Rheumatoid Arthritis Disease Activity and Sub Clinical Atherosclerosis

Rheumatoid Arthritis Clinical Trial

Official title:

A Study in Subclinical Atherosclerosis in Patients With Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03821090
• Other study ID #: cardiac affection in RA
• Status: Completed
• Start date: April 15, 2019
• Est. completion date: July 1, 2021

Study information

• Verified date: January 2023
• Source: Assiut University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

RA is associated with traditional cerebrovascular risk factors as subclinical atherosclerosis.

Chronic inflammation and high disease activity are associated with atherosclerotic burden, higher incidence of cerebrovascular disease ,chronic heart failure , and mortality of patients with RA .

High-sensitivity cardiac troponin I (hs-cTnI) predicted a greater risk coronary heart disease, heart failure hospitalization and overall mortality in the general population .

So the aim of the study is to correlate between high sensitive cardiac troponin I , TNF-α to disease activity and presence of subclinical atherosclerosis in RA patients

Description:

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by progressive joint destruction, associated with extra-articular manifestations, affecting different internal organs .

Interestingly, these patients show an increased risk of mortality when compared to general population and recent evidence clearly confirmed that this risk is largely due to cerebro-cardiovascular events (CV Es), this may be explained by the greater prevalence, severity, burden and different composition of occult coronary lesions in RA compared with age- and gender-matched controls.

RA is associated with traditional CV risk factors ,subclinical atherosclerosis,arrhythmias , and coronary calcifications .

Increased subclinical atherosclerosis, mainly carotid artery plaques, may be observed in RA patients, the increased carotid intima-media thickness (cIMT) and presence of plaques are accepted as strong predictors of generalized atherosclerosis and major CVEs in both non-RA and RA subjects.

The evidence of traditional CV risk factors and subclinical atherosclerosis does not fully explain the increased incidence of CVEs in these patients; suggesting that the CV risk may be independently associated with RA and in fact, this risk has been shown to be associated with additional features specific of RA, such as the systemic inflammatory process, disease duration and therapeutic strategies .

Chronic inflammation and high disease activity are reportedly associated with atherosclerotic burden, higher incidence of cerebrovascular disease (CVD), chronic heart failure (CHF), and mortality of patients with RA . Residual disease activity may further associate with more advanced, complex and prone-to-rupture coronary plaques .

Pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), reflect clinical activity and structural damage in RA and are elevated in the blood of RA patients compared with controls , the same cytokine have been identified in atherosclerotic plaque and correlated with subclinical atherosclerosis independent of cardiac risk factors coronary plaque complexity , plaque destabilization and CVEs in subjects without autoimmune disease .

Cardiac troponins (cTn) are components of the cardiomyocyte contractile apparatus, and circulating concentrations are elevated in the setting of myocardial injury, such as acute coronary syndromes (ACS) .

High-sensitivity (hs) cTn assays allow measurement of troponin concentrations below conventional levels of detection and have revealed a spectrum of circulating cTn concentrations spanning low and high levels in both healthy subjects and in patients with overt cardiovascular disease

Additionally, both high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) predicted a greater risk of fatal and non-fatal coronary heart disease, heart failure hospitalization and overall mortality in the general population .

Aim of the study

1. Detection of subclinical atherosclerosis in RA patients by means of carotid Doppler

2. Detection of levels of high sensitive cardiac troponin I and TNF-α in RA patients

3. Correlation between high sensitive cardiac troponin I and TNF- α to disease activity and to the presence of subclinical atherosclerosis in RA patients

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: July 1, 2021
• Est. primary completion date: March 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• RA patients fulfilling ACR 2010 classification criteria over the age of 18 who have active RA (either early with symptoms lasting < 6 months or established disease lasting > 6 months) .

Exclusion Criteria:

Patients who have previously experienced cardiovascular illness, e.g., heart failure, acute coronary syndrome, revascularization, transient ischemic attacks, and cerebrovascular stroke. Patients who have concomitant hepatic or renal diseases, active infections, malignancy, smoking, hypertension, dyslipidemia, obesity, diabetes mellitus, and hyperuricemia. Patients who are receiving anti-TNF-a therapy.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Atherosclerosis
• Rheumatoid Arthritis

Locations

Country	Name	City	State
Egypt	Assiut university hospital	Assiut

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (12)

Amar J, Fauvel J, Drouet L, Ruidavets JB, Perret B, Chamontin B, Boccalon H, Ferrieres J. Interleukin 6 is associated with subclinical atherosclerosis: a link with soluble intercellular adhesion molecule 1. J Hypertens. 2006 Jun;24(6):1083-8. doi: 10.1097/01.hjh.0000226198.44181.0c. — View Citation

Ambrosino P, Lupoli R, Di Minno A, Tasso M, Peluso R, Di Minno MN. Subclinical atherosclerosis in patients with rheumatoid arthritis. A meta-analysis of literature studies. Thromb Haemost. 2015 May;113(5):916-30. doi: 10.1160/TH14-11-0921. Epub 2015 Feb 26. — View Citation

Baghdadi LR, Woodman RJ, Shanahan EM, Mangoni AA. The impact of traditional cardiovascular risk factors on cardiovascular outcomes in patients with rheumatoid arthritis: a systematic review and meta-analysis. PLoS One. 2015 Feb 17;10(2):e0117952. doi: 10.1371/journal.pone.0117952. eCollection 2015. — View Citation

Bradham WS, Bian A, Oeser A, Gebretsadik T, Shintani A, Solus J, Estis J, Lu QA, Todd J, Raggi P, Stein CM. High-sensitivity cardiac troponin-I is elevated in patients with rheumatoid arthritis, independent of cardiovascular risk factors and inflammation. PLoS One. 2012;7(6):e38930. doi: 10.1371/journal.pone.0038930. Epub 2012 Jun 28. — View Citation

deFilippi CR, de Lemos JA, Christenson RH, Gottdiener JS, Kop WJ, Zhan M, Seliger SL. Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. JAMA. 2010 Dec 8;304(22):2494-502. doi: 10.1001/jama.2010.1708. Epub 2010 Nov 15. — View Citation

Fransen J, Kazemi-Bajestani SM, Bredie SJ, Popa CD. Rheumatoid Arthritis Disadvantages Younger Patients for Cardiovascular Diseases: A Meta-Analysis. PLoS One. 2016 Jun 16;11(6):e0157360. doi: 10.1371/journal.pone.0157360. eCollection 2016. — View Citation

Gupta S, de Lemos JA. Use and misuse of cardiac troponins in clinical practice. Prog Cardiovasc Dis. 2007 Sep-Oct;50(2):151-65. doi: 10.1016/j.pcad.2007.01.002. — View Citation

Karpouzas GA, Malpeso J, Choi TY, Li D, Munoz S, Budoff MJ. Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthritis without symptoms or prior diagnosis of coronary artery disease. Ann Rheum Dis. 2014 Oct;73(10):1797-804. doi: 10.1136/annrheumdis-2013-203617. Epub 2013 Jul 25. — View Citation

Lazzerini PE, Capecchi PL, Acampa M, Galeazzi M, Laghi-Pasini F. Arrhythmic risk in rheumatoid arthritis: the driving role of systemic inflammation. Autoimmun Rev. 2014 Sep;13(9):936-44. doi: 10.1016/j.autrev.2014.05.007. Epub 2014 May 27. — View Citation

McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011 Dec 8;365(23):2205-19. doi: 10.1056/NEJMra1004965. No abstract available. — View Citation

Navarro-Millan I, Yang S, DuVall SL, Chen L, Baddley J, Cannon GW, Delzell ES, Zhang J, Safford MM, Patkar NM, Mikuls TR, Singh JA, Curtis JR. Association of hyperlipidaemia, inflammation and serological status and coronary heart disease among patients with rheumatoid arthritis: data from the National Veterans Health Administration. Ann Rheum Dis. 2016 Feb;75(2):341-7. doi: 10.1136/annrheumdis-2013-204987. Epub 2015 Jan 21. — View Citation

Niemann-Jonsson A, Dimayuga P, Jovinge S, Calara F, Ares MP, Fredrikson GN, Nilsson J. Accumulation of LDL in rat arteries is associated with activation of tumor necrosis factor-alpha expression. Arterioscler Thromb Vasc Biol. 2000 Oct;20(10):2205-11. doi: 10.1161/01.atv.20.10.2205. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	detection of subclinical atherosclerosis in RA patients who have no cardiovascular risk factors	Correlation between high sensitive cardiac troponin I and TNF- a to disease activity and presence of subclinical atherosclerosis in RA patients	baseline