Luigi Gianturco

Effects of long-term disease-modifying antirheumatic drugs on endothelial function in patients with early rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of the disease and the quality of life of these patients, but little is known about the effects of DMARDs on CV risk and endothelial dysfunction. Our goal was to examine the effects of long-term therapy with DMARDs on endothelial function and disease activity in early RA (ERA). Twenty-five ERA patients (mean age 52 ± 14.6 years, disease duration 6.24 ± 4.10 months) without evidence of CV involvement were evaluated for disease activity score (DAS-28), 2D-echo derived coronary flow reserve (CFR), common carotid intima-media thickness (IMT) and plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 18 months of treatment with DMARDs (10 patients with methotrexate and 10 with adalimumab). DMARDs significantly reduced DAS-28 (6.0 ± 0.8 vs. 2.0 ± 0.7; P < 0.0001) and improved CFR (2.4 ± 0.2 vs. 2.7 ± 0.5; P < 0.01). Common carotid IMT and plasma ADMA levels did not show significant changes. The present study shows that DMARDs, beyond the well known antiphlogistic effects, are able to improve coronary microcirculation without a direct effect on IMT and ADMA, clinical markers of atherosclerosis. Treatment strategies in ERA patients with high inflammatory activity must be monitored to identify beneficial effects on preclinical markers of vascular function.

Coronary Flow Reserve and Asymmetric Dimethylarginine Levels: New Measurements for Identifying Subclinical Atherosclerosis in Patients with Psoriatic Arthritis

Objective. To identify the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) and healthy controls using intima-media thickness (IMT), coronary flow reserve (CFR), and the plasma concentration of asymmetric dimethylarginine (ADMA), to evaluate the correlations among ADMA, IMT, and CFR. Methods. The study involved 22 patients who fulfilled the ClASsification of Psoriatic ARthritis study group criteria for PsA and a cohort of 35 healthy controls with no history or current signs of coronary artery disease (CAD). Common carotid IMT was measured using high-resolution B-mode ultrasonography. Dipyridamole transthoracic stress echocardiography was used to evaluate CFR. Blood samples were obtained to assess ADMA levels. The clinical manifestations were recorded. All patients were treated with disease-modifying antirheumatic drug, but none had received any biological or steroid therapy. Results. Plasma ADMA levels were significantly higher in the patients with PsA (0.71 ± 0.07 μmol/l vs 0.48 ± 0.07 μmol/l; p = 0.00) and CFR was significantly reduced in that group (2.86 ± 0.70 vs 3.3 ± 0.43; p < 0.01) compared to controls. Common carotid IMT was greater in the patients with PsA, but the difference was not significant (0.64 ± 0.26 mm vs 0.62 ± 0.5 mm; p = 0.65). There was a significant correlation between CFR and plasma ADMA levels in the PsA group (R = 0.28; p < 0.01), but no correlation between plasma ADMA levels and IMT (R = 0.02; p = 0.32), Disease Activity Score 28 (p = 0.52), or Psoriasis Area and Severity Index (p = 0.98). Conclusion. Our patients with PsA showed a profile of subclinical atherosclerosis. ADMA may be a useful marker of endothelial dysfunction in PsA.

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross-sectional study.

An association between systemic autoimmune diseases and atherosclerosis has been described in many connective tissue diseases, and this association is known to lead to increased cardiovascular morbidity and mortality. Systemic sclerosis (SSc) is characterized by multisystem organ inflammation, endothelial wall damage, and vasculopathy. There are many markers of endothelial dysfunction and/or atherosclerotic risk, such as asymmetric dimethylarginine (ADMA), arterial stiffness parameters, carotid intima‐media thickness (CIMT), and coronary flow reserve (CFR) assessed by transthoracic echocardiography. The aim of this pilot study was to use various endothelial and atherosclerosis markers to identify early cardiovascular involvement in a group of SSc patients.

The heart in rheumatoid arthritis.

Morbidity and mortality rates are higher in rheumatoid arthritis (RA) patients than in the general population. Many studies have shown that coronary artery disease is one of the most common causes of death in RA and seems to occur at a younger age than in the general population. RA per se is as much a cardiovascular (CV) risk factor as diabetes, arterial hypertension and dyslipidemia etc., and so it is necessary to plan a follow-up using the same diagnostic and therapeutic approaches as those commonly used for primary and secondary prevention in non-RA patients at high CV risk. All of the cardiac structures can be affected during the course of RA (valves, the conduction system, the myocardium, endocardium and pericardium, and the coronary arteries), and cardiac complications include a variety of clinical manifestations. As these are all associated with an unfavourable prognosis, it is essential to detect subclinical cardiac involvement in still asymptomatic RA patients in order to assure adequate long-term treatment.

Role of cardiovascular imaging in systemic autoimmune diseases

Systemic autoimmune diseases are characterized by an excess of cardiovascular (CV) morbidity and mortality compared to the general population, mainly due to chronic inflammation that promotes the development of endothelial dysfunction and enhanced atherosclerosis. Early diagnosis of silent CV involvement is mandatory to improve the long term prognosis of these patients and CV imaging provides valuable information as a reliable diagnostic tool. Transthoracic echocardiography, with several applications (e.g. coronary flow reserve evaluation, tissue Doppler imaging, speckle tracking and the transesophageal approach), represents a first line evaluation, in association with biomarkers of endothelial dysfunction, such as asymmetric dimethylarginine. Nuclear medicine provides useful information on myocardial perfusion. The aim of this editorial is to provide a brief but complete review of the diagnostic tools available for screening and follow up of CV involvement in systemic autoimmune diseases.

Investigating the potential side effects of anti-TNF therapy for rheumatoid arthritis: cause for concern?

There are now five anti-TNF drugs available for clinical use, and it will not be long before they are joined by biosimilar drugs. Some patients treated with selective TNF drugs may develop adverse events such as infections, malignancies, acute infusion and injection reactions, autoimmunity and cardiovascular effects. Registry data consistently show that, particularly during the first 6 months, anti-TNF drugs slightly increase the risk of serious infections of the skin, soft tissues and joints, but it does not seem to increase the risk of cancer other than nonmelanoma skin cancers. A number of studies have shown that the administration of biological agents can lead to the formation of neutralizing and nonneutralizing antibodies. Lipid levels increase, but the atherogenic index remains stable and qualitative changes to lipid particles may reduce the risk of cardiovascular diseases. Patients treated with anti-TNF drugs therefore need to be monitored regularly.

Cardiovascular injury in systemic autoimmune diseases: an update

It is well known in literature that systemic autoimmune diseases (SADs) are associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease. Cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality in SADs. There is considerable evidence suggesting a pathogenetic role of chronic inflammation and immune dysregulation for enhanced atherosclerosis in SADs, as demonstrated in several recent studies. Moreover, chronic inflammation, accelerated atherosclerosis and functional abnormalities of the endothelium suggest a subclinical CV involvement beginning rapidly soon after the onset of the disease and progressing with disease duration.

THU0320 New Parameters for Identifying Subclinical Atherosclerosis in Patients with Primary SjöGren’s Syndrome: A Pilot Study

Background Clinical and biochemical data suggest that autoimmune diseases are associated with endothelial dysfunction and increased atherosclerosis. We have previously shown that asymmetric dimethylarginine (ADMA) levels and coronary flow reserve (CFR) are impaired in patients with early rheumatoid arthritis (1), but it is not known whether the same is true for patients with primary Sjögren’s syndrome (pSS). Objectives To investigate sub-clinical cardiovascular involvement in pSS patients by means of ADMA, coronary flow reserve (CFR), intima media thickness (cIMT), pulse wave velocity (PWV) and myocardial deformation. Methods The study involved 22 outpatients with pSS (6 males, 16 females; mean age 60.14±7.81 years) and no documentable cardiovascular disease, and 22 age- and gender-matched controls. Dipyridamole transthoracic stress echocardiography was used to evaluate wall motion and CFR in the distal segment of the left anterior descending coronary artery before and after dipyridamole infusion (0.84 mg/kg over six minutes). A CFR value of <2.5 was considered a sign of impaired coronary function. We also evaluated cIMT arterial stiffness PWV and plasma ADMA levels, and made a speckle tracking echocardiography (STE) analysis. Results All of the patients were affected by pSS and most were being treated with hydroxychloroquine (HCQ) at a dose of 400 mg/day. They were also ANA or RF and anti-SSB or anti-SSA positive. There were no significant differences in ejection fraction (EF) or E/A ratios between the patients and controls. Although within the normal range, the patients’ CFR was lower than that of the controls (median 2.70; IQR 2.40-2.90 vs 3.20; IQR 3.06-3.33; p <0.0001), whereas their ADMA levels were significantly higher (median 0.81 mM; IQR 0.79-0.85 mM vs 0.54 mM; IQR 0.52-0.58 mM; p< 0.0001). Both left and right PWV values were significantly higher in the patients than in the controls (median 8.8 m/s right and 8.9 m/s left vs 6.86 and 6.89 m/s, p<0.0001), whereas cIMT was substantially similar in the two groups (0.60 mm, IQR 060-0.70 mm vs 0.60 mm, IQR 0.50-0.70, p=NS). Speckle tracking analysis was significantly different between the two groups, with longitudinal strain deformation in the apical four chambers view (Long. ɛ 4c) (median 15.28%, IQR 12.30-16.20% vs 19.80%, IQR 19.30-20.40%, p<0.0001) and radial strain deformation in short axis view (Radial ɛ SAX) (median 26.00%, IQR 24.26-31.90% vs 31.50%, IQR 28.30-34.50%, p=0.02) being significantly less in the pSS patients. Conclusions Higher ADMA levels suggest the presence of endothelial dysfunction and sub-clinical atherosclerosis in pSS patients, even in the case of a normal CFR. This finding is supported by the PWV values, which were higher in the pSS patients. These preliminary data indicate that ADMA levels and PWV values may be useful markers for identifying early endothelial dysfunction in pSS patients. References Turiel M, Atzeni F, Tomasoni L, et al Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients. Rheumatology (Oxford). 2009;48:834-9. Disclosure of Interest None Declared

Cardiovascular Imaging Techniques in Systemic Rheumatic Diseases

The risk of cardiovascular (CV) events and mortality is significantly higher in patients with systemic rheumatic diseases than in the general population. Although CV involvement in such patients is highly heterogeneous and may affect various structures of the heart, it can now be diagnosed earlier and promptly treated. Various types of assessments are employed for the evaluation of CV risk such as transthoracic or transesophageal echocardiography, magnetic resonance imaging (MRI), and computed tomography (CT) to investigate valve abnormalities, pericardial disease, and ventricular wall motion defects. The diameter of coronary arteries can be assessed using invasive quantitative coronarography or intravascular ultrasound, and coronary flow reserve can be assessed using non-invasive transesophageal or transthoracic ultrasonography (US), MRI, CT, or positron emission tomography (PET) after endothelium-dependent vasodilation. Finally, peripheral circulation can be measured invasively using strain-gauge plethysmography in an arm after the arterial infusion of an endothelium-dependent vasodilator or non-invasively by means of US or MRI measurements of flow-mediated vasodilation of the brachial artery. All of the above are reliable methods of investigating CV involvement, but more recently, introduced use of speckle tracking echocardiography and 3-dimensional US are diagnostically more accurate.

Foot and Soccer Referees’: A Pilot Study Searching “Performance” Throughout Prevention

Soccer refereeing is a “not-conventional” sport in which aerobic workload is prevalent. Along the years, several studies have attempted to define best markers of referees’ performance. Many studies focused their attention on field tests and their relationship with aerobic power. Instead, in this study, starting by a medical assessment satisfying the FIFA 11+ criteria for injuries prevention, we have investigated the foot of soccer referees and we have also wanted to find possible and/or unexpected improvements in performance. As performance marker, we have used the referral field test for soccer referees that is internationally validated and known as Yo-Yo test (YYiR1). While standardized foot posture index (FPI) questionnaire was used for screening foot referees conditions (40 young, all men by sex, with mean age 23.47 ± 4.36). Analyzing collected data, we have demonstrated by means of Read–Cressie Chi square test that neutral FPI is an important favor item affecting YYiR1 results. Further studies will be necessary in order to confirm our pilot investigation.