1. The document discusses managing comorbidities that can arise from inflammatory arthritis, including cardiovascular disease. 2. It notes that patients with inflammatory rheumatic diseases have an increased risk of cardiovascular issues compared to the general population. Several guidelines are mentioned for assessing and managing cardiovascular risk in these patients. 3. The challenges of accurately quantifying cardiovascular risk specific to inflammatory arthritis patients and determining appropriate lipid treatment targets for these patients are discussed. Modification of traditional risk prediction models to account for arthritis-related inflammation is an area lacking guidance.

1. Managing Co-Morbidities
of Inflammatory Arthritis
Dr. Mazen Al Zo’ubi
Fellow of Rheumatology
Internal Medicine Specialist
DRMS, Jordan

2. Learning Objectives
► Become familiar with important comorbidities arising in the context of
inflammatory arthritis and its treatment, including cardiovascular disease and
increased risk of infection
► Become familiar with steps to be taken to mitigate the risk of these comorbid
conditions

3. Major Co-Morbidities
▪ Cardiovascular
▪ Chronic Kidney Disease
▪ Chronic Liver Disease
▪ Cancer
▪ Respiratory
▪ Infections
▪ Metabolic
▪ Osteoporosis
▪ Mental illness

5. Premise
1. Patients with inflammatory rheumatic diseases are at increased cardiovascular risk
2. Cardiovascular disease is widely acknowledged as among the most significant
morbidities stemming from inflammatory rheumatic diseases; mechanisms are
protean and the cumulative impact is difficult to quantify (and underestimated in our
patients)
3. There are countless national and international guidelines published to assist
physicians in managing CV risk
4. There is a dearth of guidance in managing these complex patients at increased risk
5. Understanding practice patterns (and then striving for improved consistency of
management) may be an early step in improving patient care

6. Objectives
1. To review the. Canadian Cardiovascular Society lipid management guidelines
and...
2. ....attempt to reconcile how these guidelines apply to the patients we see.
3. To review the most recent recommendations on prevention of cardiovascular
comorbidity in rheumatic diseases
4. Issue a call to arms: How can we do better for our patients?

9. CV risk in the rheumatic diseases
► RA and SLE: known excess atherosclerotic CV risk
► Prevalence a DM2
► 50% increased risk of death from MI or stroke c/w general population
► Independent from traditional RFs
► APS, SS, PsA: likely similar
► Accelerated atherosclerosis: leading cause of morbidity/mortality in systemic
autoimmune disease

10. RA-specific risk
Traditional risk factors
Effects of traditional and biologic DMARDs
Inflammation
Seropositivity
Erosive disease
Extraarticular
features
Articular damage
Physically inactive
NSAID use

11. The HDL paradox
▪ HDL is classically atheroprotective (reverse lipid transport, anti-inflammatory, anti-
oxidant, anti-thrombotic).
▪ In RA, HDL function (efflux capacity) impaired +/-pro-inflammatory effects.

12. Evidence for subclinical CVD in early RA
 Numerous studies suggest surrogate markers for atherosclerosis are present in
(early) RA.
Increased CRP associated with increased vascular stiffness, as evidenced by:
1. Flow-mediated dilation.
2. Augmentation index.
3. Pulse wave velocity.
4. Carotid intima-media thickness
5. Coronary artery calcification score.

13. CV risk is based on overall phenotype, with LDL
being one factor
▪ Introduction of alternate lipid measurements and imaging modalities for patients
in whom decision to treat is not obvious.
▪ Emphasis on health behavior modification.
▪ Address of statin-related adverse effects .

14. Who to screen
Men 40 years of age, and women of 50 years of age or postmenopausal (consider earlier in
ethnic groups at increased risk such as South Asians or First Nations Individuals Or All
patients with any of the following conditions, regardless of age:
 Current cigarette smoking
 Diabetes
 Arterial hypertension
 Family history of premature CVD
 Family history of hyperlipidemia
 Erectile dysfunction
 Chronic Kidney disease
 Inflammatory disease
 HIV infection
 Chronic obstructive pulmonary disease
 Clinical evidence of atherosclerosis or
abdominal aneurysm
 Clinical manifestation of
hyperlipidemia
 Obesity (body mass index >27)
“inflammatory disease”
Rheumatoid Arthritis
Psoriatic Arthritis
Lupus
Ankylosing Spondylitis

15. How to screen
For all: History and examination, LDL, HDL, TG, non-HDL (will be calculated from profile),
glucose, eGFR
Optional: apoB (instead of standard lipid panel), urine albumin: creatinine ration (if eGFR ,60,
hypertension, diabetes)
Framingham Risk Score < 5%
Repeat every 3-5 years
Framingham Risk Score > 5%
Repeat every year

16. How to screen
Framingham criteria:
1. Age
2. Sex
3. Smoking history
4. Lipid profile (total, HDL)
5. SBP/DBP ► Treated?
6. DM
7. Premature CVD in 1° relative (M <
55, F < 65) doubles risk.

17. Check #1
Do you routinely calculate Framingham risk?

18. Levels of risk
Stratify by Risk Features
Low Risk
• No high risk features
• FRS <10%
Intermediate Risk
• No high risk features
• FRS 10%19%
• See figure 3 (slide
below)
High Risk
• FRS a 20%
• Clinical vascular disease
• Abdominal Aortic Aneurysm
• Diabetes and age a 40 yrs
or >15 yrs duration and age
30 yrs or microvascular
disease’
• Chronic kidney disease
• High risk hypertension
LDL < 5mmol/L LDL > 5mmol/L
FRS > 5% FRS 5%-9%
 Health behavior
modification
 No statin therapy
Optional secondary
testing Indicates higher
risk
No Yes
 Health behavior modification
 Stalin therapy

19. Targets of therapy are based on patient risk
category (above)

20. Stratified by sex, age, country, smoking status and cholesterol level
No mention of modification for inflammatory disease

21. CHECK #2:
Who primarily manages lipids in your
patients?
Are your patients achieving target lipid levels?

22. Relative cardiovascular
risk reduction: 25 - 35%
Remain first-line for
treatment of elevated LDL

23. 50% of patients discontinue their statin within 1 year of
its initiation
As few as 25% being treated for primary prevention
will remain on a statin 2 years later

24. The problem
1) We know that inflammation begets increased cardiovascular risk
2) We know "our" diseases are inflammatory
3) We do not know how to quantify increased risk associated with inflammatory
disease states, how to modify well-validated risk models to incorporate this risk,
or what lipid treatment targets are most appropriate in our patients

25. CV risk prediction
Canadian Dermatology/Rheumatology comorbidity guidelines for RA/PsA (2015):
Eight research questions relating to comorbidities in patients with RA, PsA, or PsO formulated by the Canadian Dermatology-Rheumatology
Comorbidity Initiative.
What are the risks of CVD in patients with RA, PsA, and PsO, including the effect of disease severity, disease duration, and comparison
with traditional CV risk factors?
1.
Does the treatment of RA, PsA, and PsO with systemic agents have an effect on CV outcomes?2.
Smoking: What is the prevalence of smoking in patients with RA, PsA, or PsO? What effect does smoking have on disease activity? What is
the efficacy of smoking cessation strategies in terms of disease activity and response to treatment?
3.
Weight: Does weight/BMI relate to disease activity in RA, PsA, and PsO? What is the effect of treatment on weight? What is the effect of
weight on response to treatment? What is the effect of weight management on disease activity?
4.
Other comorbidities: Are there any differences in malignancies and infections between patients with RA, PsA, and PsO? How common are
malignancies and infections in these populations? What is the effect of treatment on malignancies and infections?
5.
Malignancies: Is there an increased risk of cancer recurrence or new cancers in patients with RA, PsA, or PsO with previous cancer treated
with traditional DMARD or biologic DMARD?
6.
Osteoporosis: Is osteoporosis related to disease activity and biomarkers? What is the effect of treatment on osteoporosis?7.
Depression: What is the prevalence of depression in patients with RA, PsA, or PsO? What are the risk factors for depression? What is the
effect of treatment on depression?
8.
What are the risks of CVD in patients with RA, PsA, and PsO, including the effect of
disease severity, disease duration, and comparison
with traditional CV risk factors?
Does the treatment of RA, PsA, and PsO with systemic agents have an effect on CV
outcomes?

26. CV risk prediction
1. Individuals with RA, PsA, and PsO have a greater risk of CVD than the general population.
The diseases themselves and traditional risk factors contribute to this risk. The risk of MI in
RA is comparable to that in DM. This should be recognized by healthcare providers and
patients.
2. Traditional modifiable risk factors should be screened for and managed appropriately to
reduce the risk of CVD in RA, PsA and Ps0 populations.
3. CS use should be minimized in RA, especially in patients with CV risk factors.
4. In patients with RA or PsA, especially those with additional CV risk factors, the risk and
benefits of NSAID use should be weighed.
5. Healthcare providers and patients should be aware that MTX and/or TNFi use may decrease
the risk of CVE in RA. Their use may help to reduce CS and NSAID use, especially in
patients with CV risk factors.
6. Healthcare providers and patients should be aware that MTX and/or TNFi use may decrease
the risk of CVD in PsA/Ps0.

27. CV risk prediction
EULAR (2010):
► Annual risk assessment for all RA patients using national guidelines
► Modification of Framingham or SCORE by applying a 1.5x modifier if:

28. CV risk prediction
EULAR (2010) - limitations:
o >10 year of disease activity
Evidence suggests accrual of cardiovascular risk prior to the first decade of disease
Underscores need for early awareness +/- intervention
o Addition of RF/anti-CCP criterion did not improve accuracy of CV risk prediction in
RA
o No clinical trials assessing validity

29. CV risk prediction
 Of RA-specific guidelines, only 5 recommended assessment of CV risk factors
EULAR, BSR, ACR, Spanish, NICE
 Of these, only EULAR and BSR recommended the use of a CV risk calculator
 EULAR was the only guideline which suggested an adjustment to a preexisting risk score
 Others suggested assessment and treatment of CV risk factors

30. CV risk prediction
Only EULAR guidelines formally recommended treating RA as a means of
decreasing CV risk
Lipid screening and monitoring were mentioned in a number of guidelines,
however no specific targets were suggested; advised to manage per national
guidelines

31. CV risk prediction
General population guidelines:
1/4 recognized RA as a factor for of CV risk
No guidelines recommended specific treatment targets in RA, but earlier screening was
recommended.

32. CV risk prediction
 NICE guidelines (2014):
 Modified to acknowledge RA and SLE as diseases that portend higher CV risk,
underestimated by current risk calculators
 No specific recommendations

34. RA/CV Quality Indicators
o 4 (!) extracted from over 16,000+ relevant papers:
I. Percentage of patients >18 years with RA on prolonged doses of prednisone
>10 mg daily with improvement or no change in disease activity,
documentation of GC management plan within 12 months (ACR 2008)
II. At least annual review of comorbidities, adverse events and risk factors related
to pharmacologic therapy (EUMUSC 2014)
III. Referral for exercise program (EUMUSC 2014)
IV. % with CV risk assessment using a CV risk assessment tool adjusted for RA in
the previous 13 months. (NICE 2012)

35. RA/CV Quality Indicators
• From this, has stemmed 11 Qls
• Process (over outcome):
"Communication of increased CV risk in RA: If a patient has RA, then the treating
rheumatologist should communicate to the primary care physician at least once within the
last 2 years that patients with RA have an increased CV risk."
"CV risk assessment: If a patient has RA, then a formal CV risk assessment according to
national guidelines should be done at least once in the first 2 years after evaluation by a
rheumatologist; and if low risk, it should be repeated once every 5 years; or if initial
assessment suggests intermediate or high risk, then treatment of risk factors according to
national posted guidelines should be recommended."

36. What can we do?
Quality indicators Quality improvement
Evidence to suggest that improvement in process measures has positive downstream
effects
 Explore:
 How we are doing?
 Where we can improve?
 What are the barriers to our improvement?
 Measure change in outcomes in our patients over time

37. Conclusion
Cardiovascular disease is the most important cause of morbidity and mortality in
patients with RA and other inflammatory/autoimmune diseases
This stems from traditional and additional risk factors
There is little - if any - guidance on how to best manage this important aspect of
our patients' care
Efforts at improving delivery of healthcare to the individual will require an
understanding of local practice to inform our management

38. Thank you