1. Exercise And Statin – Associated Myopathy Paul D. Thompson, MD Director of Cardiology Henry Low Heart Center Hartford Hospital Hartford, CT

2. Statins In the Water ? Paul D. Thompson, MD Director of Cardiology Henry Low Heart Center, Hartford Hospital Hartford, CT

3. Not So Fast There Are No Long Term Studies of Continuous Statin Treatment The Number Needed to Treat for Low Risk Patients is Huge Statins Have Side Effects That No Pharmaceutical Company Wants to Study

4. Collaborators Brown University – Peter Herbert, Eileen Cullinane, Stan Sady, University of Pittsburgh – Joe Zmuda, Rich Zimet, Susan Yurgalevitch Duke University – John Guyton Hartford Hospital - Beth Parker, Jeff Capizzi, Amanda Augieri, William Roman, Lindsay Lorson, Mauren Yuscavitch, Brenda Foxen, Mary Beth Moran, Cherie Biblie, Rick Seip, Gualberto Ruano Umass - Priscilla Clarkson, Maria Urso, Amy Kearns Tufts University – Richard Karas Washington Children’s Medical Center - Eric Hoffman UConn – Linda Pescatello

5. Thompson - Conflicts of Interest Grant / Research Support: GlaxoSmithKline / Merck / Roche / Pfizer / AstraZeneca / NIH / B. Braun / Genomas Consultant: Astra Zenica / Merck / Schering- Plough / Takeda / Roche / Genomas /Abbott / Runners World Speaker’s Bureau: Merck / Pfizer / Abbott / Astra Zenica / Schering-Plough Stock Shareholder: Zoll / General Electric / JA Wiley Publishing / Zimmer / Medtronic / Abbott /

6. Acetyl CoA HMG-CoA Reductase Cholesterol ACAT Cholesterol Esters Bile Acids Bile Bile Acids Cholesterol Fecal Excretion Low-Affinity VLDL Uptake High-Affinity Uptake High-Affinity Uptake Low-Affinity Uptake Peripheral Cells FFA LPL Capillary

7. Increased High-Affinity LDL Uptake Inhibition of Cholesterol Synthesis ß-hydroxy-ß- methylglutaryl CoA Mevalonate Cholesterol Decreased LDL Cholesterol HMG-CoA REDUCTASE INHIBITORS

8. There Are Three Principles of Managing Lipids With Medications

9. First Principle of Lipid Drug Management Start a Statin

10. They Produce Remarkable Reductions in LDL Levels

11. 10 mg 10 mg 10 mg 10 mg Adapted from Jones PH et al Am J Cardiol 2003;92:152–160 Change in LDL-C from baseline (%) 0 -1020-30-40-50-60-5-15-25-35-45-55 rosuvastatin atorvastatin simvastatin pravastatin 40 mg 40 mg 40 mg 40 mg 20 mg 20 mg 20 mg 20 mg 80 mg 80 mg P<0.002 vs CRESTOR 10 mg P<0.002 vs CRESTOR 20 mg P<0.002 vs CRESTOR 40 mg LDL-C Reductions with Different Statin Strategies

12. Second Principle of Lipid Drug Management Start a Statin

13. They Cure Almost Every Lipid Problem That Ails You LDL – Cholesterol Triglycerides HDL – Cholesterol LDL Particle Size Hs CRP

14. Simvastatin Expanded-Dose Study Lipid Changes Am J Cardiol 1997;79:38-42 % change from baseline (median) Total Cholesterol LDL Cholesterol HDL Cholesterol Triglycerides 10 0 -10 -20 -30 -40 -50 -60 +6 +7 +8 -30 -35 -40 -41 -47 -53 -21 -23 -33 N=156 Simvastatin 40mg Simvastatin 80mg Simvastatin 100mg

15. Third Principle of Lipid Drug Management Start a Statin

16. They Have Incredible Outcome DATA

17. Multiple Studies Showed a Relationship Between LDL-C Reduction and CHD Relative Risk MI = myocardial infarction. Adapted with permission from Robinson JG et al. J Am Coll Cardiol. 2005;46:1855–1862. 152025303540 –20 0 20 40 60 80 100 LDL-C reduction, % Nonfatal MI and CHD death relative risk reduction, % 4SCARDS POSCHASCOT-LLA NHLBI PROSPER LRCALERT UpjohnHPS Los Angeles AF/TexCAPS MRC LIPID OsloCARE LondonWOSCOPS

18. Statins Lower Risk - Even if the Risk Factor is Not LDL- Cholesterol

19. Statins In the Water ?

20. Not So Fast There Are No Long Term Studies of Continuous Statin Treatment The Number Needed to Treat for Low Risk Patients is Huge Statins Have Side Effects That No Pharmaceutical Company Wants to Study

21. I Came Here Not To Bury Statins But To Praise Them But There Is A Problem

22. Statin – Associated Myopathy

23. Exercise & Statin Myopathy - Take Home Messages 1.Statins Are Remarkably Effective at Reducing CAD Risk 2.But Can Produce Myopathic (and Possibly Neurological) Side Effects 3.Exercise Causes Many of The CK Elevations Attributed to Statins 4.Exercise Magnifies Statin Myalgia & CK Increases 5.Some Patients Report Weakness, But There is Little Objective Data on Muscle Strength 6.Long Term Muscle Effects of Statins Are Unknown

24. Exercise & Statin Myopathy - Take Home Messages 1.Statins Are Remarkably Effective at Reducing CAD Risk 2.But Can Produce Myopathic (and Possibly Neurological) Side Effects 3.Exercise Causes Many of The CK Elevations Attributed to Statins 4.Exercise Magnifies Statin Myalgia & CK Increases 5.Some Patients Report Weakness, But There is Little Objective Data on Muscle Strength 6.Long Term Muscle Effects of Statins Are Unknown

25. Statin - Related Muscle Complaints Myositis and Rhabdomyolysis - CK > 10 X ULN Increased CK < 10 X ULN  Symptoms Myalgia With No CK Increases Muscle Weakness - Virtually Unstudied Muscle Cramps Persistent Myalgia ± CK  ’s Even After Withdrawal

26. Exercise & Statin Myopathy - Take Home Messages 1.Statins Are Remarkably Effective at Reducing CAD Risk 2.But Can Produce Myopathic (and Possibly Neurological) Side Effects 3.Exercise Causes Many of The CK Elevations Attributed to Statins 4.Exercise Magnifies Statin Myalgia & CK Increases 5.Some Patients Report Weakness, But There is Little Objective Data on Muscle Strength 6.Long Term Muscle Effects of Statins Are Unknown

27. Exercise ALONE Can Produce Remarkable CK Increases So That Many CK Increases Attributed to Statins Are Due to Exercise

28. Siegel AJ, Silverman LM, Lopez RE. Yale J Biol Med. 1980 Jul-Aug;53(4):275-9.

30. Thompson, et al Med & Science in Sports & Exercise. 2004: 36: 1132-1139. NIH RO1-NS40606-01A1

31. 10 Men Performed 45 Minutes Of Non-Dominant Arm Exercises Standing Curls, Preacher Curls, Triceps Extensions On Days 1 & 3 CK’s Obtained on Daily For 5 Days

32. Bilbie SM, Seip RL, Bilbie CL, Clarkson, PM, Thompson, PD. Submitted.

33. Exercise & Statin Myopathy - Take Home Messages 1.Statins Are Remarkably Effective at Reducing CAD Risk 2.But Can Produce Myopathic (and Possibly Neurological) Side Effects 3.Exercise Causes Many of The CK Elevations Attributed to Statins 4.Exercise Magnifies Statin Myalgia & CK Increases 5.Some Patients Report Weakness, But There is Little Objective Data on Muscle Strength 6.Long Term Muscle Effects of Statins Are Unknown

34. Collected Cases Among 22 Professional Athletes With LDL Receptor Defects Only 6 Could Tolerate Statins Despite Multiple Attempts With Fluva, Lova, Prava, Atorva, & Simva Sinzinger Br J Clin Phar 2004

35. PRedIction of Muscular Risk in Observational Conditions or PRIMO Study 7,924 French Patients on Fluva 80, Atorva 40-80, Prava 40, Simva 40-80, for 3 mos 10.5% Reported Muscular Symptoms The Rate was 14.7% in Patients Practicing “Intense Form of Sport” vs 10.8% Who Did “Only Leisure Time Activities” Pain Was Triggered in 41% - 53% by “Unusual Physical Activity” Bruckert CV Drugs & Therapy 2005

36. Exercise & Statin Myopathy - Take Home Messages 1.Statins Are Remarkably Effective at Reducing CAD Risk 2.But Can Produce Myopathic (and Possibly Neurological) Side Effects 3.Exercise Causes Many of The CK Elevations Attributed to Statins 4.Exercise Magnifies Statin Myalgia & CK Increases 5.Some Patients Report Weakness, But There is Little Objective Data on Muscle Strength 6.Long Term Muscle Effects of Statins Are Unknown

37. Do Statins Increase the Muscle Injury of Exercise ?

38. Exercise - Induced CK Elevations - 59 Men Aged 18-65 LDL > 130 mg/dl Randomly to Placebo or Lova 40 mg At 4 Weeks: Maximal EXT, Downhill Walking at 65% HR for 3 X 15 Min Bouts Thompson et al Metabolism 1997

39. CK Elevations After Downhill Walking

40. Exercise - Induced CK Elevations - Two Men Excluded Because of Marked CK Increases Thompson et al Metabolism 1997

41. Med Sci Sports Exercise 2009

42. Study Design 3 blood draws –CK isoenzymes EXPO: 24 HRS PRE FINISH LINE: POST 24 HOURS POST

43. Study Population 43 controls –51 ± 7 yrs –29 men and 8 women 37 statin users –56 ± 8 yrs –30 men and 13 women

44. Log Transformed CK Response * p = 0.02

45. Exercise & Statin Myopathy - Take Home Messages 1.Statins Are Remarkably Effective at Reducing CAD Risk 2.But Can Produce Myopathic (and Possibly Neurological) Side Effects 3.Exercise Causes Many of The CK Elevations Attributed to Statins 4.Exercise Magnifies Statin Myalgia & CK Increases 5.Some Patients Report Weakness, But There is Little Objective Data on Muscle Strength 6.Long Term Muscle Effects of Statins Are Unknown

46. The Effect of Statins on Skeletal Muscle Function NIH RO1 081893 440 Subjects Randomized to Atorvastatin 80 or Placebo 6 Months Strength - Handgrip, Biceps, Quadriceps - Static & Dynamic Strength Quadriceps Endurance Exercise Oxygen Uptake & Respiratory Quotient

47. What Causes Statin Myopathy ?

48. I DON’T KNOW

50. Possible Mechanisms of Statin Induced Muscle Injury 1. Reduced Sarcolemmal Cholesterol 2. Reduced T-Tubule & Sarcoplamic Recticulum Cholesterol Draeger JPath 2006 3. Reduced Isoprenoids: Ubiquinone - Co-enzy Q10 4. Reduced Prenylation of GTP Binding Proteins - Ras, Rac and Rho - Cell Maintenance, Growth & Reduced Apoptosis Coleman Cell Death Differ 2002 5. Changes in Fat Metabolism (Phillips P Atherosclerosis 2005) 6. Increased Muscle Cholesterol & ? Plant Sterol 2 nd to LDL Receptor Activity (Paiva Clin Pharmacol Ther 2005) 7.Failure to Appropriately Repair Damaged Muscle (Urso …. Thompson ATVB 2005) 8.Vitamin D Deficiency 9.Inflammation (Inflammatory Myopathy)

51. Possible Mechanisms of Statin Induced Muscle Injury 1. Reduced Sarcolemmal Cholesterol 2. Reduced T-Tubule & Sarcoplamic Recticulum Cholesterol Draeger JPath 2006 3. Reduced Isoprenoids: Ubiquinone - Co-enzy Q10 4. Reduced Prenylation of GTP Binding Proteins - Ras, Rac and Rho - Cell Maintenance, Growth & Reduced Apoptosis Coleman Cell Death Differ 2002 5. Changes in Fat Metabolism (Phillips P Atherosclerosis 2005) 6. Increased Muscle Cholesterol & ? Plant Sterol 2 nd to LDL Receptor Activity (Paiva Clin Pharmacol Ther 2005) 7.Failure to Appropriately Repair Damaged Muscle (Urso …. Thompson ATVB 2005) 8.Vitamin D Deficiency 9.Inflammation (Inflammatory Myopathy)

52. Coenzyme Q10 in Statin Myopathy 1 RC1 AT005836-01 NIH/NCCAM

53. Run-In: Initial – Simvastatin Simvastatin 20 mg for 8 weeks or Until Symptoms Persist for 1 Week or are Intolerable 100 Subjects Symptomatic on Statins Only: Baseline Strength and Exercise Performance Testing, Accelerometer, Pain Questionnaire Randomization to Treatment: Placebo or 600 mg CoQ10 Load Subjects for 2 weeks on Treatment Simvastatin 20mg + Placebo (N=50)Simvastatin 20mg + CoQ10 (N=50) 4 week washout At 8 Weeks or Until Symptoms Persist 1 Week or are Intolerable: Strength and Exercise Performance Testing, Accelerometer, Pain Questionnaire Run-In: Initial - Placebo Placebo for 8 Weeks or Until Symptoms Persist for 1 Week or are Intolerable 4 week washout Run-In: Initial - Placebo Placebo for 8 Weeks or Until Symptoms Persist for 1 Week or are Intolerable Run-In: Initial – Simvastatin Simvastatin 20 mg for 8 weeks or Until Symptoms Persist for 1 Week or are Intolerable Weekly phone calls: Pain Questionnaires used to assess muscle symptoms and document myalgia 135 Subjects with Prior Statin Complaints

54. Total & LDL Reductions Were Greatest in “True Myalgics” D-C Morales, B Parker, L Lorson, D Polk, PD Thompson. ACC 2011 True = 12 Non = 19

55. Possible Mechanisms of Statin Induced Muscle Injury 1. Reduced Sarcolemmal Cholesterol 2. Reduced T-Tubule & Sarcoplamic Recticulum Cholesterol Draeger JPath 2006 3. Reduced Isoprenoids: Ubiquinone - Co-enzy Q10 4. Reduced Prenylation of GTP Binding Proteins - Ras, Rac and Rho - Cell Maintenance, Growth & Reduced Apoptosis Coleman Cell Death Differ 2002 5. Changes in Fat Metabolism (Phillips P Atherosclerosis 2005) 6. Increased Muscle Cholesterol & ? Plant Sterol 2 nd to LDL Receptor Activity (Paiva Clin Pharmacol Ther 2005) 7.Failure to Appropriately Repair Damaged Muscle (Urso …. Thompson ATVB 2005) 8.Vitamin D Deficiency 9.Inflammation (Inflammatory Myopathy)

56. Decreases in Serum Q10 & LDL-C With Statin Therapy Ghirlanda J Clin Pharmacol 1993

57. Most (me Marcoff & Thompson, JACC 2007 ) Attributed the Q10 Decrease to Decreases in LDL/VLDL….But Kawashiri et. al. Clin Pharm & Therapeutics

58. Co Q10 ? Muscle Biopsies From 132 Patients With “Statin Myopathies” 50 % - Co Q10 Levels - 2-4 SD’s < Normal Vladutiu et al Am C Rheum 2004 Abstract 1784

59. Is The Reduced Q10 The Cause or The Result of Mitochondrial / Muscle Problems Something Else Could Be Hurting The Muscle, Decreasing Mitochondria Numbers, and Q10 Levels

60. StudyStatin, dosage Duratio n Participants%Change Paiva et al. ( (RCT) simvastatin, 80 mg/day atorvastatin, 40 mg/day 8 weeks48 pts with hypercholesterol (-)33.5%* NS Laaksonen et al. simvastatin, 20 mg/day 4 weeks20 patients, age 25-55 (+)46.6% ‡ Laaksonen et al. simvastatin, 20 mg/day 6 months 19 patients, age 25-55 NS Lamperti et al.VariableNR18 patients with statin myopathy, age 31-76 NS v Studies of Skeletal Muscle CoQ10 levels after treatment with statins * p<0.05; † p<0.01; ‡ p<0.001; (Marcoff & Thompson, JACC 2007)

61. There Are Two Appropriately Designed (& Published) Trials

62. Coenzyme Q10 Improves Myopathic Pain in Statin Treated Patients Prospective, Randomized, Blinded Trial Vitamin E 400 IU vs. Q10 100 mg QD 30 Days in Statin Myopathic Patients 14 Patients to E, 18 to Q10 Pain Severity  40% With Q10 Pain Severity  9% With E Caso Am J Card 2007

63. Coenzyme Q10 Does Not Improve Simvastatin Tolerability in Dylipidemic Patients with Prior Statin-Induced Myalgia Prospective, Randomized, Blinded Trial 44 Patients Prior Myalgia Simva 10-40 mg & Q-Gel 200 QD or Simva & Placebo No Difference in Simva Tolerance No Difference in Myalgia Scores Young JM et al Circ 2007;114:II-41

64. Ubiquinone or Co Enzyme Q10 ? There is No Convincing Evidence

65. Coenzyme Q10 in Statin Myopathy 1 RC1 AT005836-01 NIH/NCCAM

66. Possible Mechanisms of Statin Induced Muscle Injury 1. Reduced Sarcolemmal Cholesterol 2. Reduced T-Tubule & Sarcoplamic Recticulum Cholesterol Draeger JPath 2006 3. Reduced Isoprenoids: Ubiquinone - Co-enzy Q10 4. Reduced Prenylation of GTP Binding Proteins - Ras, Rac and Rho - Cell Maintenance, Growth & Reduced Apoptosis Coleman Cell Death Differ 2002 5. Changes in Fat Metabolism (Phillips P Atherosclerosis 2005) 6. Increased Muscle Cholesterol & ? Plant Sterol 2 nd to LDL Receptor Activity (Paiva Clin Pharmacol Ther 2005) 7.Failure to Appropriately Repair Damaged Muscle (Urso …. Thompson ATVB 2005) 8.Vitamin D Deficiency 9.Inflammation (Inflammatory Myopathy)

67. Fat Myopathy ??

68. Damage to Type 1 Fibers Phillips et al., 2003 Patients who experienced muscle symptoms with normal CK levels Statins withdrawn for 3 mo When placebo was used, Symptoms disappeared Stained For Lipid STATIN NO STATIN

69. Capillary Increased High-Affinity LDL Uptake Inhibition of Cholesterol Synthesis ß-hydroxy-ß- methylglutaryl CoA Mevalonate Cholesterol Decreased LDL Cholesterol HMG-CoA REDUCTASE INHIBITORS

70. Possible Mechanisms of Statin Induced Muscle Injury 1. Reduced Sarcolemmal Cholesterol 2. Reduced T-Tubule & Sarcoplamic Recticulum Cholesterol Draeger JPath 2006 3. Reduced Isoprenoids: Ubiquinone - Co-enzy Q10 4. Reduced Prenylation of GTP Binding Proteins - Ras, Rac and Rho - Cell Maintenance, Growth & Reduced Apoptosis Coleman Cell Death Differ 2002 5. Changes in Fat Metabolism (Phillips P Atherosclerosis 2005) 6. Increased Muscle Cholesterol & ? Plant Sterol 2 nd to LDL Receptor Activity (Paiva Clin Pharmacol Ther 2005) 7.Failure to Appropriately Repair Damaged Muscle (Urso …. Thompson ATVB 2005) 8.Vitamin D Deficiency 9.Inflammation (Inflammatory Myopathy)

71. Failure to Repair Damaged Muscle The Ubiquitin Proteosome Pathway (Urso …. Thompson ATVB 2005)

72. Hoffman EP, Nader GA. Nat Med. 2004;10:584-5.

73. Atrogin 1 Background #1 Hanai... Lecker. J. Clin. Invest. 2007 Ubiquitin Proteosome Pathway Breaks Down Skeletal Muscle Ubiquitin Protein Ligase E3 or Atrogin 1 (AT- 1) AT-1 Increases with Denervation & Precedes Muscle Loss AT-1 Increases in Failing Hearts, Post Partum Uterus Muscles W/O AT-1 Do Not Atrophy & Grow Normally

74. Our Gene Expression Studies Also Suggest a Role for Atrogin

75. 4 wks 8h 8h Statin/ Placebo EXPERIMENTAL DESIGN Exercise Right Leg Biopsy Right & Left Vastus Lateralis Exercise Left Leg Biopsy Right & Left Vastus Lateralis D1 D31

76. GENE EXPRESSION GeneChip ® Human Genome U133 plus 2.0 array 47,000 transcripts and variants 38,500 genes

77. There Are Few Changes With Statin Treatment & No Exercise, But Lots of Gene Change With Statin & Exercise

78. qRT-PCR Results- Atrogin-1

79. Hanai... Lecker. J. Clin. Invest. 2007

80. Possible Mechanisms of Statin Induced Muscle Injury 1. Reduced Sarcolemmal Cholesterol 2. Reduced T-Tubule & Sarcoplamic Recticulum Cholesterol Draeger JPath 2006 3. Reduced Isoprenoids: Ubiquinone - Co-enzy Q10 4. Reduced Prenylation of GTP Binding Proteins - Ras, Rac and Rho - Cell Maintenance, Growth & Reduced Apoptosis Coleman Cell Death Differ 2002 5. Changes in Fat Metabolism (Phillips P Atherosclerosis 2005) 6. Increased Muscle Cholesterol & ? Plant Sterol 2 nd to LDL Receptor Activity (Paiva Clin Pharmacol Ther 2005) 7.Failure to Appropriately Repair Damaged Muscle (Urso …. Thompson ATVB 2005) 8.Vitamin D Deficiency 9.Inflammation (Inflammatory Myopathy)

82. Possible Mechanisms of Statin Induced Muscle Injury 1. Reduced Sarcolemmal Cholesterol 2. Reduced T-Tubule & Sarcoplamic Recticulum Cholesterol Draeger JPath 2006 3. Reduced Isoprenoids: Ubiquinone - Co-enzy Q10 4. Reduced Prenylation of GTP Binding Proteins - Ras, Rac and Rho - Cell Maintenance, Growth & Reduced Apoptosis Coleman Cell Death Differ 2002 5. Changes in Fat Metabolism (Phillips P Atherosclerosis 2005) 6. Increased Muscle Cholesterol & ? Plant Sterol 2 nd to LDL Receptor Activity (Paiva Clin Pharmacol Ther 2005) 7.Failure to Appropriately Repair Damaged Muscle (Urso …. Thompson ATVB 2005) 8.Vitamin D Deficiency 9.Inflammation (Inflammatory Myopathy)

84. Exercise & Statin Myopathy - Take Home Messages 1.Statins Are Remarkably Effective at Reducing CAD Risk 2.But Can Produce Myopathic (and Possibly Neurological) Side Effects 3.Exercise Causes Many of The CK Elevations Attributed to Statins 4.Exercise Magnifies Statin Myalgia & CK Increases 5.Some Patients Report Weakness, But There is Little Objective Data on Muscle Strength 6.Long Term Muscle Effects of Statins Are Unknown

85. Statins and Cognition Pilot Studies of Cognitive Side Effects

86. It All Started With A Case

87. Case Study #1 65-year-old Caucasian On atorvastatin 10 mg/day –Mood alteration, memory difficulties Cognitive evaluation and fMRI of the brain On and off (2 months) statin therapy Significant improvement in cognitive function off statins

88. Using MRI to Investigate Snapshot of VR Pool Environment

89. fMRI Results Neuronal activation during the difficult version of the Sternberg Task, depicted by colored regions on the 3D- rendered brains, during encoding (left) and response selection (right) while the subject was on 10 mg atorvastatin (bottom) and 2 months following atorvastatin cessation (top).

90. Pilot Study #2 fMRI during two tasks – Sternberg Task – Figural Memory Test 19 adults from 6 month statin study – 14 on atorvastatin and 5 on placebo Pre-post scans

91. FMRI Results: FIG MEM Figure 2. FMRI activation on 3D-rendered brain showing changes in activation with statin use displayed at p=0.005 uncorrected level during the encoding (left) and recognition (right) phase of the Figural Memory Test.

93. Now…Don’t Get Crazy I Came Here Not to Bury Statins, But to Praise Them But We Should Only Use Them When Their is Likely to Be Benefit And Not Put Them in the Drinking Water Until We Are Sure There is no Harm

94. Myalgia Treatment ? Are Symptoms Tolerable? Measure CK Stop Drug Until No SX Try Another Statin Try Lower Doses Plus Minus Ezetimibe Try Another Class of Drug Try Chinese Red Rice Yeast 2 Tabs HS Try Atorva or Rosuva QOD or BIW Use Tonic (Quinine) Water HS for Cramps Do “Pulse Therapy” Use Q10 Supplements

95. Rosuvastatin (5 mg or 10 mg) Twice a Week in Patients Intolerant to Daily Statins Gadarla, Kearns, Thompson: Am J Cardiol 2008

96. Collaborators Brown University – Peter Herbert, Eileen Cullinane, Stan Sady, University of Pittsburgh – Joe Zmuda, Rich Zimet, Susan Yurgalevitch Duke University – John Guyton Hartford Hospital - Beth Parker, Jeff Capizzi, Amanda Augieri, William Roman, Lindsay Lorson, Mauren Yuscavitch, Brenda Foxen, Mary Beth Moran, Cherie Biblie, Rick Seip, Gualberto Ruano Umass - Priscilla Clarkson, Maria Urso, Amy Kearns Tufts University – Richard Karas Washington Children’s Medical Center - Eric Hoffman

97. An Overview of: Statin – Associated Myopathy Paul D. Thompson, MD Director of Cardiology Henry Low Heart Center, Hartford Hospital Hartford, CT