Is Rheumatoid Arthritis a Metabolic Disorder.pptx

Is Rheumatoid
Arthritis a
metabolic
Disease ?
Samar Tharwat Radwan
Assistant Professor of Rheumatology and Immunology
(Internal Medicine Department )
Musculoskeletal Ultrasound –EULAR
Mansoura University

Agenda
• Rheumatoid arthritis
• Metabolic Syndrome
• Cachexia
• Insulin Resistance
• Dyslipidemia
• Cardiovascular Risk
• Osteoporosis
• Medications

Rheumatoid
Arthritis
• Rheumatoid arthritis (RA) is a systemic
autoimmune disease
• Female predominance and an increased
incidence in people over 60 years old.
• Presented with arthritis —which is
disabling in some cases—morning
stiffness, and joint swelling
Sharif K, Sharif A, Jumah F, Oskouian R, Tubbs RS. Rheumatoid arthritis in review: clinical, anatomical, cellular and
molecular points of view. Clin Anat. 2018;31(2):216–223. doi:10.1002/ca.22980

Epidemiology
In 2020, an estimated 17·6 million (95% uncertainty interval 15·8–20·3)
people had rheumatoid arthritis worldwide. The age-standardised global
prevalence rate was 208·8 cases (186·8–241·1) per 100 000 population

Pathophysio
logy of
Rheumatoid
Arthritis
Guo, Qiang, et al. "Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies."
Bone research 6.1 (2018): 15.

Structural Phenotypes of
Rheumatoid Arthritis
Aletaha, Daniel, and Josef S. Smolen. "Diagnosis and management of rheumatoid arthritis: a
review." Jama 320.13 (2018): 1360-1372.

Comorbidi
ties in
Rheumatoi
d
Arthritis

Also, Rheumatoid arthritis is
associated with Metabolic
Abnormalities
Metabolic syndrome
• Arterial hypertension
• Atherosclerosis
• Diabetes mellitus
• Insulin resistance
• Obesity or cachexia
• Dyslipidemia (↑Triglycerides, ↑ Total cholesterol, ↓High-
density lipoprotein cholesterol)
Osteoporosis
• Decreased bone mineral density
• Imbalance of osteoblast/osteoclast
Santos-Moreno, Pedro, et al. "Metabolic abnormalities, cardiovascular disease, and metabolic syndrome in adult rheumatoid arthritis patients: current perspectives and clinical implications." Open
Access Rheumatology: Research and Reviews (2022): 255-267.

Common Pathophysiological
Pathways Between Rheumatoid
Arthritis And Metabolic Disorders
Santos-Moreno, Pedro, et al. "Metabolic abnormalities, cardiovascular disease, and metabolic syndrome in adult rheumatoid arthritis patients: current perspectives and clinical implications." Open
Access Rheumatology: Research and Reviews (2022): 255-267.

Metabolic syndrome is pro
inflammatory and
prothrombotic state that
leads to atherosclerosis
and vasculopathy
Fahed, Gracia, et al. "Metabolic syndrome: updates on pathophysiology and management in 2021." International journal of molecular s

A cross-sectional
relationship between the
inflammatory activity of
RA and metabolic syndrome
has been suggested
Verma, Amit K., et al. "Association of rheumatoid arthritis with diabetic comorbidity: correlating accelerated insulin resistance to inflammatory responses in patients." Journal of
Multidisciplinary Healthcare (2021): 809-820.

A meta-analysis involving a
total of 2,283 patients with RA
and 4,403 controls without RA
confirmed a significant
association between RA and
metabolic syndrome

Notably, the strength of the
association with metabolic
syndrome might differ between
long-standing and early RA
Kerekes, György, et al. "Rheumatoid arthritis and metabolic syndrome." Nature Reviews Rheumatology
10.11 (2014): 691-696.

RA is also an independent
risk factor for CVD
Johri, Nishant, et al. "Association of cardiovascular risks in rheumatoid arthritis patients: Management, treatment and future perspectives." Health Sciences Review 8 (2023): 100108.

The level
of CVD risk
is
influenced
by the
occurrence
of
metabolic
syndrome
Johri, Nishant, et al. "Association of cardiovascular risks in rheumatoid arthritis patients: Management, treatment and future perspectives." Health Sciences Review 8 (2023): 100108.

In women with RA,
independent predictors
of metabolic syndrome
development
• High erythrocyte sedimentation rate
• 28-joint disease activity score
• Health assessment questionnaire
score
• Decreased methotrexate use
Dessein, P. H., Tobias, M. & Veller, M. G. Metabolic syndrome and subclinical atherosclerosis in rheumatoid arthritis. J. Rheumatol. 33,
2425–2432 (2006).

With respect to markers of atherosclerosis in patients with RA, metabolic
syndrome was associated with increased carotid intima–media thickness

Obesity And Rheumatoid
Cachexia
The issue of obesity in patients with RA is rather controversial.
Obesity is common in these
patients

inflammation,
which is
associated
with abundant
production of
TNF, often
leads to
rheumatoid
cachexia
Kerekes, György, et al. "Rheumatoid arthritis and metabolic syndrome." Nature Reviews
Rheumatology 10.11 (2014): 691-696.

• Summers, Gregory D., et al. "Rheumatoid cachexia and cardiovascular disease." Nature Reviews
Rheumatology 6.8 (2010): 445-451.
Cachexia has been associated with both high levels of RA
disease activity and increased mortality from CVD whereas
obesity has been related to decreased CVD mortality in
patients with RA

• Classic cachexia :both muscle and fat mass are decreased
• RA cachexia: increased fat mass and decreased lean mass, resulting in little or no change in
BMI…. elevated fasting glucose levels and hypertension, as well as metabolic syndrome

Rheumatoid cachexia is
associated with abundant
production of proinflammatory
cytokines (primarily TNF and
IL-1) as well as anti-citrullinated
protein antibody (ACPA)
positivity
Wesley, Annmarie, et al. "Association between body mass index and anti–citrullinated protein antibody–positive and anti–citrullinated protein antibody–negative rheumatoid arthritis: results from a population‐based case–
control study." Arthritis care & research 65.1 (2013): 107-112.

Insulin
resistance
• Increased insulin
resistance is
associated with RA
• Increased insulin resistance
has been associated with
carotid plaque formation
Lanchais, Kassandra, Frederic Capel, and Anne Tournadre. "Could omega 3 fatty acids preserve muscle health in rheumatoid arthritis?." Nutrients
12.1 (2020): 223.

Reduced β- cell activity has been linked to
increased disease activity

Dyslipidaem
ia
In RA, high-grade inflammation and
associated factors, such as
increased levels of C-reactive protein
(CRP) and inflammatory cytokines
Venetsanopoulou, Aliki I., Paraskevi V. Voulgari, and Alexandros A. Drosos. "Hyperlipidemia and rheumatoid arthritis." Cholesterol. Academic
Press, 2022. 969-997.

Lipids may have paradoxical associations with
the risk of CVD in RA, whereby lower TCh and
LDL levels are associated with increased
cardiovascular risk.

C-reactive protein (CRP) and
inflammatory cytokines, can
influence commonly measured lipid
levels , leading to their
misinterpretation

Cardiovascular
Risk
• Despite that mortality figures from RA have improved.
• In 2021, the data were still worrying and showed a higher mortality
rate in RA patients than in the general population.
• This mortality increase is due to CVR factors

CVR
increas
es
Changes in the
patient’s
metabolism
Unhealthy
lifestyle
Chen, Jianmin, Lucy V. Norling, and Dianne Cooper. "Cardiac dysfunction in rheumatoid arthritis: the role of inflammation." Cells 10.4 (2021): 881.

Various
cardiac and
vascular
complication
s of
rheumatoid
arthritis
Rawla, Prashanth. "Cardiac and vascular complications in rheumatoid arthritis."
Reumatologia/Rheumatology 57.1 (2019): 27-36.

Specialists (rheumatologists,
cardiologists,
endocrinologists) and general
practitioners should
implement interventions to
reduce CVR in these patients
• Promoting a healthy lifestyle
• Choosing medicines with a dual
effect (to impact RA and
metabolic alterations)
• Performing a proper follow-up
Bartels CM, Saucier JM, Thorpe CT, et al. Monitoring diabetes in patients with and without rheumatoid arthritis: a Medicare study. Arthritis Res Ther. 2012;14(4):R166. doi:10.1186/ar3915

CV Risk
Stratificati
on
• An important part
• Used to make decisions on
management and follow-up
• RA is an independent risk
factor for cardiovascular
events
• These patients are a
particular population when
stratifying CVR.
Martín-Martínez MA, González-Juanatey C, Castañeda S, et al. Recommendations for the management of cardiovascular risk in patients with rheumatoid arthritis: scientific evidenc e and expert opinion. Semin Arthritis Rheum.
2014;44(1):1–8. doi:10.1016/j. semarthrit.2014.01.002

Cardiovascular Risk
Management in Rheumatoid
Arthritis Patients
Martín-Martínez MA, González-Juanatey C, Castañeda S, et al. Recommendations for the management of cardiovascular risk in patients with rheumatoid arthritis: scientific evidence and expert opinion. Semin Arthritis Rheum. 2014;44(1):1–8.
doi:10.1016/j.semarthrit.2014.01.002

For those patients with a
moderate CVR, the use of
non-invasive tools such as
carotid ultrasound, which
analyzes the thickness of
the intima-media or ankle-
arm index, looking for
subclinical atherosclerosis,
is recommended

Rheumatoid Arthritis and
Osteoporosis
• Alterations in bone composition have been
strongly associated with RA
• Imbalance between the action of osteoblasts
and osteoclasts that damages the bone
structure
• RA patients who develop OP have an
increased risk of fragility
fractures and increased mortality
Raterman HG, Bultink IE, Lems WF. Osteoporosis in patients with rheumatoid arthritis: an update in epidemiology, pathogenesis, and fracture prevention. Expert Opin Pharmacother. 2020;21(14):1725–1737. doi:10.1080/14656566.2020.178738161

Fractures in Rheumatoid
Arthritis Patients
There is an increased risk of fractures in RA patients, which is even higher in patients under
glucocorticoid treatment; this condition is known as glucocorticoid-induced OP

• A meta-analysis
• 46,711 glucocorticoid-treated RA subjects
• Lumbar BMD and femoral neck BMD was lower in patients receiving glucocorticoid management
• The BMD-lowering effect was also associated with the daily dose administered
• Patients receiving a dose of 5–10 mg had lower BMD than those receiving less than 5 mg.
• Vertebral fracture in this group of patients had a prevalence of 13.0% in RA patients treated with
glucocorticoids

Fractures directly impact RA patients’ mortality since these patients have more
years lived with disability, less physiological reserve, fragility, and immobility
syndrome

Medicines Commonly
Used in Rheumatoid
Arthritis and
Their Impact on
Metabolic
Comorbidities

Medicine
s
Commonly
Used in
Rheumato
id
Arthriti

Some have dual
effects that benefit
the disease and
comorbidities
Some have beneficial
effects on the
disease but
detrimental effects
on metabolic
abnormalities
Ozen G, Pedro S, Michaud K. The risk of cardiovascular events associated with disease-modifying antirheumatic drugs in rheumatoid arthritis. J Rheumatol. 2020;48(5):648–655. doi:10.3899/jrheum.200265

At the beginning of
the pharmacological
management of RA, two
essential premises must be
considered :
1) csDMARD or bDMARDs
management impacts the
disease’s activity and
reduces CVR.
2) The use of medicines that increase
CVR should be avoided.
Ozen G, Pedro S, Michaud K. The risk of cardiovascular events associated with disease-modifying
antirheumatic drugs in rheumatoid arthritis. J Rheumatol. 2020;48(5):648–655.
doi:10.3899/jrheum.200265

Non-
Steroidal
Anti-
Inflammat
ory Drugs
Used as adjuvants
in acute episodes
in RA patients’
pain management
Braun J, Baraliakos X, Westhoff T. Nonsteroidal anti-inflammatory drugs and cardiovascular risk - a matter of indication. Semin Arthritis Rheum. 2020;50(2):285–288.
doi:10.1016/j.semarthrit.2019.07.01274

Glucocorticoids
• Metabolic effects are linked to the use of doses higher than 7 mg.
• Therefore, using the lowest effective doses in the shortest time possible is recommended.

Hydroxychloroq
uine
• Hydroxychloroquine
improves insulin resistance.
• Reduces the risk of the
development of DM .
• Reduces glycated
hemoglobin levels by more
than 50%.
• Improves the lipid panel,
specifically total cholesterol
and low-density lipoprotein
levels
Solomon DH, Garg R, Lu B, et al. Effect of hydroxychloroquine on insulin sensitivity and lipid parameters in rheumatoid arthritis patients without diabetes mellitus: a randomized, blinded crossover
trial. Arthritis Care Res. 2014;66(8):1246–1251. doi:10.1002/acr.2228578

Methotrexat
e
• Methotrexate positively affects
CVR by reducing metabolic
syndrome risk and blood glucose
levels
• Associated with a decrease in CVD
mortality (HR: 0.72, 95% CI: 0.53–
0.97, P = 0.031)
Xu J, Xiao L, Zhu J, Qin Q, Fang Y, Zhang J. Methotrexate use reduces mortality risk in rheumatoid arthritis: a systematic review and meta-analysis of cohort studies. Semin Arthritis Rheum. 2022;55:152031. doi:10.1016/j.semarthrit.2022.152031

Effect of
DMARDs on
atheroscle
rosis
progressio
n
Atzeni, Fabiola, et al. "Cardiovascular effects of approved drugs for rheumatoid arthritis." Nature Reviews Rheumatology 17.5 (2021): 270-290.

Is
Rheumato
id
Arthriti
s a
metaboli
c
Disease
?
Rheumatoid arthritis is a systemic inflammatory
disease that shares pathogenic mechanisms
with the metabolic syndrome and independent
risk factor for other metabolic disorders

Is Rheumatoid Arthritis a Metabolic Disorder.pptx

Is Rheumatoid Arthritis a Metabolic Disorder.pptx

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