Correlation between endothelial function and carotid atherosclerosis in rheumatoid arthritis patients with long-standing disease

Introduction In this study, we aimed to determine the relationship between flow-mediated endothelium-dependent vasodilatation (FMD) and carotid artery intima-media wall thickness (IMT), two surrogate markers of atherosclerosis, in a series of Spanish patients with rheumatoid arthritis (RA) without clinically evident cardiovascular (CV) disease. Methods One hundred eighteen patients who fulfilled the 1987 American College of Rheumatology classification criteria for RA, had no history of CV disease and had at least one year of follow-up after disease diagnosis were randomly selected. Brachial and carotid ultrasonography were performed to determine FMD and carotid IMT, respectively. Results Carotid IMT values were higher and FMD percentages derived by performing ultrasonography were lower in individuals with a long duration from the time of disease diagnosis. Patients with a disease duration ≤ 7 years had significantly lower carotid IMT (mean ± SD) 0.69 ± 0.17 mm than those with long disease duration (0.81 ± 0.12 mm in patients with ≥ 20 years of follow-up). Also, patients with a long disease duration had severe endothelial dysfunction (FMD 4.0 ± 4.0% in patients with disease duration from 14.5 to 19.7 years) compared with those with shorter disease duration (FMD 7.4 ± 3.8% in patients with disease duration ≤ 7 years). Linear regression analysis revealed that carotid IMT was unrelated to FMD in the whole sample of 118 patients. However, carotid IMT was negatively associated with FMD when the time from disease diagnosis ranged from 7.5 to 19.7 years (P = 0.02). Conclusions In patients with RA without CV disease, endothelial dysfunction and carotid IMT increased with the duration of RA. The association between FMD and carotid IMT values was observed only in patients with long disease duration

Psoriasis: a skin disease associated with increased cardiovascular risk

La psoriasis y la artritis psoriásica se asocian con un mayor riesgo de eventos cardiovasculares y de mortalidad cardiovascular. Además de los factores clásicos de aterosclerosis, la gravedad de la afección cutánea influye en el aumento del riesgo cardiovascular en estos pacientes. En ambos procesos se observa la presencia de disfunción endotelial y un grosor aumentado de la íntima-media de la arteria carótida, como expresión de enfermedad cardiovascular subclínica. El tratamiento activo de la enfermedad y el manejo de los factores de riesgo cardiovascular clásicos son fundamentales para disminuir la morbilidad cardiovascular en estos pacientes. El establecimiento de guías clínicas para el manejo del riesgo cardiovascular abrirá, en el futuro, un nuevo abordaje clínico integral del paciente con psoriasis y la artritis psoriásicaPsoriasis and psoriatic arthritis are associated with increased risk of cardiovascular events and cardiovascular mortality. Alongside classic risk factors such as atherosclerosis, the severity of psoriatic skin disease also influences cardiovascular risk in these patients. In both cases, endothelial dysfunction and increased intima-media thickness in the carotid artery are indicators of subclinical cardiovascular disease. Active treatment of the psoriasis and management of traditional cardiovascular risk factors are essential in order to reduce cardiovascular morbidity in these patients. Clinical practice guidelines on the management of cardiovascular risk will define a new integrated approach to the care of patients with psoriasis and psoriatic arthritis

Lack of association between carotid intima-media wall thickness and carotid plaques and markers of endothelial cell activation in rheumatoid arthritis patients undergoing anti-TNF therapy

Introduction: To determine the relationship between biomarkers of endothelial cell activation, and carotid artery intima-media wall thickness (IMT) and plaques, two surrogate markers of atherosclerosis, in a series of rheumatoid arthritis (RA) patients undergoing anti-TNF therapy. Methods: 29 consecutive Spanish patients who fulfilled the 1987 American College of Rheumatology classification criteria for RA, had no history of cardiovascular (CV) disease, and had at least one year of follow-up after disease diagnosis were selected. All patients were undergoing anti-TNF-infliximab therapy because of severe disease refractory to conventional disease modifying antirheumatic drugs. Carotid ultrasonography was performed to determine IMT and carotid plaques. Levels of sICAM-3, sICAM-1, sVCAM-1, sPselectin and sE-selectin were assessed by ELISA immediately before an infusion of infliximab. Results: The median disease duration was 14 years. Despite infliximab, no patient experienced a disease remission (DAS28: median 4.17). Only a marginally significant correlation between sVCAM-1 and carotid IMT was observed when both total correlation using Spearman correlation coefficient (p= 0.08) or partial correlation adjusting for sex, age at the time of study, disease duration, rheumatoid factor, and classic CV risk factors was performed (p= 0.09). Also, no association between presence of carotid plaques and levels of biomarkers of endothelial cell activation was observed. Conclusion: In long-standing RA patients without CV disease undergoing anti-TNF therapy no association between levels of soluble markers of endothelial cell activation and carotid ultrasonography abnormalities was observed. Further studies are needed to establish the best tools to be used in the assessment of CV risk of RA.Acknowledgements. This study was supported by two grants from "Fondo de Investigaciones Sanitarias" PI06-0024 and PS09/00748 and by RETICS Program, RD08/0075 (RIER) from "Instituto de Salud Carlos III" (ISCIII

SCORE and REGICOR function charts underestimate the cardiovascular risk in Spanish patients with rheumatoid arthritis

Introduction: Our objective was to determine which one of the two function charts available in Spain to calculate cardiovascular (CV) risk, Systematic COronary Risk Evaluation (SCORE) or Framingham-REgistre GIroní del COR (REGICOR), should be used in patients with rheumatoid arthritis (RA). Methods: A series of RA patients seen over a one-year period without history of CV events were assessed. SCORE, REGICOR, modified (m)SCORE and mREGICOR according to the European League Against Rheumatism (EULAR) recommendations were applied. Carotid ultrasonography (US) was performed. Carotid intima-media thickness (cIMT) > 0.90 mm and/or carotid plaques were used as the gold standard test for severe subclinical atherosclerosis and high CV risk (US+). The area under the receiver operating curves (AUC) for the predicted risk for mSCORE and mREGICOR were calculated according to the presence of severe carotid US findings (US+). Results: We included 370 patients (80% women; mean age 58.9 ± 13.7 years); 36% had disease duration of 10 years or more; rheumatoid factor (RF) and/or anticyclic citrullinated peptide (anti-CCP) were positive in 68%; and 17% had extra-articular manifestations. The EULAR multiplier factor was used in 122 (33%) of the patients. The mSCORE was 2.16 ± 2.49% and the mREGICOR 4.36 ± 3.46%. Regarding US results, 196 (53%) patients were US+. The AUC mSCORE was 0.798 (CI 95%: 0.752 to 0.844) and AUC mREGICOR 0.741 (95% CI; 0.691 to 0.792). However, mSCORE and mREGICOR failed to identify 88% and 91% of US+ patients. More than 50% of patients with mSCORE ≥1% or mREGICOR >1% were US+. Conclusions: Neither of these two function charts was useful in estimating CV risk in Spanish RA patients

Anti-TNF-alpha-adalimumab therapy is associated with persistent improvement of endothelial function without progression of carotid intima-media wall thickness in patients with rheumatoid arthritis refractory to conventional therapy

To determine whether treatment with the anti-TNF-alpha blocker adalimumab yields persistent improvement of endothelial function and prevents from morphological progression of subclinical atherosclerosis in patients with rheumatoid arthritis (RA) refractory to conventional therapy, a series of 34 consecutive RA patients, attending hospital outpatient clinics and who were switched from disease modifying antirheumatic drug therapy to anti-TNF-alpha-adalimumab treatment because of severe disease, were assessed by ultrasonography techniques before the onset of adalimumab therapy (at day 0) and then at day 14 and at month 12. Values of flow-mediated endothelium-dependent vasodilatation at day 14 and at month 12 were significantly higher (mean ± standard deviation (SD): 6.1 ± 3.9%; median: 5.7% at day 14, and mean ± SD: 7.4 ± 2.8%; median: 6.9% at month 12) than those obtained at day 0 (mean: 4.5 ± 4.0%; median: 3.6%; P = 0.03 and P < 0.001, resp.). Endothelium-independent vasodilatation results did not significantly change compared with those obtained at day 0. No significant differences were observed when carotid artery intima-media wall thickness values obtained at month 12 (mean ± SD: 0.69 ± 0.21 mm) were compared with those found at day 0 (0.65 ± 0.16 mm) (P = 0.3). In conclusion, anti-TNF-alpha-adalimumab therapy has beneficial effects on the development of the subclinical atherosclerosis disease in RA

Metabolic Syndrome in Rheumatoid Arthritis

Insulin resistance is an essential feature of the metabolic syndrome that has been linked to rheumatoid arthritis (RA). Understanding how inflammation arising in one tissue affects the physiology and pathology of other organs remains an unanswered question with therapeutic implications for chronic conditions including obesity, diabetes mellitus, atherosclerosis, and RA. Adipokines may play a role in the development of atherogenesis in patients with RA. Biologic therapies, such as TNF-α antagonists, that block proinflammatory cytokines have beneficial effects on the insulin resistance that is often observed in patients with RA

Subclinical carotid atherosclerosis predicts all-cause mortality and cardiovascular events in obese patients with negative exercise echocardiography

BACKGROUND: Obesity is a major health problem due to its high prevalence. The relationship between obesity and cardiovascular disease is unclear. Some studies agree that certain conditions associated with obesity, such as physical inactivity or cardiovascular risk factors, are responsible for cardiovascular risk excess among obese people. Carotid intima-media thickness and carotid plaques (CP) have been associated with cardiovascular adverse events in healthy populations, and recent data suggest a higher prevalence of subclinical carotid atherosclerosis in obese and metabolically unhealthy patients. However, there are no studies correlating subclinical atherosclerosis and adverse events (AE) in obese subjects. AIM: To determine the association between carotid disease and AE in obese patients with negative exercise echocardiography (EE). METHODS: From January 1, 2006 to December 31, 2010, 2000 consecutive patients with a suspicion of coronary artery disease were submitted for EE and carotid ultrasonography. Exclusion criteria included previous vascular disease, left ventricular ejection fraction < 50%, positive EE, significant valvular heart disease and inferior to submaximal EE. An AE was defined as all-cause mortality, myocardial infarction and cerebrovascular accident. Subclinical atherosclerosis was defined as CP presence according to Manheim and the American Society of Echocardiography Consensus. RESULTS: Of the 652 patients who fulfilled the inclusion criteria, 226 (34.7%) had body mass indexes ≥ 30 kg/m2, and 76 of them (33.6%) had CP. During a mean follow-up time of 8.2 (2.1) years, 27 AE were found (11.9%). Mean event-free survival at 1, 5 and 10 years was 99.1% (0.6), 95.1% (1.4) and 86.5% (2.7), respectively. In univariate analysis, CP predicted AE [hazard ratio (HR) 2.52, 95% confidence interval (CI) 1.17-5.46; P = 0.019]. In multivariable analysis, the presence of CP remained a predictor of AE (HR 2.26, 95%CI 1.04-4.95, P = 0.041). Other predictors identified were glomerular filtration rate (HR 0.98, 95%CI 0.96-0.99; P = 0.023), peak metabolic equivalents (HR 0.83, 95%CI 0.70-0.99, P = 0.034) and moderate mitral regurgitation (HR 5.02, 95%CI 1.42-17.75, P = 0.012). CONCLUSION: Subclinical atherosclerosis defined by CP predicts AE in obese patients with negative EE. These patients could benefit from aggressive prevention measures