IntroductionThe nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in ...this regard are yet to be assessed.MethodsStudy including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment.ResultsAfter a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (β coefficient: −1.2 (95% CI: −0.3 to −0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (β coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high–very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis.ConclusionInflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.
To determine the potential impact of sex-specific disease-related characteristics on cardiovascular (CV) disease in axial spondyloarthritis (axSpA).
Cross-sectional study of the Spanish AtheSpAin ...cohort to study CV disease in axSpA. Data on carotid ultrasound and CV disease and disease-related features were collected.
611 men and 301 women were recruited. Classic CV risk factors were significantly less prevalent in women, who also showed a lower frequency of carotid plaques (p = 0.001), lower carotid intima-media thickness (IMT) values (p<0.001) and CV events (p = 0.008). However, after adjustment for classic CV risk factors, only the differences with respect to carotid IMT remained statistically significant. Women showed higher ESR at diagnosis (p = 0.038), and more active disease (ASDAS, p = 0.012, and BASDAI, p<0.001). They had shorter disease duration (p<0.001), lower prevalence of psoriasis (p = 0.008), less structural damage (mSASSS, p<0.001), and less mobility limitation (BASMI, p = 0.033). To establish whether these findings could lead to sex differences in CV disease burden, we compared the prevalence of carotid plaques in men and women with the same level of CV risk stratified according to the Systematic Coronary Risk Evaluation (SCORE). Men included in the low-moderate CV risk SCORE category had more carotid plaques (p = 0.050), along with longer disease duration (p = 0.004), higher mSASSS (p = 0.001) and psoriasis (p = 0.023). In contrast, in the high-very high-risk SCORE category, carotid plaques were observed more frequently in women (p = 0.028), who were characterized as having worse BASFI (p = 0.011), BASDAI (p<0.001) and ASDAS (p = 0.027).
Disease-related features may influence the expression of atherosclerosis in patients with axSpA. This may be especially applicable to women at high CV risk, characterized by greater disease severity and more severe subclinical atherosclerosis than men, suggesting a stronger interaction between disease activity and atherosclerosis in women with axSpA.
•Identifying pro-atherogenic factors in rheumatic diseases can help prevent cardiovascular events.•Axial spondyloarthritis features associated with atherosclerosis remain unclear.•Inflammation and ...disease severity are associated with atherosclerosis in axial spondyloarthritis.
To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA).
This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection.
639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients.
Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA.
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Cardiovascular (CV) disease is the main cause of mortality in axial spondyloarthritis (axSpA). CV risk is enhanced by dysregulation of adipokines. Low omentin levels were associated with metabolic ...dysfunction and CV disease in conditions different from axSpA. Accordingly, we evaluated the genetic and functional implication of omentin in CV risk and subclinical atherosclerosis in a cohort of 385 axSpA patients. Subclinical atherosclerosis was evaluated by carotid ultrasound. Omentin rs12409609, in linkage disequilibrium with a polymorphism associated with CV risk, was genotyped in 385 patients and 84 controls. Serum omentin levels were also determined. omentin mRNA expression was assessed in a subgroup of individuals. Serum and mRNA omentin levels were lower in axSpA compared to controls. Low serum omentin levels were related to male sex, obesity, inflammatory bowel disease (IBD) and high atherogenic index. rs12409609 minor allele was associated with low omentin mRNA expression in axSpA. No association was observed with subclinical atherosclerosis at the genetic or functional level. In conclusion, in our study low omentin serum levels were associated with CV risk factors in axSpA. Furthermore, rs12409609 minor allele may be downregulating the expression of omentin. These data support a role of omentin as a CV risk biomarker in axSpA.
Abstract
Objective
The aim was to assess clinical improvement after US-guided injection of CSs into the SI joint of patients with SpA.
Methods
This was an observational, descriptive, retrospective ...study of patients with SpA and sacroiliitis who received an US-guided injection into the SI joint between 1 June 2020 and 31 May 2021. Means were compared using Student’s paired t-test for the variables visual analog scale (VAS), BASDAI, ASDAS, CRP and ESR before and after the procedure. We evaluated the association between these variables and the clinical response using the odds ratio.
Results
We analysed 32 patients with SpA age 42.69 (8.19) years; female sex, 56.25%, with a VAS score of 7.88 (0.79), BASDAI of 5.43 (1.48) and ASDAS of 3.27 (0.86) before the procedure. At 2–3 months, 75% of patients had improved: VAS 3.81 (2.33) (−4.07, P < 0.0001) and BASDAI 3.24 (1.6) (−2.19, P < 0.0001). At 5–6 months, 59.37% had improved: VAS 4.63 (2.31) (−3.25, P < 0.0001), BASDAI 3.57 (1.67) (−1.86, P < 0.0001) and ASDAS 2.27 (0.71) (−1.0, P < 0.0001). Bone marrow oedema resolved in 87.5% of cases compared with the previous MRI scan. No significant association was identified with the clinical response to the injection.
Conclusion
US-guided injection of CSs into the SI joint of patients with SpA and active sacroiliitis leads to an improvement in symptoms that is maintained at 5–6 months. The procedure is effective, safe, inexpensive and easy to apply.
Background:
Axial spondyloarthritis (axSpA) patients are known to have a higher prevalence of several comorbidities, including, among others, an increased risk of atherosclerosis, hypertension, ...dyslipidemia, and diabetes. The purpose of the present study was to determine whether the sum of traditional cardiovascular (CV) risk factors is related to disease characteristics, such as disease activity, in patients with axSpA.
Methods:
A cross-sectional study that encompassed 804 patients with axSpA was conducted. Patients were assessed for the presence of five traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking status), and disease activity measurements. A multivariable regression analysis was performed to evaluate whether the number of classic CV risk factors was independently associated with specific features of the disease, to include disease activity.
Results:
A multivariable analysis showed that Ankylosing Spondylitis Disease Activity Score–C reactive protein (ASDAS-CRP) activity score was significantly higher in patients with 1 beta coefficient 0.3 (95% confidence interval (CI) 0.1–0.5), p = 0.001 and ⩾2 beta coefficient 0.5 (95% CI 0.3–0.7), p = 0.000 CV risk factors compared with those without CV risk factors. Similarly, patients with 1 OR 2.00 (95%CI 0.99–4.02), p = 0.053 and ⩾2 OR 3.39 (95%CI 1.82–6.31), p = 0.000 CV risk factors had a higher odds ratio for the presence of high disease activity compared with the zero CV category. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) activity score was significantly associated with the number of CV risk factors, being higher in patients with more CV risk factors. These relationships showed a CV risk factor-dependent effect being beta coefficients and ORs higher for the effect of ⩾2 over 1 CV risk factor.
Conclusion:
Among patients with axSpA, as the number of traditional CV risk factors increased, disease activity similarly increases in an independent manner.
To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA).
This is a ...cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected.
888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs.
Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids.
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To compare the atherosclerosis disease burden between ankylosing spondylitis (AS) and non-radiographic (nr) axial spondyloarthritis (axSpA) and establish a model that allows to identify ...high-cardiovascular (CV) risk in axial spondyloarthritis patients.
Cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort aimed to study atherosclerosis in axSpA. Carotid ultrasound (US) was performed to determine the carotid intima-media wall thickness (cIMT) and detect the presence of carotid plaques. The European cardiovascular disease risk assessment model, the Systematic COronary Risk Evaluation (SCORE), was also applied.
A set of 639 patients with AS and 167 patients with nr-axSpA without history of CV events were recruited. AS patients were older showing more CV risk factors and higher values of C reactive protein and erythrocyte sedimentation rate (ESR) than those with nr-axSpA. However, no difference in the prevalence of carotid plaques or in the cIMT was found between both groups in the adjusted analysis. The percentage of patients reclassified from the low and moderate CV risk categories to the very high-risk category due to the presence of carotid plaques was comparable in AS and nr-axSpA (10.7% versus 10.1% and 40.5% versus 45.5%, respectively). A model containing age, BASFI and ESR applied to moderate risk axSpA patients identified 41% of these patients as having very high-risk patients with high specificity (88%).
The atherosclerosis burden is similar in nr-axSpA and AS. As occurred for AS, more than 40% of axSpA patients included in the category of moderate CV risk according to the SCORE are reclassified into very high risk after carotid US, and a clinically relevant proportion of them can be detected by applying a model containing age, BASFI and ESR.
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Rheumatoid Arthritis (RA) has a mortality rate 1,3 to 3 times higher than the general population, with cardiovascular mortality accounting for 40–50% of cases. Currently, cardiovascular disease is ...considered an extraarticular manifestation of RA (OR: 1,5–4,0). Ultrasound measurement of the intima-media thickness (IMT) of the common carotid artery and the presence of atherosclerotic plaques (AP) is a non-invasive method and a surrogate marker of subclinical arteriosclerosis.
To determine if subclinical arteriosclerosis findings through carotid ultrasound can serve as a good predictor of cardiovascular events (CVE) development in a cohort of RA patients over a 10-year period.
A cohort of RA patients seen in the Rheumatology outpatient clinic of a hospital in Castilla La Mancha in 2013 was evaluated. A prospective evaluation for the development of CVE over the following 10 years was conducted, and its correlation with previous ultrasound findings of IMT and AP was analyzed.
Eight (24%) patients experienced a CVE. Three (9%) had heart failure, three (9%) had a stroke, and two (6%) experienced acute myocardial infarction. RA patients who developed a CVE had a higher IMT (0,97 +/− 0.08 mm) compared to the RA patients without CV complications (0,74 +/− 0.15 mm) (p = 0,003). The presence of IMT ≥ 0.9 mm and AP had a relative risk of 12,25 (p = 0,012) and 18,66 (p = 0,003), respectively, for the development of a CVE.
Carotid ultrasound in RA patients may allow for early detection of subclinical atherosclerosis before the development of CVE, with IMT ≥ 0.9 mm being the most closely associated finding with CVE, unaffected by age.
La Artritis Reumatoide (AR) presenta una mortalidad de 1,3 a 3 veces superior a la población general donde destaca la mortalidad de origen cardiovascular con un 40–50%. Actualmente se considera a la enfermedad cardiovascular como una manifestación extraarticular de la AR, siendo un factor de riesgo independiente de los tradicionales, con un riesgo elevado de enfermedad cardiovascular (OR: 1,5–4,0). La medición ecográfica del grosor íntimo medial (GIM) de la arteria carótida común y la presencia de placas ateromatosas (PA) es un método no invasivo y marcador subrogado de arterioesclerosis subclínica.
Establecer si los hallazgos de arterioesclerosis subclínica por ecografía carotídea pueden ser un buen predictor del desarrollo de eventos cardiovasculares (ECV) en una cohorte de pacientes con AR a 10 años.
Se evaluó una cohorte de pacientes con AR atendidos en consulta externa de Reumatología de una hospital de Castilla La Mancha durante el año 2013. Se realizó una evaluación para el desarrollo de ECV a los 10 años siguientes de comenzado el estudio y se analizó su correlación con los hallazgos ecográficos previos de GIM y PA.
8 (24%) pacientes presentaron un ECV. 3 (9%) episodio de Fallo cardiaco, 3 (9%) accidente cerebro vascular y 2 (6%) episodio de infarto agudo al miocardio. Los pacientes con AR que desarrollaron un ECV habían presentado un GIM mayor (0,97 +/− 0,08 mm) en comparación con los pacientes con AR que no tuvieron complicaciones CV (0,74 +/− 0,15 mm) (p = 0,003). La presencia de un a GIM ≥ 0,9 mm y PA presentó un riesgo relativo de 12,25 (p = 0,012) y 18,66 (p = 0,003), respectivamente, para el desarrollo de un ECV.
La ecografía carotídea en pacientes con AR nos podría permitir la detección precoz de aterosclerosis subclínica antes del desarrollo de ECV, siendo fundamentalmente el GIM ≥ 0,9 mm el hallazgo más asociado a ECV y no influenciado por la edad.
Introduction
Patients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher ...incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients.
Methods
A large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four
irisin
polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA.
Results
Low irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ≥4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p<0.001) and negatively correlated with visual analogue scale and Bath Ankylosing Spondylitis Metrology Index (p<0.05 in all the cases). Moreover, lower irisin levels were observed in patients with sacroiliitis and in those with a negative HLA-B27 status (p<0.001 and p=0.006, respectively), as well as in those treated with non-steroidal anti-inflammatory drugs and conventional disease-modifying antirheumatic drugs (p<0.001 and p=0.002, respectively). Interestingly, the TT genotype and the T allele of rs16835198 were less frequent in axSpA patients with ASDAS >2.1 (Odds Ratio (OR): 0.48 0.28-0.83 and OR: 0.73 0.57-0.92, respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 1.08-1.97, p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 1.13-2.66, p=0.01).
Conclusions
Our results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition,
irisin
may also constitute a genetic biomarker of disease activity in axSpA.
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