Cardiovascular Disease in Lupus: The Impact a Pediatrician - PowerPoint Presentation

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Cardiovascular Disease in Lupus: The Impact a Pediatrician Can Have

Christina McConnell, PGY-3Slide2

Which of the following is NOT one of the diagnostic criteria for lupus?

Biopsy proven lupus nephritis with a positive ANA

Hemolytic anemia

Psychosis

Single joint swelling

None of the above. Slide3

Which of the following is true of cardiovascular risk factor screening in lupus?

There are established guidelines for how often to screen for dyslipidemia.

Screening is always performed by the rheumatologist.

Risk factors to screen for include BMI, blood pressure, hyperlipidemia and fasting glucose

Screening for dyslipidemia in adult patients is routine and intervention is promptly initiated.Slide4

Which of the following was an outcome of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) study?

Atorvastatin decreased the mean-mean common carotid intima-media thickening (CIMT).

Atorvastatin is associated with serious side effects in children.

The atorvastatin group achieved lower total cholesterol levels compared to the placebo group.

There was no difference between placebo and treatment group in the CIMT across all CIMT outcomes.Slide5

You are seeing a 12yo AAF for well child check. You review her recent hospital admission and see that she was diagnosed with lupus. She is not scheduled to see a rheumatologist for 2 months. Which of the following labs should you obtain at this visit?

Vitamin D

Fasting lipid profile

ESR

Urinalysis with urine culture

1 & 2Slide6

Disclosures

Dr. Harmon and I have no financial disclosuresSlide7

Objectives

Be able to identify clinical manifestations of lupus and the criteria for diagnosis

Discuss the association of lupus and increased cardiovascular risk factors

Review the role of the general pediatrician in screening and treatment of cardiovascular risk factors Slide8

Case Presentation

You are seeing a 16yo AAF for joint pain. When reviewing her chart you notice that she has been seen multiple times over the past 3 months for complaints including fatigue and lymphadenopathy. Outpatient lab work reveals the following:

CBC: WBC 10,000/ Hemoglobin 9.8/ Platelets 350,000

EBV and CMV titers negative

CMP unremarkable

On exam, her vital signs are

stable and she

is well appearing. Exam is remarkable for cervical lymphadenopathy, malar rash, oral ulcers, a painful papular rash on her palms, and swelling of both of her knees. Slide9

What is lupus?

Chronic systemic autoimmune disorder

Etiology

?

Antibody production→ Immune complex formation→ Inflammation and ischemiaSlide10

Epidemiology

Prevalence is 25 cases per 100,000 children

Average age of onset is 12 years old

Female predominance

M:F ratio is 1:3 before puberty; M:F ratio is 1:9 after puberty

10% have a 1st degree relative who is affected

The 5 to 10 year survival rate is greater than 85%Slide11
Slide12

Health Care Cost

Chronic disease= chronic health care

cost

Garris

et alUnadjusted

health care cost per patient= $

30,000 over 2 year period

Average

cost per flare was between $900 and $1700 depending on disease severity

No studies looking at health care cost in pediatricsSlide13

Clinical Manifestations

Presentation is diverse

Commonly presents with vague systemic symptomsSlide14
Slide15

American College of Rheumatology Criteria

Malar rash

Discoid rash

Photosensitivity

Oral ulcers

Nonerosive arthritis

Pleuritis or Pericarditis

Renal disease

Neurologic involvement

Hematologic disorder

Immunologic disorder

Anti-DNA

Anti-Sm

Antiphospholipid Abs

Antiphospholipid antibody

Clinical Criteria

Lab Criteria

In general, you must have at least 4 criteria to establish diagnosis

**Exception= Biopsy proven lupus nephritisSlide16

Mucocutaneous Findings & Nonerosive ArthritisSlide17
Slide18

Hematologic FindingsSlide19

CNS Disease and Immunologic Labs

CNS involvement more prevalent in pediatric disease

Immune labs include:

ANA

Anti-DNAAnti-Smith

Antiphospholipid antibodiesSlide20

Back to the Case

After seeing the patient, you are suspicious that she may have lupus.

You obtain a repeat CBC, urinalysis, ANA, and Anti-Smith.

CBC: WBC 9,000/Hemoglobin 9.2/ Platelet 275,000

UA: >300 protein+ ANA and Anti-Smith

Based on her history, physical exam, and lab work you diagnose her with lupus. You speak with the rheumatologist who

agrees.Slide21

Pediatric Rheumatologist Demand>Supply

*The United States Rheumatology Workforce. Deal, et al.Slide22
Slide23

Preventative Health in Lupus

Immunization status

Pneumococcal, Meningococcal, Flu

Mental health

Depression and Non-compliance

Reproductive Health

Contraceptives

Fertility preservationSlide24

Cardiovascular Disease in Lupus

Cardiovascular disease is the number one cause of death in patients affected by lupus for greater than 5 years

Risk of MI is up to 50-fold higher in

women

10 % of lupus patients will have major cardiovascular event by the age of 34Slide25

Cardiovascular Disease in Pediatric Lupus

Asymptomatic abnormalities in myocardial perfusion in patients as young as 11 years old

Perfusion defect in 16% of

patients

1 large perfusion defect at both stress and rest

Case reports of pediatric myocardial infarctionSlide26

Progression of AtherosclerosisSlide27

Traditional risk factors

Obesity

Hypercholesterolemia

Diabetes

Hypertension

SmokingSlide28

Dyslipidemia in Pediatric LupusSlide29

Intrinsic non traditional risk factors

*** Lupus is known to be an independent risk factor for development of atherosclerosis***

Dyslipidemia in Lupus

Cytokines

Antiphospholipid Abs

Oxidized LDL

Renal disease

HomocysteineSlide30

Intrinsic non traditional risk factors

Cytokines

TNF-𝛼

Homocysteine

Degree of renal disease Increased susceptibility of LDL to be oxidized

Antiphospholipid

antibodiesSlide31

Iatrogenic Non traditional risk factors

Steroid use

Fine line between control of underlying disease and risk of chronic steroid use

Cyclosporine

Reduced risk when used with tacrolimus

Beta blockers

Anticonvulsants - carbamazepine and phenytoin

Hydroxychloroquine IMPROVES lipid profilesSlide32

Cardiovascular Screening

While there are established guidelines for screening in healthy children, there is limited data for children with diseases associated with increased risk of accelerated atherosclerosis

AAP recommendations:

Universal dyslipidemia screening for children between 9-11 years old and 17-19 years oldSlide33

Dyslipidemia ScreeningSlide34

Who is responsible for screening?

Varies depending on resources

Chart review of adult patients showed only 31% of had lipid

screening

Of the ones with hyperlipidemia, only 36% had a documented response to the hyperlipidemia at subsequent visitsSlide35

Screening for Other CVD Risk Factor

Body mass Index

Blood Pressure

Fasting Glucose

A1CSlide36

Case presentation The patient is back in the office for follow-up since her diagnosis of lupus. You review her growth curve and see that her height is at the 50

th

percentile and her BMI is at the 95

th percentile. Her BP for todays visit is 105/60.You review her FH and discover that her mother has hypertension and had a heart cath

1 year ago due to chest pain. She was 50 years old at the time.Because you are aware of increased cardiovascular disease in lupus patients, you obtain a fasting glucose, A1C, and lipid panel. *Glucose = 80 *A1C = 5.0 *LDL=90 *TGs=70Slide37
Slide38

The Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents Full ReportSlide39

The Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents Full ReportSlide40

Management: Diet

American Heart Association Therapeutic Lifestyle Changes diet

Less than 7 percent of your daily calories from saturated fat

Less than 200 mg a day of cholesterol

25–35 percent of daily calories from total fat (includes saturated fat calories)

Diet options you can use for more LDL lowering • 2 grams per day of plant stanols or sterols • 10–25 grams per day of soluble fiber Slide41

Management: Exercise

Modifiable risk factor

The AAP recommendation for children older than 6 years is at least 60 minutes of active play per day

Improves traditional risk facotrs

Lower exerise tolerance at baseline

Aerobic exercise is safe Slide42

Management: Hydroxychloroquine

Antimalarial drug

Widely used in management of lupus

In patients also taking steroids, showed significant reduction in total cholesterol, LDL, and TGs and signficant increase in HDL.

Effect on atherosclerosis not well studied Slide43

Back to the officeRemember that at our patients last visit, her BMI was above desired levels.

2 months later, she is excited to tell you about the dance team she has joined. Her BMI is still higher than goal, but has come down to the 93

rd

percentile. Mom has been doing some research and ask you if there are treatment options to decrease her risk of cardiovascular disease?Slide44

Atherosclerosis Prevention in Pediatric Lupus Erythematosus Study

Aim was to determine efficacy and safety of statins in preventing subclinical atherosclerosis

Randomized double-blind, placebo controlled Slide45

Primary and Secondary endpoints

Primary end point

Progression of mean-mean common carotid intima-media thickening

Secondary

end points

Other

segment carotid intima-media thickening

Lipid profile

CRP level

Disease activity

Damage

outcomesSlide46

Intima Media

T

hicknessSlide47

Methods

221 participants

10-21 years old

Randomized to Atorvastatin or placebo

Also received routine lupus management

Followed every 3 months x 36

months

Atorvastatin and placebo provided by PfizerSlide48

Imaging

Ultrasound images from 3 arterial segments

Common carotid

Carotid bifurcation

Proximal 10mmg of internal carotid artery

Total of 12 intima media measurements which were each imaged from 4 angles

Mean-max CIMT & mean-mean CIMT calculatedSlide49

Results

Defined clinically significant change as a 0.0045mm/year difference

Mean-mean common CIMT progression was not significantly different between atorvastatin and placebo groups for the primary outcome

Secondary endpoint of mean-max CIMT did not reach clinical significance

Other carotid intima secondary end points did show lower progression rates in the atorvastatin group.Slide50
Slide51
Slide52

Limitations

The primary end point was calculated off of adult studies

Medication provided by Pfizer

Excluded

patients who may have benefited the most from a statinNo standardized routine care, although medication recommendations were madeSlide53

Vitamin D

Role in atherosclerosis is not well characterized

Vitamin D deficiency in this patient population is multifactorial

Goal >30ng/mL

Further studies are neededSlide54

Summary

Shift in focus from short term outcomes to prevention and management of long term

complications has opened the door for primary care involvement

Cardiovascular disease is becoming a more recognized cause of morbidity and mortality

Screening and treatment of cardiovascular risk factors is key, but further studies are necessary to help guide our management Slide55

Which of the following is NOT one of the diagnostic criteria for lupus?

Biopsy proven lupus nephritis with a positive ANA

Hemolytic anemia

Psychosis

Single joint swelling

None of the above. Slide56

Which of the following is true of cardiovascular risk factor screening in lupus?

There are established guidelines for how often to screen for dyslipidemia.

Screening is always performed by the rheumatologist.

Risk factors to screen for include BMI, blood pressure, hyperlipidemia and fasting glucose

Screening for dyslipidemia in adult patients is routine and intervention is promptly initiated.Slide57

Which of the following was an outcome of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) study?

Atorvastatin decreased the mean-mean common carotid intima-media thickening (CIMT).

Atorvastatin is associated with serious side effects in children.

The atorvastatin group achieved lower total cholesterol levels compared to the placebo group.

There was no difference between placebo and treatment group in the CIMT across all CIMT outcomes.Slide58

You are seeing a 12yo AAF for well child check. You review her recent hospital admission and see that she was diagnosed with lupus. She is not scheduled to see a rheumatologist for 2 months. Which of the following labs should you obtain at this visit?

Vitamin D

Fasting lipid profile

ESR

Urinalysis with urine culture

1 & 2Slide59

Thank you to Dr. Natasha Ruth and Dr. Jim Oates from MUSC for their help!Slide60

References

Weiss, J. (2012). Pediatric Systemic Lupus Erythematosus: More Than a Positive Antinuclear Antibody.

Pediatrics in Review,

62-74.

Kliegman, R. (2006). Nelson essentials of pediatrics (5th ed.). Philadelphia, PA.: Elsevier Saunders.

ACR-endorsed Criteria for Rheumatic Diseases. (

n.d.

). Retrieved November 1, 2015, from http://www.rheumatology.org/Practice-Quality/Clinical-Support/Criteria/ACR-Endorsed-Criteria

Deal, C., Hooker, R., Harrington, T., Birnbaum, N., Hogan, P.,

Bouchery

, E., Barr, W. (

n.d.

). The United States rheumatology workforce: Supply and demand, 2005–2025.

Arthritis Rheum Arthritis & Rheumatism,

722-729.

The Pediatric Rheumatology Workforce: A Study of the Supply and Demand for Pediatric Rheumatologists. Department of Health & Human Services Health Resources and Service Administration Bureau of Health Professions February 2007.

Priority: Increase Access to Pediatric Rheumatologists. (

n.d.

). Retrieved November 1, 2015, from http://www.arthritis.org/advocate/our-policy-priorities/increase-access-to-pediatric-rheumatologists.php

Manzi

, S.,

Meilahn

, E.,

Rairie

, J., Conte, C.,

Medsger

, T., Jansen-

Mcwilliams

, L., ...

Kuller

, L. (1997). Age-specific Incidence Rates of Myocardial Infarction and Angina in Women with Systemic Lupus Erythematosus: Comparison with the Framingham Study.

American Journal of Epidemiology,

408-415.

Gazarian

, M., Feldman, B., Benson, L.,

Gilday

, D., Laxer, R., & Silverman, E. (

n.d.

). Assessment of myocardial perfusion and function in childhood systemic lupus erythematosus.

The Journal of Pediatrics,

109-116.

Ardoin

, S.,

Sandborg

, C., &

Schanberg

, L. (2007). Review: Management of dyslipidemia in children and adolescents with systemic lupus erythematosus.

Lupus,

618-626.

Robinson, A.,

Tangpricha

, V., Yow, E.,

Gurion

, R.,

Schanberg

, L., &

Mccomsey

, G. (

n.d.

). A31: Vitamin D Status is a Determinant of the Effect of Atorvastatin on Carotid Intima Medial Thickening Progression Rate in Children with Lupus: An Atherosclerosis Prevention in Pediatric Lupus Erythematosus

Substudy

.

Arthritis & Rheumatology

. Slide61

References

Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Full Report. (

n.d.

). PsycEXTRA Dataset.

Lichtenstein, A. (2006). Diet and Lifestyle Recommendations Revision 2006: A Scientific Statement From the American Heart Association Nutrition Committee. Circulation, 82-96. Image Source: Color Atlas of Pediatric Dermatology. Samuel Weinberg, Neil S. Prose, Leonard KristalCopyright

2008, 1998, 1990, 1975, by the McGraw-Hill Companies, Inc

.

Ruiz-

Irastorza

, G., Ramos-Casals, M., Brito-

Zeron

, P., &

Khamashta

, M. (2008). Clinical efficacy and side effects of

antimalarials

in systemic lupus erythematosus: A systematic review.

Annals of the Rheumatic Diseases,

20-28

.

Urowitz

et al. Atherosclerotic

Vascular Events in a Single Large Lupus Cohort: Prevalence and Risk Factors

. Journal of Rheumatology 2007; 34:1.

Garris

, C.,

Jhingran

, P., Bass, D., Engel-

Nitz

, N., Riedel, A., & Dennis, G. (

n.d.

). Healthcare utilization and cost of systemic lupus erythematosus in a US managed care health plan. 

Journal of Medical Economics,

 667-677

.

Elliott, J., &

Manzi

, S. (

n.d.

). Cardiovascular risk assessment and treatment in systemic lupus erythematosus. 

Best Practice & Research Clinical Rheumatology,

 481-494

.

Al-

Herz, et al. Cardiovascular risk factor screening in systemic lupus erythematosus. Journal of Rheumatology. 2003. 30: 493-496.Slide62

GO TIGERS!!!!Slide63

Thank you!