Exercise And Statin

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 Childrens 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
• Speakers Bureau Merck / Pfizer / Abbott /
  Astra Zenica / Schering-Plough
• Stock Shareholder Zoll / General Electric /
  JA Wiley Publishing / Zimmer / Medtronic /
  Abbott /

6
Peripheral Cells
High-Affinity Uptake
Low-Affinity Uptake
FFA
Capillary
LPL
Low-Affinity VLDL Uptake
High-Affinity Uptake
Acetyl CoA
HMG-CoA Reductase
Bile Acids
Cholesterol
Bile
ACAT
Cholesterol Esters
Bile Acids
Cholesterol
Fecal Excretion
7
Capillary
Increased High-Affinity LDL Uptake
Decreased LDL Cholesterol
ß-hydroxy-ß-methylglutaryl CoA
Inhibition of Cholesterol Synthesis
Mevalonate
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
LDL-C Reductions with Different Statin Strategies
Change in LDL-C from baseline ()
-10
20
-30
-40
-50
-60
-5
-15
-25
-35
-45
-55
0
rosuvastatin
atorvastatin
simvastatin
pravastatin
Adapted from Jones PH et alAm J Cardiol
200392152160
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
10 0 -10 -20 -30 -40 -50 -60
8
7
6
change from baseline (median)
-21
-23
-30
-33
-35
Simvastatin 40mg Simvastatin 80mg Simvastatin
100mg
-40
-41
-47
-53
N156
HDL Cholesterol
Triglycerides
Total Cholesterol
LDL Cholesterol
Am J Cardiol 19977938-42
15
Third Principle of Lipid Drug Management

• Start a Statin

16

• They Have Incredible Outcome DATA

17
Multiple Studies Showed a Relationship
BetweenLDL-C Reduction and CHD Relative Risk
MI myocardial infarction. Adapted with
permission from Robinson JG et al. J Am Coll
Cardiol. 20054618551862.
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 gt 10 X ULN
• Increased CK lt 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-Aug53(4)275-9.
29
(No Transcript)
30
Functional SNPs Associated with
Human Muscle Size and
Strength
FAMuSS
NIH RO1-NS40606-01A1
Study

• Thompson, et al Med Science in Sports
  Exercise. 2004 36 1132-1139.

31
10 Men

• Performed 45 Minutes Of Non-Dominant Arm
  Exercises
• Standing Curls, Preacher Curls, Triceps
  Extensions
• On Days 1 3
• CKs 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 orPRIMO 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 gt 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
Thompson et al Metabolism 1997
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
FunctionNIH 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 DONT KNOW
49
(No Transcript)
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 2nd to LDL Receptor Activity (Paiva
  Clin Pharmacol Ther 2005)
• Failure to Appropriately Repair Damaged
  Muscle (Urso . Thompson ATVB 2005)
• Vitamin D Deficiency
• 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 2nd to LDL Receptor Activity (Paiva
  Clin Pharmacol Ther 2005)
• Failure to Appropriately Repair Damaged
  Muscle (Urso . Thompson ATVB 2005)
• Vitamin D Deficiency
• Inflammation (Inflammatory Myopathy)

52
Coenzyme Q10 in Statin Myopathy

• 1 RC1 AT005836-01
• NIH/NCCAM

53
135 Subjects with Prior Statin Complaints
Weekly phone calls Pain Questionnaires used to
assess muscle symptoms and document myalgia
54
Total LDL Reductions Were Greatest in
True Myalgics
True 12 Non 19
D-C Morales, B Parker, L Lorson, D Polk, PD
Thompson. ACC 2011
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 2nd to LDL Receptor Activity (Paiva
  Clin Pharmacol Ther 2005)
• Failure to Appropriately Repair Damaged
  Muscle (Urso . Thompson ATVB 2005)
• Vitamin D Deficiency
• 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 SDs lt 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
Studies of Skeletal Muscle CoQ10 levels after
treatment with statins plt0.05 plt0.01
plt0.001 (Marcoff Thompson, JACC 2007)
v
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 2007114II-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 2nd to LDL Receptor Activity (Paiva
  Clin Pharmacol Ther 2005)
• Failure to Appropriately Repair Damaged
  Muscle (Urso . Thompson ATVB 2005)
• Vitamin D Deficiency
• Inflammation (Inflammatory Myopathy)

67
Fat Myopathy ??
68
Damage to Type 1 Fibers
STATIN
NO STATIN
Patients who experienced muscle symptoms
with normal CK levels Statins withdrawn for 3
mo When placebo was used, Symptoms
disappeared Stained For Lipid
Phillips et al., 2003
69
Capillary
Increased High-Affinity LDL Uptake
Decreased LDL Cholesterol
ß-hydroxy-ß-methylglutaryl CoA
Inhibition of Cholesterol Synthesis
Mevalonate
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 2nd to LDL Receptor Activity (Paiva
  Clin Pharmacol Ther 2005)
• Failure to Appropriately Repair Damaged
  Muscle (Urso . Thompson ATVB 2005)
• Vitamin D Deficiency
• Inflammation (Inflammatory Myopathy)

71
Failure to Repair Damaged Muscle

• The Ubiquitin Proteosome Pathway

(Urso . Thompson ATVB 2005)
72
Hoffman EP, Nader GA. Nat Med. 200410584-5.
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
EXPERIMENTAL DESIGN
D31
D1
Statin/ Placebo
Biopsy Right Left Vastus Lateralis
Biopsy Right Left Vastus Lateralis
Exercise Left Leg
Exercise Right Leg
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 2nd to LDL Receptor Activity (Paiva
  Clin Pharmacol Ther 2005)
• Failure to Appropriately Repair Damaged
  Muscle (Urso . Thompson ATVB 2005)
• Vitamin D Deficiency
• Inflammation (Inflammatory Myopathy)

81
(No Transcript)
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 2nd to LDL Receptor Activity (Paiva
  Clin Pharmacol Ther 2005)
• Failure to Appropriately Repair Damaged
  Muscle (Urso . Thompson ATVB 2005)
• Vitamin D Deficiency
• Inflammation (Inflammatory Myopathy)

83
(No Transcript)
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 p0.005 uncorrected level during the
encoding (left) and recognition (right) phase of
the Figural Memory Test.
92
(No Transcript)
93
NowDont 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 Childrens Medical Center - Eric
  Hoffman

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