Abstract
Background
Previous studies have shown that risk chart algorithms, such as the Systematic Coronary Risk Assessment (SCORE), often underestimate the actual cardiovascular (CV) risk of ...patients with rheumatoid arthritis (RA). In contrast, carotid ultrasound was found to be useful to identify RA patients at high CV. In the present study, we aimed to determine if specific disease features influence the CV risk reclassification of RA patients assessed by SCORE risk charts and carotid ultrasound.
Methods
1279 RA patients without previous CV events, diabetes, or chronic kidney disease were studied. Disease characteristics including disease activity scores, CV comorbidity, SCORE calculation, and the presence of carotid plaque by carotid ultrasound were assessed. A multivariable regression analysis was performed to evaluate if the reclassification into very high CV risk category was independently associated with specific features of the disease including disease activity. Additionally, a prediction model for reclassification was constructed in RA patients.
Results
After carotid ultrasound assessments, 54% of the patients had carotid plaque and consequently fulfilled definition for very high CV risk. Disease activity was statistically significantly associated with reclassification after fully multivariable analysis. A predictive model containing the presence of dyslipidemia and hypertension, an age exceeding 54 years, and a DAS28-ESR score equal or higher than 2.6 yielded the highest discrimination for reclassification.
Conclusion
Reclassification into very high CV risk after carotid ultrasound assessment occurs in more than the half of patients with RA. This reclassification can be independently explained by the activity of the disease.
The aim of this study was to determine the role of endothelin-1 (ET-1), a molecule involved in multiple vascular and fibrosing abnormalities, as a biomarker of interstitial lung disease (ILD), as ...well as its use for the differential diagnosis between idiopathic pulmonary fibrosis (IPF) and ILD associated with autoimmune diseases (AD-ILD), using a large and well-defined cohort of patients with ILD. A total of 112 patients with IPF, 91 patients with AD-ILD (28 rheumatoid arthritis (RA), 26 systemic sclerosis, 20 idiopathic inflammatory myositis and 17 interstitial pneumonia with autoimmune features) and 44 healthy controls were included. ET-1 serum levels were determined by enzyme-linked immunosorbent assay. A significant increase in ET-1 levels was found in patients with IPF compared to controls. Likewise, AD-ILD patients also showed higher ET-1 levels than controls when the whole cohort was stratified by the type of AD. Similar ET-1 levels were found in IPF and AD-ILD patients, regardless of the underlying AD. Interestingly, increased ET-1 levels were correlated with worse lung function in IPF and RA-ILD patients. Our study supports that serum ET-1 may be useful as a biomarker of ILD, although it could not help in the differential diagnosis between IPF and AD-ILD. Moreover, ET-1 levels may be associated with ILD severity.
Background Chronic inflammatory diseases have been associated with increased prevalence of subclinical atherosclerosis. Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving ...intertriginous skin. Objective We sought to investigate the potential association between HS and subclinical atherosclerosis. Methods This study included 68 patients with HS and 136 age- and sex-matched healthy control subjects. Patients with history of cardiovascular events, diabetes mellitus, chronic kidney disease, or another concomitant inflammatory condition were excluded. Carotid intima-media thickness and carotid plaques were measured by carotid ultrasonography. Adjustments were made for age, sex, and traditional cardiovascular risk factors. Results Patients had greater carotid intima-media thickness values than control subjects (0.615 ± 0.097 vs 0.578 ± 0.098 mm; P = .012). Carotid plaques were also more frequent in patients than in control subjects (30.9% vs 22.1%). In the multivariable regression model adjusted for age, sex, and traditional cardiovascular risk factors, HS was significantly related to the presence of carotid plaques (odds ratio 2.99, 95% confidence interval 1.26-7.13; P = .013). Limitations Causality could not be assessed. Conclusions These results indicate an increased frequency of subclinical atherosclerosis in patients with HS. Accordingly, HS should be considered a disease associated with potentially increased cardiovascular risk.
Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA). Given the ...high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients, we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce. For this reason, we aimed to evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA.
This study included 510 patients diagnosed with axSpA. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242, rs7159023, and rs35262691) were genotyped by TaqMan probes. Serum vaspin levels were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed using STATA® v.11.1.
Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (p < 0.05). At the genetic level, we disclosed that the minor allele of rs2236242 (A) was associated with lower serum vaspin levels in axSpA, while the rs7159023 minor allele (A) was linked to higher serum levels (p < 0.05). When the three polymorphisms assessed were combined conforming haplotypes, we disclosed that the TGC haplotype related to high serum levels of vaspin (p = 0.01). However, no statistically significant association was observed between vaspin and markers of subclinical atherosclerosis, both at the genetic and serological level.
Our results revealed that vaspin is linked to CV risk factors that may influence on the atherosclerotic process in axSpA. Additionally, we disclosed that serum vaspin concentration is genetically modulated in a large cohort of patients with axSpA.
Interstitial lung disease (ILD) constitutes the most critical comorbidity in autoimmune diseases (ADs) and its early diagnosis remains a challenge for clinicians. Accordingly, we evaluated whether ...E-selectin, ICAM-1, and ET-1, key molecules in endothelial damage, could be useful biomarkers for the detection of AD-ILD
. We recruited patients with rheumatoid arthritis (RA)-ILD
(
= 21) and systemic sclerosis (SSc)-ILD
(
= 21). We included comparison groups of patients: RA-ILD
(
= 25), SSc-ILD
(
= 20), and idiopathic pulmonary fibrosis (IPF) (
= 21). Serum levels of these proteins were determined by ELISA. E-selectin, ICAM-1, and ET-1 serum levels were increased in RA-ILD
and IPF patients in comparison to RA-ILD
patients. Additionally, SSc-ILD
and IPF patients exhibited higher ICAM-1 levels than those with SSc-ILD
. The ability of E-selectin, ICAM-1, and ET-1 to discriminate RA-ILD
from RA-ILD
patients, and ICAM-1 to distinguish SSc-ILD
from SSc-ILD
patients was confirmed using ROC curve analysis. Furthermore, elevated levels of ET-1 and E-selectin correlated with lung function decline in RA-ILD
and SSc-ILD
patients, respectively. In conclusion, our findings support the relevant role of E-selectin, ICAM-1, and ET-1 in RA-ILD
patients as well as of ICAM-1 in SSc-ILD
patients, constituting potential screening blood biomarkers of ILD in AD. Moreover, this study suggests ET-1 and E-selectin as possible indicators of worsening lung function in RA-ILD
and SSc-ILD
patients, respectively.
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.
Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin‐2 (Ang‐2), asymmetric ...dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case–control study, we aimed to investigate serum Ang‐2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy‐five patients with HS and 60 controls were assessed. Serum Ang‐2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang‐2 and ADMA levels than controls after adjusting for confounders. Besides, Ang‐2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang‐2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang‐2 might be a suitable marker of HS severity.
The aim of the present study was to determine if the use of the anti‐tumor necrosis factor (TNF)‐α monoclonal antibody adalimumab could improve endothelial function and arterial stiffness in patients ...with moderate to severe psoriasis. This was a prospective study on a series of consecutive patients with moderate to severe psoriasis who completed 6 months of therapy with adalimumab. Patients with history of cardiovascular events, diabetes mellitus, kidney disease, hypertension or body mass index of 35 kg/m2 or more were excluded. Assessment of endothelial function by brachial artery reactivity measuring flow‐mediated endothelial dependent vasodilatation (FMD%), and carotid arterial stiffness by pulse wave velocity (PWV) was performed at the onset of treatment (time 0) and at month 6. Twenty‐nine patients were studied. Anti‐TNF‐α adalimumab therapy yielded a significant improvement of endothelial function. The mean ± standard deviation (SD) FMD% values increased from 6.19 ± 2.44% at the onset of adalimumab to 7.46 ± 2.43% after 6 months of treatment with this biologic agent (P = 0.008). Likewise, following the use of adalimumab, PWV levels decreased from 6.28 ± 1.04 m/s at the onset of adalimumab to 5.69 ± 1.31 m/s at 6 months (P = 0.03). In conclusion, patients with moderate to severe psoriasis exhibit improvement of endothelial function and arterial stiffness following anti‐TNF‐α therapy. These findings are of potential relevance due to increased risk of cardiovascular disease in patients with severe psoriasis.
Patients with rheumatoid arthritis (RA) have a higher incidence of subclinical atherosclerosis and cardiovascular (CV) disease. It is postulated that the appearance of accelerated atherosclerosis in ...these patients is a consequence of the inflammation present in the disease. In this study, we aim to determine if baseline disease activity in patients with RA predicts the future development of carotid plaque. A set of consecutive RA patients without a history of CV events, cancer or chronic kidney disease, who did not show carotid plaque in a carotid ultrasound assessment, were prospectively followed up for at least 5 years. At the time of recruitment, CV risk factors and disease-related data, including disease activity scores, were assessed. At the end of the follow-up, a carotid ultrasound was repeated and patients were divided into two groups; those who developed carotid plaque, and those who did not. A multivariable regression analysis was performed to define the predictors for the development of carotid plaque. One hundred and sixty patients with RA were followed up for an average of 6 ± 1 years. After this time, 66 (41%) of the patients had developed carotid plaque, and 94 (59%) did not. Patients with carotid plaque were significantly older (47 ± 13 vs. 55 ± 9 years, p < 0.001) at baseline, were more frequently diabetic (0% vs. 6%, p = 0.028), and had higher total cholesterol (197 ± 36 vs. 214 ± 40 mg/dL, p = 0.004) and LDL cholesterol (114 ± 35 vs. 126 ± 35 mg/dL, p = 0.037) at the beginning of the study. After multivariable adjustment, patients who were in the moderate and high disease activity (DAS28-CRP) categories displayed a higher odds ratio for the appearance of carotid plaque (OR 2.26 95% CI 1.02–5.00, p = 0.044) compared to those in the DAS-28-CRP remission category. Remarkably, when patients were divided in patients within the low-risk SCORE category, and patients included in the remaining SCORE categories (moderate, high and very high), the relation between DAS28-CRP and the development of carotid plaque was only significant in the low-risk SCORE category. In conclusion, disease activity predicts the future development of subclinical atherosclerosis in patients with RA.
To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid ...arthritis (RA).
A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US).
RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed.
In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA.
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