Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients

BACKGROUND: Rheumatoid arthritis (RA) patients carry a high risk of cardiovascular morbidity and mortality. The excess of cardiovascular disease cannot be entirely explained by traditional risk factors and the immune system contributes to the development of atherosclerosis. Moreover, post-translational modifications such as citrullination and carbamylation have been linked to inflammation and atherosclerosis. Anti-carbamylated proteins antibodies (anti-CarP) are a new subset of autoantibodies identified in RA patients. This study aimed to investigate a possible association between anti-CarP and subclinical atherosclerosis in RA patients. METHODS: We enrolled RA patients and normal healthy controls (NHS) without known cardiovascular risk factors or heart disease. Cardiovascular risk was assessed using the Modified Systemic Coronary Risk Evaluation (mSCORE). Anti-CarP were investigated by a solid phase "home-made" ELISA. Anti-citrullinated protein antibodies (ACPA) and Rheumatoid Factor (RF) were investigated by ELISA assays. Subclinical atherosclerosis was evaluated by brachial artery Flow-Mediated Dilatation (FMD) and Carotid Intima-Media Thickness (c-IMT) while arterial stiffness by Ankle-Brachial Index (ABI) and Cardio-Ankle Vascular Index (CAVI). RESULTS: We enrolled 50 RA patients (34 F and 16 M, mean age 58.4 ± 13.1 years, mean disease duration 127 ± 96.7 months) and 30 age and sex matched NHS. According to the mSCORE, 58% of patients had a low risk, 32% a moderate and 8% a high risk for cardiovascular disease. FMD was significantly lower in RA patients than in NHS (5.6 ± 3.2 vs 10.7 ± 8.1%; p < 0.004) and CAVIs significantly higher in a RA patients compared to NHS (left CAVI 8.9 ± 1.7 vs 8.1 ± 1.5; p < 0.04 for and right CAVI 8.8 ± 1.6 vs 8.0 ± 1.4; p < 0.04 for the). ABI and c-IMT did not differ between the two populations. The multivariate regression analysis showed a significant association of anti-CarP antibodies with FMD, left and right CAVI and both c-IMT (r = 1.6 and p = 0.05; r = 1.7 and p = 0.04; r = 2.9 and p = 0.05; r = 1.5 and p = 0.03; r = 1.1 and p = 0.03 respectively). CONCLUSIONS: This study confirms that RA patients, without evidence of cardiovascular disease or traditional risk factors, have an impaired endothelial function. Moreover, we found an association with anti-CarP antibodies suggesting a possible contribution of these autoantibodies to endothelial dysfunction, the earliest stage of atherosclerosis. Besides ultrasound assessment, anti-CarP should be assessed in RA patients and considered an additional cardiovascular risk factor

Prevalence of dyslipidemia and hypercholesterolemia awareness: results from the Lookup 7+ online project

Background: Cardiovascular disease still represents the leading cause of death worldwide. Management of risk factors remains crucial; despite this, hypercholesterolemia, which is one of the most important modifiable cardiovascular risk factor, is still high prevalent in general population. The aim of this study is to determine the prevalence of dyslipidemia and hypercholesterolemia awareness in a very large population. Methods: More than 65 000 users completed the online, self-administered survey. It was structured like a 'journey' where each stage corresponded to a cardiovascular risk factor: blood pressure, body mass index, cholesterol, diet, physical exercise, smoke and blood sugar. At the end, the user received a final evaluation of his health status. Results: The mean age was 52.5 years (SD 13.9, range 18-98), with 35 402 (53.7%) men. About 56% of all participants believed to have normal cholesterol values, when only 40% of them really showed values &lt;200 mg/dl. Only about 30% of all participants self-predicted to have abnormal cholesterol values whereas we found high cholesterol levels in about 60% of people. Conclusions: Dyslipidemia is very prevalent and half of the people with high cholesterol is not aware of having high values

Malnutrition in COVID-19 survivors: prevalence and risk factors

Background: Nutritional status is a critical factor throughout COVID-19 disease course. Malnutrition is associated with poor outcomes in hospitalized COVID-19 patients. Aim: To assess the prevalence of malnutrition and identify its&nbsp;associated factors in COVID-19 survivors. Methods: Study cohort included 1230 COVID-19 survivors aged 18-86 attending a post-COVID-19 outpatient service. Data on clinical parameters, anthropometry, acute COVID-19 symptoms, lifestyle habits were collected through a comprehensive medical assessment. Malnutrition was assessed according to Global Leadership Initiative on Malnutrition (GLIM) criteria. Results: Prevalence of malnutrition was 22% at 4-5&nbsp;months after acute disease. Participants who were not hospitalized during acute COVID-19 showed a higher frequency of malnutrition compared to those who needed hospitalization (26% versus 19%, p&nbsp;&lt;&nbsp;0.01). Malnutrition was found in 25% COVID-19 survivors over 65&nbsp;years of age compared to 21% younger participants (p&nbsp;&lt;&nbsp;0.01). After multivariable adjustment, the likelihood of being malnourished increased progressively and independently with advancing age (Odds ratio [OR] 1.02; 95% CI 1.01-1.03) and in male participants (OR 5.56; 95% CI 3.53-8.74). Malnutrition was associated with loss of appetite (OR 2.50; 95% CI 1.73-3.62), and dysgeusia (OR 4.05; 95% CI 2.30-7.21) during acute COVID-19. Discussion: In the present investigation we showed that malnutrition was highly prevalent in a large cohort of COVID-19 survivors at 4-5&nbsp;months from acute illness. Conclusions: Our findings highlight the need to implement comprehensive nutritional assessment and therapy as an integral part of care for COVID-19 patients

Serum Levels of Asymmetric Dimethylarginine and Apelin as Potential Markers of Vascular Endothelial Dysfunction in Early Rheumatoid Arthritis

Objectives. Impaired endothelial function represents the early stage of atherosclerosis, which is typically associated with systemic inflammatory diseases like rheumatoid arthritis (RA). As modulators of endothelial nitric oxide synthase expression, asymmetric-dimethylarginine (ADMA) and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes. We conducted a prospective, case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA (ERA) before and after disease-modifying antirheumatic drug (DMARD) therapy. Methods. We enrolled 20 consecutively diagnosed, treatment-naive patients with ERA and 20 matched healthy controls. Serum ADMA and apelin levels and the 28-joint disease activity scores (DAS28) were assessed before and after 12 months of DMARDs treatment. All patients underwent ultrasonographic assessment for intima-media tickness (IMT) evaluation. Results. In the ERA group, ADMA serum levels were significantly higher than controls at baseline (P = 0.007) and significantly decreased after treatment (P = 0.012 versus controls). Baseline serum apelin levels were significantly decreased in this group (P = 0.0001 versus controls), but they were not significantly altered by treatment. IMT did not show significant changes. Conclusions. ERA is associated with alterations of serum ADMA and apelin levels, which might be used as biomarkers to detect early endothelial dysfunction in these patients

Effect of Therapeutic Inhibition of TNF on Circulating Endothelial Progenitor Cells in Patients with Rheumatoid Arthritis

Endothelial dysfunction has been detected in RA patients and seems to be reversed by control of inflammation. Low circulating endothelial progenitor cells (EPCs) have been described in many conditions associated with increased cardiovascular risk, including RA. The aim of this study was to investigate the effect of inhibition of TNF on EPCs in RA patients. Seventeen patients with moderate-severe RA and 12 sex and age-matched controls were evaluated. Endothelial biomarkers were tested at baseline and after 3 months. EPCs were identified from peripheral blood mononuclear cells by cytofluorimetry using anti-CD34 and anti-vascular endothelial growth factor-receptor 2. Asymmetric dimethylarginine (ADMA) was tested by ELISA and flow-mediated dilatation (FMD) by ultrasonography. Circulating EPCs were significantly lower in RA patients than in controls (P=0.001). After 3 months EPCs increased significantly (P=0.0006) while ADMA levels significantly decreased (P=0.001). An inverse correlation between mean increase in EPCs number and mean decrease of DAS28 after treatment was observed (r=-0.56, P=0.04). EPCs inversely correlated with ADMA (r=-0.41, P=0.022). No improvement of FMD was detected. Short-term treatment with anti-TNF was able to increase circulating EPCs concurrently with a proportional decrease of disease activity suggesting that therapeutic intervention aimed at suppressing the inflammatory process might positively affect the endothelial function. © 2013 F. R. Spinelli et al

Suicide Risk in Post-COVID-19 Syndrome

Post-acute sequelae of COVID-19 include several neuropsychiatric disorders. Little is known about the relationship between post-COVID-19 syndrome and suicidality. The aim of the study was to investigate the risk of suicide in subjects with persistent post-COVID-19 syndrome. One-thousand five-hundred eighty-eight subjects were assessed in the Post-Acute Care Service at the Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS of Rome. Assessment included: (a) sociodemographic characteristics; (b) symptoms during and after COVID-19; (c) psychopathological evaluation. Participants were divided in those with (SUI) or without (NON SUI) suicide risk according to the Mini International Neuropsychiatric Interview. Additionally, subjects with SUI were split into those with high (HIGH SUI) and low (LOW SUI) suicide risk. Between-group comparisons were made with t-tests for continuous variables and χ2 tests for categorical variables. SUI showed greater percentages of physical complaints during and after COVID-19, greater percentages of psychiatric history and presence of psychiatric history in relatives, greater percentages of subjects previously undergoing psychopharmacotherapy, and greater levels of anxiety, mixed depressive symptoms, general psychopathology than NON SUI. HIGH SUI showed greater number of symptoms during and after COVID-19 and higher levels of mixed depressive symptoms than LOW SUI. Percentages of subjects undergoing psychotherapy was higher in LOW SUI than HIGH SUI. Greater levels of physical complaints and psychopathology during post-COVID-syndrome might enhance the risk of committing suicide. Treatment of physical complaints and psychotherapy might reduce suicide risk

Lower Adherence to a Mediterranean Diet Is Associated with High Adiposity in Community-Dwelling Older Adults: Results from the Longevity Check-Up (Lookup) 7+ Project

High adiposity impacts health and quality of life in old age, owing to its association with multimorbidity, decreased physical performance, and frailty. Whether a high adherence to a Mediterranean diet (Medi-Diet) is associated with reduced body adiposity in older adults is unclear. The present study was conducted to assess the prevalence of high adiposity in a large sample of community-dwelling older adults. We also explored the relationship between whole-body adiposity estimated through relative fat mass (RFM) and Medi-Diet adherence. Data were obtained from the Longevity Check-up 7+ (Lookup7+) project database. RFM was estimated from anthropometric and personal parameters using a validated equation. RFM was categorized as high if ≥40% in women and ≥30% in men. Information on diet was collected using a food frequency questionnaire, while Medi-Diet adherence was assessed through a modified version of the Medi-Lite scoring system. Analyses were conducted in 2092 participants (mean age 73.1 ± 5.9 years; 53.4% women). Mean RFM was 39.6 ± 5.14% in women and 29.0 ± 3.6% in men. High adiposity was found in 971 (46.4%) participants and was more frequent in those with a low (54.2%) or moderate (46.4%) Medi-Diet adherence compared with the high-adherence group (39.7%, p < 0.001). Logistic regression indicated that older adults with high Medi-Diet adherence were less likely to have a high RFM. Other factors associated with a greater risk of having high adiposity were older age, female sex, and physical inactivity. Our findings support an association between healthy lifestyles, including a greater adherence to a Mediterranean-style diet, and lower body adiposity in older adults

Prognostic relevance of right heart reverse remodeling in idiopathic pulmonary arterial hypertension

BACKGROUND: Right ventricular (RV) failure is a major determinant of symptoms and shortened survival in pulmonary arterial hypertension (PAH). This study assessed the prognostic relevance of increased right heart (RH) dimensions determined by echocardiography and RH reverse remodeling (RHRR) with targeted therapies in idiopathic PAH (IPAH). METHODS: The study prospectively monitored 102 therapy-naïve IPAH patients for the presence of clinical worsening. Baseline evaluation included RH catheterization and echocardiography. RHRR at the 1-year follow-up was defined by a decrease in RV end-diastolic area, right atrial area, and the left ventricular systolic eccentricity index. RESULTS: At the 1-year follow-up, 18 of 102 patients (17.6%) presented with RHRR. A decrease in pulmonary vascular resistance was the only independent determinant of RHRR. The 94 surviving patients were monitored for 995 ± 529 days. RHRR was an independent prognostic factor and significantly improved the power of the prognostic model based on traditional clinical and hemodynamic parameters. The respective event-free survival rates at 1, 3, and 5 years were 94%, 94%, and 94% in patients with RHRR and 75%, 55%, and 24% in those without RHRR (p ¼ 0.0001). Interestingly, RHRR was able to further stratify patients’ risk assessment through the Registry to Evaluate Early And Long-term PAH Disease Management risk score. CONCLUSIONS: RHRR after 1 year of treatment is an independent predictor of prognosis in IPAH. The likelihood of RHRR is proportional to decreased pulmonary vascular resistance