Lupus and cardiovascular disease


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Lupus and cardiovascular disease

  1. 1. Systemic Lupus and Cardiovascular Disease A Brief Overview Mark A. Menegus, MD, FACC, FSCAI October 2010 Disclosures--none
  2. 2. ACR Criteria for Lupus* <ul><li>Malar Rash </li></ul><ul><li>Discoid Rash </li></ul><ul><li>Photosensitivity </li></ul><ul><li>Oral Ulcers </li></ul><ul><li>Arthritis </li></ul><ul><li>Serositis (pericard.-pleura) </li></ul><ul><li>Renal Disorder: (eg proteinuria) </li></ul><ul><li>Neuro Disorder: (seizures/psychosis) </li></ul><ul><li>Heme Disorder: (low platelets, etc) </li></ul><ul><li>Immunologic Disorder (AntiDS DNA; Anti Sm; APL Ab) </li></ul><ul><li>+ Antinuclear Ab (ANA) </li></ul>4 required to include in SLE cohort * These are NOT Diagnostic Criteria
  3. 3. Lupus
  4. 4. Lupus and Inflammation <ul><li>SLE is a chronic, inflammatory disease with circulating Autoantibodies (“anti-self”); activated T cells (tissue autoimmunity); immune complexes (Antigen-Antibody) and inflammatory Cytokines (cell messenger proteins) </li></ul><ul><li>Lupus Therapy over the last 4 decades has converted a rapidly fatal disease into a chronic condition </li></ul>
  5. 5. Cardiac Involvement in Lupus <ul><li>All “layers” of the heart can be involved: </li></ul><ul><li>Pericardium </li></ul><ul><li>Myocardium </li></ul><ul><li>Valves </li></ul><ul><li>Conducting System </li></ul><ul><li>Coronary Vessels </li></ul>
  6. 6. Pericardium <ul><li>The thin layer(s) covering the heart </li></ul><ul><li>Inflammation (Pericarditis) occurs in 11-54% of Lupus patients </li></ul><ul><li>Often occurs at Onset or with Relapses </li></ul><ul><li>Pericarditis is the most characteristic feature and is one of the ACR/ARA Classification Criteria for Lupus </li></ul><ul><li>Treated with NSAIDs or Steroids </li></ul>A. Doria; Lupus; 14; 2005
  7. 7. Pericardium and Pleura
  8. 8. Myocardium <ul><li>The active muscle (“pump”) of the heart </li></ul><ul><li>Inflammation (“Myocarditis”) occurs in 7-10% of cases (and is treated with Steroids) </li></ul><ul><li>Myocardial Dysfunction , however, is more commonly due to early coronary artery disease, hypertension, renal failure, valvular disease </li></ul>Doria; Lupus; 2005
  9. 9. Myocardium and Valves
  10. 10. Cardiac Valves <ul><li>Connective Tissues that control blood flow into and out of the heart </li></ul><ul><li>Inflammatory lesions usually on Mitral or Aortic Valves (both active and healed) </li></ul><ul><li>Some thickening seen in 40-50% of Echos </li></ul><ul><li>“ Verrucous” or Libman-Sacks lesions characteristic but not usual </li></ul><ul><li>Significant clinical valve pathology is unusual (leaking or narrowing) </li></ul>Doria; Lupus; 2005
  11. 11. Focal Mitral Valve Thickening (51 year-old Lupus patient) Farzaneh-Far; ArthritisRheum; Dec 2006
  12. 12. Conducting System <ul><li>Carries the electrical impulses from the heart’s “pacemaker” (Sinus Node) in the atria (top chambers) thru the Atrioventricular Node to the ventricular (pump) muscles (lower chambers) </li></ul><ul><li>Conduction “Block” rare in adults </li></ul><ul><li>Seen in 2% of children born to mothers with Anti-Ro/SSA positive Lupus </li></ul>Doria; Lupus; 2005
  13. 13. Coronary Arteries <ul><li>Larger (surface) and smaller (myocardial) vessels that supply the working muscle of the heart </li></ul><ul><li>Coronary Artery Disease in 6-10%; Lupus patients have a 4-8 fold increased risk of developing CAD </li></ul><ul><li>Smaller vessel inflammation ( vasculitis )-usually in younger patients with active SLE </li></ul><ul><li>Larger vessel inflammation ( atherosclerosis )-usually in older patients with long-standing SLE </li></ul>Doria; Lupus; 2005
  14. 14. Coronary Artery Stenoses (Atherosclerosis)
  15. 15. Acute Coronary Thrombosis
  16. 16. Definitions: <ul><li>ACS : Acute Coronary Syndrome, ie chest pain with/without blood enzyme elevation </li></ul><ul><li>MI : Myocardial Infarction—”heart attack” </li></ul><ul><li>PCI : Percutaneous Coronary Intervention, ie angioplasty/stent placement </li></ul><ul><li>CABG : Coronary Artery Bypass Grafting, ie open heart bypass surgery </li></ul>
  17. 17. Vascular Disease in Lupus <ul><li>Prevalence of M.I., Angina and Peripheral Vascular Disease in Lupus Cohorts: </li></ul><ul><li>Toronto Lupus Cohort = 10% </li></ul><ul><li>Baltimore Cohort = 8.3% </li></ul><ul><li>Pittsburgh Cohort = 6.7% </li></ul><ul><li>Mean Age at 1 st “Event” was 48-49 years old </li></ul><ul><li>Frequently affected: Pre-menopausal Women </li></ul>Bruce I; Rheum. Dis. Clinics North America 26; 2 May 2000
  18. 18. Cohort Commonality <ul><li>The Toronto, Baltimore and Pittsburgh Lupus Cohorts each had clinical predictors for early Coronary Heart Disease. </li></ul><ul><li>The Three Cohorts all shared two common </li></ul><ul><li>features: a. Older Age at Diagnosis of SLE </li></ul><ul><li> b. Dyslipidemia (high cholesterol) </li></ul>Bruce, I.; Rheum.Dis.Clinics North Amer.; 26; 2 May 2000
  19. 19. Vascular Disease and Lupus Hahn,B; NEJM; Dec 18, 2003
  20. 20. Inflammation and Vascular Disease <ul><li>Atherosclerosis is also a chronic inflammatory disorder, with characteristic Cellular (monocyte-macrophage) and Circulating (C-reactive protein-”CRP”) </li></ul><ul><li>40% of Lupus patients ages 40-45 have established Carotid Artery Plaque </li></ul><ul><li>Later mortality in SLE is more frequently due to Atherosclerosis—aggressive risk reduction is essential. </li></ul>Salmon; Curr.Opin.Rheum; 13(5) Sept 2001
  21. 21. Carotid Plaque and Lupus <ul><li>197 registry patients from H.S.S.-NYC </li></ul><ul><li>Well matched to controls by age, sex, BP and race </li></ul><ul><li>Carotid Ultrasound (focal protrusion > 50% of wall thickness= Plaque) </li></ul><ul><li>Cardiac Echo to examine valve thickening </li></ul><ul><li>Measured hs-CRP and routine serology </li></ul>Roman, M: NEJM; 349: Dec 18, 2003
  22. 22. Carotid Ultrasound-I.M.T.
  23. 23. Carotid Plaque and Lupus Roman; NEJM; 2003
  24. 24. Carotid Ultrasound-Plaque
  25. 25. Carotid Plaque and Lupus Roman; NEJM; 2003
  26. 26. Coronary Calcium and Lupus <ul><li>65 lupus patients (85% female; avg 40 yo) </li></ul><ul><li>69 age, sex, race-matched controls </li></ul><ul><li>Excluded prior history vascular disease (stroke, MI, angina) </li></ul><ul><li>Assessed SLEDAI and SLE Damage Scores </li></ul><ul><li>Measured degree (score) of Coronary Calcium on EBCT scan </li></ul>Asanuma,Y; NEJM; 349; Dec 18 2003
  27. 27. Coronary Calcium and Lupus Asanuma; NEJM; Dec 18, 2003 * * *
  28. 28. Calcified and Non-Calcified Coronary Plaque Kiani, A; J.Rheumatology;37: 579; 2010
  29. 29. Coronary Calcium and Lupus Asanuma; NEJM; Dec 18, 2003
  30. 32. Summary-Vascular Disease and Lupus <ul><li>Odds ratio for Atherosclerosis in SLE patients= 4.8 in Roman’s study </li></ul><ul><li> 9.8 in Asanuma’s study </li></ul><ul><li>Neither found significant correlation with inflammatory markers (CRP, etc) </li></ul><ul><li>Both found less disease in patients with greater use of steroids or chloroquine </li></ul><ul><li>Traditional risk factors are often under-treated in the SLE population </li></ul>Hahn, B; NEJM; Dec 18, 2003
  31. 33. Framingham Risk Assessment <ul><li>Ongoing study of Cardiovascular Risk in a US cohort; study inception in 1940’s </li></ul><ul><li>Allows calculation of Expected 10 year risk of developing Coronary Disease </li></ul><ul><li>Factors in: </li></ul><ul><li>Age/Sex Diabetes </li></ul><ul><li>Blood Pressure LV Hypertrophy </li></ul><ul><li>Smoking </li></ul><ul><li>Cholesterol </li></ul>
  32. 34. Lupus-Beyond Framingham <ul><li>296 Canadian and Parisian Lupus patients </li></ul><ul><li>Excluded 33 with prior Vascular Event </li></ul><ul><li>Tabulated vascular outcomes (non-fatal MI, fatal Coronary event or Stroke) over 8.6 years </li></ul><ul><li>Compared these to the “expected” outcome rates by traditional Framingham risk assessment. </li></ul><ul><li>Observed events far exceeded expected events in this lupus cohort (note: retrospective study) </li></ul>Esdaile; Arthrit.Rheum.;44; Oct. 2001
  33. 35. Beyond Framingham Esdaile; Arthritis.Rheumat; 44; Oct. 2001
  34. 36. Myocardial Perfusion (Blood Flow) Imaging
  35. 37. Perfusion Imaging in Asymptomatic Lupus Patients* Nikpour, M; J. Rheumatology; 36: 2009 * f/u for 8.7 years
  36. 39. Statins and Vasodilation in SLE <ul><li>64 women with SLE (avg age 31) rec’d Atovastatin 20mg x 8 weeks </li></ul><ul><li>24 women with SLE (avg age 34) rec’d Placebo x 8 weeks </li></ul><ul><li>16 healthy female controls </li></ul><ul><li>Baseline and 8 week analysis: Brachial Artery Ultrasound with BP cuff “reactive hyperemia” –artery diameter and flow </li></ul>G.Ferreira; Rheumatology 46; 1560; 2007
  37. 40. Flow-Mediated Dilation (%) STATIN PLACEBO Ferreira; Rheumatology 2007
  38. 41. Atorvastatin and Vasodilation <ul><li>At 8 weeks of active treatment, Total and LDL Cholesterol and TG all decreased* </li></ul><ul><li>Resting Diameter and Flow-Mediated dilation of Brachial Artery increased* </li></ul><ul><li>SLEDAI scores decreased (4.47 to 3.08)* but not in the Placebo group </li></ul><ul><li>Short-term Statin Therapy improved Endothelial function in SLE patients </li></ul>Ferreira; Rheumatology; 2007 * Indicates statistical significance
  39. 42. Clinical Trials of Statins in Lupus <ul><li>10 Trials registered with the NIH </li></ul><ul><li>4 are recruiting </li></ul><ul><li>4 are completed </li></ul><ul><li>1 not recruiting; 1 is terminated </li></ul><ul><li>Trials using either Atorvastatin or Rosuvastatin </li></ul><ul><li>End-points: ↓ Coronary Calcium; ↓ Carotid Disease; ↓ SLEDAI score, etc </li></ul><ul><li>To Date: no published results by my search </li></ul>
  40. 43. Vascular Health and Disease Moreno, P; JACC; 53 Nov 25, 2009
  41. 44. Therapy: Post MI / Post ACS <ul><li>A—Aspirin and ACE Inhibitors (the “prils”) </li></ul><ul><li>B—Beta Blockers and Blood Pressure </li></ul><ul><li>C—Cholesterol / Cigarettes / Clopidogrel </li></ul><ul><li>D—Diet (for Weight and Diabetes) </li></ul><ul><li>E—Exercise and Education </li></ul><ul><li>Conti, CR Clin. Cardiology 2007 </li></ul>
  42. 45. Aspirin <ul><li>“ Class I” for all CAD, MI and PVD patients </li></ul><ul><li>325 mg/day initially; 81-162mg/d long term </li></ul><ul><li>Post MI: 35 vascular events prevented per 1000 patients x 30d </li></ul><ul><li>1 life saved at cost of $13 per year! </li></ul><ul><li>ASA allergic?—can use Clopidogrel (Plavix) </li></ul>
  43. 46. Angiotensin Converting Enzyme (ACE) Inhibitors (the “prils”) <ul><li>For post MI; overt CHF and Heart (LV) dysfunction even without symptoms </li></ul><ul><li>HOPE trial: 25% women; had 22-25% decline in death rates in MI/CAD/Diabetic patients without CHF </li></ul><ul><li>ex: Lisinopril 10-40 mg/d </li></ul><ul><li>If ACE intolerant (allergy or dry cough) use and ARB (ex: Losartan) </li></ul>
  44. 47. Lipid Lowering <ul><li>13-33 death/Mi prevented per 1000 patients x 5 yr </li></ul><ul><li>Measure lipids on initial blood draw </li></ul><ul><li>Start Rx acutely—statins are Anti-Inflammatory (ex: Atorvastatin 10-80/d) </li></ul><ul><li>Muscle : usually Myalgias—check CPK; rechallenge or use different statin (pravastatin) </li></ul><ul><li>Liver : about 1/1000 asymptomatic mild elevation in liver enzymes </li></ul>
  45. 48. NCEP-ATP III Guidelines <ul><li>Total Cholesterol </li></ul><ul><li>< 200 desirable </li></ul><ul><li>200-239 borderline high </li></ul><ul><li>> 240 high </li></ul>
  46. 49. NCEP-ATP III Guidelines <ul><li>LDL </li></ul><ul><ul><li><100 optimal </li></ul></ul><ul><ul><li>100-129 near-opt. </li></ul></ul><ul><ul><li>130-159 borderline high </li></ul></ul><ul><ul><li>160-189 high </li></ul></ul><ul><ul><li>>190 very high </li></ul></ul>
  47. 50. Risk Factors (that modify LDL goal) <ul><li>Smoking </li></ul><ul><li>High BP </li></ul><ul><li>Low HDL (< 40) </li></ul><ul><li>Family history CAD </li></ul><ul><li>Central Obesity </li></ul><ul><li>Physical Inactivity </li></ul><ul><li>NOTE: Diabetes, PVD, Aortic Aneurysm and Coronary Calcium are CHD “Equivalents ” </li></ul>
  48. 51. LDL Goals < 10% <160 mg/dl 0-1 Risk Factors 10-20% < 130 mg/dl 2 or more Risk Factors > 20% < 100 mg/dl CHD or Equivalent 10 year event rate LDL Goal Risk Factor
  49. 52. Framingham Risk: 10 vs 30 year (25 yo female) Pencina, M; Circulation; 119; 2009
  50. 53. Framingham Risk: 10 vs 30 year (45 yo female) Pencina, M; Circulation; 119; 2009
  51. 54. Therapy = “T.L.C.” (Therapeutic Lifestyle Change) <ul><li>Decrease Saturated Fat in diet </li></ul><ul><li>Decrease Weight (ideal BMI = 18.5 to 24.9 kg/m2) </li></ul><ul><li>Increase Physical Activity—even walking 30 min day </li></ul>
  52. 55. Incorporating Triglycerides into the Mix <ul><li>The typical “Lupus” Lipid profile often has low HDL (“good” cholesterol), elevated Triglycerides and elevated levels of Lp(a) (a lipoprotein that ties into the clotting cascade) </li></ul><ul><li>This profile is similar to the average patient with Diabetes </li></ul><ul><li>Calculation of “Non-HDL” Cholesterol allows us to set goals with TG as well </li></ul><ul><li>Lp(a) may be modifiable with exercise and Niacin </li></ul>
  53. 56. Incorporating Triglycerides (Total Chol – HDL = “Non HDL” ) <190 <160 0-1 risk factors <160 <130 2 or more risk factors <130 <100 CHD or equiv. Non-HDL Goal LDL Goal Risk
  54. 57. Lipid Lowering, cont’d <ul><li>High Total and LDL Cholest  Statins </li></ul><ul><li>(zocor, lipitor,etc) </li></ul><ul><li>High Trig and Low HDL Cholest  Fibrates (lopid, tricor) </li></ul><ul><li>High LDL and Trig and low HDL Cholest  Niacin (niaspan) </li></ul><ul><li>High Triglycerides  prescript. Fish oil ( Omega 3 FAs) (lovaza) </li></ul>
  55. 58. Diet Modification: Healthy Choices <ul><li>Fruits and Vegetables </li></ul><ul><li>Whole Grain and High Fiber </li></ul><ul><li>Oily (cold water) fish 2 x / week </li></ul><ul><li>Alcoholic drink not > 1/day </li></ul><ul><li>Sodium (Na+) < 2.3 gram/day </li></ul><ul><li>Saturated Fat < 10% of total calories </li></ul><ul><li>Limit Trans-Fat: Baked Goods and Fried Foods </li></ul>
  56. 59. Hormone Therapy <ul><li>Estrogen Replacement with or w/o Progestin—of no benefit in preventing CHD </li></ul><ul><li>Small but increased risk of Stoke </li></ul><ul><li>Use short term for peri-menopausal Sx only </li></ul><ul><li>Estrogen receptor modulators (raloxifene) of no benefit for CHD. </li></ul>
  57. 60. Cardiac (Exercise) Rehab <ul><li>Prevents 23 deaths per 1000 patients </li></ul><ul><li>Safety: Mortality 1 / 784,000 pt-hours </li></ul><ul><li>Cost: $1200 / QOL-year (comparable to Left main surgery!) By comparison, Dialysis costs $40,000 / QOL-yr </li></ul><ul><li>Usually 3 x /week for 12-16 weeks </li></ul><ul><li>YET-- < 20% of patients get referred?? </li></ul>
  58. 61. Smoking Cessation <ul><li>Smokers have 3 x the risk of MI of non-smokers </li></ul><ul><li>Cessation prevents 70 deaths per 1000 patients x 1 year </li></ul><ul><li>YET: few are asked and few are counseled </li></ul><ul><li>My motto: “Attack ‘em in the hospital and kick ‘em when they’re down”!! </li></ul>
  59. 62. Still Lacking Evidence <ul><li>Although it’s argued that Lupus and other disorders (RA) are “vascular risk equivalents” this is NOT proven or accepted </li></ul><ul><li>No evidence (yet) for routine (imaging) screening in Lupus for asymptomatic vascular disease </li></ul><ul><li>No evidence (yet) for empiric therapy with statins, etc in Lupus </li></ul><ul><li>Major organizations (ACC, AHA, ACR) as yet, have no specific guidelines for Lupus and Vascular disease (“evidence-based medicine”) </li></ul>
  60. 63. Do….. <ul><li>See your MD regularly and report new signs or symptoms </li></ul><ul><li>If you have routine vascular risk factors (or a prior “event”, take your medications (statins, aspirin, etc) </li></ul><ul><li>Take the lowest dose of steroids and continue antimalarials </li></ul><ul><li>Exercise 4-5 x week for 30-40 min (even a good walk) </li></ul><ul><li>Stop Smoking! </li></ul><ul><li>Eat fresh and “colorful” foods—avoid processed </li></ul><ul><li>If asked to participate in clinical trials—consider it strongly--that’s how we develop evidence-based treatment </li></ul>