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The extension of infection in native valve infective endocarditis (IE) from valvular structures to the periannular tissue is incompletely understood. It is unknown, for example, whether the prognosis of patients with aortocavitary fistulae is worse than that of those with nonruptured abscesses. The aims of this study were to determine the distinct clinical characteristics of patients with aortocavitary fistulae and nonruptured abscesses in native valve IE and to evaluate the impact of fistulization on the outcomes of patients with native aortic valve IE complicated with periannular lesions. In a retrospective multicenter study of 2,055 native valve IE episodes, 201 patients (9.8%) with periannular complications in aortic valve IE were identified (46 with aortocavitary fistulization and 155 with nonruptured abscesses). Rates of heart failure (p = 0.07), ventricular septal defect (p <0.001), and third-degree atrioventricular block (p = 0.07) were higher in patients with fistulization. Surgical treatment was undertaken in 172 patients (86%), and in-hospital mortality in the overall population was 29%. Multivariate analysis identified age >60 years (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.3 to 5.2), renal failure (OR 3.0, 95% CI 1.5 to 6.0), and moderate or severe heart failure (OR 2.5, 95% CI 1.2 to 5.2) as independent risk factors for death. There was a trend toward increased in-hospital mortality in patients with aortocavitary fistulae (OR 1.5, 95% CI 0.7 to 3.0). The actuarial 5-year survival rate in surgical survivors was 80% in patients with fistulae and 92% in patients with nonruptured abscesses (log-rank p = 0.6). In conclusion, aortocavitary fistulous tract formation in the setting of native valve IE is associated with higher rates of heart failure, ventricular septal defect, and atrioventricular block than nonruptured abscess. Despite these higher rates of complications, fistulous tract formation in the current era of IE is not an independent risk factor for mortality.

Secondary vasculitis resulting from unusual pathologic expressions of infections has been described and has important clinical significance. Infectious agents have also been implicated in the pathogenesis of different primary systemic necrotizing vasculitides. Infectious endocarditis is of particular importance in the differential diagnosis of a patient presenting with ANCA associated vasculitis. We report a well-documented case of a patient with recurrent Staphylococcus aureus bacteremia who developed bacterial endocarditis and also fulfilled the Chapel Hill Conference definitions for microscopic polyangiitis. To the best of our knowledge, it is the second case of bacterial endocarditis associated with both pANCA and anti-MPO specificity that fulfilled definitions for systemic necrotizing vasculitis. We emphasize the potential pathogenic role of infection as the trigger factor for the development of systemic vasculitis.

Objective: Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). Soluble (s) adhesion molecules were found significantly increased in RA patients with active disease. Since increased levels of some adhesion molecules were closely linked to the development of endothelial dysfunction and atherosclerosis and administration of anti-TNF-alpha-infliximab resulted in a rapid and dramatic improvement of endothelial function in long-term infliximab treated RA patients, we assessed whether infusion of the chimeric anti-TNF-alpha infliximab might also yield a rapid and favorable effect on serum levels of soluble adhesion molecules in RA patients periodically treated with this drug because of severe disease., Methods: We recruited patients with RA refractory to conventional therapy seen over a period of 2 months at Hospital Xeral-Calde, Lugo, Spain, who were on periodical treatment with infliximab for at least 14 weeks. Blood samples for determination of sICAM-1, sICAM-3, sVCAM-1, sE-selectin, and sP-selectin levels by ELISA were taken immediately before and after infliximab infusion., Results: Thirty-four RA patients (25 women; mean age: 55.4 years; mean DAS28: 4.27) fulfilled the inclusion criteria. Following infliximab infusion a reduction of the overall mean values of the five adhesion molecules was observed. However, when a Wilcoxon signed-rank test was used, only significant differences for sICAM-3 and sP-selectin were observed. In this regard, sICAM-3 and sP-selectin levels fell in 26 (77%) and 28 (82%) of the 34 patients., Conclusion: Our study confirms a rapid and beneficial effect of infliximab infusion on expression of some adhesion molecules in RA patients treated periodically with this anti-TNF-alpha monoclonal antibody because of severe disease.

Objective: Endothelial dysfunction has been found in patients with rheumatoid arthritis (RA). In this study we aimed to assess whether adalimumab, a fully human monoclonal antibody directed against TNF-alpha, was able to improve endothelial function in RA patients with long-standing disease refractory to infliximab., Methods: Eight RA patients (7 women; range: 24- 74 years) were studied. They had been treated with the chimeric monoclonal anti-TNF-alpha antibody-infliximab for at least 1 year and were switched to adalimumab therapy because of loss of efficacy following periodical treatment with infliximab. Endothelial dependent (EDV) and independent vasodilatation (EIV) were measured by brachial ultrasonography. Patients were assessed prior to (day 0) and at day 2, and weeks 2 and 12 after the onset of adalimumab therapy., Results: Following adalimumab administration a rapid increase in the percentage (%) of EDV was found in all patients (mean +/- SD: 10.1 +/- 5.1% at day 2 compared to 5.8 +/- 4.1% at day 0). At weeks 2 and 12 the %EDV was also significantly increased compared to day 0. All patients showed decrease in the disease activity score 28 and C-reactive protein levels (P = 0.012). Moreover, at week 12 the atherogenic index was reduced in all patients (P = 0.012)., Conclusion: Our study confirms that short-term adalimumab therapy yields an active and positive effect on endothelial function in long-standing RA patients with severe disease. This observation emphasizes the potential role of the TNF-alpha blockade in the mechanisms implicated in the development of atherogenesis in RA.

Objective: To assess the prevalence of echocardiographic and Doppler abnormalities in psoriatic arthritis (PsA) patients without clinically evident cardiovascular manifestations or classic atherosclerosis risk factors., Methods: Fifty PsA patients were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients seen during the period of recruitment that had classic cardiovascular risk factors or had suffered cardiovascular or cerebrovascular events were excluded. Fifty healthy matched controls were also studied. Echocardiographic and Doppler studies were performed in all cases and controls., Results: In PsA patients the frequency of aortic and tricuspid (10%) and mitral regurgitation (16%) was not different from that seen in matched controls (10, 4, and 12%). Also, the pulmonary artery systolic pressure was normal in the group of PsA patients (23.4+/-3.9 mm Hg). The prevalence of diastolic dysfunction, in all cases due to impaired relaxation, was similar in PsA patients (28%) and controls (24%) (P=0.65). In addition, no significant echocardiographic and Doppler differences were observed when PsA patients with polyarticular pattern were compared with the remaining PsA patients., Conclusions: The present study shows that actively treated PsA patients without cardiovascular risk factors or clinically evident cardiovascular disease do not exhibit silent subclinical echocardiographic abnormalities.

Objective: Systemic inflammation, insulin resistance, and endothelial dysfunction have been implicated in the development of cardiovascular disease in rheumatoid arthritis (RA). Since insulin resistance can promote endothelial dysfunction and anti-TNF-alpha blockade yield a rapid improvement of endothelial function, we have sought to assess whether TNF-alpha blockade may also result in a reduction of insulin serum levels and improvement of insulin resistance in RA patients who require this therapy because of severe and refractory disease., Methods: We recruited patients with RA seen over a period of 1 month at Hospital Xeral-Calde, Lugo, Spain, that were on treatment with anti-TNF-alpha monoclonal antibody-infliximab. Patients with diabetes mellitus or plasma glucose > 110 mg/dl were excluded. Fasting blood samples were taken for determination of plasma glucose and serum insulin levels immediately prior to and after infliximab infusion., Results: Twenty-seven RA patients (21 women; mean age: 57.1 years; mean DAS28: 4.43) fulfilled the inclusion criteria. Dramatic reduction in the serum insulin levels and insulin/glucose index was observed following infliximab infusion. Also, a significant improvement of insulin resistance and insulin sensitivity was found., Conclusion: Our study confirms a rapid beneficial effect of infliximab on insulin resistance and insulin sensitivity in RA patients treated periodically with this drug. It may support the long-term use of drugs that act blocking TNF-alpha function to reduce the mechanisms implicated in the development of atherosclerosis in patients with RA.

Objective: Endothelial dysfunction has been found to be present in subjects with both small and medium-size blood vessel vasculitides. We assess whether endothelial dysfunction was also present in patients with biopsy-proven giant cell arteritis (GCA) and whether it might be improved following steroid treatment., Methods: Endothelial function was determined in cross-sectional and longitudinal studies of 6 patients with biopsy-proven GCA diagnosed between January and May 2002 by measuring flow-mediated endothelial-dependent and independent vasodilatation (EDV and EIV) by brachial ultrasonography. Patients were assessed for endothelial function within 48 hours after the onset of steroid therapy, 4 weeks after the onset of steroid therapy, and 2 years after the disease diagnosis., Results: EDV was significantly impaired in patients with GCA compared with 12 matched controls [mean 2.9%, median 2.45% (range 2.1% to 4.7%) vs mean 6.5%, median 6.6% (range 3.9% to 9.3%) in matched controls; p = 0.002]. However, no significant difference existed between patients and controls in EIV. Significant improvement of EDV after the suppression of inflammation was achieved. At Week 4 after the onset of steroid therapy all 6 patients showed enhanced responses (p = 0.028). This improvement of EDV was still present when steroid treatment was ended, 2 years after diagnosis., Conclusion: Endothelial function is significantly impaired in individuals with active biopsy-proven GCA. The results highlight the importance of steroid therapy to improve endothelial function after suppression of the inflammation of GCA.

Cardiac involvement is a not uncommon complication in patients with antiphospholipid syndrome (APS). Herein, the case is reported of cardiac failure in a female patient with Libman-Sacks endocarditis and with primary APS diagnosed eight years previously. Aggressive anticoagulation therapy and medical treatment for the cardiac failure over a 12-month period resulted in a partial regression of the severe mitral regurgitation. Close clinical and echocardiographic surveillance during the follow up of patients with APS and heart valve disease is mandatory. Optimal treatment, including adequate aggressive anticoagulation therapy and specific treatment for heart failure, may play a pivotal role in reducing the severity of valve dysfunction in these patients.

Objectives: Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with an increased prevalence of coronary heart disease and a high cardiovascular (CV) mortality. In this article, a review of mechanisms implicated in the development of accelerated atherogenesis in RA was performed. The potential role of treatment to reduce the incidence of CV events in RA was also discussed., Methods: Retrospective review of the literature. The potential mechanisms implicated in the development of accelerated atherogenesis in RA, information on carotid ultrasonography, and the potential implication of treatment to prevent accelerated atherogenesis in individuals with RA were examined., Results: Endothelial dysfunction, which is an early step in the development of atherosclerosis, has been observed in patients with RA. Deleterious effects resulting from persistent chronic inflammation may lead to endothelial dysfunction, insulin resistance, and a dyslipidemic pattern in these patients. Other mechanisms different from those related to classic atherogenesis risk factors, such as hyperhomocysteinemia and increased oxidative stress, are considered to be implicated in the pathogenesis of atherosclerosis in RA. Increased carotid intima-media thickness and carotid plaques have been found in RA patients compared with matched controls. Active MTX treatment of the disease has been associated with decreased CV mortality. Additional drugs such as statins may be considered in the management of these patients., Conclusions: The increased prevalence of CV mortality rate in RA cannot only be explained by the presence of traditional atherosclerotic risk factors. A chronic inflammatory response may promote the development of accelerated atherogenesis in these patients. Active treatment of the disease is required to reduce the risk of developing CV complications in individuals with RA.

Objective: Patients with rheumatoid arthritis (RA) are at greater risk of developing cardiovascular events compared with individuals without RA. Increased risk for cardiovascular disease in these patients is a consequence of atherosclerosis. Case-control studies have shown that increased intima-media thickness (IMT) of the common carotid artery is an indicator of generalized atherosclerosis. Some investigators have suggested that the development of atherosclerosis in RA may be related to the magnitude and chronicity of the systemic inflammation. We examined the relationship between carotid IMT to C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which are the most commonly assessed markers of inflammatory response in patients with RA., Methods: Retrospective review of CRP and ESR values in 47 patients with longterm actively treated (at least 5 years) RA without clinically evident atherosclerosis or its complications, who had been studied for carotid IMT with high resolution B-mode ultrasound., Results: No correlation between ESR and carotid IMT was observed. However, a correlation was found between the maximum CRP values and the carotid IMT (p = 0.009). The distribution of patients in 4 quartiles according to the average CRP values showed significant differences in the carotid IMT (p = 0.03). Those exhibiting the highest mean CRP values (quartile 4) had greater carotid IMT. There was no correlation between CRP at the time of disease diagnosis or at the time of the ultrasound study and the carotid IMT., Conclusion: Our study confirms that the magnitude and chronicity of the inflammatory response measured by CRP correlates directly with the presence of atherosclerosis in patients with RA.

Objective: To assess the incidence, mortality, and predictors of ischemic heart disease (IHD) in patients from the Lugo region of Northwest Spain with biopsy-proven giant cell arteritis (GCA)., Methods: Retrospective study of patients with biopsy-proven GCA diagnosed from 1981 to 2001 at the single hospital for a population of 250,000 people. A survival analysis was performed. Hazard ratios and standardized mortality ratio (SMR) as well as predictors of IHD in patients with biopsy-proven GCA were also assessed., Results: Nineteen (9%) of the 210 patients with biopsy-proven GCA diagnosed during the period of study had IHD. The incidence of IHD in patients with GCA was 12.6/1000 person-years at risk (95% CI 6.9-21.0). During the study period 1981-2000 the population aged > or = 50 years in Lugo was roughly 100,000, and the mortality rate due to IHD in patients with GCA for that population was 8/100,000. The SMR in patients with GCA due to IHD was 1.62 (95% CI 0.70-3.20). Mortality in patients with GCA who had IHD was higher than in those patients without IHD (age and sex adjusted hazard ratio 2.81, 95% CI 1.51-5.21; p = 0.001). Age (hazard ratio 1.15), hypertension (hazard ratio 2.51), and abnormal temporal artery on physical examination (hazard ratio 0.36) at the time of diagnosis of GCA were the best predictors of IHD over the followup period in patients with biopsy-proven GCA., Conclusion: Our observations suggest that mortality due to IHD in patients from Lugo with GCA is not much higher than that reported in the Spanish population aged 50 years and older. However, mortality in patients with GCA with IHD is higher than in GCA patients without IHD.

Aims: To investigate the clinical features, echocardiographic characteristics, management, and prognostic factors of mortality of aorto-cavitary fistulization (ACF) in infective endocarditis (IE). Extension of infection in aortic valve IE beyond valvular structures may result in peri-annular complications with resulting necrosis and rupture, and subsequent development of ACF. Aorto-cavitary communications create intra-cardiac shunts, which may result in further clinical deterioration and haemodynamic instability., Methods and Results: In a retrospective multi-centre study over 4681 episodes of IE, a total of 76 patients with ACF [1.6%, confidence interval (CI) 95%: 1.2-2.0%] diagnosed by echocardiography or during surgery were identified. Fistulae were found in 1.8% of cases of native valve IE and in 3.5% of cases of prosthetic valve IE from the general population and in 0.4% of drug abusers. PVE was present in 31 (41%) cases of ACF. Transthoracic and transoesophageal echocardiography detected the fistulous tracts in 53 and 97% of cases, respectively. Peri-annular abscesses were detected in 78% of cases, fistulae originated in similar rates from the three sinuses of Valsalva, and the four cardiac chambers were equally involved in the fistulous tracts. Heart failure (HF) developed in 62% of cases and surgery was performed in 66 (87% CI 95% 77-93%) patients with a mortality of 41% (95% CI 30-53%) in the overall population. Multivariate analysis identified HF (OR 3.4, CI 95% 1.0-11.5), prosthetic IE (OR 4.6, CI 95% 1.4-15.4) and urgent or emergency surgical treatment (OR 4.3, CI 95% 1.3-16.6) as variables significantly associated with an increased risk of death. Major complications during follow-up (death, re-operation, or re-admission for HF) among the five operative survivors with residual fistulae occurred in 20 and 100% of patients at 1 and 2 years, respectively., Conclusion: Aorto-cavitary fistulous tract formation is an uncommon but extremely serious complication of IE. In-hospital mortality was exceptionally high despite aggressive management with surgical intervention in the majority of patients. Prosthetic IE, urgent surgery, and the development of HF identify the subgroup of patients with IE and ACF that have significantly increased risk of in-hospital death.

Background: Aspergillus infections of pacing systems are extremely uncommon, and most cases reported are characterized by an aggressive behavior that may lead to death of the patient., Hypothesis: The study was undertaken to assess the incidence of pacemaker infection due to Aspergillus in a defined population., Methods: A retrospective review of the case histories of all patients who underwent pacemaker implantation in the reference center for a defined population over a 13-year period was undertaken. A literature review of pacemaker infections due to Aspergillus was conducted., Results: Of the 1,321 patients who required pacemaker implantation at Hospital Xeral-Calde in the Lugo region of northwestern Spain, 38 suffered a pacemaker infection. A pacemaker pocket infection due to Aspergillus fumigatus was found in two patients. Both patients had a previous history of diabetes mellitus. Cultures from pacemaker pocket inflammatory fluid yielded positive results. Following pacemaker explantation and antifungal therapy, clinical improvement was achieved. A literature review showed another five cases of pacemaker infection due to Aspergillus. However, two peculiarities were found in our patients: In both cases an etiological diagnosis was achieved prior to surgery and, to the best of our knowledge, they also constitute the first cases of pacemaker pocket infection due to Aspergillus., Conclusion: Although pacemaker infections due to Aspergillus species are uncommon, they should be considered in immunocompromised patients.

Background: Persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly., Hypothesis: This study examines the epidemiologic, clinical, and morphologic characteristics of a cohort of patients with PLSVC draining into the coronary sinus., Methods: We examined the clinical and morphologic characteristics of patients with PLSVC draining into the coronary sinus diagnosed at a single referral hospital for a defined population in northwestern Spain. We designed a prospective study of the case records of all patients diagnosed with PLSVC draining into the coronary sinus at the echocardiography laboratory of the Hospital Xeral-Calde from January 2001 through December 2002. Patients were included if they had a PLSVC diagnosed by transthoracic echocardiogram (TTE) using an echo-contrast enhancement and confirmed by a magnetic resonance (MR) imaging. Ten patients (6 women) fulfilled the inclusion criteria described above. All patients were adults and had associated heart disease, including a congenital heart disease in three cases., Results: Magnetic resonance imaging examination confirmed the presence of PLSVC and the site of drainage into the coronary sinus. Absence of the right superior vena cava was observed only in three patients, in whom the main coronary sinus size was significantly increased. Absence of the left brachiocephalic vein was diagnosed in five patients., Conclusion: This study describes 10 new cases of PLSVC and supports the necessity of considering PLSVC draining into the coronary sinus in the diagnosis of patients presenting with dilated coronary sinus diagnosed by TTE. It also underlines the important role of MR imaging in the evaluation of these abnormalities. An associated heart disease must always be excluded in these patients.

Objective: Cardiovascular disease is the major cause of excessive mortality in rheumatoid arthritis (RA). Atherosclerosis and RA share similar inflammatory mechanisms that include involvement of tumor necrosis factor alpha (TNF alpha). Anti-TNF alpha antibody improved endothelial function in RA patients after a 12-week treatment. The aim of the present study was to assess whether improvement of endothelial function is still effective in long-term infliximab-treated RA patients., Methods: Seven RA patients (5 women; age range 25-73 years) were studied. They had been treated with infliximab for at least 1 year and were currently being treated with this drug every 8 weeks. Endothelial-dependent and independent vasodilatation were measured by brachial ultrasonography., Results: Following infliximab infusion, a rapid increase in the percentage of endothelial-dependent vasodilatation was found in all patients (mean +/- SD 9.4 +/- 5.5% 2 days postinfusion compared with 2.8 +/- 2.5% 2 days before infusion). However, values returned to baseline by 4 weeks after infusion. There were no differences in the percentage of endothelial-independent vasodilatation prior to and after infusion. A decrease in the individual disease activity score for each patient was observed at day 7 postinfusion (P = 0.02)., Conclusion: Our study confirms an active but transient effect of infliximab on endothelial function in RA patients treated periodically with this drug. It may support long-term use of drugs that block TNF alpha function to reduce the high incidence of cardiovascular complications in RA.

Cardiovascular disease is the commonest cause of premature mortality in rheumatoid arthritis (RA) patients. Vascular endothelial injury is the primary event in atherosclerosis. It has been associated with endothelial dysfunction. We have recently observed that actively treated RA patients had endothelial dysfunction. HLA-DRB1 shared epitope alleles, in particular HLA-DRB1*0404, seem to be implicated in the development of endothelial dysfunction. These results underline the influence of genetic factors in the risk of atherosclerosis in RA patients.

Objective: To assess the frequency of echocardiographic and Doppler abnormalities in long-term treated rheumatoid arthritis (RA) patients without clinically evident cardiovascular manifestations., Methods: Forty-seven patients with RA were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years and to be on treatment with 1 or more disease-modifying antirheumatic drugs. Patients seen during the period of recruitment who had cardiovascular risk factors or had suffered cardiovascular or cerebrovascular events were excluded. Forty-seven healthy matched controls were also studied. Echocardiographic and Doppler studies were performed in all cases and controls. Patients were HLA-DRB1 genotyped by using molecular-based methods., Results: In patients with RA, the prevalence of aortic regurgitation (17%) and tricuspid regurgitation (17%) was not higher than that seen in controls (15% and 6%). The pulmonary artery systolic pressure was higher in patients with RA (30.3 +/- 8.0 mm Hg) than in controls (26.2 +/- 4.8) (P =.004). Incidence of pulmonary artery systolic pressure >35 mm Hg was significantly higher in patients with RA (21% versus 4% in controls; P =.03). Diastolic dysfunction caused by impaired relaxation was also more common in patients with RA (66%) than in controls (43%) (P =.02). It was more frequent in the older patients. Extra-articular manifestations were more common in patients with RA with diastolic dysfunction (P =.05). The HLA-DRB1 genotype was not implicated in the risk of developing diastolic dysfunction., Conclusions: The present study confirms a high frequency of left ventricular diastolic dysfunction and pulmonary hypertension in patients with RA without evident cardiovascular disease.

We conducted the current study to search for subclinical atherosclerosis in patients with rheumatoid arthritis (RA) without clinically evident atherosclerosis or its complications who had been treated for a long duration, and to assess whether demographic or clinical factors affect the development of atherosclerotic disease. Forty-seven white patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with 1 or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, hypertension, cardiovascular or cerebrovascular disease, and smokers were excluded. Forty-seven matched controls were also studied. Carotid intima-media wall thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high-resolution B-mode ultrasound. Patients had greater carotid IMT (0.779 +/- 0.164 mm) than did controls (0.699 +/- 0.129 mm); (p = 0.010). Sixteen (34%) patients showed carotid plaques compared with only 7 (15%) controls (p = 0.031). There was a positive correlation between the age at the time of study and the carotid IMT. Patients with carotid plaques had significantly greater carotid IMT (0.859 +/- 0.116 mm) than those without plaques (0.739 +/- 0.171 mm) (p = 0.014). Also, RA patients with carotid plaques had a significantly longer disease duration (mean, 21.0 yr) and more extraarticular manifestations (63%) than those without plaques (mean, 12.7 yr and 26%, respectively). Age at the time of the study and disease duration were the best predictive factors for the development of severe morphologic expression of atherosclerotic disease. The present study confirms an increased frequency of severe subclinical atherosclerotic findings in long-term actively treated RA patients from northwest Spain.

Purpose: To examine endothelial function in rheumatoid arthritis patients and to assess whether clinical or genetic factors affect the development of endothelial dysfunction., Methods: Fifty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with one or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, or cardiovascular disease were excluded. Thirty-one age-, sex-, and ethnically matched controls were also studied. Endothelium-dependent (postischemia) and -independent (postnitroglycerin) vasodilatation were measured by brachial ultrasonography. Patients were genotyped for human leukocyte antigen (HLA)-DRB1., Results: Patients had decreased endothelium-dependent vasodilatation (mean [+/- SD], 3.8% +/- 4.9%) compared with controls (8.0% +/- 4.5%; P <0.001). There were no differences in endothelium-independent vasodilatation. Clinical features were not associated with endothelial dysfunction. Endothelium-dependent vasodilatation was lower in the 30 rheumatoid arthritis patients with the HLA-DRB1*04 shared epitope alleles (2.4% +/- 4.1%) than in the remaining patients (5.5% +/- 5.3%; P = 0.01). Similar results were seen for patients with the HLA-DRB1*0404 shared epitope allele (-0.4% +/- 2.5%) compared with other patients (4.4% +/- 4.9%; P = 0.01)., Conclusion: Patients with chronically treated rheumatoid arthritis had evidence of endothelial dysfunction, especially those with certain HLA-DRB1 genotypes. If confirmed, our results suggest that HLA-DRB1 status may be a predictor of cardiovascular risk in these patients.