Diana Carmona-Fernandes - Academia.edu (original) (raw)

Papers by Diana Carmona-Fernandes

PubMed, Oct 26, 2016

Introduction: An excess in cardiovascular (CV) morbidity and mortality has been recognized in Rhe... more Introduction: An excess in cardiovascular (CV) morbidity and mortality has been recognized in Rheumatoid Arthritis (RA) patients when compared to the general population. Given the paucity of prospective data, our aim was to estimate the incidence of CV events and the contribution of traditional CVD risk factors and RA-related parameters to future events. Methods: Incident fatal and non-fatal CV events (hospitalizations due to unstable angina, myocardial infarction, coronary artery revascularization procedures, stroke, or CV death) were assessed in a prospective cohort of RA women followed since 2007 and without CV events at cohort entry. The presence of traditional CV risk factors, disease characteristics, medication, carotid ultrasound, and biomarkers of inflammation and endothelial activation were evaluated at baseline. Univariate Cox proportional hazard models were used to identify risk factors for CV events. Results: Among 106 women followed over 565 patient-years we identified 4 CV events (1 fatal stroke, 2 myocardial infarction and 1 unstable angina), which contributed to an incidence rate of 7 per 1000 person-years (95%CI 2.0- 13.9). Patients who developed CV events were older, but the distribution of other traditional CV risk factors was otherwise similar in both groups. Also, corticosteroid dosage and proportion of patients with carotid atherosclerotic plaques was higher in those with CV events. Erythrocyte sedimentation rate (ESR) (HR 1.036; 95%CI 1.005-1.067) and soluble intercellular adhesion molecule-1 (sICAM-1) serum levels (HR 1.002; 95%CI 1.000-1.003) significantly contributed to CV events. These results remained significant after adjusting for patients' age. Conclusion: We found an incidence of cardiovascular events in women with RA of 7 per 1000 patent-years. This value is similar to that found in other Portuguese cohort of RA patients1 and much higher than the incidence reported for the general Portuguese population. Markers of inflammation and endothelial activation contributed significantly to CV events, but the limited number of events prevents further analysis.

Clinical and Experimental Rheumatology, Jul 1, 2022

The excel file contain the raw data supporting the findings of this work.

xv seguir. Inês Perpétuo, um dia escreveste que "amigos recentes podem ser os melhores amigos" e ... more xv seguir. Inês Perpétuo, um dia escreveste que "amigos recentes podem ser os melhores amigos" e contigo aprendi que é realmente assim. Ana Maria Rodrigues, sempre acreditaste neste projecto e me incentivaste a levá-lo para a frente, ainda que por vezes por caminhos diferentes do que eu queria, já para não falar das partilhas de almoços, congressos, e muitos outros momentos de lazer (que são tão bons e tanta falta fazem para adoçar o dia-a-dia!). Obrigada também a vocês as três pela ajuda no delinear deste projecto.

Frontiers in Medicine, 2021

Background and Aims: Atherosclerosis and osteoporosis share common risk factors, as well as infla... more Background and Aims: Atherosclerosis and osteoporosis share common risk factors, as well as inflammatory mechanisms. Our aim was to understand how atherosclerotic lesions are related with disturbances in bone.Methods: Gene expression of pro-inflammatory and bone metabolism related proteins (IL-1β, IL-6, IL-17A, TNF, RANKL, OPG, COL1, CTSK, OCL, TRAP, CBFA1, DKK1, SOST, ADIPOQ, and ADIPOR1) were analyzed in arteries and bones from 45 deceased donors and adipose tissue was used as control. Additionally, in 139 patients with advanced atherosclerosis submitted to carotid endarterectomy we compared calcium content (Alizarin red) and plaque inflammatory scores (CD3+, CD68+, and adiponectin) of patients with normal bone mineral density (BMD) with those with low BMD and explored the associations between gene expression in atherosclerotic plaques and BMD. Serum levels of pro-inflammatory and bone related proteins were measured both in donors and patients. Associations were investigated by th...

Acta reumatologica portuguesa, Jan 3, 2016

An excess in cardiovascular (CV) morbidity and mortality has been recognized in Rheumatoid Arthri... more An excess in cardiovascular (CV) morbidity and mortality has been recognized in Rheumatoid Arthritis (RA) patients when compared to the general population. Given the paucity of prospective data, our aim was to estimate the incidence of CV events and the contribution of traditional CVD risk factors and RA-related parameters to future events. Incident fatal and non-fatal CV events (hospitalizations due to unstable angina, myocardial infarction, coronary artery revascularization procedures, stroke, or CV death) were assessed in a prospective cohort of RA women followed since 2007 and without CV events at cohort entry. The presence of traditional CV risk factors, disease characteristics, medication, carotid ultrasound, and biomarkers of inflammation and endothelial activation were evaluated at baseline. Univariate Cox proportional hazard models were used to identify risk factors for CV events. Among 106 women followed over 565 patient-years we identified 4 CV events (1 fatal stroke, 2 m...

Lupus, 2016

Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specifi... more Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). A total of 1431 samples (SLE, n = 843; disease controls, n = 588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n = 566). The SLEDAI-2K scores were available for 805 SLE patient...

Annals of the Rheumatic Diseases, 2015

Overnight fasting serum samples were obtained from early RA, late RA and HC. Lipid levels and glu... more Overnight fasting serum samples were obtained from early RA, late RA and HC. Lipid levels and glucose were determined with biochemical kits. High sensitivity C-reactive protein (hsCRP) was measured using turbidometric technique. Insulin levels were measured by ELISA. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was calculated using glucose and insulin values. Atherosclerotic indices like mean carotid intima-media thickness (cIMT) and endothelial dependent flow mediated vasodilatation (ED-FMD) were measured using HRUS. One way ANOVA with post hoc tests and linear regression analyses were used. All statistical analyses were performed using GraphPad Prism software v 5.0. Results: Mean disease duration of Late RA patients was 9.6±3.3 yrs and that of early RA was 0.46±0.36 yrs. There were no significant differences in the demographic variables and lipid profile among the three groups. Unlike ESR, hsCRP levels were significantly lower in the late RA patients as compared to that of the early RA (p=0.04). DAS 28 did not show significant difference among the two patients group. HOMA-IR was significantly higher in the Late RA group [1.04 (0.3-7.04)] when compared to early RA [0.59 (0.007-1.8)] and HC [0.42 (0.07-1.5)]. Mean cIMT was significantly higher in both the early RA patients (0.49±0.08mm) and late RA patients group (0.51±0.09mm) than in the HC (0.42±0.07 mm). In early RA patients median FMD% was significantly lower (6.71±4.32) as compared to late RA patients (11.75±7.67) and HC (12.23±4.6). Regression analysis showed significant associations of HOMA-IR with Mean cIMT, DAS 28 and hsCRP (figure 1) and also with age, disease duration, ESR and trends in association with FMD% values for late RA group. Conclusions: Underlying inflammation prevailing in RA patients probably leads to stimulation of an insulin resistant state which further enhances the already significant atherosclerotic milieu in these patients.

Annals of the Rheumatic Diseases, 2013

ABSTRACT Background Systemic lupus erythematosus (SLE) is characterized by multi-organ involvemen... more ABSTRACT Background Systemic lupus erythematosus (SLE) is characterized by multi-organ involvement and the production of autoantibodies directed against several nuclear proteins, among which the most specific are anti-Sm, anti-dsDNA and anti-ribosomal P protein (Rib-P) [1]. Yet anti-Rib-P is not part of the SLE classification criteria [2]. Objectives We aimed to evaluate the diagnostic performance of anti-Rib-P in comparison to anti-Sm and anti-dsDNA antibodies in SLE patients and also to identify its association with clinical manifestations. Methods In a cross-sectional evaluation we included 127 SLE patients, 100 healthy controls and 256 rheumatic disease controls (100 Rheumatoid Arthritis, 99 Ankylosing Spondylitis, 34 Juvenile Idiopathic Arthritis and 23 Psoriatic Arthritis). We have used EliA™ Rib-P, EliA™ Sm and EliA™ DNA, from Phadia®, to simultaneously determine autoantibodies titers. Receiver operating characteristic (ROC) curves were performed and the cut-off values of positivity determined. The relationship between demographic parameters, clinical features, and the autoantibodies titers was assessed by univariable followed by multivariable linear regression analyses. Results The cut-off values of positivity were 4.45 U/ml, 3.4 U/ml and 15.0 U/ml for anti-Rib-P, anti-Sm and anti-dsDNA, respectively. Anti-Rib-P autoantibodies were positive in 14.2% of the SLE patients (mean concentration of 4.9±20.2 U/ml), in 0.8% of the rheumatic diseases control group (2 RA patients) and in none of the healthy controls. Anti-Sm antibodies were positive in 9.4% (mean concentration 2.8±13.8 U/ml) and anti-dsDNA autoantibodies in 49.6% of the SLE patients (mean concentration 44.6±73.8 U/ml). There was no positivity for anti-Sm in groups other than SLE, while anti-dsDNA was found in 6 (6%) healthy control subjects and in 5 (2%) patients with other rheumatic diseases. The tests performance was evaluated and the outcome was as follows (PPV – Positive Predictive Value; NPV – Negative Predictive Value): Among the 18 anti-Rib-P positive samples, 12 were also positive for anti-dsDNA, 2 were positive for the three autoantibodies, and 4 tested positively only for anti-Rib-P antibodies. In multivariable analysis Caucasian ethnicity was negatively associated with anti-Rib-P antibody titers (β=-0.190, p=0.034); serositis positively associated with anti-Sm titers; anti-dsDNA autoantibodies titers were related to a more active lupus (higher SLEDAI2K and renal involvement) and to shorter disease duration. No relationship was found between anti-Rib-P antibodies titers and neuropsychiatric manifestations as defined by SLE classification criteria. Conclusions Anti-Rib-P autoantibodies determination should be considered for inclusion in the SLE classification criteria as it is highly specific and has a good predictive diagnostic value. Disclosure of Interest D. Carmona-Fernandes Grant/Research support from: Phadia, M. J. Santos Grant/Research support from: Phadia, J. E. Fonseca Grant/Research support from: Phadia

BioMed Research International, 2015

Background. The aim of our work was to replicate, in a Southern European population, the associat... more Background. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations betweenPTPRClocus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response.Methods. We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients.Results. No association was found betweenPTPRCrs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP inTRAF1/C5region, was associated with a poor...

PLoS ONE, 2012

Accelerated atherosclerosis represents a major problem in both systemic lupus erythematosus (SLE)... more Accelerated atherosclerosis represents a major problem in both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients, and endothelial damage is a key feature of atherogenesis. We aimed to assess early endothelial changes in SLE and RA female patients (127 SLE and 107 RA) without previous CV events. Biomarkers of endothelial cell activation (intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), thrombomodulin (TM), and tissue factor (TF)) were measured and endothelial function was assessed using peripheral artery tonometry. Reactive hyperemia index (RHI), an indicator of microvascular reactivity, and augmentation index (AIx), a measure of arterial stiffness, were obtained. In addition, traditional CV risk factors, disease activity and medication were determined. Women with SLE displayed higher sICAM-1 and TM and lower TF levels than women with RA (p = 0.001, p,0.001 and p,0.001, respectively). These differences remained significant after controlling for CV risk factors and medication. Serum levels of vascular biomarkers were increased in active disease and a moderate correlation was observed between sVCAM-1 levels and lupus disease activity (rho = 0.246) and between TF levels and RA disease activity (rho = 0.301). Although RHI was similar across the groups, AIx was higher in lupus as compared to RA (p = 0.04). Also in active SLE, a trend towards poorer vasodilation was observed (p = 0.06). In conclusion, women with SLE and RA present with distinct patterns of endothelial cell activation biomarkers not explained by differences in traditional CV risk factors. Early vascular alterations are more pronounced in SLE which is in line with the higher CV risk of these patients.

Bone Abstracts, 2013

To estimate the prevalence and ultrasonographic morphology of the carotid plaques in a cohort of ... more To estimate the prevalence and ultrasonographic morphology of the carotid plaques in a cohort of Rheumatoid Arthritis (RA) patients without prevalent CV events. • In this group of young RA women with moderately active disease, subclinical atherosclerosis was mainly determined by traditional CV risk factors, in particular by age. No distinct disease characteristics could be identified among those with plaques. • Despite the limitations of our sample size, we found some differences regarding the US type of plaques in RA and controls. Surprisingly, atherosclerotic plaques of RA patients displayed ultrasonographic characteristics of less instability, with higher amount of calcium and lower amount of lipids than controls. This is an interesting finding that is in agreement with the higher content of coronary calcium previously documented by other authors in RA and stresses the need for a tight control of traditional CV risk factors in patients with arthritis.

Journal of Translational Medicine, 2012

The Journal of Rheumatology, 2011

Objective.Rheumatoid arthritis (RA) is associated with higher levels of inflammatory mediators an... more Objective.Rheumatoid arthritis (RA) is associated with higher levels of inflammatory mediators and with a more atherogenic lipid profile. Dyslipidemia can be present years before arthritis develops. Lymphotoxin-α (LTA) is a cytokine that mediates proinflammatory responses while also participating in lipid homeostasis, and its transcriptional activity is in part genetically determined. We examined the role of the single-nucleotide polymorphism at position 252 of the LTA gene in the genetic background of RA and dyslipidemia.Methods.The association between the LTA 252 A>G polymorphism and disease status was examined in a nested case-control study of 388 patients with RA and 269 unrelated healthy controls, all white. Demographics and disease features were assessed, fasting lipids measured, and the use of lipid-lowering agents evaluated.Results.The LTA 252 A allele was more frequent in cases compared to controls (70.5% and 64.3%, respectively; p = 0.018, OR 1.325, 95% CI 1.049–1.675),...

Clinical Rheumatology, 2010

Interleukin-6 (IL-6) is a multifunctional cytokine with an important pathophysiological role in s... more Interleukin-6 (IL-6) is a multifunctional cytokine with an important pathophysiological role in systemic lupus erythematosus (SLE). The polymorphism of the IL-6 gene promoter at position −174, which appears to influence the production of this cytokine, has been associated with susceptibility to some rheumatic diseases. The aim of this study is to investigate whether the IL-6 −174 G/C polymorphism associates with lupus susceptibility or affects disease characteristics in Portuguese patients with SLE. The association between −174 G/C and lupus diagnosis was studied in 115 adult SLE patients (95.7% females) and 152 healthy controls (94.7% females), all Caucasians. There were no significant differences in genotype or allele frequency between patients and controls. The −174 C/C genotype was independently associated with renal disease and the C allele with the presence of irreversible damage. The IL-6 gene promoter polymorphism at position −174 does not contribute to SLE susceptibility in Portuguese Caucasian patients but may predispose to specific manifestations of the disease.

$Research paper thumbnail of Upregulation of inflammatory genes and downregulation of sclerostin gene expression are key elements in the early phase of fragility fracture healing$

Bone, 2011

Background: Fracture healing is orchestrated by a specific set of events that culminates in the r... more Background: Fracture healing is orchestrated by a specific set of events that culminates in the repair of bone and reachievement of its biomechanical properties. The aim of our work was to study the sequence of gene expression events involved in inflammation and bone remodeling occurring in the early phases of callus formation in osteoporotic patients. Methodology/Principal Findings: Fifty-six patients submitted to hip replacement surgery after a low-energy hip fracture were enrolled in this study. The patients were grouped according to the time interval between fracture and surgery: bone collected within 3 days after fracture (n = 13); between the 4 th and 7 th day (n = 33); and after one week from the fracture (n = 10). Inflammation-and bone metabolism-related genes were assessed at the fracture site. The expression of proinflammatory cytokines was increased in the first days after fracture. The genes responsible for bone formation and resorption were upregulated one week after fracture. The increase in RANKL expression occurred just before that, between the 4 th-7 th days after fracture. Sclerostin expression diminished during the first days after fracture. Conclusions: The expression of inflammation-related genes, especially IL-6, is highest at the very first days after fracture but from day 4 onwards there is a shift towards bone remodeling genes, suggesting that the inflammatory phase triggers bone healing. We propose that an initial inflammatory stimulus and a decrease in sclerostin-related effects are the key components in fracture healing. In osteoporotic patients, cellular machinery seems to adequately react to the inflammatory stimulus, therefore local promotion of these events might constitute a promising medical intervention to accelerate fracture healing.

BMC Medicine, 2013

Background This study was devised to assess the performance of anti-ribosomal P (anti-Rib-P) anti... more Background This study was devised to assess the performance of anti-ribosomal P (anti-Rib-P) antibodies in the diagnosis of systemic lupus erythematosus (SLE) and the association of these antibodies with the clinical features of SLE. Methods We used a fluorescence enzyme immunoassay to determine anti-Rib-P levels in an SLE group, a rheumatic disease control (RDC) group (rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis), and a healthy control (HC) group. We also determined anti-Smith antigen (anti-Sm) and anti-double-stranded DNA (anti-dsDNA) antibody levels. Receiver operating characteristic (ROC) curves were constructed and the best cut-off points for positivity were determined. Using regression analysis, the relationship between clinical variables and autoantibody levels was analyzed. Results In total, 127 patients with SLE, 256 controls with other rheumatic diseases, and 100 HCs were studied. Anti-Rib-P autoantibodies were p...

Annals of the Rheumatic Diseases, 2011