Rheumatoid Arthritis Disease Activity and Sub Clinical Atherosclerosis

NCT ID: NCT03821090

Last Updated: 2023-01-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

160 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-04-15

Study Completion Date

2021-07-01

Brief Summary

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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

Detailed Description

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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

Conditions

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Rheumatoid Arthritis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

OTHER

Study Groups

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cases

Eighty rheumatoid arthritis patients fulfilling American College of Rheumatology (ACR) 2010 classification criteria, all of them will be subjected to

1. History including disease duration , course and associated diseases
2. Clinical examination with specific joint examination
3. RA disease activity will be evaluated by a 28- joint DAS (DAS28). 4-12-lead ECG

5-Echocardiography 6-Carotid intima media thickness using carotid doppler 7-Venous blood will be withdrawn to do the following laboratory tests

1. Complete Blood Count(CBC)
2. Erythrocyte Sedimentation Rate (ESR) \&C Reactive Protein(CRP)
3. Rheumatoid Factor (RF)\& anti cyclic citrullinated peptide (Anti-CCP)
4. Urine analysis , Urea and creatinine ,
5. Uric acid level
6. Lipogram
7. HA1C
8. TNF α
9. hs-cTnI

No interventions assigned to this group

control

Eighty healthy subjects age and sex matched will be included , all of them will be subjected to

1. History
2. Clinical examination . 3-12-lead ECG

4-Echocardiography 5-Carotid intima media thickness using carotid doppler 6-Venous blood will be withdrawn to do the following laboratory tests

1. Complete Blood Count (CBC)
2. ESR \& CRP
3. RF\& Anti-CCP
4. Urine analysis , Urea and creatinine
5. Uric acid level
6. Lipogram
7. HA1C
8. TNF α
9. hs-cTnI

No interventions assigned to this group

Eligibility Criteria

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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-α therapy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Sabrin Refaat Mahmoud

principle investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Assiut university hospital

Asyut, , Egypt

Site Status

Countries

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Egypt

References

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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.

Reference Type BACKGROUND
PMID: 25716931 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25689371 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16685208 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22761714 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21078811 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17765476 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23887286 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24874445 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27310259 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22150039 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25609412 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11031205 (View on PubMed)

Other Identifiers

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cardiac affection in RA

Identifier Type: -

Identifier Source: org_study_id

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