A STUDY ON CLINICAL & CARDIOVASCULAR PROFILE OF RHEUMATOID ARTHRITIS PATIENTS & IT’S CORRELATION
WITH DISEASE ACTIVITY
DISSERTATION SUBMITTED TO THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY, CHENNAI In partial fulfilment of the requirements for the degree of
M.D. BRANCH – I (GENERAL MEDICINE)
DEPARTMENT OF GENERAL MEDICINE TIRUNELVELI MEDICAL COLLEGE HOSPITAL
TIRUNELVELI – 627011
BONAFIDE CERTIFICATE
This is to certify that the dissertation entitled “A STUDY ON CLINICAL &
CARDIOVASCULAR PROFILE OF RHEUMATOID ARTHRITIS PATIENTS & IT’S CORRELATION WITH DISEASE ACTIVITY”
submitted by Dr. R.NANDINI @ KIRUTHIKA, to the Tamilnadu Dr. M.G.R Medical University, Chennai, in partial fulfillment of the requirement for the award of M.D. Degree Branch – I (General Medicine) is a bonafide research work carried out by her under direct supervision & guidance.
Professor & Head of the Department, Department of General Medicine
Tirunelveli Medical College, Tirunelveli.
Unit Chief,
Department of General Medicine Tirunelveli Medical College,
Tirunelveli.
CERTIFICATE BY THE DEAN
I hereby certify that this dissertation entitled “A STUDY ON CLINICAL & CARDIOVASCULAR PROFILE OF RHEUMATOID ARTHRITIS PATIENTS & IT’S CORRELATION WITH DISEASE ACTIVITY” is a record of work done byDr. R.NANDINI @ KIRUTHIKA, in the Department of General Medicine, Tirunelveli Medical College, Tirunelveli, during her postgraduate degree course period from 2016- 2019.
This work has not formed the basis for previous award of any degree.
Date :
Place : TIRUNELVELI The DEAN
Tirunelveli Medical College, Tirunelveli - 627011.
DECLARATION
I solemnly declare that the dissertation entitled “A STUDY ON CLINICAL & CARDIOVASCULAR PROFILE OF RHEUMATOID ARTHRITIS PATIENTS & IT’S CORRELATION WITH DISEASE ACTIVITY” is done by me at Tirunelveli Medical College Hospital, Tirunelveli Under the guidance and supervision of Prof.Dr.G.Rathnakumar M.D, the dissertation is submitted to The Tamilnadu Dr. M.G.R. Medical University towards the partial fulfilment of requirements for the award of M.D.
Degree (Branch I) in General Medicine.
Place: Tirunelveli
Date: Dr.R.NANDINI @ KIRUTHIKA
Postgraduate Student, M.D General Medicine, Department of General Medicine,
Tirunelveli Medical College Tirunelveli.
CERTIFICATE – II
This is to certify that this dissertation work entitled “A STUDY ON CLINICAL & CARDIOVASCULAR PROFILE OF RHEUMATOID ARTHRITIS PATIENTS & IT’S CORRELATION WITH DISEASE ACTIVITY” of the candidate Dr.R.NANDINI @ KIRUTHIKA with registration Number 201611357 for the award of M.D. Degree in the branch of GENERAL MEDICINE (I). I personally verified the urkund.com website for the purpose of plagiarism check. I found that the uploaded thesis file contains from introduction to conclusion page and result shows 6 percentage of plagiarism in the dissertation.
Guide & Supervisor sign with Seal.
ACKNOWLEDGEMENT
I wish to express my heartfelt gratitude to our Dean Prof.Dr. S. M. .Kannan M.S., MCh., Tirunelveli Medical College for allowing me to do the
study in this institution.
I would like to express my humble thanks to our professor & Head of the Department Prof .Dr .M.Ravichandran M.D., Department of General Medicine.
I express my sincere thanks to my renowned teacher and my guide Dr.G.Rathnakumar M.D., Professor, Department of General Medicine, Tirunelveli Medical College for his guidance, valuable suggestions and constant encouragement throughout the study.
I express my sincere thanks to my former professors, Dr.S.Arumugapandian @ Mohan, M.D., Dr.S.S.Nazar M.D., for their constant support, encouragement and suggestions which helped me greatly to expedite this dissertation .
I am greatly obliged to Dr.Vidya M.D, D.M(Rheumatology), Dr.S.Jawahar M.D, Dr.Govindarajan M.D, Dr.Rajkumar M.D, Assistant Professors, Dept .of General Medicine for their valuable suggestions in
CONTENT
S.NO TITLE PAGE.NO
1. INTRODUCTION 1
2. AIM AND OBJECTIVES OF THE STUDY 2
3. REVIEW OF LITERATURE 3
4. MATERIALS AND METHODS 39
5. RESULTS 43
6. DISCUSSION 76
8. CONCLUSION 81
9. LIMITATIONS OF THE STUDY 83
10. BIBILIOGRAPHY 11. MASTER CHART
INTRODUCTION
Rheumatoid arthritis (RA) is a chronic inflammatory disorder, characterised by both articular and extra - articular manifestations. The chronic subclinical inflammation in rheumatoid arthritis contributes to accelerated atherosclerosis and various cardiovascular events. A recent study showed that 50% mortality in rheumatoid arthritis is due to cardiovascular disease related deaths. RA is associated with disability, shortened life expectancy, and increased mortality as compared to the general population. Cardiovascular events seems to occur approximately a decade earlier in Rheumatoid arthritis patients like that in diabetes mellitus.
Moreover, like Diabetes mellitus and Dyslipidemia, there is an independent association of RA with preclinical and overt cardiovascular disease and most of the time it is silent with unfavourable outcome leading to premature death.
In a study, if the clinical disease activity index score falls by 10, the risk of developing cardiovascular disease decreases by 26% has been formulated. So it is necessary to do screening for cardiovascular disease in all Rheumatoid arthritis patients. Also, the influence of disease activity on development of cardiovascular disease should also be studied.
AIMS AND OBJECTIVES
1) To study and document the occurrence of various cardiovascular manifestations in Rheumatoid arthritis patients
2) To assess the disease severity in Rheumatoid arthritis patients
3) To correlate and compare the association between disease severity and various clinical and cardiovascular manifestations in rheumatoid arthritis patients
REVIEW OF LITERATURE
Rheumatoid arthritis is a chronic autoimmune inflammatory disorder, characterised by both articular and extra-articular manifestations. It is a progressive disease characterised by exacerbations and remissions . The disease has various environmental triggering factors and genetic influences.
EPIDEMIOLOGY
Females are affected more than males in a ratio of 3:1 ; whereas around 60 years of age the ratio equilibrates
Onset peaks around mid 50s.
40% of the patients may have extra articular manifestations.
Risk of Rheumatoid Arthritis is high among Smokers.
ETIOLOGY
Genetic predisposition plays an important role in this disease. It is due to a shared epitope present on chromosome 6 which encodes the class II Histocompatibility locus; HLA-DRB1*0401, HLA-DRB1*0404, HLA-Dw4, HLA-Dw14.
Genetic Polymorphisms in genes PTPN22, PADI4, STAT4, TRAFI- C5, CTLA4, Cytokines like TNF –alpha, IFN –gamma disequilibrium have been associated with the occurrence of Rheumatoid arthritis
Heavy Tobacco smoking along with genetic predisposition as evidenced by carriage of HLA – DR SE genes have been known to show more citrllinated proteins in bronchoalveolar lavage and subsequent immune reaction leading to anti citrullinated antibodies.
PATHOGENESIS
The cell mediated immunity, mainly CD4 cells are the main culprit behind the activation of cytokines which causes local destruction of synovial membrane & other joint structures.
In Individuals with immune hyper reactivity and genetic predisposition, some unknown trigger activates components of innate immunity such as dendritic cells, macrophages & fibroblast like synoviocytes in joint tissue. Dendritic cells act as antigen presenting cells and activate T and B lymphocytes in central lymphoid organs. These lymphocytes migrate back to joint tissue, enhance and sustain chronic inflammation in both articular and extra articular regions.
CYTOKINE DYSREGULATION
Th1, Th2 and Th17 type of CD4 cells which are activated produce excess cytokines like IFN – gamma, TNF –alpha, IL-4, IL-5, IL-6, IL-17.
These cytokines also suppress regulatory cytokines such as IL -10, IL-35,
causes synovial inflammation – later becomes chronic and hypertrophic forming a tumour like pannus that invades and causes cartilage destruction, bone erosions and also responsible for extra articular manifestations.
TNF – alpha and IL-1 promote fibroblast proliferation and adhesion.
IL – 6 produces B cell activation and produces inflammatory mediators such as C-Reactive Protein.
Later, Osteoclast and NK cell also plays a role. Overtime, most patients develop erosions within cartilage and bone, narrowing of joint space and peri-articular decalcification usually visualised as radiographic changes in X-ray film.
PATHOGENESIS OF RHEUMATOID ARTHRITIS
Infectious trigger causes
infiltration of synovial membrane with lymphocytes,macrophages,plasma cells
T cell activation.
T-cells interact with B-cells to cause
production of cytokines, autoantibodies &
B cells acts antigen presenting calls
Proinflammatory cytokines acting on synovial fibroblast
causes swelling of synovial membrane and damage of soft tissues and cartilage
(pannus formation)
local tissue damage and remodelling
neovascularisation and further leucocyte infiltration
and chronic inflammation
CLINICAL FEATURES:
It includes
Articular
Extra articular
ARTICULAR MANIFESTATIONS:
Usually Presents as Chronic inflammatory symmetric polyarthropathy.
Can occasionally present as oligo or mono arthropathy.
Affects small joints of hand and feet in symmetric pattern. Also produces chronic irreversible deformities which presents as
Swan neck deformity – Hyperextension of PIP joint with Flexion of DIP joint
Boutonniere deformity – Flexion of PIP joint with Hyperextension of DIP joint
Mallet finger,
Z line deformity – Subluxation of 1st Metacarpophalangeal joint with hyperextension of first interphalangeal joint.
boxing glove appearance
Piano Key movement of ulnar styloid due to tenosynovitis of extensor carpi ulnaris and ulnar styloid inflammation leading to subluxation of distal ulna.
Hallux valgus.
Pes Planovalgus – Flat foot due to involvement of Ankle and Midtarsal joint
Causes morning stiffness which lasts for 1hour.
Also presents as synovitis – Flexor tendon more commonly involved which results in
Decreased range of motion
Decreased hand grip strength &
Trigger finger
Cervical spine (Atlantoaxial joint subluxation) involvement can occur – causes compressive myelopathy
Aymptomatic Temporomandibular joint involvement can occur Later in disease, shoulders and knees can get affected.
EXTRA ARTICULAR:
Rheumatoid Nodules
Subcutaneous Nodules is one of the common extra articular manifestations of rheumatoid arthritis.
Occurs over extensor aspects of elbow, hand, sacral prominences and over Achilles tendon. Nodules are usually nontender, firm can be adherent to underlying periosteum, tendons or bursae.
Correlates with Rheumatoid factor positivity, high disease activity and presence of joint erosions.
May also occur in lungs, can be attached to pleura, pericardium or peritoneum.
Pleuropulmonary manifestations
Pleuritis is the most common pulmonary manifestation Can be accompanied with pleural effusion, usually presents with pleuritic chest pain and dyspnoea. Pleural effusion will usually be exudative in nature, rich in neutrophils and monocytes.
Interstitial fibrosis usually presents with dry cough and progressive dyspnoea. Occurs in smokers and patients with high disease activity.
It is characterised by early inflammatory phase followed later by pulmonary fibrosis. Interstitial lung disease associated with
rheumatoid arthritis shows good response on treatment with immunological agents.
Caplan syndrome – characterised by single or multiple pulmonary nodules along with pneumoconiosis can occur after silica exposure
Bronchiectasis and Bronchiolitis can also in Rheumatoid arthritis patients
Haematological manifestations
Anaemia is the most common haematological manifestation in rheumatoid arthritis. It will be usually normocytic and normochromic in nature. Cause of anaemia is multifactorial like drug-induced, nutritional, gastrointestinal bleed induced, bone marrow suppression, ineffective erythropoiesis and due to anaemia of chronic disease.
Lymphocytosis and eosinophilia can occur and can directly reflects disease activity
Thrombocytosis occurs more commonly than thrombocytopenia
Lymphadenopathy can occur, usually will be benign as proved by biopsy.
Felty syndrome – triad of rheumatoid arthritis, splenomegaly and neutropenia occurs in patients with high disease activity and has propensity to develop into Non Hogdkin’s lymphoma. T cell Large
granulocytic leukemia has also been known to occur in rheumatoid arthritis.
Ophthalmic involvement
Keratoconjunctivitis sicca occurs most commonly along with xerostomia as a part of secondary sjogren syndrome
Episcleritis, scleritis, scleromalacia perforens occurs with an incidence of 1 % in Rheumatoid arthritis.
Rheumatoid vasculitis
The development of vasculitis in Rheumatoid arthritis is due to intravascular deposition of immune complexes containing Rheumatoid Factor with immunoglobulin, & associated complement mediated vascular damage.
Usually manifests as
Petechiae, purpura, Livedo Reticularis
polyneuropathy and mononeuritis multiplex
Distal gangrene, skin and deep subcutaneous ulcerations, Nail fold infarcts.
Visceral infarctions resulting in stroke, MI, mesenteric arteritis.
Occurrence of vasculitis is directly proportional to the occurrence of long standing disease, rheumatoid factor positivity and hypocomplementemia.
GI And Hepatic manifestations
Xerostomia, gastritis, peptic ulcer disease
Nodular regenerative hyperplasia, portal fibrosis
Neurological Manifestations
Nerve entrapment syndrome (carpal and tarsal tunnel syndrome)
Spinal compression due to atlanto axial subluxation and Peripheral neuropathy. (due to vasculitis)
CARDIOVASCULAR MANIFESTATIONS OF RHEUMATOID ARTHRITIS
Cardiovascular disease is the leading cause of mortality in RA. The majority of increased cardiovascular risk in RA patients was due to accelerated atherosclerosis, independent of other traditional cardiovascular risk factors such as diabetes, dysplipidemia etc. Cause of increased cardiovascular mortality is multifactorial like Inflammation, decreased mobility, dyslipidemia, low levels of antioxidants, increased levels of homocysteine, and side-effects of medication have all been implicated.
Amongst the above causes, inflammation has the strongest association with premature atherosclerosis in RA.
STAGES OF ATHEROSCLEROSIS
ENDOTHELIAL ACTIVATION
ENDOTHELIAL DYSFUNCTION
STAGE OF PREMATURE / SUBCLINICAL ATHEROSCLEROSIS
Finally leads to overt clinical atherosclerosis and development of myocardial infarction, cerebrovascular accident or peripheral vascular disease.
PATHOGENESIS
Cytokine dysregulation mainly increased cytokines such as TNF – alpha plays main role in vascular inflammation and subsequent atherosclerosis.
ENDOTHELIAL ACTIVATION
TNF alpha has direct effects on endothelium – usually activates endothelial cell by upregulating various adhesion molecules like VCAM- 1and characterised by influx of inflammatory cells within the vascular wall.
This stage is studied by increase in molecules such as VCAM -1, vonWillebrand factor, osteoprotegrin (decoy for TRAIL), GlyA in serum(newer molecule correlates with coronary calcification)
ENDOTHELIAL DYSFUNCTION
Endothelial dysfunction is recently explained by the TNF alpha induced sphingolipid signalling cascade by release of sphingomyelinase(SMase)
The main feature of endothelial dysfunction is depression of vasodilator Nitric Oxide, produced by action of eNOS (Ca+ dependent enzyme). TNF alpha induces sphingomyelinase which produces ceramide from sphingosine and depresses Ca+ influx thereby inhibiting eNOS related production of Nitric oxide. This results in the subsequent endothelial dysfunction which is characterised by stiffening of vascular wall.
Arterial stiffness can be measured by the pulse wave analysis visualised in tonometry. In stiff arteries, pulse wave is augmented. Low small artery elasticity is indicative for stiff arteries. Measuring Arterial stiffness by tonometry is a valid method in identifying endothelial dysfunction in Rheumatoid Arthritis.
STAGE OF PRECLINICAL ATHEROSCLEROSIS
Dysfunctional Endothelium is described as the birth place of plaque.
Dysfunction of endothelium favours adhesion of monocytes, provides substrate for deposition of altered lipids and eventually leads to atheromatous plaque formation. The inflammation in vascular wall causes oxidation of low density lipoproteins, which are absorbed by mononuclear cells and transforming them into foam cells.
Carotid Intima Media Thickness is an non-invasive marker to detect subclinical atherosclerosis and can be used as screening test in healthy
individuals. Increased intima media thickness in carotid arteries holds true for atherosclerosis in multiple vascular beds including coronaries, and so measurement of carotid IMT is an important marker of increased cardiovascular risk.
NON-ATHEROSCLEROTIC CARDIAC MANIFESTATIONS Pericarditis
Pericarditis is the most common cardiovascular manifestation seen in Rheumatoid Arthritis
Clinically symptomatic pericarditis occurs rarely while detection of pericarditis with minimal effusion via echocardiography in asymptomatic RA patients is high
Symptomatic pericarditis occurs more commonly in male RA patients with high disease activity.
Constrictive pericarditis and rapidly progressive effusive pericarditis adds to mortality and morbidity in rheumatoid arthritis. It is diagnosed via Transthoracic echocardiography. Cardiac MRI aids in diagnosis of minimal pericardial thickening.
NSAIDS, corticosteroids, immune suppressive drugs are the drug of choice.
Severe cases are subjected to pericardiectemy or other surgical treatment
PERICARDIAL EFFUSION IN RHEUMATOID ARTHRITIS PATIENTS
Rheumatoid Arthritis Cardiomyopathy
Both ischaemic and nonischaemic secondary cardiomyopathy can occur, the latter being specific due to rheumatoid disease activity.
Cardiomyopathy is very rare when compared to pericardial diseases.
Can be focal, diffuse necrotising or granulomatous myocarditis.
Evaluation includes 2D – ECHO and cardiac MRI. Cardiac MRI is helpful in assessing myocardial perfusion which in turn differentiates ischaemic from non-ischaemic cardiomyopathy. Features specific such as increased odema score in T2 weighted imaging, global EF reduction, global late gadolinium enhancement score can be seen.
Myocarditis may be asymptomatic and self limiting, but can also present with sequalae such as Heart failure, arrhythmias and conduction defects
Treatment includes Systemic Steroids and DMARDs.
Antimalarial induced cardiomyopathy was an important differential diagnosis and should always be ruled out.
CARDIAC AMYLOIDOSIS
It is a rare complication of Rheumatoid arthritis leading to Restrictive cardiomyopathy
Sparkling granular pattern in ECHO suggests Amyloidosis.
Amyloidosis increases the rate of heart failure in RA patient.
Prognosis is usually poor.
Arrhythmias
It is the important cause of sudden cardiac death in RA patients
Arrhythmias may be due to ischemia, rheumatoid nodule, amyloidosis or congestive heart failure
Atrial arrhythmias, conduction abnormalities and ventricular tachycardia can occur in Rheumatoid arthritis.
Treatment targeted towards the particular arrhythmia is indicated. No other specific treatment have been proposed
Valve Disease
The pathophysiology behind the development of valvular heart disease in rheumatoid arthritis are 1) Fibrosis, 2) Calcification and 3) Granuloma Formation
Aortic valve fibrosis
Rheumatoid arthritis patients Mitral Valve Fibrosis in a patient with rheumatoid arthritis
More commonly affects the left sided valves – mitral being the commonest.
RA patients are prone to develop mitral regurgitation and aortic regurgitation due to valvulitis and subsequent fibrosis.
Calcification involving valves – may lead to both stenosis and regurgitation. Rheumatoid nodules also contribute to valvular lesions.
NonBacterial Thrombotic Endocarditis (NBTE) like Libmann sacks endocarditis has also been associated with Rheumatoid Arthritis like SLE.
Congestive Heart Failure (CHF)
RA patients are more subjected to Congestive Heart Failure than non RA patients.
Increased ESR, rheumatoid vasculitis, rheumatoid lung disease are associated with increased incidence of congestive cardiac failure.
Smoking, increased BMI, diabetes, ischemic heart diseases and hypertension influence the risk of cardiovascular disease.
Mostly RA patients don’t complain of anginal symptoms therefore there is high incidence of unrecognised myocardial infection and sudden death in such patients.
Besides CHF, LV systolic dysfunction has been reported to be 3 times more common than general population.
Corticosteroids, TNF blockers, methotrexate, NSAIDS and Cox inhibitors are also incriminated in the causation of cardiac dysfunction in RA patients
Coronary Vasculitis
Non atherosclerotic cause of myocardial ischaemia in rheumatoid arthritis patients is due to coronary vascultis, which is characterised by the inflammation of the vessel wall.
Involvement of epicardial arteries can lead to presentation of Myocardial infarction similar to that caused by atherosclerosis.
It is a life threatening manifestation, which should be treated promptly with immunosuppressive therapy.
DIAGNOSIS OF RHEUMATOID ARTHRITIS
HISTORY
PHYSICAL EXAMINATION
SEROLOGICAL EVIDENCE
IMAGING MODALITIES
SEROLOGY:
RA FACTOR
RA factor is an IgM antibody against the Fc portion of IgG. RA factor and IgG form immune complex deposition responsible for the disease process.
Sensitivity 60-70%
Specificity 78%
More than 20 IU/ml is significant. Very high values are associated with greater probability of destructive disease. But, RA factor is nonspecific as it becomes positive in other auto immune diseases,
ANTI –CCP ANTIBODY
Anti citrullinated protein antibodies are highly specific to RA but not sensitive and it is done in suspected cases with RA factor negativity. Concomitant positivity of RF and ACPA is highly specific to RA. It will be positive in very early disease, and also predict the severity and irreversible damage.
IMAGING:
Bony changes in the imaging may not be seen early in less than 2 year period of disease.
Changes may start with osteopenia near the joint called as PERIARTICULAR OSTEOPENIA (characteristic feature of Rheumatoid arthritis), soft tissue swelling and smaller joint space.
Bony erosions and subluxations of joint is seen in advanced disease.
Ultrasonography may show synovitis and bony erosions in early disease.
MRI reveals the bone edema in addition to synovitis and bone erosions.
MRI and USG are more sensitive for early erosive RA.
SYNOVIAL FLUID ANALYSIS
Reveals high leucocyte count
AMERICAN COLLEGE OF RHEUMATOLOGY CLASSIFICATION CRITERIA FOR RA(2010):
FEATURES SCORE
JOINT INVOLVEMENT:
1 large joint
2 – 10 large joints
1-3 small joints with or without involvement of large joints
4-10 small joints with or without involvement of large joints
>10 joints( atleast 1 small joint )
0 1 2 3 5
SEROLOGY:
Negative RF and negative ACPA Low positive RF or Low positive ACPA
High positive RF or High positive ACPA
0 2 3
ACUTE PHASE REACTANTS:
Normal CRP and Normal ESR Abnormal CRP or Abnormal ESR
0 1 DURATION OF SYMPTOMS:
<6 weeks
≥6 weeks
0 1
INFERENCE:
Score ≥6/10 – definite RA
RHEUMATOID ARTHRITIS DISEASE ACTIVITY MEASURES
The American College of Rheumatology (ACR) have recommended various scoring systems to use in Rheumatoid arthritis patients for assessing the disease activity in them and to use in clinical practice. The scoring systems used are,
1. CDAI score ( Clinical Disease Activity Index Score)
2. DAS -28 score –ESR/CRP ( Disease Activity Score with 28 joint counts)
3. PAS (Patient Activity Scale) 4. PAS –II
5. RAPID – 3 (Routine assessment of Patient Index Data with 3 measures)
6. SDAI (Simplified Disease Activity Index)
CLINICAL DISEASE ACTIVITY INDEX SCORE (CDAI score)
The CDAI score were developed in order to provide quantifiable measures of Rheumatoid arthritis activity. Calculated using the formula
CDAI = SJC(28) + TJC(28) + PGA + EGA. (SJC and TJC denotes swollen, tender joints respectively. PGA and EGA are patient and evaluator global assessment scale which ranges from 1-10 each)
An reduction of CDAI score by 6.5 represents moderate improvement.
MERITS:
In contrast to DAS- 28 score and SDAI score which uses CRP in their assessment, CDAI can be used as a pure clinical score without adding any laboratory investigations, used in clinical practice.
DEMERITS:
Does not include Ankle and foot joints
CALCULATION FORMULAS FOR VARIOUS DISEASE ACTIVITY SCORING SYSTEMS
Table 4. Formulas for measurement tools*
Measurement tool Formula
CDAI 28SJC 28TJC PrGA PtGA
DAS28
DAS28-ESR 0.56(28TJC) 0.28(28SJC) 0.70 ln(ESR) 0.014 PtGA
DAS28-CRP 0.56(28TJC) 0.28(28SJC) 0.36 ln(CRP 1) 0.014 PtGA 0.96
PAS (HAQ 3.33 pain VAS PtGA VAS)/3 PAS-II (HAQ-II 3.33 pain VAS PtGA VAS)/3 RAPID-3 (MDHAQ 3.33 pain VAS PtGA VAS)/3
SDAI 28SJC 28TJC PrGA PtGA CRP
* Numerical rating scales may be substituted for visual analog scales (VAS) in all measures. CDAIClinical Disease Activity Index; 28SJC28 swollen joint count; 28TJC 28 tender joint count; PrGA provider global assessment of disease activity; PtGA patient global assessment of disease activity;
DAS28 Disease Activity Score with 28-joint counts; ESR erythrocyte sedimentation rate; CRP C-reactive protein; PAS Patient Activity Scale;
HAQ Health Assessment Questionnaire; RAPID-3 Routine Assessment of Patient Index Data with 3 measures; MDHAQ Multidimensional HAQ;
SDAI Simplified Disease Activity Index.
COMPARISON OF DISEASE SEVERITY BY VARIOUS SCORING SYSTEMS
TREATMENT:
Rheumatoid arthritis causes irreversible damage and hence it is necessary to get treated as early as possible.
The various modalities of treating RA are as follows:
NON PHARMACOLOGICAL PHARMACOLOGICAL
SURGICAL THERAPY Instruments Remission Low
Activity Moderate
Activity High Activity DAS-28
(range 0 to 9.4) < 2.6 ≥2.6 to < 3.2 ≥ 3.2 to≤5 > 5.1 SDAI
(range 0 to 86.0) ≤3.3 > 3.3 to≤11 > 11 to≤26 > 26 CDAI
(range 0 to 76) ≤2.8 > 2.8 to 10.0 >10.0 to 22 > 22
NON PHARMACOLOGICAL:
PHYSICAL THERAPIES
OCCUPATIONAL THERAPIES
PSYCHOTHERAPY
PHYSICAL THERAPIES
Therapies such as splinting of joints, heat therapy and joint range of motion exercise are used to prevent joint stiffness that limits many patients with RA.
PHARMACOLOGICAL THERAPY:
Goals of drug therapy:
Ameliorate pain, swelling and joint stiffness
Prevent articular damage and bony erosion
Prevent deformity and preserves joint functions
NOS. DRUGS MOA ADVERSE
EFFECTS INDICA TIONS
1 NSAIDs
(aspirin) and corticosteroids
Suppression of inflammation and immunosuppression
Steroid induced
osteoporosis early RA
2. DMARDS
Reduces inflammation and prevents damage to
joints, bones and ligaments
GI intolerance, hepatotoxicity,
alopecia, homocystinemia
First line drugs
3. Biological agents
Blocks immune response leading to
RA
Pruritis, influenza like
symptoms, headache, hypotension
NSAIDS AND CORTICOSTEROIDS
Aspirin and low dose corticosteroids are used in early RA.
Used for symptomatic relief. 5-10 mg (low dose) prednisolone are used to supplement or substitute NSAIDs. Low dose steroids are also used as bridge therapy before starting biological therapy/DMARDs. If steroids are used for long term (> 3 months), prophylactic therapy with bisphosphonates for osteoporosis should be started.
INTRA- ARTICULAR STEROIDS
In cases with single or few joint involvement, intra - articular injection of a soluble glucocorticoid affords relief and slows down the joint damage.
Treatment of choice in acute flare (monoarticular) of Rheumatoid arthritis.
DISEASE MODIFYING ANTI-RHEUMATIC AGENTS
They are called so due to their ability to prevent or slow the progression of disease both structurally and functionally.
There are 2 types namely
CONVENTIONAL DMARDS – immunosuppressants, sulfasalazine, leflunomide, Hydroxychloroquine
BIOLOGICAL- TNFα Inhibitors, Anakinra, Abatacept, Rituximab, Tocilizumab & Newer drugs.
METHOTREXATE:
It inhibits production of cytokines; chemotaxis and cell mediated immune response.
Exerts anti-inflammatory effect by releasing adenosine from cells.
Starting dose – 7.5 to 10mg/week orally.
To reduce the adverse effects, folic acid 5mg once a week is given
HYDROXYCHLOROQUINE:
Has moderate effect, used in mild or early disease
Used as adjunctive therapy with other DMARDs
Cardiac and retinal toxicity are major side effects LEFLUNOMIDE:
It inhibits dihydroorotate dehydrogenase and pyrimidine synthesis in actively dividing cells.
Dosage- 10 to 20mg/day.
Can be used as monotherapy or in combination with methotrexate
Other drugs such as sulfasalazine, minocycline, pencillamine, azathioprine, cyclosporine , gold salts has also been used as DMARDs.
BIOLOGICAL AGENTS:
It includes
TNF α inhibitors (Infliximab, Adalimumab, Etanercept,
IL – 1 antagonists (Anakinra)
Anti- CD20 B cell agents(Rituximab)
Anti- IL 6 agents (Tocilizumab) INFLIXIMAB:
It is a IgG1 chimeric monoclonal antibody which is administered at a initial dose of 3mg/kg i.v over 2 hrs.
Soft tissue and joint infections, fungal infections, demyelination and reactivation of TB can occur as side effects.
ETANERCEPT:
It is the recombinant fusion protein of TNF receptor and Fc portion of human IgG.
Administered by s.c. injection 50mg weekly.
Pain, redness, itching at the injection site can occur.
ANAKINRA
Used in juvenile onset inflammatory arthritis ABATACEPT
It is a soluble fusion protein containing CTLA -4 and human
It inhibits costimulatory molecules CD28/80 and thereby prevents T cell activation.
Reduces disease activity and retards progression of disease.
RITUXIMAB
Used for treatment of refractory Rheumatoid arthritis.
Usually used in combination with methotrexate, provides good results.
Infusion reactions and Progressive multifocal leuko encephalopathy are the major side effects.
TOCILIZUMAB
It is the IL-6 receptor monoclonal antibody used in Rheumatoid arthritis, as IL-6 plays important role in pathogenesis of RA.
TOFACITINIB
Newer drug which inhibits JAK 1 and 3, thereby blocks cytokines such as IFN – gamma and IL-6.
SURGICAL THERAPY:
It is indicated for patients with destructive rheumatoid arthritis.
The various surgical methods include
Arthroplasty
Joint replacement surgeries
Synovectomy
MTX+ NSAIDs First Line
In 12% of the cases, physicians could switch from
one of the products, mainly from NSAIDs for the first line to
Hydroxychloroquine or Steroids
MTX or NSAID HQ or Steroid+
In most of the cases, physicians add Hydroxychloroquine or
Steroids
to the products for the first line
MTX + NSAIDs HQ or Steroids+ Second Line
Biologics + Sometimes, physicians
switch from the second line therapy to the biologics and they use them as monotherapy in
third line
More often, the biologics are added to the MTX containing regimens and
they are used in combination in third line
therapy
Reasons for switching to
another medication are in 100% of the cases
the inadequate response to the
previous one.
Adding another medication is always due to the inadequate
response to the previous one.
Physicians take
also into
consideration the ability of the
MATERIALS AND METHODS
Sample Size: 50
Type of Study : Prospective Cross sectional Study
Duration of Study: 12 months ( April 2017 to April 2018) Inclusion Criteria
Patients more than 16 years of age
Known Rheumatoid Arthrithis patients who have been clinically examined and investigated and found to be fulfilling the American College of Rheumatology criteria for Rheumatoid arthritis 2010 Exclusion Criteria
Rheumatoid arthritis Patients with known Overt cardiovascular disease like coronary artery disease, cerebrovascular disease, peripheral vascular disease
Rheumatoid arthritis patients with other independent risk factors for developing cardiovascular diseases such as Diabetes, Hypertension, Smoking and alcoholism
Patients less than 16 years of age
Patients not fulfilling the American College of Rheumatology criteria for Rheumatoid Arthritis 2010.
Rheumatoid Arthritis patients not willing to participate in the study.
Methodology
This prospective cross sectional study is carried out in known Rheumatoid Arthritis patients attending General Medicine & Rheumatology outpatient clinic or ward of Tirunelveli Medical College Hospital between April 2017 and April 2018. They have been selected after detailed investigations and found to be fulfilling ACR criteria for Rheumatoid Arthritis 2010 and also the inclusion , exclusion criteria of our case study.
Written informed consent was obtained from the patients selected for the study. They have been subjected to detail clinical and laboratory investigations. Routine investigations such as complete blood count, Hemoglobin, Total leukocyte count, Differential count, Platelet count, Renal Function test, Liver Function Test, Serum Electrolytes, Fasting Lipid Profile , Urine Routine Investigations and Blood sugar.
In addition, investigations such as ESR, CRP, RA factor, Anti- CCP antibody, Electrocardiogram, Chest X-Ray PA view, Echocardiogram and Carotid Doppler to detect Carotid Intima Media Thickness were done for all
Carotid Intima Media Thickness was assessed by Ultrasonagraphy B – Mode with a probe of frequency 5 Hz and was confirmed with colour Doppler sonography. Intima Media Thickness was measured at three sites - along common carotid artery in the distal 1 cm before its bifurcation, at the carotid bulb, and at the internal carotid artery. Measurements are taken at diastole, at both sides and the average of six measurements were taken which denotes the mean Carotid Intima Media Thickness of the patient.
Clinical Disease Severity Index score (CDAI score ) was calculated for all selected patients in the study which denotes the disease severity and activity in the patient. It was calculated using the formula,
CDAI = SJC(28) + TJC(28) + PGA + EGA.
Whereas
SJC denotes swollen joint count(28) ,
TJC denoted tender joint count(28) ,
PGA denotes Patient Global disease activity scale and
EGA denotes Evaluator’s Global disease activity scale , latter two ranging from 1-10.
Interpretation was made by studying the occurrence of various clinical
correlating them with the disease activity and severity in those patients which is assessed by the CDAI score.
RESULTS
DEMOGRAPHIC DISTRIBUTION
TABLE NO 1 : AGE DISTRIBUTION
Our study group consists of 50 Rheumatoid arthritis patients who fell in age group of 21 -74 yrs
FIGURE NO 1: AGE DISTRIBUTION
AGE GROUP NO OF PATIENTS
<30 3
30-50 24
>50 23
3
24 23
0 5 10 15 20 25 30
<30 30-50 >50
TABLE NO 2 : GENDER DISTRIBUTION
GENDER NO OF PATIENTS
Male 9
Female 41
FIGURE NO 2 : GENDER DISTRIBUTION
Male, 9
Female, 41
TABLE NO 3 : DISTRIBUTION OF JOINT INVOLVEMENT
JOINT INVOLVEMENT NO OF PATIENTS
MCP 46
PIP 33
Wrist 32
Knee 10
Elbow 15
Shoulder 4
Ankle 8
RA hand 3
FIGURE NO 3 : DISTRIBUTION OF JOINT INVOLVEMENT
46
33 32
10
15
4
8
3 0
5 10 15 20 25 30 35 40 45 50
MCP PIP Wrist Knee Elbow Shoulder Ankle RA hand
TABLE NO 4 : DISTRIBUTION OF DISEASE DURATION
DISEASE DURATION NO OF PATIENTS
< 5 years 15
5-10 years 11
10-15 years 16
> 15 years 8
FIGURE NO 4 : DISTRIBUTION OF DISEASE DURATION
15
11
16
8
0 2 4 6 8 10 12 14 16 18
< 5 years 5-10 years 10-15 years > 15 years
TABLE NO 5: DISTRIBUTION OF TREATMENT DURATION
TREATMENT DURATION NO OF PATIENTS
Not on Treatment 1
< 10 years 29
>10 years 20
FIGURE NO 5 : DISTRIBUTION OF TREATMENT DURATION
Not on treatment , 1
< 10 years, 29
>10 years, 20
TABLE NO 6: DISTRIBUTION OF ANAEMIA IN STUDY GROUP
HAEMOGLOBIN (G / dl) NO OF PATIENTS
>11 14
9-11 15
7-9 15
<7 6
FIGURE NO 6 : DISTRIBUTION OF ANAEMIA IN STUDY GROUP
14
15 15
6
0 2 4 6 8 10 12 14 16
>11 9-11 7-9 <7
TABLE NO 7 : VARIATION IN TOTAL LEUCOCYTE COUNT IN STUDY GROUP
TOTAL LEUCOCYTE COUNT NO OF PATIENTS
Normal 45
Leucocytosis 3
Leucopenia 2
FIGURE NO 7 : VARIATION IN TOTAL LEUCOCYTE COUNT IN STUDY GROUP
Normal, 45 Leucocytosis, 3Leucopenia, 2
TABLE NO 8 : LYMPHOCYTOSIS IN STUDY GROUP
DIFFERENTIAL COUNT NO OF PATIENTS
LYMPHOCYTOSIS 10
NORMAL LYMPHOCYTE COUNT 40
FIGURE NO 8: LYMPHOCYTOSIS IN STUDY GROUP
Normal, 40 Lymphocytosis, 10
TABLE NO 9 : PLATELET COUNT DISTRIBUTION IN STUDY GROUP
PLATELET COUNT NO OF PATIENTS
Thrombocytopenia 7
Normal 41
Thrombocytosis 2
FIGURE NO 9: PLATELET COUNT DISTRIBUTION IN STUDY GROUP
Normal, 41 Thrombocytopeni
a, 7
Thrombocytosis, 2
TABLE NO 10: DYSLIPIDEMIA IN STUDY GROUP
LIPID PROFILE NO OF PATIENTS
Normal 43
Hypercholesterolemia 5
Hypertriglyceridemia 2
FIGURE NO 10: DYSLIPIDEMIA IN STUDY GROUP
Normal, 43 HyperCholesterole
mia, 5
Hypertriglyceridem ia, 2
TABLE NO 11 : ESR CORRELATION IN STUDY POPULATION
ESR NO OF PATIENTS
< 20 2
20-50 15
50-70 23
> 70 10
FIGURE NO 11 : ESR CORRELATION IN STUDY POPULATION
< 20 4%
20-50 30%
50-70 46%
> 70 20%
ESR
TABLE NO 12 : CRP CORRELATION IN STUDY POPULATION
CRP NO OF PATIENTS
Positive 23
Negative 27
FIGURE NO 12: CRP CORRELATION IN STUDY POPULATION
Positive , 23 Negative, 27
TABLE NO 13: ECG CHANGES IN STUDY GROUP
ECG CHANGES NO OF PATIENTS
Right axis duration 4
Left axis duration 15
RBBB 11
LAFB 2
LVH 5
Left Atrial enlargement 2
Nonspecific ST-T changes 12
Coronary artery disease / specific ST-T changes
9
ARRHYTHMIA (BradyArrhythymia /
TachyArrhythymia)
3
Normal 12
Low voltage complexes 5
TABLE NO 13: ECG CHANGES IN STUDY GROUP
4
15 11
2
5 2
12 9
3
12 5
0 2 4 6 8 10 12 14 16
Right axis duration Left axis duration RBBB
LAFB LVH Left Atrial enlargement Nonspecific ST-T changes Coronary artey disease / specific ST-T changes Arrythmias (Brady / Tachy)
Normal Low voltage complexes
TABLE NO 14: X-RAY CHANGES IN STUDY POPULATION
CHEST X-RAY CHANGES NO OF PATIENTS
Normal 26
Cardiomegaly 20
Other changes 4
FIGURE NO 14: X-RAY CHANGES IN STUDY POPULATION
Normal , 26 Cardiomegaly ,
20
others, 4
TABLE NO 15: CDAI SCORE DISTRIBUTION
The disease severity was high among our study group with 60 % of cases occupying High CDAI score with no patients under remission.
CDAI SCORE NO OF PATIENTS
Remission <2.8 Nil
Low 2.8 – 10 3
Moderate 10-22 17
High > 22 30
FIGURE NO 15: CDAI SCORE DISTRIBUTION
3
17
30
0 5 10 15 20 25 30 35
Low Moderate High
TABLE NO 16: MEAN CIMT DISTRIBUTION IN STUDY GROUP
MEAN CIMT NO OF PATIENTS
Increased CIMT 34
Normal 12
Plaque 4
FIGURE NO 16: MEAN CIMT DISTRIBUTION IN STUDY GROUP
12
34
4
0 5 10 15 20 25 30 35 40
Normal Increased CIMT Plaque
TABLE NO 17: DESCRIPTIVE STATISTICS
Mean age, Duration of disease, CDAI score, ESR, CRP, mean CIMT, mean EF in our study population were listed.
N Minimum Maximum Mean Std. Deviation
Age 50 21.00 74.00 47.76 11.09
CDAI_Score 50 5.00 44.00 25.16 10.40
Duration 50 .20 20.00 8.63 5.85
CIMT 50 0.00 .99 0.72 0.26
EF 50 38.00 75.00 59.46 9.25
ESR 50 15.00 120.00 49.50 27.97
CRP 50 1.00 2.00 1.46 0.50
TABLE NO 18: CORRELATION OF MEAN CAROTID INTIMA MEDIA THICKNESS IN STUDY POPULATION
Mean CIMT of study population was correlated with various parameters such as Age of patient, Duration of disease, Duration of treatment, ESR and CDAI score.
Correlation Coefficient P value
CIMT
Age 0.136 0.347
Duration of RA 0.342 0.015
CDAI 0.187 0.043
ESR 0.05 0.732
Duration of Treatment 0.364 0.010
FIGURE NO 18: CORRELATION OF MEAN CAROTID INTIMA MEDIA THICKNESS VS CDAI SCORE
There is a significant relationship between the mean Carotid Intima Media Thickness (CIMT) and Clinical Disease Activity Index (CDAI) score.
(p value 0.043)
FIGURE NO 19: CORRELATION OF MEAN CAROTID INTIMA MEDIA THICKNESS VS DISEASE DURATION
There is a significant relationship between the mean Carotid Intima Media Thickness (CIMT) and Duration of Rheumatoid Arthritis, Duration of treatment (p value of 0.015, 0.010 respectively.)
There is no significant relationship between mean Carotid Intima Thickness (CIMT) and Age of the patient and ESR values (p value 0.347, 0.732
TABLE NO 19: CIMT CORRELATION WITH C-REACTIVE PROTEIN LEVELS
CRP N Mean
Std.
Deviation P value
CIMT Negative 27 0.71 0.19
0.603
Positive 23 0.74 0.33
There is no significant relationship between mean Carotid Intima media Thickness (CIMT) and C-Reactive Protein Levels
DISTRIBUTION OF ECHOCARDIOGRAPHIC FINDINGS IN STUDY POPULATION
The distribution of various echocardiographic findings such as Left Venticular Systolic Function, Left Ventricular Diastolic function, Pericardial Effusion, Pulmonary Hypertension, Valvular Abnormalities such as Mitral Regurgitation, Aortic sclerosis, coronary calcifications were listed.
TABLE NO 20: LV SYSTOLIC DYSFUNCTION DISTRIBUTION
Frequency Percent Valid Percent
Cumulative Percent
Valid No 42 84.0 84.0 84.0
Yes 8 16.0 16.0 100.0
Total 50 100.0 100.0
TABLE NO 21: LV DIASTOLIC DYSFUNCTION DISTRIBUTION
Frequency Percent Valid Percent
Cumulative Percent
Valid No 28 56.0 56.0 56.0
Yes 22 44.0 44.0 100.0
Total 50 100.0 100.0
TABLE NO 22: PERICARDIAL EFFUSION DISTRIBUTION
Frequency Percent Valid Percent
Cumulative Percent
Valid No 37 74.0 74.0 74.0
Yes 13 26.0 26.0 100.0
Total 50 100.0 100.0
TABLE NO 23: PULMONARY HYPERTENSION DISTRIBUTION
Frequency Percent
Valid Percent
Cumulative Percent
Valid No 46 92.0 92.0 92.0
Yes 4 8.0 8.0 100.0
Total 50 100.0 100.0
TABLE NO 24: MITRAL REGURGITATION DISTRIBUTION
Frequency Percent
Valid Percent
Cumulative Percent
Valid No 40 80.0 80.0 80.0
Yes 10 20.0 20.0 100.0
Total 50 100.0 100.0
TABLE NO 25: AORTIC SCLEROSIS DISTRIBUTION
Frequency Percent
Valid Percent
Cumulative Percent
Valid No 45 90.0 90.0 90.0
Yes 5 10.0 10.0 100.0
Total 50 100.0 100.0
TABLE NO 26: CORONARY CALCIFICATION DISTRIBUTION
Frequency Percent
Valid Percent
Cumulative Percent
Valid No 48 96.0 96.0 96.0
Yes 2 4.0 4.0 100.0
Total 50 100.0 100.0
FIGURE NO 26: DISTRIBUTION Of ECHO CARDIO GRAPHIC FINDINGS
16%
44%
26%
8%
20%
10%
4%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Percentage of Patients
CORRELATION OF ECHOCARDIOGRAPHIC FINDINGS WITH CLINICAL DISEASE ACTIVITY INDEX SCORE
TABLE NO 27: EJECTION FRACTION vs CDAI SCORE
Correlation Coefficient P value
EF CDAI Score 0.311 0.030
There is significant relationship between variation in ejection fraction and Clinical Disease activity index score (p value 0.030)
TABLE NO 28: LEFT VENTRICULAR SYSTOLIC DYSFUNCTION vs CDAI SCORE
LVSD N Mean Std.
Deviation
P value
CDAI_Score No 42 22.93 9.56 <0.0001
Yes 8 36.88 5.87
There is strong correlation between Left Ventricular Systolic Dysfunction and Clinical Disease Severity Index score (p value < 0.0001)
TABLE NO 29: LEFT VENTRICULAR DIASTOLIC DYSFUNCTION vs CDAI SCORE
LVDD N Mean Std.
Deviation
P value
CDAI_Score No 28 23.46 11.35 0.196
Yes 22 27.32 8.83
There is no significant relationship between left ventricular diastolic dysfunction and Clinical Disease activity index score (p value 0.196)
TABLE NO 30: PERICARDIAL EFFUSION vs CDAI SCORE
PERICARDIAL EFFUSION
N Mean Std.
Deviation
P value
CDAI_Score No 37 22.86 10.60 0.007
Yes 13 31.69 6.47
There is significant relationship between occurrence of pericardial effusion and Clinical Disease Severity Index score (p value 0.007 )
TABLE NO 31: PULMONARY HYPERTENSION vs CDAI SCORE
PULMONARY HYPERTENSION
N Mean Std.
Deviation
P value
CDAI_Score No 46 25.17 10.51 0.975
Yes 4 25.00 10.39
There is no significant relationship between occurrence of Pulmonary hypertension and Clinical Disease Severity Index score (p value 0.975).
TABLE NO 32: MITRAL REGURGITATION vs CDAI SCORE
MITRAL REGURGITATION
N Mean Std.
Deviation
P value
CDAI_Score No 40 23.88 10.01 0.080
Yes 10 30.30 10.87
There is no significant relationship between occurrence of Mitral regurgitation and Clinical Disease Severity Index score (p value 0.080).
TABLE NO 33: AORTIC SCLEROSIS vs CDAI SCORE
AORTIC SCLEROSIS N Mean Std.
Deviation
P value
CDAI_Score No 45 25.84 10.35 0.165
Yes 5 19.00 9.62
There is no significant relationship between occurrence of Aortic Sclerosis and Clinical Disease Severity Index score (p value 0.165).
TABLE NO 34: CORONARY CALCIFICATIONS vs CDAI SCORE
CORONARY CALCIFICATIONS
N Mean Std.
Deviation
P value
CDAI_Score No 48 24.96 10.57 0.507
Yes 2 30.00 1.41
There is no significant relationship between occurrence of coronary calcifications and Clinical Disease Severity Index score (p value 0.507).
CORRELATION OF ECHOCARDIOGRAPHIC FINDINGS WITH DURATION OF RHEUMATOID ARTHRITIS
TABLE NO 35: EJECTION FRACTION vs DURATION OF RHEUMATOID ARTHRITIS
Correlation Coefficient P value
EF Duration of disease -0.516 <0.0001
There is strong significant relationship between variation in ejection fraction and duration of rheumatoid arthritis (p value < 0.0001).
TABLE NO 36: LEFT VENTRICULAR SYSTOLIC DYSFUNCTION vs DURATION OF RHEUMATOID ARTHRITIS
LVSD N Mean Std.
Deviation
P value
Duration of disease
No 41 5.62 3.98 0.003
Yes 8 10.50 3.82
There is strong significant relationship between left ventricular systolic
TABLE NO 37: LEFT VENTRICULAR DIASTOLIC
DYSFUNCTION vs DURATION OF RHEUMATOID ARTHRITIS
LVDD N Mean Std.
Deviation
P value
Duration of disease
No 28 5.20 4.62 0.021
Yes 21 8.05 3.34
There is strong significant relationship between left ventricular diastolic dysfunction and duration of rheumatoid arthritis (p value 0.021).
TABLE NO 38: PERICARDIAL EFFUSION vs DURATION OF RHEUMATOID ARTHRITIS
PERICARDIAL EFFUSION
N Mean Std.
Deviation
P value
Duration of disease
No 37 6.29 4.65 0.707
Yes 12 6.83 3.24
There is no significant relationship between occurrence of pericardial effusion and duration of rheumatoid arthritis (p value 0.707).
TABLE NO 39: PULMONARY HYPERTENSION vs DURATION OF RHEUMATOID ARTHRITIS
PULMONARY HYPERTENSION
N Mean Std.
Deviation
P value
Duration of disease
No 45 6.64 4.44 0.246
Yes 4 4.00 1.15
There is no significant relationship between occurrence of Pulmonary hypertension and duration of rheumatoid arthritis (p value 0.246).
TABLE NO 40:MITRAL REGURGITATION vs DURATION OF RHEUMATOID ARTHRITIS
MITRAL REGURGITATION
Mean Std.
Deviation
P value
Duration of disease
No 39 5.68 4.12 0.016
Yes 10 9.32 4.01
There is significant relationship between occurrence of Mitral Regurgitation and duration of rheumatoid arthritis (p value 0.016).
TABLE NO 41: AORTIC SCLEROSIS vs DURATION OF RHEUMATOID ARTHRITIS
AORTIC SCLEROSIS N Mean Std.
Deviation
P value
Duration of disease
No 44 5.99 4.25 0.038
Yes 5 10.20 3.19
There is significant relationship between occurance of Aortic sclerosis and duration of rheumatoid arthritis (p value 0.038).
TABLE NO 42: CORONARY CALCIFICATIONS vs DURATION OF RHEUMATOID ARTHRITIS
CORONARY CALCIFICATIONS
N Mean Std.
Deviation
P value
Duration of disease
No 47 6.44 4.33 0.890
Yes 2 6.00 5.66
There is no significant relationship between occurrence of coronary calcifications and duration of rheumatoid arthritis (p value 0.890).
DISCUSSION
We found that patients among our study group fell in age group of 21- 74 yrs with mean age of 47.76 years. Males among study group occupy 28%
& females 72 % respectively. The Mean duration of rheumatoid arthritis among study population is 8.63 ± 5.85 yrs.
The disease severity among patients was assessed with clinical disease severity score and Mean CDAI score among them are 25.16 ± 10.4.
The disease severity was high among our study group with 60 % of cases occupying High CDAI score with no patients under remission.
Metacarpophalangeal, proximal interphalangeal joint and wrist joints are the most commonly involved joints among study population.
Anaemia seems to be occur more commonly in rheumatoid arthritis patients, being in 72 % of our study population. Lymphocytosis were found in 20% of our study group. Thrombocytopenia and thrombocytosis occurs in minority group of patients (14 %, 4% respectively).
Dyslipidemia in form of Hypercholesterolemia and hypertriglyceridemia was found in 10% and 4% of our study population respectively.
Markers of inflammation such as ESR and CRP are raised more commonly among rheumatoid arthritis patients, ESR being more commonly raised in 96 % of patients, and CRP raised in 46 % of patients in study group.
Most Common ECG abnormality found in study group was Left axis deviation (30%) followed by nonspecific ST-T changes (24%). ST –T changes suggestive of coronary artery disease in asymptomatic patients of our study group was found in 18 % of individuals, which was comparable to Masooleh SI et al(21) in which 15% cases had ST-T changes .
In chest X-ray screening, cardiomegaly was found in 40 % of patients and other abnormalities such as fibrotic changes in lungs, prosthetic heart valve shadows, bronchiectactic changes in lungs were present in minority of patients.
Mean Carotid Intima media thickness (CIMT) (cut off among normal individuals is 0.57 mm) is increased in Rheumatoid Arthritis patients when matched with age related controls which signifies presence of premature atherosclerosis. In our case series, Mean CIMT was found to be increased in 68 % of patients. Asymptomatic Carotid Plaque was present in 8% of patients. Presence of carotid plaque suggests that the patients are in stage of preclinical atherosclerosis and emphasis the need for more aggressive risk reduction strategies in these patients.
ECHOCARDIOGRAPHIC FINDINGS
In our study group, Echo abnormalities were found in 68 % of patients.
In our case series, Most common Echocardiographic abnormality is LV diastolic dysfunction which contributes 44% of study group, comparable to 14.54%in study conducted by Raof RM et al(24)followed by Pericardial effusion contributing to 26 %, which was comparable to the study conducted by Selcuket al(28 ) in which it was 15%. .High prevalence of this complication (47%) was found in study done by Masooleh SI et al(21).
Other abnormalities such as Mitral Regurgitation , LV systolic dysfunction were present in 20 % and 16 % of study population respectively, whereas it was as high as 31%(LVSD) in the study by Dawson et al. Coronary calcifications were found in 2 patients.
ESR correlates positively with Clinical disease activity Index score, duration of Rheumatoid arthritis & Mean Carotid Intima Media Thickness.
This proves that increased CIMT was associated with inflammatory burden due to more severe disease, and also the chronic inflammation which reflects the duration of the disease.
Dyslipidemia & CRP shows no significant correlation with CIMT or
Mahajan et al. [10] who did not find significantly correlated dyslipidaemia with accelerated atherosclerosis in RA patients.
According to Homa et al, CIMT increases linearly from 0.48 mm at 40 years of age to 1.02 mm at 100 years of age.
Mean age group in our study was 47.76 yrs & mean CIMT was 0.72 mm So, In our study group CIMT was higher than age related controls and correlates positively with severity of disease as evidenced by high CDAI score( p value 0.043) & duration of disease(p value 0.015), similar observation made by Gonzalez et al and Alkabbi et al in their respective studies. In an Indian study, Mahajan et al. also showed similar observations which showed higher CIMT values in RA patients when compared to control group matched age and related parameters. [10].
Among echocardiographic findings, LV systolic dysfunction (LVSD), variation in Ejection Fraction and Pericardial Effusion positively correlates with clinical disease severity index (CDAI) score in our study group.
Left Ventricular Systolic Function, Left Ventricular Diastolic Dysfunction, and valvular abnormalities such as Mitral Regurgitation and Aortic sclerosis correlates positively with duration of rheumatoid arthritis.
Coronary Calcification was found in 4 % patients in our study, was an indirect marker of subclinical atherosclerosis and serves as a marker of cardiovascular events. In our case series, Coronary calcification has no significant association with disease severity and duration of disease, in contrast to the study by Giles et al., which shows increasing disease severity in RA is associated with increased prevalence and extent of coronary calcification, irrespective of gender and age.
CONCLUSION
Cardiovascular abnormalities such as nonatherosclerotic features like LV diastolic & systolic dysfunction , valvular abnormalities, pericardial effusion and mainly premature atherosclerosis occurs commonly in Rheumatoid arthritis patients & their occurrence positively correlates with Clinical disease activity Index (CDAI)score, disease duration and treatment duration.
All Rheumatoid arthritis patients should be screened for CVS abnormalities through modalities like Electrocardiography, Echocardiography & CIMT periodically. CIMT, a non-invasive marker of accelerated atherosclerosis is also a marker of coronary atherosclerosis serves as an important tool in developing countries like India , due to its low cost, non-invasive patient convenient procedure and so has been recommended by American Heart Association (AHA) as a screening test for cardiovascular diseases in apparently healthy individuals.
DMARDs & Biological agents have been shown to have cardio protective effects in many studies. In a study cohort, Methotrexate have shown to reduce cardiovascular morbidity and mortality, ranging from 15%
to 85%.Biological Agents such as TNF alpha inhibitor therapy improves endothelial function and arterial stiffness in patients with RA as shown in a
Tocilizumab (IL -6 inhibitor) and Rituximab improves both endothelial function and arterial stiffness, also reduces carotid atherosclerosis respectively.
Therefore, Early identification & effective control of disease activity by DMARDS/Biological agents at correct time can prevent or halt the progression of cardiovascular manifestations in Rheumatoid arthritis patients thereby reducing the mortality and morbidity caused by them.
LIMITATION
1. The Study population is too small
2. History of usage of drugs such as DMARDs or Biological agents were not obtained
3. Effects of patients medication for rheumatoid arthritis on patients disease severity and its influence and correlation on cardiovascular manifestations were not studied.
4. RA Factor and Anti-CCP antibody titre levels were not correlated with patients cardiovascular manifestations.