortic dilation in AS. The present study sought to underscore the risk factors influencing aortic root diameter via integrating data on disease severity, treatment exposure, and comorbidities (Trung et al., 2022; Ncube et al., 2023).
Materials and Methods
Study Design
A cross-sectional clinical study was conducted in a private clinic in Duhok City (Kurdistan region, Iraq). The study protocol was reviewed and approved by the College of Medicine (University of Duhok), and informed consent was obtained from individual participants.
Inclusion criteria included adult patients (≥18 years) diagnosed with AS according to the modified New York criteria. Patients were excluded from the final analysis for any of the following reasons:
Data Collection
Statistical Analysis
The data analyses were conducted using IBM SPSS Statistics (V28, USA). A two-tailed p-value of < 0.05 was considered statistically significant. Continuous variables expressed as mean ± SD, compared using a t-test. Categorical variables expressed as n (%), compared using chi-square/Fisher’s exact test. Pearson’s r is used for continuous predictors. Significance threshold considered at p < 0.05.
Results and Discussion
The present study enrolled 31 patients with ankylosing spondylitis, predominantly male (n=25, 80.6%), aged 37.3±11.2 years. The disease duration was 9.5±8.3years. The duration of biological therapy was 15.6±16.4 months (Table 1).
Table 1. Demographic and clinical characteristics of ankylosing spondylitis patients
|
demography |
Mean±SD (Range) |
|
Age, years |
37.3 ± 11.2 (17–56) |
|
Sex, M/F |
25/6 |
|
Disease duration, years |
9.5 ± 8.3 (0.25–35) |
|
Biological Agent Duration, months |
15.6 ± 16.4 |
The ECG findings demonstrated a high frequency of subclinical cardiac involvement, mild aortic valve regurgitation (29.0%), aortic root dilation (22.6%), and, less frequently, including diastolic impairment (16.1%), mild left ventricular systolic dysfunction (9.7%), and chamber abnormalities (9.7%) (Table 2).
Table 2. Echocardiographic Findings of Ankylosing Spondylitis Patients
|
Parameter |
Normal |
Abnormal (any grade) |
Abnormal (%) |
|
Aortic valve |
22 |
9 (mostly mild AR) |
29.0% |
|
Aortic root |
24 |
7 (mildly dilated/dilated) |
22.6% |
|
LV systolic function |
27 |
3 (mild dysfunction) |
9.7% |
|
Diastolic impairment |
25 |
5 (grade 1–mild) |
16.1% |
|
Cardiac chambers |
27 |
3 (mild dilation or LVH) |
9.7% |
|
Pericardial effusion |
30 |
0 |
0% |
Comparative study revealed that patients in the dilated aortic root group (n=7; 46.3±7.1 years) were older than those in the normal aortic root group (n=24; 34.8±8.4 years) (p = 0.008). The disease duration was significantly longer in the dilation group (13.1±5.4 years vs. 7.8±6.0 years, p=0.031). However, no significant differences were found between aortic root dilation and gender, duration of biologic therapy, or the extra-articular manifestations of peripheral arthritis and uveitis (p>0.05) (Table 3).
The most frequent associated abnormality was aortic regurgitation, affecting five patients (71%). Functional impairments were also common, with diastolic dysfunction noted in three patients (43%). Structurally, two patients (29%) presented with left ventricular hypertrophy (LVH), and in both cases, this was accompanied by mild systolic dysfunction, indicating a complex and severe cardiac phenotype (Table 3).
Table 3. Comparison between ankylosing spondylitis patients with and without aortic root dilation
|
Variables |
Normal Aortic Root (n = 24) |
Dilated Aortic Root (n = 7) |
p- value |
|
Age, years |
34.8±8.4 |
46.3 ± 7.1 |
0.008 |
|
Male gender |
18 (75 %) |
5 (71 %) |
0.81 |
|
Disease duration, years |
7.8 ± 6.0 |
13.1 ± 5.4 |
0.031 |
|
Biologic therapy duration, years |
2.4 ± 2.8 |
3.1 ± 2.9 |
0.52 |
|
Peripheral arthritis, yes |
7 (29 %) |
3 (43 %) |
0.48 |
|
Uveitis, yes |
5 (21 %) |
1 (14 %) |
0.68 |
The ECG findings in 7 cases with aortic root dilation have been shown that 4 patients presented with AR (2 mild AR and two trivial AR), and three with normal valvular results (Table 4).
Table 4. Echocardiographic abnormalities in patients with aortic root dilation (n = 7)
|
Age |
Gender |
Valvular Lesion |
LV Function |
Diastolic Grade |
Other Findings |
|
48 |
Male |
Trivial AR |
Normal EF |
None |
– |
|
55 |
Male |
Normal |
Normal EF |
None |
– |
|
38 |
Male |
Mild AR |
Normal EF |
Mild |
– |
|
56 |
Female |
Trivial AR |
Mild LV Dysfunction |
Mild |
LVH, Hypokinesia |
|
26 |
Female |
Normal |
Normal EF |
None |
– |
|
47 |
Male |
Mild AR |
Mild LV Dysfunction |
Mild |
LVH |
|
38 |
Male |
Mild AR |
Normal EF |
Mild |
– |
Aortic root diameter demonstrated a moderate positive correlation with patient age (r=+0.46, p=0.01) and a modest positive correlation with disease duration (r=+0.39, p=0.03), while the duration of biologic therapy, a history of peripheral arthritis, and a history of uveitis demonstrated no significant correlation with aortic root diameter (p>0.05) (Table 5).
Table 5. Correlation of clinical and demographic parameters with aortic root diameter
|
Variable |
Correlation with Aortic Root Diameter (r) |
p-value |
|
Age |
+0.46 |
0.01 |
|
Disease duration |
+0.39 |
0.03 |
|
Biologic therapy duration |
+0.12 |
0.55 |
|
Peripheral arthritis |
+0.18 |
0.33 |
|
Uveitis |
+0.09 |
0.64 |
The patients enrolled in the present study are characteristic of the phenotypic presentation of AS, as reflected by a higher male prevalence and early disease onset. The male-to-female ratio is 4:1 (80.6% male), which is consistent with published epidemiological data (Ncube et al., 2023; Tam et al., 2023; Anderson et al., 2024; Gentile et al., 2024; Kariri et al., 2024), that consistently report a higher rate and more severe disease in male patients (Bakland et al., 2011; van der Horst-Bruinsma et al., 2013; Rutten et al., 2022). The age of patients (37.3 years) and the disease duration (9.5 years) reflect the chronic nature of AS, which is evident in immediate adulthood, with a wider disease duration (0.25 to 35 years) (Ebrahimiadib et al., 2021; Hwang et al., 2021; Machate et al., 2022; Xie et al., 2023).
The duration of biological agent administration (15.6 months) indicates that a large number of patients have been subjected to long-term therapy (Lindström et al., 2019; Tański, Świątoniowska-Lonc, et al., 2021). These results are crucial, as they confirm that the study population is matched for investigating cardiac indices of AS in settings pertinent to rheumatological practice (Candemir et al., 2020; Sen et al., 2021; Januszewicz et al., 2022).
ECG results demonstrated subclinical cardiac association in patients with AS, confirming the systemic inflammatory potential of this condition (Grygiel-Górniak et al., 2020; Tański et al., 2021; Hassan & Hatah, 2022). The findings related to the aortic root and valve align with the known predilection of AS for aortitis, leading to chronic inflammation and, in turn, scarring of the aortic wall at the base of the valve cusps, resulting in root dilation and valvular deficits (Grygiel-Górniak et al., 2020; Willerson & Buja, 2020; Silva-Hormazábal & Alsina, 2023). Moreover, diastolic and systolic impairment, diastolic dysfunction is a consequence of myocardial inflammation, which can interrupt ventricular relaxation (Triantafyllou et al., 2021; Guo et al., 2022; Gulhane & Ordovas, 2023; Khalil, 2023), reflecting the disconnect between rheumatic and cardiac disease, because some of these ECG findings were positive in asymptomatic patients (Candemir et al., 2020; Sen et al., 2021; Constantin et al., 2022), necessitating the routine care of AS patients to mitigate long-term morbidity.
Older age and longer disease duration are non-modifiable risk factors; patients with aortic root dilation were older and had 5 more years of disease duration on average compared to those with normal aortic roots (Naser et al., 2023; Singh et al., 2023; Fabris et al., 2025). The long-term effects of insults on elastic aortic tissue lead to continuous dilation over time (Mitchell, 2018; Zhou et al., 2022; Kajanova & Badrov, 2024).
The duration of biologic therapy may be insufficient to halt the progression of subclinical aortopathy in all patients (Williams, 2024). Moreover, the lack of correlation with other extra-articular manifestations (e.g., peripheral arthritis and uveitis) necessitates echocardiographic screening (van der Horst-Bruinsma et al., 2013; Uccello et al., 2024) in older AS patients and those with long disease duration, to enable early diagnosis and management (Toussirot, 2015; Crossfield et al., 2021; Lembo et al., 2023). The high prevalence of AR in 71% of these patients reflects a direct mechanistic link; dilation of the aortic root mechanically dilates the valve base, leading to valvular dysfunction.
Other cardiac involvements, such as diastolic impairment, left ventricular hypertrophy, and mild systolic dysfunction, are consistent with a phenotype of AS cardiomyopathy, which is thought to arise from inflammation, vasculopathy, and secondary hemodynamic collapse from chronic AR (Ciarambino et al., 2021; Januszewicz et al., 2022; Ajmone Marsan et al., 2024; Uccello et al., 2024; Gasimova et al., 2025).
This clustering of cardiac abnormalities in patients with aortic root dilation suggests that the diagnosis of an aortic root abnormality should not be viewed as a singular finding but rather as a cluster of diseases to differentiate from associated progressive valvular and myocardial disease (Willerson & Buja, 2020; Zhou et al., 2022). The progressive nature of aortopathy in AS reflects that the inflammatory damage to the aortic wall is not a single event but a continuous process, in which cumulative inflammation leads to progressive structural deterioration and dilation (Hwang et al., 2021; Assadiasl & Soleimanifar, 2022). This finding solidifies the concept that time is a determinant of cardiac risk in AS. No correlation with the duration of biologic therapy exists, perhaps due to the intrinsic nature of the disease, or it may reflect that treatment was started after irreversible damage had already been initiated.
Conclusion
The study found that aortic root diameter in AS is more frequent in males, and that disease duration and systemic inflammation are associated with greater strength, highlighting a subset of AS patients who may need cardiovascular screening and thereby mitigate the long-term cardiovascular sequelae of this inflammatory condition.
Acknowledgments: The author is grateful to the University of Duhok for the provided support that encourage conducting this study.
Conflict of interest: None
Financial support: None
Ethics statement: The present study registered for approval in the College of Medicine, University of Duhok (Approval Code 10552 on 01 Aug 2024).
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