A. Martínez-Moreno

Comparison of statin eligibility according to the Adult Treatment Panel III, ACC/AHA blood cholesterol guideline, and presence of carotid plaque by ultrasound in Mexican mestizo patients with rheumatoid arthritis

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in rheumatoid arthritis (RA) patients. Guidelines of the American College of Cardiology and the American Heart Association (ACC/AHA) 2013 and the Adult Treatment Panel III (ATP-III) differ in their strategies to recommend initiation of statin therapy. The presence of carotid plaque (CP) by carotid ultrasound is an indication to begin statin therapy. We aimed to compare the recommendation to initiate statin therapy according to the ACC/AHA 2013 guidelines, ATP-III guidelines, and CP by carotid ultrasound. We then carried out an observational, cross-sectional study of 62 statin-naive Mexican mestizo RA patients, aged 40 to 75, who fulfilled the 1987 or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria. CP was evaluated with B-mode ultrasound. Cohen’s kappa (k) was used to assess agreement between ACC/AHA 2013 guidelines, ATP-III guidelines, and the presence of CP, considering a p < 0.05 as statistically significant. Agreement was classified as slight (0.01–0.20), fair (0.21–0.40), moderate (0.41–0.60), substantial (0.61–0.80), and an almost perfect agreement (0.81–1.00). Slight agreement (k = 0.096) was found when comparing statin recommendation between CP and ATP-III. Fair agreement (k = 0.242) was revealed between ACC/AHA 2013 and ATP-III. Comparison between ACC/AHA 2013 and CP showed moderate agreement (k = 0.438). ACC/AHA 2013 guidelines could be an adequate and cost-effective tool to evaluate the need of statin therapy in Mexican mestizo RA patients, with moderate agreement with the presence of CP by ultrasound.

AB1317 Identification of cardiometabolic abnormalities in the first visit to a preventive cardio-rheuma clinic

Background Rheumatoid arthritis (RA) is a chronic, systemic and autoimmune disease with articular and extra-articular manifestations. RA is associated with increased prevalence of comorbidities and higher cardiovascular risk when compared to general population. Atherosclerotic cardiovascular (CV) events are the leading cause of death in RA. In a recent meta-analysis, hypertension, type 2 diabetes mellitus (T2DM) and hypercholesterolemia were shown to increase the risk of CV disease in this population.1 A study reported a prevalence of hypertension 29.8%; dyslipidemia 27.1% and T2DM 12.4% in Mexican-mestizo RA patients.2 The cardio-rheuma clinics were designed to provide healthcare for CV diseases in patients with rheumatic conditions. Specific guidelines recommendations have been published to enhance detection and management of specific comorbidities associated to RA.3 Objectives To identify the prevalence of unknown cardiometabolic risk factors in a Mexican-mestizo cohort with RA. Methods Cross-sectional, observational study. Patients who fulfilled the 1987 ACR and/or the 2010 ACR/EULAR classification criteria were consecutively recruited. Patients were divided in two groups, with and without history of cardiovascular comorbidities. Clinical history and physical exam were performed by a general physician in a cardio-rheuma clinic. Fasting blood glucose and lipid profile were performed on all subjects. Categorical variables are expressed as percentages and numerical variables as means±standard deviations. Results A total of 296 patients were included. Demographical characteristics are shown in Figure 1. Hypertension was the most frequent comorbidity (27.7%), followed by dyslipidemia (26.7%) and T2DM (13.5%). Many of the patients without history of cardiometabolic risk factor had important findings on baseline visit: 18.7% had altered blood pressure without history of hypertension, 76.5% had an abnormal lipid profile without history of dyslipidemia, and 21.5% had an altered fasting glucose without history of T2DM.Abstract AB1317 – Figure 1 *Altered lipid profile was defined as TC ≥200 mg/dL, HDL-C <50 mg/dL, TG ≥150 mg/dL, LDL-C ≥100 mg/dL. SD=Standard deviation; T2DM=Type 2 diabetes mellitus; bDMARDs=biological agents; DAS 28-CRP=Disease Activity Score 28 joints C-reactive protein. Conclusions In our cohort of Mexican-mestizo RA patients there is a high prevalence of cardiometabolic risk factors. An important amount of these were discovered in patients without previous diagnosis at their first visit to a cardio-rheuma clinic. References [1] Dougados, et al. (2014). Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Annals of the rheumatic diseases, 73(1), 62–68. [2] Galarza-Delgado, et al. (2017). Prevalence of comorbidities in Mexican mestizo patients with rheumatoid arthritis. Rheumatology international, 37(9), 1507–1511. [3] Perk, J., et al. (2012). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Atherosclerosis, 223(1), 1–68. Acknowledgements None Disclosure of Interest None declared

THU0140 Speckle tracking echocardiography evaluation of coronary territories in mexican mestizo patients with rheumatoid arthritis

Background The main cause of death in patients with rheumatoid arthritis (RA) is atherosclerotic cardiovascular disease. Speckle Tracking Echocardiography (STE) is an imaging technique that analyses the local and global myocardial function by assessing the myocardial deformation (strain). This technique is useful in addressing early alterations in ischemic pathologies (1,3). Objectives The aim of this study was to analyze if longitudinal strain abnormalities correspond with vascular territories, and compare the results between RA-patients and matched controls. Methods An observational cross-section case-control study was designed. Patients that fulfilled the 1987 ACR and/or 2010 ACR/EULAR classification criteria for RA, were 40–75 years old, with no overlap syndromes and no history of atherosclerotic cardiovascular disease were included. The control group was integrated by age- and sex-matched subjects, with no rheumatologic or cardiovascular diseases. A standard transthoracic echocardiogram was performed by a board-certified echocardiographer. Affection of coronary territories was compared between groups using longitudinal strain by speckle tracking according to the European Society of Cardiology and the American Society of Echocardiography recommendations. Results A total of 53 RA-patients and 24 control subjects were included. Demographic characteristics for each group are shown in table 1. There was no statistical difference in global longitudinal strain between RA-patients and controls (-20.86±2.82 vs -21.19±2.46, p=0.62). Comparison of longitudinal strain values of the three vascular territories evaluated between RA-patients and controls did not reach statistical difference (Table 2).Table 1. Demographic characteristics RA group (n=53) Control group (n=24) p Age, mean ± SD 55.54±9.11 52.81±6.61 0.172 Women, n (%) 51 (96.2) 26 (96.3) 0.988 Body Mass Index, mean ± SD 27.53±5.85 28.05±4.66 0.956 Hypertension, n (%) 18 (33.96) 5 (18.5) 0.149 Type 2 Diabetes mellitus, n (%) 7 (13.2) 4 (14.8) 0.844 Conclusions Contrary to previous published evidence (1, 2), there was no statistical difference in global longitudinal strain between RA patients and controls. Coronary territories are not affected in RA patients in comparison with controls. Further studies with a larger cohort are necessary to determine the usefulness of strain in the evaluation of subclinical cardiovascular disease. References Fine et al. Evaluation of myocardial function in patients with rheumatoid arthritis using strain imaging by speckle-tracking echocardiography, Ann Rheum Dis. 2014 Oct;73(10):1833–9. Sitia S, Tomasoni L, Cicala S, et al. Detection of preclinical impairment of myocardial function in rheumatoid arthritis patients with short disease duration by speckle tracking echocardiography. Int J Cardiol 2012;160:8–14. Batir et al, Herz. 2015 Jun;40(4):669–74. Preclinical impairment of myocardial function in rheumatoid arthritis patients. Detection of myocardial strain by speckle tracking echocardiography. Disclosure of Interest None declared

AB0205 Carotid intima-media thickness linked to the presence of cardiovascular risk factors in mexican mestizo patients with rheumatoid arthritis

Background Rheumatoid Arthritis (RA) is associated to subclinical atherosclerosis. Traditional risk factors for cardiovascular outcomes do not explain completely the higher risk, which could be caused by chronic systemic inflammation. Objectives The aim of this study is to relate abnormal carotid intima-media thickness (CIMT) to the presence of cardiovascular risk factors. Methods Observational cross-section design. We included patients who fulfilled the 1987 ACR and/or 2010 ACR/EULAR classification criteria for RA, 40 to 75 years old, with no personal history of atherosclerotic CV disease. A board-certified radiologist performed carotid duplex ultrasounds. Patients were distributed in two groups according to the absence (Group 1) or presence (Group 2) of traditional risk factors for cardiovascular disease (smoking status, dyslipidemia, high blood pressure and diabetes). Results A total of 82 patients were included. Demographic characteristics for each group are shown in Table 1. Ultrasound findings are shown in Table 2. CIMT alterations were more common in Group 2 (66.7%) than in Group 1 (38.7%), with statistical significance (p=0.013). Presence of carotid plaque was more common in Group 2 (27.5%) than in Group 1 (16.1%), shown clinical relevance, although did not shown statistical significance (p=0.18).Table 1. Demographic characteristics Variable Total Group 1 (n=31) Group 2 (n=51) p (CVRF−) (CVRF+) Patients, n (%) 82 (100) 31 (37.80) 51 (62.20) – Female gender, n (%) 77 (93.9) 29 (93.5) 48 (94.1) 0.0917 Age (years), mean ± SD 57±9.96 51.90±8.43 59.82±9.69 0.001 Disease duration (years), mean ± SD 12.45±8.39 11.74±8.76 12.89±8.32 0.554 BMI (kg/m2), mean ± SD 28.22±4.9 29.05±5.09 27.72±4.92 0.248 Smoking status, n (%) 8 (9.75) – 8 (15.68) – Diabetes, n (%) 13 (15.85) – 13 (25.49) – HBP, n (%) 28 (34.14) – 28 (54.90) – Dyslipidemia, n (%) 8 (9.75) – 8 (15.68) – CVRF: Cardiovascular Risk Factors, HBP: High Blood Pressure. Conclusions In this cohort of Mexican patients with RA, we demonstrate relation between the presence of alterations in CIMT (carotid hypertrophy and carotid plaque) and risk factors for cardiovascular disease, which can be enhanced by intrinsic risk of RA. These findings reaffirm the importance of global health assessment in patients with RA to reduce morbidity. References Avina-Zubieta JA. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2012;71(9):1524–9. Galarza-Delgado DA, Serna-Pena G. Carotid atherosclerosis in patients with rheumatoid arthritis and rheumatoid nodules. Reumatol Clin. 2013;9(3):136–41. Mateo I, What measure of carotid wall thickening is the best atherosclerotic loading score in the hypertensive patient: maximum or mean value?]. Rev Esp Cardiol. 2011;64(5):417–20. Disclosure of Interest None declared

AB0310 Prevalence of comorbidities of rheumatoid arthritis in a mexican mestizo population

Background Patients with rheumatoid arthritis (RA) have an increased risk of developing comorbid conditions which are associated to increased mortality, hospital admissions, higher costs of care and inability to work (1, 2). Objectives To evaluate the prevalence of comorbidities in a Mexican mestizo population of RA patients. Methods We performed a cross-sectional study in which RA patients who were admitted to our outpatient clinic between August 2014 and December 2016 were consecutively enrolled. We collected data regarding demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, and osteoporosis), and performed blood tests at the time of the patients visit to the clinic. Results We analyzed 225 patients. Their characteristics are shown in Table 1. Age, 55.7±8.3 years (mean ± SD); disease duration, 9.5 (4 – 15.5) (median (IQR)); female gender, 93.7%; Disease Activity Score using 28 joints–C-reactive protein (DAS28-CRP), 3 (2 – 4) (median (IQR)); past or current methotrexate use, 84.9%; past or current use of any other conventional disease modifying anti-rheumatic drug (cDMARD), 52.4%; past or current use of biological agents, 8%. The most frequently associated diseases were: hypertension, 29.8%; dyslipidemia, 27.1%; osteoporosis, 19.1%; diabetes, 12.4%; hypothyroidism, 6.2%; solid malignancies (excluding basal cell carcinoma), 4.4%. Risk factors were also evaluated, the most prevalent was overweight (BMI ≥25 <30) present in 101 (44.9%) of our patients. A total of 71 (31.6%) had obesity (BMI ≥30). The systematic evaluation of our patients allowed us to detect abnormalities in vital signs, such as elevated blood pressure in 12.4%, and to identify conditions that manifest as laboratory test abnormalities, such as hyperglycemia in 27.1% and hyperlipidemia in 49.8%. Conclusions This study confirms the high prevalence of comorbidities in RA patients. Among our cohort, 63.5% had at least one comorbidity, being those associated with cardiovascular disease the most common. With a systematic assessment (3) including a thorough physical examination, vital signs and laboratory tests, it is possible to detect comorbid conditions that would otherwise remain unrecognized. References Dougados M, Soubrier M, Antunez A, Balint P, Balsa A, Buch MH, et al. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis. 2014;73(1):62–8. Gabriel SE, Michaud K. Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res Ther. 2009;11(3):229. Baillet A, Gossec L, Carmona L, Wit M, van Eijk-Hustings Y, Bertheussen H, et al. Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative. Ann Rheum Dis. 2016;75(6):965–73. Disclosure of Interest None declared

FRI0141 Left ventricular concentric remodeling is more prevalent in rheumatoid arthritis: a case-control study

Background Patients with rheumatoid arthritis (RA) have a higher risk to develop cardiovascular complications than general population (1), leading to a decrease in life expectancy of 3 to 10 years (2). RA is associated to increased left ventricle mass, pericardial effusion and diastolic dysfunction (3). Objectives The aim of this study was to assess the structure and function of the left ventricle in patients with RA and compare the results with matched controls. Methods We designed an observational cross-section case-control study. Patients diagnosed with RA according to the 1987 ACR and/or 2010 ACR/EULAR classification criteria, 40–75 years old, with no overlap syndromes, atherosclerotic cardiovascular disease or hypertension were included. Subjects for the control group were matched by sex, age and comorbidities. A board-certified cardiologist performed a transthoracic echocardiogram. Results We included a total of 44 RA-patients and 26 control subjects. Table 1 summarizes the demographic characteristics for each group. Left ventricular concentric remodeling (LVCR), defined as a relative wall thickness (RWT) >0.42 cm and a left ventricular mass index (LVMI) ≤95 gm/m2 in women and ≤115 gm/m2 in men, was found in 14 patients (32.6%) of the RA-group and 2 subjects (8%) of the control group; this difference was statistically significant (p=0.021). When we analyzed general abnormalities of left ventricle (either LVCR or left ventricular concentric hypertrophy [RWT >0.42 cm and LVMI >95 gm/m2 in women, >115 gm/m2 in men]) we found 15 RA patients (34.1%) with abnormalities and 3 subjects in the control group (11.5%) (p=0.037). There were no statistically significant differences among the groups in LVMI, diastolic dysfunction, global longitudinal strain or ejection fraction.Table 1. Demographic characteristics RA group (n=44) Control group (n=26) p Age, mean ± SD 52.35±7.34 53.94±6.81 0.371 Disease duration (years), mean ± SD 10.682±8.3321 – – DAS-28 CRP, mean ± SD 3.36±1.42 – – Women, n (%) 43 (97.7) 24 (92.3) 0.279 Body Mass Index, mean ± SD 26.98±6.13 28.3±4.12 0.956 Active smoking, n (%) 4 (9.1) 0 (0) 0.113 Type 2 Diabetes mellitus, n (%) 2 (4.5) 2 (7.7) 0.584 DAS-28 CRP - Disease activity score 28 using C-reactive protein. Conclusions Left ventricle concentric remodeling is more prevalent in RA-patients when compared to controls. Further research is needed to determine the impact of these findings in the clinical prognosis of RA-patients. References Solomon DH, Curhan GC, Rimm EB, Cannuscio CC, Karlson EW. Cardiovascular risk factors in women with and without rheumatoid arthritis. Arthritis & Rheumatism. 2004;50(11):3444–9. Myasoedova E, Davis JM, Crowson CS, Gabriel SE. Epidemiology of Rheumatoid Arthritis: Rheumatoid Arthritis and Mortality. Current Rheumatology Reports. 2010;12(5):379–85. Corrao S, Messina S, Pistone G, Calvo L, Scaglione R, Licata G. Heart involvement in Rheumatoid Arthritis: Systematic review and meta-analysis. International Journal of Cardiology. 2013;167(5):2031–8. Disclosure of Interest None declared

AB0204 Disease factors associated to abnormal intima-media thickness in mexican mestizo rheumatoid arthritis patients

Background Atherosclerotic cardiovascular disease (ASCVD) is the main mortality cause in patients with rheumatoid arthritis (RA) (1). It has been proven that the carotid intima-media thickness (CIMT) measured with carotid duplex ultrasonography (US) is an important ASCVD predictor with a measurement ≥0.9 mm (2–4). Objectives To characterize the disease factors related with abnormal carotid duplex US findings in Mexican mestizo patients with RA. Methods In a cross-sectional setting, we enrolled consecutive RA patients. Patients with overlap syndromes, personal history of ASCVD, dyslipidemia and previous use of any statin were excluded. A board-certified radiologist performed a bilateral carotid duplex US to all patients. Abnormal CIMT was defined as ≥0.9 mm (hypertrophy ≥0.9 – 1.2 mm and carotid plaque ≥1.2 mm). A clinical history and blood tests were performed at the time of the patients visit. Disease activity was measured with Disease Activity Score using 28 joints–C-reactive protein (DAS28-CRP). Results We enrolled 57 patients. Demographic characteristics are shown in table 1. A total of 30 (52.2%) patients had an abnormal CIMT. US findings are shown in table 2. A significant correlation between abnormal CIMT and RA disease duration (p=0.04), as well as between the former and anti-cyclic citrullinated peptide antibodies (ACPA) positivity (p=0.033) was found.Table 1. Demographic and disease characteristics Variable Results Female gender, n (%) 54 (94.7) Age (years), mean ± SD 56±9.9 Disease duration (years), mean ± SD 12.4±8.3 BMI (kg/m2), mean ± SD 28.22±4.9 Smoking status, n (%) 5 (8.77) DAS 28- CRP, mean ± SD 3.33±1.19 Disease Activity, n (%)  Remission 17 (29.8)  Low 11 (19.3)  Moderate 25 (43.8)  Severe 4 (7.1) Positive Anti-CCP, n (%) 44 (77.19) Positive RF, n (%) 51 (89.47) BMI: Body Mass Index. Conclusions There is a strong relationship between CIMT and the chronic inflammatory process of RA, as well as ACPA positivity. These results might be influenced by the high mean disease duration of our patients. Prospective studies that evaluate CIMT among disease duration intervals are necessary to support these findings. References Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2012;71(9):1524–9. Galarza-Delgado DA, Esquivel-Valerio JA, Garza-Elizondo MA, Gongora-Rivera F, Munoz-De Hoyos JL, Serna-Pena G. Carotid atherosclerosis in patients with rheumatoid arthritis and rheumatoid nodules. Reumatol Clin. 2013;9(3):136–41. Mateo I, Morillas P, Quiles J, Castillo J, Andrade H, Roldan J, et al. What measure of carotid wall thickening is the best atherosclerotic loading score in the hypertensive patient: maximum or mean value? Rev Esp Cardiol. 2011;64(5):417–20. Disclosure of Interest None declared

SAT0106 Valvular Heart Disease in A Mexican Mestizo Cohort of Patients with Rheumatoid Arthritis: A Case-Control Study

Background Rheumatoid arthritis (RA) is associated with a higher rate of cardiovascular mortality. The prevalence of valvular heart disease (VHD) varies greatly in the published reports. Data in Mexican mestizo patients with RA is scarce. Objectives We aimed to evaluate the presence of VHD in a cohort of RA Mexican mestizo patients and compare it to matched controls. Methods An observational, comparative, case control study was designed. Patients with RA aged 40 to 75 years that fulfilled the 2010 ACR/EULAR criteria were included. Exclusion criteria included prior atherosclerotic cardiovascular disease (myocardial infarction, stroke and peripheral arterial disease) and overlap syndromes. Patients were matched using age, sex and comorbidities. A standard transthoracic echocardiography was performed according to the American Society of Echocardiography guidelines. Valvular regurgitation was classified as mild, moderate or severe according to the European Association of Echocardiography and American Society of Echocardiography recommendations. Results A total of 56 patients and 28 controls were included in the final analysis. Characteristics of both groups are shown in Table 1. There was no statistical difference in sex, age, type 2 diabetes mellitus and body mass index between the two groups. VHD was reported in 45 (80.4%) RA-patients and 13 (46.4%) individuals in the control group (p<0.003). Statistical difference was found in mitral and tricuspid regurgitation (p<0.001 and p<0.003, respectively) in RA-patients when compared with the control group. In the RA group, 5 (8.9%) showed mild aortic regurgitation; 28 had mild and 1 had moderate (50% and 1.8%, respectively) mitral regurgitation; 8 (14.3%) showed mild pulmonary regurgitation; 39 had mild and 4 had moderate (69.6% and 7.1%, respectively) tricuspid regurgitation. In the control group, 1 (3.6%) showed mild aortic regurgitation; 3 (10.7%) had mild mitral regurgitation; 1 (3.6%) showed mild pulmonary regurgitation; 12 (42.9%) had mild tricuspid regurgitation. Conclusions In our cohort, 80.4% of the RA-patients had VHD, with the tricuspid valve being the most affected (76.8%). Prospective studies are needed to evaluate the role of VHD in RA-patients morbi-mortality. References Roldan, C. A., DeLong, C., Qualls, C. R., & Crawford, M. H. (2007). Characterization of valvular heart disease in rheumatoid arthritis by transesophageal echocardiography and clinical correlates. The American journal of cardiology, 100(3), 496–502. Zoghbi, W. A., Enriquez-Sarano, M., Foster, E., Grayburn, P. A., Kraft, C. D., Levine, R. A., … & Stewart, W. J. (2003). American Society of Echocardiography: Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. European Heart Journal-Cardiovascular Imaging, 4(4), 237–261. Disclosure of Interest None declared

SAT0122 Comorbidities in A Mexican Mestizo Cohort of Patients with Early Rheumatoid Arthritis

Background Patients with rheumatoid arthritis (RA) are at an increased risk of comorbidities and it has been linked to a decrease in life expectancy in comparison with the general population. Early recognition and treatment of comorbidities is important. Objectives We aimed to evaluate the presence of comorbidities in a Mexican mestizo cohort of patients with early-RA. Methods A descriptive, cross-sectional study of patients with early-rheumatoid arthritis (disease duration <12 months) was designed. Information on comorbidities, weight, height and body mass index (BMI) was collected. Results Data of fifty patients was included in the final analysis, 46 (92.0%) of them were women. Patients characteristics are shown in Table 1. Mean age was 44.3 ± 13.12 years. Mean disease duration was 6.09 ± 2.91 months. Tuberculosis (TB) infection was found in 12 (24.0%) patients, 7 (58.3%) of them were latent tuberculosis infection. Four cases of extra-pulmonary TB were reported. Hypertension was the second most prevalent comorbidity, being reported in 11 (22.0%) patients. Conclusions In this cohort of Mexican mestizo patients with early-RA, TB infection was found in 24.0% of the patients. Hypertension was the second most prevalent comorbidity in our cohort, being reported in 22.0% of the patients. Other cardiovascular heart disease risk factors were also reported. Early recognition of these comorbidities is needed because of the higher risk of cardiovascular heart disease in RA-patients in comparison to the general population. References Emery, P., Breedveld, F. C., Dougados, M., Kalden, J. R., Schiff, M. H., & Smolen, J. S. (2002). Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Annals of the rheumatic diseases, 61(4), 290–297. Disclosure of Interest None declared