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Dr. Maureen McMahon Presents "“Heart Disease and Preventive Measures” at Lupus LA's Annual Patient Education Conference
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Dr. Maureen McMahon Presents "“Heart Disease and Preventive Measures” at Lupus LA's Annual Patient Education Conference

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June 2007

June 2007

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  • 1. Atherosclerosis in Systemic Lupus Erythematosus Maureen McMahon, MD, MCR Assistant Professor of Medicine David Geffen School of Medicine UCLA
  • 2. Overall Survival in Lupus has Improved Gabriel, S. et al., Arthritis Rheum 1999;42:46-50. 1950-1979 1980-1992
  • 3. Late Deaths in SLE are due to Heart Disease (Atherosclerosis) Abu-Shakra M, et al. J Rheum. 1995;22:1265–1270. [Evidence Level B]
  • 4. There is an Increased Risk for Atherosclerosis (ATH) in SLE CVA = cerebrovascular accident. Esdaile JM, et al. Arthritis Rheum . 2001;44:2331–2337 [Evidence Level B]; Karrar A, et al. Semin Arthritis Rheum . 2001;30:436–443 [Evidence Level C]; Manzi S, et al. Am J Epidemiol . 1997;145:408–415 [Evidence Level B]; Manzi S, et al. Arthritis Rheum . 1999;42:51–60. [Evidence Level B]
  • 5. Prevalence of ATH Plaque Among Control Subjects and Patients With SLE, According to Decade of Life Roman MJ, et. al. N Engl J Med . 2003;349:2399–2406. [Evidence Level B]  4th 5th 6th  7th Decade of Age P = .009 P = .01 P = .001 P = .08
  • 6. Why do SLE patients have an increased risk of Heart Disease?
  • 7. Patients with SLE Do Have Traditional Cardiac Risk Factors Petri et al. Medicine 1992
  • 8. Traditional Risk Factors Do Contribute to ATH in SLE % of patients with plaque, age adjusted p=0.05 p=0.0001 p=0.07 Maksimowicz-McKinnon et al. J Rheum 2006
  • 9. SLE Disease Activity Influences Standard Lipid Levels Posadas-Romero et al. Arthritis Rheum . 2004;50:160-165 .
  • 10. Influence of treatment on lipid levels in SLE
    • Steroid therapy is associated with
      • increased total cholesterol,
      • Increased VLDL
      • increased triglycerides
      • increased LDL
      • Increased insulin resistance
      • Increased risk of obesity
        • Ettinger Am J Med 1987;
  • 11. Prevalence and Risk Factors of Carotid Plaque in SLE
      • Independent predictors of increased ATH in SLE
      • (multivariate analysis)
        • Higher amount of damage (SLICC damage index)
        • Longer disease duration
        • Less use of cyclophosphamide (Cytoxan)
      • Predictors using univariate analysis
        • Presence of pulmonary hypertension
        • Older age
        • Less use of prednisone and hydroxychloroquine (Plaquenil)
        • Absence of antiphospholipid antibodies
        • Roman, et al., NEJM 2003;349:25.
  • 12.  
  • 13. Traditional Framingham Risk Factors Do Not Fully Explain Risk of ATH in SLE
    • Canadian cohort
      • 296 Patients
      • Even after controlling for age, sex, cholesterol, HTN, DM, tobacco use
        • 10 x Increased risk for nonfatal MI
        • 17 x Increased risk for death due to CAD
        • 8 x Increased risk for stroke
    Esdaile JM, et al. Arthritis Rheum . 2001;44:2331–2337. [Evidence Level B]
  • 14. Hypothesis
    • One study in non-SLE patients with ATH but no cardiac risk factors found that 90% had “Pro-Inflammatory HDL”, HDL with abnormal protective function
    Ansell et al. Circulation 2003 Could “Pro-Inflammatory HDL be a factor in SLE??
  • 15. LDL: the “Bad Cholesterol” LDL Mackness MI et al. Biochem J 1993. Lipids Online 2004 (Baylor) Blood Vessel White Blood Cells: Monocytes White Blood Cell: Macrophage HDL are anti-inflammatory Foam Cell HDL Remove “Bad Cholesterol” HDL Prevent Oxidation of LDL Oxidized LDL PLAQUE
  • 16. Pro-Inflammatory HDL Assay DCFH (chemical that turns green when oxidized) LDL Fluorescent Signal Patient HDL (normal) -- + Patient HDL (pro-inflammatory)
    • Values in the absence of test HDL are standardized to 1.0
    • “ Normal” Anti-Inflammatory HDL is defined as having a value <1.0
    • “ Pro-Inflammatory” HDL is defined as having a value >1.0
  • 17.  
  • 18. Populations of Women studied
    • Not taking medicines for cholesterol
    • 154 Women with SLE
    • 72 Control Subjects
    • 48 Female Rheumatoid Arthritis patients
  • 19. 45% of SLE patients have pro-inflammatory HDL
  • 20. Pro-inflammatory HDL may be associated with heart disease 4 patients with a history of heart attack were included (all patients had SLE): All 4 had pro-inflammatory HDL!
  • 21. Populations of Women studied
    • No history of statin use
    • 123 Women with SLE
    • 53 Control Subjects
    All subjects had blood drawn to measure HDL function All subjects had a carotid artery ultrasound to look for thickening of the arteries, or “plaque”
  • 22.  
  • 23. 86% of SLE patients with ATH have piHDL * Chi-squared or Fisher’s Exact
  • 24. Presence of piHDL Greatly Increases Risk for Carotid Plaque in SLE
    • Statistical Analysis was performed to take traditional cardiac risk factors into account (age, high blood pressure, diabetes, high cholesterol and current smoking)
    • After taking traditional risk factors into account, there was still increased ODDS FOR PLAQUE IN piHDL POSITIVE SLE = 8.8
  • 25. Summary
    • HDL are abnormal and “Pro-Inflammatory” in a
    • substantial proportion of patients with SLE and
    • RA.
    Pro-Inflammatory HDL are significantly associated with plaque on carotid ultrasound in women with SLE but not in healthy controls. Pro-Inflammatory HDL may be one marker that can be used to predict which patients are at risk for ATH
  • 26. Future Research Directions
    • Future: Develop risk profile including piHDL to predict levels of risk for accelerated ATH
    • Develop new treatments : Anti-oxidant peptides?
  • 27. What Can Lupus Patients Do to Decrease Their Risk of Heart Disease?
  • 28. Ways to Improve ATH Risk Factors Without Medications
    • Reduced intakes of saturated fat and cholesterol
    • Increased physical activity
    • Weight control
    • Stop smoking
  • 29. Control High Blood Pressure
    • Blood Pressure Targets should be
    • <130 mm/Hg systolic blood pressure
    • <80 mm/Hg diastolic blood pressure
    • Minimize salt intake
    • If borderline, may be helpful to have a home blood pressure cuff
  • 30. NIH CV Risk Calculator
  • 31. hp2010.nhlbihin.net/atpiii/ calculator .asp
  • 32.  
  • 33. Status of Statins in Rheumatic Diseases
    • RA : 116 patients treated 6 months with atorvastatin 40 mg qd
      • Disease activity score was significantly lower in statin group, P =.004 but small change (-0.5)
      • Markers of inflammation (ESR, CRP) lower in patients taking statins
    McCarey et al. Lancet . 2004;363:2015-2021
  • 34. Statins in SLE
    • LAPS trial: RCT of Atorvastatin 40 mg vs. placebo in 200 SLE patients, followed for 2 years
      •  No effect on coronary calcium progression
      • No significant improvement in disease activity
      •  No significant difference in mean artery thickness (IMT) change, although there was a significant difference in the proportion of patients in whom IMT improved, stayed the same, or got worse, favoring atorvastatin
    • Further long-term studies need to be performed; for now, treat according to NCEP guidelines
    Petri et al., Arthritis Rheum 2006; 54: suppl 1246
  • 35. Summary of Statins in Rheumatology Practice
    • Statins have the expected effects on lipid levels
    • They lower markers of inflammation (ESR and CRP)
    • Effects on disease activity in RA and SLE are not large in doses and preparation studied to date.
    • They lower piHDL but not to normal
  • 36. Antimalarial Drugs and Heart disease in SLE
    • Antimalarial drugs may have a beneficial effect on lipid profiles in SLE
      • Compare 160 patients on stable dosage prednisone (mean, 9.7 mg/d) with 180 patients on stable prednisone dosage (mean, 10.2 mg/d) and antimalarial
      • Antimalarial patients had 11% reduction in TC when compared with patients on prednisone alone ( P <.01)
    Rahman P, et al. J Rheum . 1999;26:325–330. [Evidence Level B]
  • 37. Hydroxychloroquine in SLE
    • Patients treated with hydroxychloroquine were nearly half as likely to increase overall damage from lupus compared to patients not taking the drug.
    • Possible decrease in risk of thrombosis may also contribute to decreased risk of ATH
    • Patients treated with hydroxychloroquine were less likely to have plaque on carotid US
    Fessler BJ et al. , Arth Rheum 05; Ho KT et al. , Rheumatol 2005; Rahman et al., J Rheum 1999.; Roman et al NEJM 2003
  • 38. Conclusions
    • Risk of atherosclerotic disease is increased in SLE
      • Likely multifactorial
      • Combination of traditional, disease-related risk factors
    • Low threshold to get screened for ATH
    • Minimize Traditional risk factors
      • BP control
      • Diet
      • Exercise
      • Control High Cholesterol
  • 39. If you or a friend are interested in participating in the carotid ultrasound /piHDL study:
    • Contact study coordinator at: 310-825-6452
    • Or email Dr. McMahon:
    • [email_address]
  • 40. Acknowledgements UCLA Rheumatology Bevra Hahn, M.D. Christina Charles, M.D. Jennifer Grossman, M.D. John FitzGerald, M.D., Ph.D. Weiling Chen, M.S. UCLA Cardiology Alan Fogelman, M.D. Mohamad Navab, Ph.D. Cedars-Sinai Medical Center Daniel Wallace, M.D. Michael Weisman, M.D. UCLA Radiology Nagesh Ragavendra, M.D. Funding Organizations Lupus Research Institute Alliance for Lupus Research The Arthritis Foundation