Malondialdehyde Serum Levels in a Full Characterized Series of 430 Rheumatoid Arthritis Patients.

Background. Oxidative stress has been involved in the pathogenesis of rheumatoid arthritis (RA). The serum malondialdehyde (MDA) level is a reliable biomarker of oxidative stress status. In the present work, we aimed to analyze how a comprehensive characterization of the disease characteristics in RA, including a lipid profile, insulin resistance, and subclinical atherosclerosis, relates to serum MDA levels. Methods. In a cross-sectional study that included 430 RA patients, serum MDA levels were evaluated. Multivariable analysis was performed to examine the relationship of MDA with disease activity scores and disease characteristics, including subclinical carotid atherosclerosis, a comprehensive lipid molecule profile, and indices of insulin resistance and beta cell function indices. Results. The erythrocyte sedimentation rate (ESR) showed a significant and positive relationship with MDA. However, this did not occur for other acute phase reactants such as C-reactive protein or interleukin-6. Although the DAS28-ESR score (Disease Activity Score in 28 joints) had a positive and significant association with MDA serum levels, other disease activity scores that do not use the erythrocyte sedimentation rate in their formula did not show a significant relationship with MDA. Other disease characteristics, such as disease duration and the existence of rheumatoid factor and antibodies against citrullinated protein, were not related to serum MDA levels. This also occurred for lipid profiles, insulin resistance indices, and subclinical carotid atherosclerosis, for which no associations with circulating MDA were found. Conclusions. The disease characteristics are not related to circulating MDA levels in patients with RA.

Interleukin-6 serum levels are associated with disease features and cardiovascular risk in patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is a chronic multisystem disease characterised by microcirculatory vascular dysfunction and progressive fibrosis of the skin and internal organs. Interleukin-6 (IL-6) is a proinflammatory cytokine that has been implicated in the pathogenesis of several autoimmune diseases and in the initiation and progression of the cardiovascular disease. In the present work we aimed to study the relationship of IL-6 with clinical manifestations and the cardiovascular risk in patients with SSc. METHODS: Cross-sectional study that included 53 individuals with SSc. A multivariate analysis was performed to study the relationship between IL-6 and disease characteristics and cardiovascular risk assessed by Systematic Coronary Risk Estimation (SCORE2) in SSc. RESULTS: The presence of digital ulcers, calcinosis, and anti-Scl70 antibody was associated with higher levels of IL-6. This was also the case for functional respiratory parameters where this association was found to be significant and negative after correction for covariates. In addition, the SCORE2 cardiovascular risk algorithm showed a positive and significant association with circulating IL-6. CONCLUSIONS: IL-6 levels are associated with disease manifestations and cardiovascular risk in patients with SSc.

The Ratio of Monocytes to HDL-Cholesterol Is Associated with Cardiovascular Risk and Insulin Resistance in Patients with Rheumatoid Arthritis.

The monocytes to high-density lipoprotein (HDL)-cholesterol ratio (MHR) indicates inflammation based on the anti-inflammatory properties of HDL-cholesterol as well as the pro-inflammatory effect of monocytes. Several studies have investigated MHR in various disorders, specifically in cardiovascular diseases. Consequently, MHR has been significantly associated with cardiovascular and all-cause mortality in the general population, regardless of established risk factors. However, its role in the augmented risk of cardiovascular disease found in rheumatoid arthritis (RA) has not been studied to date. This is a cross-sectional study that encompassed 430 patients with RA and 208 controls matched by sex and age. Complete blood cell count and complete lipid profile were evaluated. Multivariable analysis was made to analyze the relationship between MHR and RA disease and features subclinical carotid atherosclerosis, and traditional CV factors including insulin resistance and beta cell function indices. MHR values did not differ between controls and patients after multivariable adjustment (12 ± 6 vs. 11 ± 6, p = 0.18). No relationship between this ratio and the characteristics of the disease was found excluding ESR, which showed a significant and positive association with MHR after adjustment for covariates. MHR significantly correlated with Systematic Coronary Risk Evaluation-2 (SCORE2) cardiovascular risk algorithm, and insulin resistance and beta cell function parameters after adjustment. In conclusion, MHR does not differ between patients with RA and controls. The relationship of this biomarker with disease-related data is poor. However, MHR is highly and positively related to cardiovascular risk and insulin resistance in RA.

Mean Platelet Volume in a Series of 315 Patients with Rheumatoid Arthritis: Relationship with Disease Characteristics, including Subclinical Atherosclerosis and Cardiovascular Comorbidity.

Mean platelet volume (MPV) refers to the average platelet size in femtoliters. Increased or decreased MPV has been associated with several disorders, including inflammatory and cardiovascular diseases. In the present study, our objective was to analyze the relationship of MPV with disease activity in a large and well-characterized series of patients with rheumatoid arthritis (RA). This is a cross-sectional study that included 315 patients with RA and 208 controls matched by sex and age. Complete blood count, including MPV, was assessed. Multivariable analysis was performed to examine the relationship of MPV with RA disease characteristics, carotid atherosclerosis, and traditional cardiovascular factors, including a comprehensive profile of lipid molecules and insulin resistance or beta cell function indices. The multivariable analysis, which includes other hematological modifications produced by the disease and platelet values, showed that MPV levels were significantly lower in RA patients than in controls. Erythrocyte sedimentation rate and interleukin-6, but not C-reactive protein, were negatively correlated with MPV after adjustment for covariates. Similarly, disease activity and MPV had a significant and independent negative correlation. No relationships were found between MPV and cardiovascular risk factors, lipid profile or insulin resistance indices or subclinical atherosclerosis. In conclusion, patients with RA have lower levels of MPV than controls. MPV is negatively related to acute phase reactants and disease activity in RA.

Red Cell Distribution Width Association with Subclinical Cardiovascular Disease in Patients with Rheumatoid Arthritis.

Red cell distribution width (RDW) is a measure of the variation in mean corpuscular volume that reflects the degree of anisocytosis on the peripheral blood smear. RDW value variation has been implicated in several disorders including chronic inflammatory processes and cardiovascular (CV) diseases. In the present work, our objective was to study the relationship that RDW has with the characteristics of the disease in patients with rheumatoid arthritis (RA), focusing on CV risk factors and subclinical atherosclerosis. A cross-sectional study was conducted that included 430 patients with RA and 208 controls matched by sex and age. Complete blood count, including RDW, was assessed. Multivariable analysis was performed to analyze the relationship of RDW with RA disease characteristics, subclinical carotid atherosclerosis, and traditional CV factors, including a comprehensive profile of lipid molecules and insulin resistance and beta cell function indices. After multivariable adjustment, the RDW was significantly higher in RA patients compared with controls (beta coefficient 1.0 [95% confidence interval 0.2 to 1.8] %, p = 0.020). Furthermore, although the erythrocyte sedimentation rate showed a positive and significant relationship with RDW, this association was not found with C-reactive protein and interleukin-6. A positive and independent relationship was observed between DAS28-ESR disease activity score and RDW. However, no association was found between the RDW and other disease activity scores that do not include erythrocyte sedimentation rate in their formula. The SCORE2 CV risk algorithm was positively and significantly associated with higher RDW values. Likewise, a negative relationship was found between RDW with total cholesterol and low-density lipoprotein cholesterol, and a positive relationship was found between RDW and insulin resistance indices. In conclusion, RDW values are higher in RA patients compared to matched controls. Although the relationship of RDW with disease activity was not consistent, RDW shows associations with subclinical CV disease risk factors, including dyslipidemia and insulin resistance, and with the SCORE2 CV disease-risk prediction algorithm.

Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus.

Interleukin-6 (IL-6) is a proinflammatory cytokine that mediates pleiotropic functions in immune responses and inflammatory diseases. The literature lacks studies, with a clinical perspective, on the relationship between IL-6 serum levels and the characteristics of the disease in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to analyze the association between circulating IL-6 and disease manifestations in a well-characterized series of patients with SLE. Serum IL-6 levels and disease activity (SLEDAI-2K), severity (Katz) and damage index (SLICC-DI), complete lipid profile, and subclinical carotid atherosclerosis were evaluated in 284 patients with SLE. In addition, a complete characterization of the complement system was performed in samples from patients with SLE. A multivariate linear regression analysis was carried out to study the relationship between clinical and laboratory characteristics of the disease and IL-6 levels. Age (beta coef. 0.07 [95%CI 0.01-0.1] pg/mL, p = 0.014), C-reactive protein (beta coef. 0.21 [95%CI 0.16-0.25] pg/mL, p < 0.01), and male gender (beta coef. 2 [95%CI 0.3-0.5] pg/mL, p = 0.024), were positively associated with higher IL-6 levels in SLE patients. Most disease characteristics and damage and activity indices did not show significant relationships with IL-6. However, after multivariate analysis, IL-6 was associated with lower serum levels of HDL cholesterol (beta coef. -0.04 [95%CI -0.08-(-0.1)] pg/mL, p = 0.011), and apolipoprotein A1 (beta coef. -0.02 [95%CI -0.04-(-0.001)] pg/mL, p = 0.035). In contrast, the alternative complement cascade, C1inh, and C3a were all positively and independently associated with higher serum levels of IL-6. Moreover, stratification of the Systematic Coronary Risk Assessment 2 (SCORE2) results according to different categories of cardiovascular risk was associated with higher circulating serum IL-6 levels (beta coef. 0.2 [95%CI 0.02-0.4], pg/mL, p = 0.028). In conclusion, in a large series of SLE patients, IL-6 was not associated with disease-related features of SLE, including damage, severity, or activity indices. However, an association was found between serum IL-6 levels and circulating C3a and cardiovascular risk. Our study emphasizes the importance that IL-6 could have in cardiovascular disease and complement system disruption of SLE patients. Therapies targeting IL-6 could have a role in these two clinical manifestations of patients with SLE.

Relationship of Fibroblast Growth Factor 23 Serum Levels with Disease Characteristics in Systemic Lupus Erythematosus Patients.

Fibroblast growth factor 23 (FGF23), a hormone secreted by osteocytes and osteoblasts, is a major regulator of vitamin D and phosphate homeostasis. FGF23 has been associated with the disturbance of mineral homeostasis, and with kidney and cardiovascular diseases. Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect virtually any organ. In the present work, we set out to analyze the relationship of FGF23 with the expression of SLE, including patterns of activity, damage, and severity. A total of 284 well-characterized patients with SLE were recruited. Activity (SLEDAI), severity (Katz), and damage index (SLICC-DI) scores were determined. The serum levels of FGF23 were also assessed. Multivariable linear regression analysis was performed to study the relationship between disease characteristics and FGF23. FGF23 and 25(OH) vitamin D were negatively correlated. Furthermore, prednisone use was associated with higher circulating FGF23 after an adjustment for confounding factors. SLICC-DI was related to higher serum levels of FGF23 after a multivariable analysis. However, when the SLICC-DI index items and domains were analyzed separately, apart from proteinuria ≥3.5 gm/24 h, only the musculoskeletal domain, encompassing arthritis and osteoporosis, was significantly associated with higher serum levels of FGF23. In conclusion, an association is observed between elevated serum FGF23 levels and disease damage, particularly related to musculoskeletal complications and proteinuria, in patients with SLE.

Relationship between Malondialdehyde Serum Levels and Disease Features in a Full Characterized Series of 284 Patients with Systemic Lupus Erythematosus.

Malondialdehyde (MDA) is a marker of oxidative stress and antioxidant status. Oxidative stress has been observed to be increased in systemic lupus erythematosus (SLE). Some studies have shown that MDA is upregulated in SLE compared to controls. However, the literature lacks reports regarding the relationship of MDA to disease manifestations. This is relevant since SLE is a multisystemic disease which may affect virtually any organ in the body. In this study, we set out to analyze how MDA serum levels are associated with disease expression in a large series of SLE patients who were fully characterized in clinical and laboratory terms. A total of 284 patients with SLE were recruited. Serum levels of MDA, and the activity (SLEDAI), severity (Katz) and damage index (SLICC-DI) scores, full lipid profile, and carotid subclinical atherosclerosis were assessed. In addition, a full characterization of the complement system was performed in SLE patients' samples. Multivariable linear regression analysis was executed to study the relationship between clinical and laboratory disease characteristics and MDA. A statistically significant negative relationship was found between disease duration and MDA. In contrast, the presence of anti-nucleosome antibodies was positively associated with MDA. Regarding the SLICC-DI areas, both the musculoskeletal domain and the cutaneous domain were significantly related to higher serum MDA values. Furthermore, after adjustment for confounding factors, lower levels of the classical complement pathway, which denotes activation, were associated with higher serum levels of MDA. In conclusion, cumulative musculoskeletal and skin damage in SLE patients is associated with superior serum levels of MDA. In addition, activation of the complement system is also related to higher circulating MDA levels.

Relationship of Blood Inflammatory Composite Markers with Cardiovascular Risk Factors and Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis.

The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been described as potential blood-derived inflammatory biomarkers in several diseases. Rheumatoid arthritis is an inflammatory disease that has been related to an increased risk of cardiovascular (CV) disease. In the present work, we analyze how these hematological composite scores of inflammation are related to classic CV risk factors and subclinical atherosclerosis in patients with RA. In this cross-sectional study that included 430 patients with RA, the NLR, MLR, PLR, and SIRI scores were calculated. Multivariable analysis was performed to examine the relationships of these composite blood scores with subclinical carotid atherosclerosis and with traditional cardiovascular factors, producing a complete profile of lipid molecules and insulin resistance or indices of beta-cell function, and a Systematic Coronary Risk Assessment (SCORE2) calculation. C-reactive protein and disease activity were significantly and positively associated with the four blood composite scores. SCORE2 was significantly associated with higher values of SIRI, NLR, and MLR, but not PLR. These relationships were maintained when SCORE 2 was considered categorical; patients in the very high CV risk category had higher values in all hematological composite scores, except PLR. In the multivariable analysis, SIRI and NLR were independently associated with higher levels of beta cell dysfunction. In conclusion, SCORE2 and the values of the hematological composite scores were positively correlated in patients with RA. In addition, there were some relationships of these scores with traditional CV risk factors, with their association with beta cell dysfunction being the most consistent.

Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus.

Background: To date a complete characterization of the components of the complement (C) pathways (CLassical, LEctin and ALternative) in patients with systemic lupus erythematosus (SLE) has not been performed. We aimed to assess the function of these three C cascades through functional assays and the measurement of individual C proteins. We then studied how they relate to clinical characteristics. Methods: New generation functional assays of the three pathways of the C system were assessed in 284 patients with SLE. Linear regression analysis was performed to study the relationship between the activity, severity, and damage of the disease and C system. Results: Lower values of the functional tests AL and LE were more frequent than those of the CL pathway. Clinical activity was not related to inferior values of C routes functional assays. The presence of increased DNA binding was negatively linked to all three C pathways and products, except for C1-inh and C3a which were positively related. Disease damage revealed a consistent positive, rather than a negative, relationship with pathways and C elements. Anti-ribosomes and anti-nucleosomes were the autoantibodies that showed a greater relationship with C activation, mainly due to the LE and CL pathways. Regarding antiphospholipid antibodies, the most related with C activation were IgG anti-ß2GP, predominantly involving the AL pathway. Conclusion: Not only the CL route, but also the AL and LE are related to SLE features. C expression patterns are linked to disease profiles. While accrual damage was associated with higher functional tests of C pathways, anti-DNA, anti-ribosomes and anti-nucleosomes antibodies, were the ones that showed a higher relationship with C activation, mainly due to the LE and CL pathways.

Circulating interleukin-6 and cardiovascular disease risk in patients with rheumatoid arthritis with low disease activity due to active therapy.

OBJECTIVES: Interleukin-6 (IL-6) has been implicated in the pathophysiology of rheumatoid arthritis (RA) and in the development of atherosclerosis in the general population. In the present work we aimed to study if IL-6 serum levels have an influence on factors associated with cardiovascular (CV) disease in a cohort of Spanish patients with RA. METHODS: Cross-sectional study that encompassed 407 patients with RA. Serum IL-6 levels were assessed. Multivariable analysis was performed to examine the relationship of IL-6 to subclinical carotid atherosclerosis and classic CV risk factors, including a comprehensive lipid molecule profile and indices of insulin resistance and beta-cell function. RESULTS: Circulating levels of IL-6 showed a correlation with acute phase reactants, disease activity, and other features of RA. However, classic CV risk factors, lipid profile and indices of insulin resistance, as well as subclinical carotid atherosclerosis, were not associated with serum IL-6 levels. CONCLUSIONS: Although a direct association between IL-6 levels and traditional CV risk factors and subclinical carotid atherosclerosis was not observed, circulating IL-6 was associated with disease activity and acute-phase reactants, which have been associated with an increased risk of CV in these patients.

Pretransplant evaluation and the risk of glucose metabolic alterations after renal transplantation: a prospective study.

BACKGROUND: Post-transplant prediabetes (PreDM) and diabetes (PTDM) are common and have an impact on cardiovascular events. We sought to investigate the pathogenesis and best approach for prediction. METHODS: We prospectively studied 115 waitlisted patients from a single center without manifest diabetes. An oral glucose tolerance test (OGTT) was performed yearly until transplantation and 12 months later. Insulin secretion, insulin sensitivity (IS) and disposition index (DI) were derived from the OGTT. RESULTS: PreDM and PTDM were observed in 27% and 28.6% of patients, respectively. Pretransplant age, body mass index (BMI), 120 min glucose, IS, DI, and prediabetes or undiagnosed diabetes were significantly associated with these alterations. In multivariate analysis, pretransplant age [odds ratio (OR) 1.5; 95% confidence interval (CI) 1.04-2.1], BMI (OR 1.16; 95% CI 1.04-1.3) and cumulative steroids (OR 1.5; 95% CI 1.02-2.2) were predictors of PreDM or PTDM. Receiver operating characteristic curve analysis showed that pretransplant BMI and 120 min glucose had the highest area under the curve (0.72; 95% CI 0.62-0.8; and 0.69; 95% CI 0.59-0.79, respectively). The highest discrimination cut-off for BMI (≥28.5 kg/m2) and 120 min glucose (≥123.5 mg/dL) yielded a similar number needed to diagnose (2.5). CONCLUSIONS: PreDM or PTDM develops in waitlisted patients with an ineffective insulin secretion and BMI shows a similar diagnostic capacity to OGTT. Pretransplant interventions may reduce post-transplant glucose alterations.

Vascular Endothelial Growth Factor and Its Soluble Receptor in Systemic Lupus Erythematosus Patients.

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.

Interleukin 1 receptor antagonist relation to cardiovascular disease risk in patients with rheumatoid arthritis.

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.

Apolipoprotein C-III is linked to the insulin resistance and beta-cell dysfunction that are present in rheumatoid arthritis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: ApoC3, insulin resistance, and beta-cell dysfunction are independently associated in patients RA.

Apolipoprotein C-III in patients with systemic lupus erythematosus.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Among SLE patients, disease activity, severity, and disease damage are independently associated with higher ApoC3 serum levels.

The angiopoietin-like protein 4, apolipoprotein C3, and lipoprotein lipase axis is disrupted in patients with rheumatoid arthritis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Hepatitis C virus infection screening reduces mortality and is cost-effective independently of the intervention test.

INTRODUCTION: Chronic infection due to hepatitis C virus (HCV) is frequently asymptomatic even in advanced stages of liver disease. Implementation of a screening program based on different HCV tests may enable an earlier diagnosis of HCV liver disease and subsequent application of highly effective treatment. PATIENTS AND METHODS: A Markov model which compares three different screening strategies for hepatitis C versus no screening in low-risk prevalence (general population) and high-risk prevalence population (people who inject drugs or prison population) was designed, taking into account age at the start of screening and participation. The three strategies were: 1) serological detection of antibodies against the HCV, 2) dried blood spot test (DBS) to detect antibodies against HCV and 3) detection of RNA from HCV. Quality-adjusted life-years (QALY) were taken as a measurement of effectiveness. The incremental cost-effectiveness ratio (ICER) was calculated and a deterministic and probabilistic sensitivity analysis was performed. RESULTS: All three screening strategies were found to be cost-effective with an ICER of €13,633, €12,015 and €12,328/QALY for AntiHCV, DBS-AntiHCV and DBS-RNA HCV, respectively. There was a decrease in mortality due to liver disease in comparison to no screening for AntiHCV (40.7% and 52%), DBS-AntiHCV (45% and 80%) and DBS-RNA HCV (45.2% and 80%) for low-prevalence and high-prevalence populations, respectively. CONCLUSION: All test interventions for HCV screening are cost-effective for the early detection of HCV infection, also achieving a reduction in mortality. Thus, implementation of screening programs for HCV should not be halted by decisions on monetary policy.

Serum Levels of Transforming Growth Factor Beta 1 in Systemic Lupus Erythematosus Patients.

Transforming growth factor beta (TGF-ß) is a highly pleiotropic cytokine that has broad anti-inflammatory and immunosuppressive effects. In patients with systemic lupus erythematosus (SLE), the immunosuppressive effect of TGF-ß1 is thought to be dysfunctional. In the present work, we aimed to study the relationship between the serum levels of TGF-ß1 with the characteristics of the disease as well as with the patterns of activity, damage, or severity of the disease. Two hundred and eighty-four patients with well-characterized SLE were recruited. The serum levels of TGF-ß1 were assessed. A multivariable linear regression analysis was performed to analyze the relation of disease characteristics to TGF-ß1. The Katz severity index (beta coefficient 179 [95% confidence interval 7-350] pg/mL, p = 0.041) and SLEDAI activity index (beta coefficient 96 [95% CI 20-171] pg/mL, p = 0.014) were associated with higher serum levels of TGF-ß1 after the multivariable analysis. When the disease-specific features were studied, ocular and cardiovascular manifestations were positively associated with serum TGF-ß1 levels. In contrast, gastrointestinal and musculoskeletal involvements were associated with lower levels of circulating TGF-ß1. Among patients with SLE, the serum levels of TGF-ß1 were highly associated with disease-related manifestations.

Disease Activity Is More Associated with IL-1 Than with IL-6 in Patients with Rheumatoid Arthritis.

Interleukin-1 receptor antagonist (IL-1ra) concentration reflects and is proportional to IL-1 production. Both IL-1 and IL-6 are involved in the pathogenesis of rheumatoid arthritis (RA). However, the relationship of serum levels of these two cytokines to each other in RA patients is not well-understood. In this study, our objective was to analyze the possible linear correlation between IL-1ra and IL-6 in patients with RA, and how both are related to the inflammatory activity of the disease. IL-6 and IL-1ra levels were measured in 407 patients with RA. Linear regression and partial correlations were conducted to analyze the relationship between both cytokines, and their association with RA characteristics. No correlation was found between serum levels of IL-6 and IL-1ra (Pearson's r 0.031, p = 0.61). However, disease activity and acute phase reactants were positively and significantly associated with both cytokines. Nevertheless, after controlling for covariates, disease activity scores were more strongly associated with IL-1ra compared to IL-6. Circulating IL-6 and IL-1ra do not correlate with each other in RA patients. Although both are associated with disease activity and acute phase reactants, the relationship of disease activity to IL-1ra is greater than that to IL-6.