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.
Modulators of triglyceride metabolism include lipoprotein lipase (LPL), angiopoietin-like protein 4 (ANGPTL4), and apolipoprotein C-3 (ApoC3). There is evidence on the influence of this triangle of ...molecules on an increased risk of atherosclerotic cardiovascular disease (CV) in the general population. Patients with rheumatoid arthritis (RA) present changes in lipid profiles and accelerated CV disease. In the present study, we set out to study whether the ANGPTL4, ApoC3, and LPL axis differs in subjects with RA compared to controls. In a further step, we investigated the relationship of this axis with subclinical atherosclerosis in patients with RA.
Cross-sectional study that included 569 individuals, 323 patients with RA and 246 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in RA patients. A multivariable analysis was performed to assess whether the ANGPTL4, ApoC3, and LPL axis was altered in RA and to study its relationship with RA dyslipidemia and subclinical carotid atherosclerosis.
Most lipid profile molecules did not differ between patients and controls. Despite this, and after fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with RA showed higher serum levels of ANGPTL4 (beta coef. 295 95% CI 213-376 ng/ml, p<0.001) and ApoC3 (beta coef. 2.9 95% CI 1.7-4.0 mg/dl, p<0.001), but lower circulating LPL (beta coef. -174 95% CI -213 to -135 ng/ml, p<0.001). ANGPTL4 serum levels were positively and independently associated with a higher cIMT in patients with RA after fully multivariable adjustment.
The axis consisting in ANGPTL4, ApoC3, and LPL is disrupted in patients with RA. ANGPTL4 serum levels are positively and independently associated with a higher cIMT in RA patients.
Systemic lupus erythematosus (SLE) has been associated with atherosclerotic cardiovascular disease (CV) and an altered lipid profile. High levels of apolipoprotein C-III (ApoC3) are associated with ...elevated triglyceride levels and an increased risk of CV. In the present study, we aimed to study circulating ApoC3 in patients with SLE and describe its relationship with the manifestations of the disease.
This is a cross-sectional study that included 186 patients with SLE. Disease-related data, CV comorbidity, full lipid profile, and serum levels of ApoC3 were assessed. A multivariable regression analysis was performed to study how ApoC3 was related to SLE features.
Classic CV risk factors were significantly and strongly associated with circulating ApoC3. After a fully multivariable analysis that included classic CV risk factors and lipid profile molecules, SLICC damage (beta coef. 0.10 95% CI 0.02-0.19 mg/dl, 0.020) and Katz severity (beta coef. 0.11 95% CI 0.03-0.19 mg/dl, p = 0.011) indices and SLEDAI activity score (beta coef. 0.05 95% CI 0.05-0.08 mg/dl, p = 0.004) were all independently associated with higher levels of circulating ApoC3.
Among SLE patients, disease activity, severity, and disease damage are independently associated with higher ApoC3 serum levels.
Objectives
To evaluate the prevalence of self-perceived depression and anxiety in patients with systemic lupus erythematosus (SLE) and to explore associated factors.
Methods
Cross-sectional study of ...unselected patients with SLE (ACR-97 criteria) and controls with chronic inflammatory rheumatic diseases. Both completed the Hospital Anxiety and Depression Scale (HADS). Demographic and clinical characteristics, comorbidity, and treatments were collected, and a multivariate analysis was performed to explore factors associated with depression and anxiety in SLE.
Results
The study population comprised 172 patients and 215 controls. Women accounted for 93% of the patients with SLE. Fibromyalgia was recorded in 12.8% and a history of depression in 17%. According to HADS, 37.2% fulfilled the diagnostic criteria for depression and 58.7% those for anxiety; prevalence was similar in the controls (32.6% and 55.1%, respectively). Up to a third of patients with self-perceived depression were not receiving antidepressants. There was no concordance between a previous history of depression and current depression. In the multivariate model, current depression was associated with single marital status (OR 2.69; 95% CI: 1.17–6.42; p = .022), fibromyalgia (7.69; 2.35–30.72; p = .001), smoking (3.12; 1.24–8.07; p = .016), severity of SLE (0.76; 0.6–0.94; p = .016), and organ damage (1.27; 1.01–1.61; p = .042). Current anxiety was only associated with fibromyalgia (3.97; 1.21–17.98; p = .036).
Conclusions
Depression and anxiety are most likely underdiagnosed in SLE. Prevalence appears to be similar to that of other chronic inflammatory rheumatic diseases. Anxiety is associated with fibromyalgia, while depression is also associated with single marital status, smoking, organ damage, and severity of SLE.
Abstract
Interleukin (IL) 1, and its family member, IL-1 receptor antagonist (IL-1ra), are involved in the pathogenesis and inflammation perpetuation of patients with rheumatoid arthritis (RA). ...Besides, IL-1 has been linked to an increased risk and greater severity of cardiovascular (CV) disease. We aimed to study if IL-1ra is related to the CV manifestations—including lipid pattern and insulin resistance or subclinical atherosclerosis—that accompanies the disease in a large series of patients with RA. Cross-sectional study that encompassed 430 patients with RA. Serum IL-1ra levels were assessed. A multivariable analysis was performed to analyze the relation of IL-1ra to subclinical carotid atherosclerosis, and to traditional CV factors including a complete lipid molecules profile and insulin resistance or beta cell function indices. Body mass index, abdominal circumference, and the presence of obesity were significantly and positively associated with circulating IL-1ra. Similarly, erythrocyte sedimentation rate, and disease activity scores were significantly related to higher IL-1ra serum levels after adjustment for confounders. Neither carotid intima-media thickness nor the presence of carotid plaque were associated with serum levels of IL-1ra. However, after multivariable analysis circulating IL-1ra was independently and positively associated with higher serum levels of total cholesterol, triglycerides, and apolipoproteins B and C-III. Similarly, IL-1ra was related to higher levels of beta-cell function in the univariable analysis, although, in this case, significance was lost after adjustment. Among patients with RA, IL-1ra is associated with both disease activity and several traditional CV risk factors such as obesity and the presence of higher lipid levels. Our findings suggest that IL-1ra can represent a link between the inflammation and the CV disease risk that are present in patients with RA.
SLE has been described as an independent risk factor for the development of cardiovascular (CV) disease. Recently, the QRESEARCH risk estimator version 3 (QRISK3) calculator has been launched for CV ...risk assessment in the general population. QRISK3 now includes the presence of SLE as one of its variables for calculating CV risk. Our objective was to compare the predictive capacity between QRISK3 and the Systematic Coronary Risk Evaluation (SCORE) for the presence of subclinical carotid atherosclerosis in patients with SLE.
Two hundred and ninety-six patients with SLE were recruited. The presence of subclinical atherosclerosis was evaluated by carotid ultrasound to identify carotid plaque and the thickness of the carotid intima-media (cIMT). QRISK3 and SCORE were calculated. The relationship of QRISK3 and SCORE with each other and with the presence of subclinical carotid atherosclerosis (both carotid plaque and cIMT) was studied.
There was no correlation between SCORE and QRISK3 in patients with SLE (Spearman's rho = -0.008, P = 0.90). Although QRISK3 showed a statistically significant correlation with cIMT (Spearman's rho = 0.420, P = 0.000), this relationship was not found between SCORE and cIMT (Spearman's rho = -0.005, P = 0.93). The discrimination capacity of QRISK3 for the presence of carotid plaque was statistically significant and superior to that of SCORE (AUC 0.765 95% CI: 0.711, 0.820 vs 0.561 95% CI: 0.494, 0.629, P = 0.000).
QRISK3 discrimination for subclinical atherosclerosis is higher than that of SCORE. QRISK3, and not SCORE, should be used for the calculation of CV risk in patients with SLE.
Insulin resistance and beta-cell dysfunction are manifestations of rheumatoid arthritis (RA). Apolipoprotein C-III (ApoC3) has been associated with such insulin resistance and beta-cell dysfunction ...in the general population. Our purpose was to study whether ApoC3 is also related to the insulin resistance and beta-cell dysfunction that are present in patients with RA.
Three hundred thirty-eight non-diabetic patients with RA who had a glycemia lower than 110 mg/dl were recruited. Insulin, C-peptide, and ApoC3 were assessed. Insulin resistance and beta-cell function were calculated using the Homeostasis Model Assessment (HOMA2) indices. A multivariable regression analysis was performed to study the relationship of ApoC3 with those molecules and indices adjusting for classic factors associated with insulin resistance that included glucocorticoids.
ApoC3 was related to significant higher levels of circulating insulin (beta coef. 0.37 95%CI 0.01-0.73 µU/ml, p = 0.044) and C-peptide (beta coef. 0.13 95%CI 0.05-0.22 ng/ml, p = 0.003), and higher insulin resistance -HOMA2-IR- (beta coef. 0.05 95%CI 0.00-0.09, p = 0.041) and beta-cell dysfunction -HOMA2-%B- (beta coef. 2.94 95%CI 0.07-5.80, p = 0.044) indices. This was found after a fully multivariable analysis that included, among others, prednisone intake and the classic factors associated with carbohydrate metabolism such as triglycerides, waist circumference, and obesity.
ApoC3, insulin resistance, and beta-cell dysfunction are independently associated in patients RA.
Transforming growth factor beta (TGF-β1) is a multifunctional cytokine that has anti-inflammatory and immunosuppressive effects. TGF-β1 has been linked to cardiovascular disease in the general ...population. The immunosuppressive effect of TGF-β1 is believed to be dysregulated in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to study the relationship of serum levels of TGF-β1 with subclinical carotid atherosclerosis in patients with SLE.
The study included 284 patients with SLE. Serum levels of TGF-β1 and subclinical carotid atherosclerosis (by carotid ultrasonography) were evaluated. In addition, the complete lipid profile and insulin resistance were analyzed. Multivariable linear and logistic regression analysis was performed to establish the relationship of TGF-β1 with carotid subclinical atherosclerosis adjusting for traditional cardiovascular risk factors that included lipid profile and insulin resistance.
Circulating TGF-β1 was positively and significantly associated with higher levels of LDL:HDL cholesterol ratio and atherogenic index. TGF-β1 was also associated with significantly lower levels of HDL cholesterol and apolipoprotein A1. Remarkably, TGF-β1 was associated with the presence of carotid plaque not only after adjustment for demographics (age, sex, body mass index, diabetes, hypertension, and aspirin use) but also after adjustment for relationships of TGF-β1 with lipid profile molecules, insulin resistance, and SLEDAI disease score (odds ratio 1.14 95% confidence interval 1.003-1.30, p = 0.045).
TGF-β1 serum levels are positively and independently associated with the presence of subclinical atherosclerosis disease in patients with SLE.
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.
Vascular endothelial growth factor (VEGF) is a major regulator of physiological and pathological angiogenesis. Its soluble receptor (sVEGFR) is a potent VEGF antagonist. Systemic lupus erythematosus ...(SLE) is an autoimmune disease with a diverse array of clinical manifestations that affect virtually any organ. We aimed to analyze the relationship of VEGF and sVEGFR with SLE disease-related features including disease activity, damage, and severity. Serum levels of VEGF165 isoform and sVEGFR (receptor 1) were assessed in 284 well-characterized patients with SLE. Linear regression analysis was performed to analyze the relationship of disease characteristics with both VEGF and sVEGFR. Patients with a disease damage index (SLICC score) equal to or greater than 1 had significantly elevated serum levels of VEGF and sVEGFR. Regarding disease-specific features, musculoskeletal manifestations were the disease feature most commonly associated with the upregulation of both VEGF and sVEGFR. SLE disease damage is associated with higher levels of VEGF and sVEGFR.
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