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.
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.
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.
The 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitides defined drug-associated immune complex vasculitis as a distinct entity included within the category of ...vasculitis associated with probable etiology. In the present study we assessed the clinical spectrum of patients with drug-associated cutaneous vasculitis (DACV).
Case records were reviewed of patients with DACV treated at a tertiary referral hospital over a 36-year period. A diagnosis of DACV was considered if the drug was taken within a week before the onset of the disease.
From a series of 773 unselected cutaneous vasculitis cases, 239 patients (30.9%; 133 men and 106 women; mean age 36 yrs) were diagnosed with DACV. Antibiotics (n=149; 62.3%), mainly β-lactams and nonsteroidal antiinflammatory drugs (NSAID; n=24; 10%) were the most common drugs. Besides skin lesions (100%), the most common clinical features were joint (51%) and gastrointestinal (38.1%) manifestations, nephropathy (34.7%), and fever (23.8%). The most remarkable laboratory data were increased erythrocyte sedimentation rate (40.2%), presence of serum cryoglobulins (26%), leukocytosis (24.7%), positive antinuclear antibodies (21.1%), anemia (18.8%), and positive rheumatoid factor (17.5%). Despite drug discontinuation and bed rest, 108 patients (45.2%) required medical treatment, mainly corticosteroids (n=71) or immunosuppressive drugs (n=7). After a median followup of 5 months, relapses occurred in 18.4% of patients, and persistent microhematuria or renal insufficiency in 3.3% and 5%, respectively.
DACV is generally associated with antibiotics and NSAID. In most cases it has a favorable prognosis, although a small percentage of patients may develop residual renal damage.
This study aimed to determine whether, besides carotid ultrasound (US), a lateral lumbar spine radiography may also help identify ankylosing spondylitis (AS) patients at high risk of cardiovascular ...(CV) disease.
A set of 125 AS patients older than 35 years without a history of CV events, diabetes mellitus, or chronic kidney disease was recruited. Carotid US and lateral lumbar spine radiography were performed in all of them. The CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) algorithm. Presence of carotid plaques was defined following the Mannheim Carotid Intima-media Thickness and Plaque Consensus. Abdominal aortic calcium (AAC) in a plain radiography was defined as calcific densities visible in an area parallel and anterior to the lumbar spine.
Carotid US showed higher sensitivity than lateral lumbar spine radiography to detect high CV risk in the 54 patients with moderate TC-SCORE (61% versus 38.9%). Using carotid plaques as the gold standard test, a predictive model that included a TC-SCORE ≥ 5% or the presence of AAC in the lateral lumbar spine radiography in patients with both moderate and low CV risk (< 5%) according to the TC-SCORE yielded a sensitivity of 50.9% with a specificity of 95.7% to identify high/very high CV-risk AS patients. A positive correlation between AAC and carotid plaques was observed (r
= 0.49, p < 0.001).
A lateral lumbar spine radiography is a useful tool to identify patients with AS at high risk of CV disease.
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.
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.
Purpose: Psoriasis patients have high risk of atherosclerosis, characterized by endothelial dysfunction. We aimed to study the association of the endothelial activation biomarkers monocyte ...chemoattractant protein 1 (MCP-1), soluble (s) E-selectin and P-selectin with disease activity and severity in psoriasis patients treated with anti-TNF-α therapy. Also, to evaluate the relationship of metabolic syndrome features with these biomarkers and the effect of anti-TNF-α therapy on these molecules.
Methods: Twenty-nine consecutive non-diabetic patients with moderate-to-severe psoriasis who underwent 6 months of anti-TNF-α-adalimumab therapy were studied. Metabolic and clinical evaluation was performed prior to anti-TNF-α treatment (time 0) and 6 months later. MCP-1, sE-selectin and sP-selectin serum levels were determined by ELISA.
Results: Dyslipidemic and obese patients showed higher MCP-1 levels at month 6 from the onset of anti-TNF-α therapy (p = .05 and .01, respectively). sE-selectin positively correlated with pro-inflammatory molecules such as asymmetric dimethylarginine, sP-selectin and resistin at baseline and month 6 (p < .05). sE-selectin levels significantly reduced after 6 months of therapy (p = .0006).
Conclusions: Metabolic syndrome features are associated with endothelial activation in patients with moderate-to-severe psoriasis. Adalimumab therapy led to a reduction in sE-selectin levels, supporting the beneficial effect of anti-TNF-α therapy on mechanisms associated with the development of atherosclerosis in psoriasis.
Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association ...studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA.
One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography.
No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP) status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA) after adjustment for demographic and classic CV risk factors (HR 95%CI=0.36 0.14-0.94, p=0.038) in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094) in the anti-CCP negative RA patients.
Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have importance to establish predictive models of CV disease in RA patients according to anti-CCP status.
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