Clinical trial NCT02341066: Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis (EDRA Study)
Official title: Evaluation of a New Score Incorporating Endothelial Dysfunction for the Assessment of Coronary Heart Disease Risk in Patients With Rheumatoid Arthritis: a 3-year Prospective Study.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Rheumatoid Arthritis
Coronary Heart Disease
Keywords: Cardiovascular risk score
Framingham risk score 2-year
Endothelial dysfunction
EndoPAT
Rheumatoid arthritis
Lead sponsor: Azienda Ospedaliero Universitaria di Sassari
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliero Universitaria di Cagliari
name: Complesso Integrato Columbus, Roma
First posted: 2015-01-19
Enrollment: 3000
Sex: ALL
Minimum age (years): 45
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Three thousand consecutive RA patients free of overt cardiovascular disease

Brief summary: To evaluate the contribution of the assessment of endothelial dysfunction (ED) in improving coronary hearth disease (CHD) risk stratification obtained by the Framingham risk score (FRS) in rheumatoid arthritis population (RA).

Detailed description: ED, determined by peripheral arterial tonometry (PAT), will be evaluated at baseline in 3000 RA patients free of previous cardiovascular events. Incident CHD events during the 3-year planned follow-up will be registered. A measure of the incremental yield of ED will be obtained comparing 2-year Framingham risk score for CHD (FRS) and FRS plus ED differential prognostic performances by C-statics and risk reclassification analysis.

Eligibility criteria: Inclusion Criteria:

* RA as defined by American College of Rheumatology/European League Against Rheumatisms 2010 RA classification criteria
* In the opinion of investigators, patients must be able to adhere to the study visit schedule and must be capable of giving informed consent

Exclusion Criteria:

* Previous cardiovascular or cerebrovascular events (acute coronary syndrome, stable angina, stroke, interventional procedures, carotid endarterectomy, symptomatic peripheral artery ischemia)
* Pathological ECG at rest
* Sign or symptoms of autonomous nervous system dysfunction
* Serious infections in the previous 6 months
* Concomitant severe illness: overt hepatic insufficiency; End stage renal disease (Glomerular Filtration Rate \<30 ml/h at Cockrofts-Gault formula); recent diagnosis of cancer
* Pregnancy
* Plans to leave target areas of each study site within three years

Primary outcomes:
measure: CHD events
timeFrame: 3 year
Secondary outcomes:
Other outcomes:
Locations:
city: Monserrato
country: Italy
facility: Policlinico Universitario di Monserrato Azienda Ospedaliera Universitaria di Cagliari
state: Cagliari
city: Roma
country: Italy
facility: Complesso Integrato Columbus, UO di Reumatologia
city: Sassari
country: Italy
facility: Azienda Ospedaliero Universitaria di Sassari, UOC di Reumatologia
Study officials:
affiliation: Azienda Ospedaliero Universitaria di Sassari
name: Gian Luca Erre, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: D'Agostino RB, Russell MW, Huse DM, Ellison RC, Silbershatz H, Wilson PW, Hartz SC. Primary and subsequent coronary risk appraisal: new results from the Framingham study. Am Heart J. 2000 Feb;139(2 Pt 1):272-81. doi: 10.1067/mhj.2000.96469.
citation: Crowson CS, Matteson EL, Roger VL, Therneau TM, Gabriel SE. Usefulness of risk scores to estimate the risk of cardiovascular disease in patients with rheumatoid arthritis. Am J Cardiol. 2012 Aug 1;110(3):420-4. doi: 10.1016/j.amjcard.2012.03.044. Epub 2012 Apr 20.
citation: Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Kuvin JT, Lerman A. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004 Dec 7;44(11):2137-41. doi: 10.1016/j.jacc.2004.08.062.
citation: Matsuzawa Y, Sugiyama S, Sugamura K, Nozaki T, Ohba K, Konishi M, Matsubara J, Sumida H, Kaikita K, Kojima S, Nagayoshi Y, Yamamuro M, Izumiya Y, Iwashita S, Matsui K, Jinnouchi H, Kimura K, Umemura S, Ogawa H. Digital assessment of endothelial function and ischemic heart disease in women. J Am Coll Cardiol. 2010 Apr 20;55(16):1688-96. doi: 10.1016/j.jacc.2009.10.073.
citation: Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Lavi S, Nelson RE, Pumper GM, Lerman LO, Lerman A. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010 May;31(9):1142-8. doi: 10.1093/eurheartj/ehq010. Epub 2010 Feb 24.
citation: Erre GL, Mangoni AA, Passiu G, Bassu S, Castagna F, Carru C, Piga M, Zinellu A, Sotgia S. Comprehensive arginine metabolomics and peripheral vasodilatory capacity in rheumatoid arthritis: A monocentric cross-sectional study. Microvasc Res. 2020 Sep;131:104038. doi: 10.1016/j.mvr.2020.104038. Epub 2020 Jul 2.
citation: Erre GL, Ferraccioli ES, Piga M, Mangoni A, Passiu G, Gremese E, Ferraccioli G. Antimalarial use and arrhythmias in COVID-19 and rheumatic patients: a matter of dose and inflammation? Ann Rheum Dis. 2021 Mar;80(3):e29. doi: 10.1136/annrheumdis-2020-217828. Epub 2020 May 18. No abstract available.
citation: Erre GL, Piga M, Fedele AL, Mura S, Piras A, Cadoni ML, Cangemi I, Dessi M, Di Sante G, Tolusso B, Gremese E, Cauli A, Mangoni AA, Saba PS, Carru C, Ferraccioli G, Mathieu A, Passiu G. Prevalence and Determinants of Peripheral Microvascular Endothelial Dysfunction in Rheumatoid Arthritis Patients: A Multicenter Cross-Sectional Study. Mediators Inflamm. 2018 Feb 1;2018:6548715. doi: 10.1155/2018/6548715. eCollection 2018.