The use of vitamin D (VitD) supplements has become widespread in the last decade due not only to the dissociation between the blood levels recommended as “optimal” and those shown by the healthy population but also to its presumed beneficial effects on multiple disorders. This work evaluated the levels of 25-hydroxyvitamin D (25(OH)D) in a healthy population of European origin living in a region with high solar irradiation. In serum samples from a population-based study conducted in the Canary Islands, levels of 25(OH)D were analyzed. In 876 individuals who had no history of kidney or malabsorption disorders and, who had not been treated with calcium and/or VitD supplementation, the median 25(OH)D level was 26.3 (5th; 95th percentile, 14.3; 45.8) ng/mL. Notably, 65.4% of the population had 25(OH)D blood levels below 30 ng/mL, 23.4% below 20 ng/mL and 6.4% below 15 ng/mL. Based on the lack of evidence supporting causality between 25(OH)D levels below what is recommended as optimal (≥20 ng/mL, or even ≥30 ng/mL) and major skeletal and non-skeletal diseases, and in light of the distribution of the concentration of this vitamin in healthy adults living under optimal conditions of solar irradiation, it seems reasonable to consider 25(OH)D levels below 20 ng/mL and close to 15 ng/mL as adequate for the general population.

Background: The Metabolic Score for Insulin Resistance (METS-IR) is a newly developed index that has been described to predict cardiovascular (CV) events. In this study, we calculated the METS-IR index in patients with rheumatoid arthritis (RA), a condition linked to an elevated CV risk. We then examined its relationship with disease characteristics and CV comorbidities, including disease activity, lipid profile, subclinical carotid atherosclerosis, and insulin resistance indices. Methods: A total of 515 RA patients were recruited. Disease-related characteristics and disease activity indices, including the Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI), and the Simple Disease Activity Index (SDAI) were calculated. Additionally, the complete lipid profile, insulin resistance indices, metabolic syndrome criteria, and carotid ultrasound for intima–media thickness and carotid plaque detection were assessed. METS-IR was calculated. A multivariable linear regression analysis was performed to examine the associations between the disease characteristics and METS-IR. Results: METS-IR was positively correlated with age, body mass index, and traditional cardiovascular risk factors such as metabolic syndrome and insulin resistance indices. Carotid intima–media thickness—but not the presence of carotid plaque—was associated with significantly higher METS-IR values. Regarding disease-related characteristics, C-reactive protein and disease activity indices demonstrated a significant positive association with METS-IR after multivariable adjustment. Specifically, C-reactive protein was associated with higher METS-IR values (beta coefficient 0.2, 95% CI: 0.1–0.3, p < 0.001). All disease activity indices, except CDAI, showed a significant positive relationship with METS-IR. Conclusions: METS-IR is linked not only to CV risk factors but also, independently, to inflammatory disease activity in patients with RA. Its association with CV events in the general population and disease activity in RA highlights the significant role of inflammation in driving excessive cardiovascular risk in RA. This underscores the intricate relationship between metabolic dysfunction, systemic inflammation, and CV outcomes in RA.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially with functional tests of the classical and alternative pathways, as well as with C2, C4, C3, and C3a. On the contrary, for platelets, significance was only observed, after multivariable adjustment, with lower C2 concentrations. In conclusion, the serum complement system and hematological profile in SLE are independently linked, after adjustment for disease activity and damage. These relationships are basically negative and are predominantly found in lymphocytes.

3-Nitrotyrosine (3-NT) is a product of tyrosine nitration mediated by reactive nitrogen species such as peroxynitrite anion and nitrogen dioxide. It serves as an indicator of inflammation, cell damage, and nitric oxide production. Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by multisystem involvement and increased oxidative stress. Notably, cardiovascular (CV) disease has emerged as the leading cause of mortality among SLE patients. Our objective was to investigate the association between serum 3-NT levels and a wide range of disease characteristics in patients with SLE, with a particular emphasis on CV comorbidity. A total of 214 patients with SLE were enrolled. The serum levels of 3-NT as well as the activity (SLEDAI) and damage index (SLICC-SDI) scores, full lipid profile, insulin resistance indices, and carotid subclinical atherosclerosis were assessed. Multivariable linear regression analysis was carried out to study the relationship between 3-NT and clinical and laboratory disease characteristics, especially focusing on CV comorbidities. Except for body mass index, which showed a significant positive correlation, the demographic data and traditional CV risk factors did not correlate with 3-NT. After multivariable adjustments, several disease characteristics, including the disease duration, activity and damage indices, and autoantibody profile, showed significant positive associations with 3-NT. Regarding CV characteristics, several lipid profile molecules showed significant relationships with 3-NT. This was not the case for insulin resistance and subclinical atherosclerosis. Remarkably, patients with a high CV risk by SCORE2 showed higher 3-NT values compared to those with a low risk, although after the multivariable adjustment, this relationship was attenuated (but still showed a trend). In conclusion, serum 3-NT levels demonstrated significant positive correlations with multiple disease characteristics, including the disease activity and damage and the autoantibody profile. The lipid pattern in the SLE subjects also significantly and independently correlated with the 3-NT values. Our findings highlight the pathophysiological role of 3-NT specifically, and peroxidation in general, in patients with SLE.

Objective: 3-Nitrotyrosine (3-NT) is a byproduct of tyrosine nitration, mediated by reactive nitrogen species such as peroxynitrite and nitrogen dioxide. It serves as a marker of cellular damage, inflammation, and nitric oxide activity. Rheumatoid arthritis (RA) is a complex autoimmune disease characterized by systemic involvement and increased oxidative stress. In RA patients, cardiovascular disease has emerged as the leading cause of mortality. This study aimed to investigate the relationship between serum 3-NT levels and various disease characteristics in RA patients, with a particular focus on cardiovascular comorbidities. Methods: A total of 168 RA patients were recruited. They underwent comprehensive evaluations, including disease-related characteristics and disease activity indices. Furthermore, a comprehensive lipid panel, measures of insulin resistance, metabolic syndrome criteria, and carotid ultrasound to evaluate intima–media thickness and the presence of carotid plaques were conducted. 3-NT serum levels were measured. A multivariable linear regression analysis was performed to examine the associations between the disease characteristics and 3-NT. Results: After multivariable analysis, C-reactive protein was independently associated with higher serum levels of 3-NT. In contrast, disease characteristics and Disease Activity Score 28-joint count (DAS28) calculated using C-reactive protein or erythrocyte sedimentation rate, showed no significant association with 3-NT levels. Likewise, cardiovascular comorbidities, including lipid profiles, insulin resistance indices, metabolic syndrome, and markers of subclinical atherosclerosis did not demonstrate any significant relationship with 3-NT levels. Conclusions: While 3-NT levels are influenced by inflammation, they do not appear to be strongly associated with disease characteristics, cardiovascular risk, or disease-modifying anti-rheumatic drugs in RA patients. This emphasizes the complexity of oxidative stress in RA.

Mean platelet volume (MPV), which represents the average platelet size in femtoliters, has emerged as a reliable biomarker in several systemic and chronic disorders. However, its relationship with disease characteristics in large series of patients with systemic lupus erythematosus (SLE) has not been exhaustively studied to date. In the present work, we aimed to analyze how disease characteristics, including disease activity and cumulative damage, relate to MPV in a well-characterized series of SLE patients. In total, 179 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood counts including MPV were assessed. Linear multivariable analysis was performed to evaluate the relationship between MPV and SLE disease characteristics, including composite scores of disease activity and damage. MPV was significantly lower in patients with SLE compared to controls after multivariable analysis (beta coefficient, −0.7 [95% confidence interval, −1.1 to −0.3)] fL, p < 0.001). Although the SLEDAI disease activity index was not related to MPV, the SLICC score measuring cumulative disease damage was significantly associated with lower MPV values after adjustment for covariates. Elements of the SLICC score that were associated with lower MPV levels were those pertaining to the kidney, peripheral vascular, and musculoskeletal manifestations of the disease. In conclusion, MPV is lower in patients with SLE compared to matched controls. This MPV downregulation is primarily due to the renal, peripheral vascular and musculoskeletal manifestations of the disease. MPV may represent a biomarker of accrual disease damage in SLE.