Transcript Evaluating the Risk of Coronary Artery Disease: A

Evaluating the Risk of Coronary Artery Disease:
A Conceptual Approach
Texas-Wide Underwriting Conference
Cliff Titcomb, MD
Hannover Life Re
March 19, 2012
Risk Assessment Revolves Around 4 Key Questions
 How
Much Myocardium is Already Lost?
 How Much Myocardium is At Short Term Risk?
 What is the Predisposition to Disease?
 How Much Myocardium Will Likely Be Jeopardized
in the Future and in What Time Frame?
2
Why the Questions?
 Ultimately,
the More Total Myocardium is Lost - the
Greater the Risk for Adverse Morbidity and
Mortality Outcomes
• Loss of Pump Reduces Function
• Losing More Than 40% of the Myocardium is Incompatible
with Life
• Each Event Carries Risk of Fatal Arrhythmia
3
Question 1: How Much Myocardium Has
Been Lost?
Numerous Studies Show an Increase in Mortality with
Reduced Ventricular Function
 Best
Surrogate Marker is the Ejection Fraction
 An Alternative is the Left Ventricular End-Diastolic
Pressure (LVEDP)
• Weaker Predictor
• Subject to Other Factors
5
3
2.5
2
1.5
1
0.5
0
ev
er
e
S
M
od
er
at
e
on
e
Mortality Risk
N
Risk Ratio
Mortality Risk By Degree of
Ventricular Dysfunction
Degree of Dysfunction
Stahle et al., Ann Thorac Surg, 1997; 64:437-44.
Relative Risk with CAD and CHF
2.50
Relative Risk
2.00
1.50
CHF
1.00
0.50
0.00
1
2
3
4
Caution - “Stunned” Myocardium

Transient Ventricular Dysfunction Due to
Profound Ischemia
Reversible with Improved Blood Flow
• Common in the Early Post Infarction Period
• Most Recent Evaluation is Probably the Best Estimate of
Actual Function
•
8
Question 3: How Much Myocardium is at
Short Term Risk?
How Much Myocardium is At Short-Term Risk?
 Traditionally
Referred to Ischemic Burden
 Number of Vessels with Hemodynamically
Significant Obstructive Disease
 Mortality Clearly Varied with Number of “Diseased”
Vessels
• Usually Defined as 50% or Greater Obstruction
10
Survival By Number of Diseased Vessels - CASS Data
80%
60%
12 Year Survival
40%
20%
el
3
Ve
ss
el
ss
Ve
2
1
Ve
ss
el
at
e
od
er
M
M
ini
m
al
al
0%
No
rm
Survival (%)
100%
Degree of Vessel Involvement
Emond M, et al., Circulation, 1994; 90:2645-57.
Relative Risk of Multivessel vs Single Vessel Disease
3.50
3.00
Relative Risk
2.50
2.00
2 Vessel
3 Vessel
1.50
1.00
0.50
0.00
1
2
3
4
5
6
7
The Number of Diseased Vessels Does Scale Risk
 But
Not By the Mechanism Traditionally Thought to
Be Operative
 Get the Right Answer for the Wrong Reason
 Relates to the New Model of CAD
Three Elements are Critical in Acute Coronary Events
 The
Vulnerable Plaque
 Endothelial Dysfunction
 Thrombosis
14
The Relatively Innocent Looking Lesions are the Killers
 Tight
Stenosis Doesn’t Kill
• Severe Stenosis Typically Causes Angina -- Not
Infarction
 For
Major Coronary Events Quality Matters More
than Quantity in Terms of Atherosclerotic Material
 Gradual Obstruction May to Some Extent Be
Beneficial
• Induces the Development of Collaterals Which Can Be
Protective
15
Vulnerable Plaques
 Large
Core of Oxidized Lipids
• Thin Fibrous Cap
 Inflammation
 Some
Degree of Calcium Deposition
 Generally Non-Obstructive
 Dynamic
• Continuous Remodeling
• Dependent on Risk Factors
16
Other Critical Elements
 Endothelial
Function
• Abnormal Blood Vessel Response to Injury
– Spasm Instead of Dilatation
– Reduced Production of Nitric Oxide
 Thrombosis
• Final Common Pathway for Acute Events
– Adverse Events Result from Clot with Occlusion
• Hypercoagulable State Increases Risk
– Minor Plaque Ruptures Become Major Events
– Important with Smoking
17
Mechanism - Acute Events
 In
Most Cases the Critical Step is the Rupture of a
Non-Obstructive Vulnerable Plaque
• Fracture of Fibrous Cap Exposes Lipid Core to Circulating
Blood
• Result is Acute Thrombosis, Endothelial Spasm and
Vessel Occlusion
 Tightly
Stenotic Lesions Cause Only a Minority of
Infarctions
• More Likely to Cause Ischemia
– Angina or Equivalent Symptoms
18
Stenotic Lesions are Associated with
Outcomes Because of the Company
They Keep
The Volume of Plaque Matters
Question 2 — Really a 2 Part Question
 What
is Total Plaque Burden?
• How Many Plaques are There?
 What
is the Stability of the Plaques That are
Present?
• Are They Likely to Rupture?
21
Total Plaque Burden
Gold Standard – Cardiac Cath
• Problem: Underestimates Volume of Plaque
• Really a Lumenogram
 Traditional
–Only Sees Inner Surface of Vessel
• Vessel Remodeling Hides the True Volume of
Disease
–Vessel expands in Size to Compensate for Disease and
Maintain Flow
• Not Effective at Finding Vulnerable Plaques
–Predictive of Events But Poorly Predictive of the Actual
Site of an Event
22
Traditional Non-Invasive Markers of
Plaque Volume Primarily Detect
Obstructive Disease
Measure Ischemia
Don’t Address Vulnerable Plaques
Newer Non-Invasive Measure of Coronary Plaque Burden
Direct and Indirect
 Direct
Measures
• Electron Beam CT Scan (EBCT)
• Intravascular Ultrasound
• Multi-Detector CT (MDCT)
• MRA
 Indirect
Measures
• Carotid Intima-Media Thickness (IMT)
24
Electron Beam CT (EBCT)
 Reflects
Overall Plaque Burden
• Measures Calcium Deposition in Plaque
• Both Obstructive and Non-Obstructive Lesions
 Overall
Score is the Most Important Factor
• Higher the Score the Greater the Likelihood of Obstructive
Disease
 Distribution
of Plaque is also Important
 Relative Risk Correlates with Percentile Ranks By
Age and Sex
• Where Do You Stand Relative to Your Peers?
25
EBCT
 More
Predictive of Risk of Cardiovascular Events
Than Risk Factor Analysis
 Ties the Risk Factors to the Individual
• Relates Population Data to the End-Organ Results in the
Individual
• Functions for CAD Like LVH for BP or Microalbumin for
Diabetes

Identifies the Vulnerable Person
• Not Necessarily the Vulnerable Plaque
26
4.5
4
3.5
3
2.5
2
1.5
1
0.5
Traditional Risk Factors
> 1000
4011000
101-400
11-100
Smoking
BP
Lipids
FH CAD
Diabetes
All Cause Mortality
Female
Relative Risk
Relative Risk for All Cause Mortality
By Risk Factors and Calcium Score
Calcium Score
Shaw et al., Radiology, , 2003; 228:826-33.
Risk Factors vs Calcium Scores
Highest vs Lowest Quartile
Risk Ratio
20
15
10
Risk Ratio
5
0
Calcium Score
Risk Factors
Factors
Raggi et al., Circulation, 2000; 101:850-55.
All Cause Mortality By Calcium Scores
4
3.5
Mortality Rate per 1000
3
2.5
2
Rate/1000
1.5
1
0.5
0
CAC 0
CAC 1-10
CAC > 10
VBT -NS
Blaha et al., J Am Coll Cardiol Img, 2009; 2:692-700.
Multidetector CT Angiography
 Probably
the Best Test to Assess Overall Plaque
Burden
 Visualizes Both Soft and Calcified Plaque
• Visualizes Lesions not Seen on Angiography
 Positive
Predictive Value (PPV) is Very Good and
Negative Predictive Value (NPV) is Excellent for
Significant Obstruction
• Often Used Clinically to Rule Out Disease
• Best Visualizes the Left Main and LAD
• Worst Visualization is in the Circumflex
30
Multidetector CT Angiography - Problems
 Heavy
Calcification May Degrade Images
 Not All Segments are Visualized Well
 Visualization of In-Stent Stenosis is Variable
 May not be Adequate for Planning for Surgery
• False Positives an Issue
• Visualization of the Vascular Run Off
 Radiation
31
Exposure is Significant
Multidetector Computed Tomography By Perfusion and Cath Status
100%
90%
80%
MDCT Nl
Percentage
70%
MDCT Abn
60%
50%
Nonobstruct
40%
Borderline
Severe
30%
Cath Obstr
20%
10%
0%
Perfusion Abnormal
Perfusion Normal
Scan Status
Schuijf et al., J Am Coll Cardiol Img, 2008; 1:190-9.
CT Angiography (64 Slice) to Identify CAD - Metanalyses
102%
100%
Percentage
98%
96%
NPV
PPV
94%
92%
90%
88%
1
2
3
Studies 2007-8
4
But is the Plaque Vulnerable ?
Quality is as Important as Quantity
Plaque Stability Varies with Risk Factor Control
 Important
Revelation from Statin Studies
 Plaques May Look the Same But They Don’t
Rupture
 Inflammation is a Key Component
 Reduction of Inflammation and Stabilization of
Plaques Leads to a Marked Decrease in Clinical
Event Rates
35
C-Reactive Protein
 Non-Specific
•
Acute Phase Reactant
Measure of Inflammation
 Produced
in the Liver
• Induced By Cytokines – Especially Interleukin 6
 Highly
Sensitive Test (hsCRP) Can Detect Low
Grade Inflammation
• Subdivide the Traditional Normal Range
36
C-Reactive Protein
 Initially
Appeared to Be Much More Predictive of
Future Events Than Other Risk Factors
 More Recent Studies Suggest Benefit May Be More
Modest
 Questionable if it Adds Substantially to Risk
Assessment When Traditional Risk Factors are
Taken into Account
 Recent USPSTF analysis showed:
• RR high risk v low risk = 1.58
• RR average risk v low risk = 1.22
37
2.5
2
1.5
1
0.5
0
Meta CRP
hsCRP
Systolic BP
Smoking
Odds Ratio
Tot
Cholesterol
Odds Ratio
Relative Odds for Heart Disease
(Upper Third v Lowest Third)
Risk Factor
Danesh et al., NEJM, 2004; 350:1387-97..
C-Reactive Protein — Practical Issues
 Variability
• Recommendation is Using Average of 2 Samples at Least
2 Weeks Apart
 Lack
of Specificity
• Other Causes of Inflammation
– Likely for Levels > 10 mg/L
– Measure again if levels are questionable
39
Relative Risk
Risk of MI or Coronary Death
By Combination Calcium Score & CRP Level
7
6
5
4
3
2
1
0
CRP Low
CRP High
Low
Medium
High
Calcium Score
Park et al., Circulation, 2002; 106:2073-7..
Plaque Stability - Rheumatoid Arthritis
 Risk
of All Cause Mortality is Increased
• 40-50% of Deaths in RA are From CV Disease
 Inflammation
Appears to Be the Mechanism
• The Disease Process in the Rheumatoid Joint is Similar to
That in the Plaque
• Increased Adhesion Molecules and Inflammatory Cells
with Production of Cytokines
 Seropositive
Status Increases CV Risk
• Risk Increased with Elevated CRP and ESR, Joint
Swelling, RA Nodules, Vasculitis, Lung Disease
 EBCT
41
Scores are Higher with RA
Plaque Stability - Rheumatoid Arthritis
Risk
of Myocardial Infarction is Increased
• Traditional Risk Factor Analysis Does Not Work
as Well to Assess Risk
Increased
Number of Vulnerable Plaques
More Likely to Have Silent Disease
–Higher Risk of Sudden Death
 Risk
Higher with Longer Duration and Greater
Severity of RA Disease
 Risk of CHF is Increased
 Treatment with Disease Modification Drugs Seems
to Improve Risk
42
Calcium Score By Age and RA Severity
350
300
Calcium Score
250
45-54
200
55-64
150
65 up
100
50
0
Non RA
RA Mild
RA Mod
RA Severe
RA Severity
Giles et al., Arthritis Res Ther, 2009; 11:ePub
Question 3: What is the Individual’s
Predisposition to Disease?
A Key Step in Customizing the Mortality
Assessment is Linking the Disease Process
to the Individual
Critical Step is Identifying the Age of Diagnosis
or
Age Standardized Percentile Rank for Disease
Burden
Age Related Disease Burden Does 2 Things:
 Provides
an Estimate of the Slope of Initial
Progression
• By Extrapolation, the Likely Future Course
 Provides
a Context for Interpreting Risk Factors
• Ties the Risk Factors to the Individual
• Terms such as High or Low are Relative Values and
Depend on Context for Meaning
46
Need to Interpret Baseline and Individual
Factors in Light of the Pattern Mortality
with the Disease
CABG Mortality Ratios By Age of Onset and Current Age
Population Comparison
400
350
300
Mortality Ratio
40's
250
50's
200
60's
150
70's
80's
100
50
0
40's
50's
60's
Current Age
70's
80's
Mortality Ratios By Duration Post Bypass
250
213
Mortality Ratio
200
150
181
139
132
113
Mortality Ratio
100
59
50
0
0-5
5-10
10-15
15-20
20-25
25-30
Years Since Bypass
van Domburg et al., Eur Heart J, 2009; 30:453-8.
Mortality Rate Post CABG by Duration
0.045
0.04
0.035
Mortality Rate
0.03
0.025
Mortality Rate
0.02
0.015
0.01
0.005
0
1
3
3-15
15-20
>20
Years Post Bypass
van Domburg et al., Eur Heart J, 2009; 30:453-8
Reintervention Rate Post Bypass
0.045
0.04
Reintervention Rate
0.035
0.03
0.025
Reintervention Rate
0.02
0.015
0.01
0.005
0
0-8
8-13
13-20
> 20
Years Post Bypass
van Domburg et al., Eur Heart J, 2009; 30:453-8
MI Mortality Ratios By Age of Onset and Current Age
Population Comparison
900
800
Age of
Onset
Mortality Ratio
700
50's
600
60's
500
70's
400
80's
300
90's
200
100
0
50's
60's
70's
Current Age
80's
90's
Mortality Ratio By Duration Post Randomization - Medical Therapy
500
450
Mortality Ratio vs Population
400
350
300
250
MR
200
150
100
50
0
0-5
5-10
10-15
15-20
20-22
Duration
Peduzzi et al., Am J Cardiol, 1998; 81:1393-99
Mortality Ratios By Duration Post MI and Age
350
Mortality Ratios vs Population
300
250
200
1-5
5-10
150
100
50
0
< 55
55-64
65-74
75-84
85 up
Age
Goldberg et al., Am J Cardiol, 1998; 82:1311-7
Mortality Ratios By Duration Post Bypass
250
213
Mortality Ratio
200
150
181
139
132
113
Mortality Ratio
100
59
50
0
0-5
5-10
10-15
15-20
20-25
25-30
Years Since Bypass
van Domburg et al., Eur Heart J, 2009; 30:453-8.
Questions 1 and 2 - Establish the Baseline
 Overall
Plaque Burden
 Stability of the Plaques That are Present
 Current Ventricular Function and Likely Cardiac
Reserve
56
Question 3 – Permits Estimation of the Likely Future Course
 Age
of Onset - Sets the Track and the Slope of
Progression Over Time
 Without Disease Modification this Historical Slope
of Progression Will Likely Continue Going Forward
57
The Younger the Onset, the Higher the
Overall Level of Risk Now and in the
Future
Cumulative Survival Post Bypass
By Age Group
1
Cumulative
Survival (%)
0.8
Age < 50
0.6
Age 50-60
0.4
Age 60-70
0.2
Age > 70
0
5
10
15
20
Year Post Bypass
Weintraub et al., Circulation, 2003; 107:1271-7.
Mortality Ratio (%)
Relative Mortality for CAD By Age Band
Group Life Table
700
600
500
400
300
200
100
0
Age < 50
Age 50-60
0-5
5-10 10-15 15-20
Age 60-70
Age 70up
Years Post Surgery
Weintraub et al., Circulation, 2003; 107:1271-7.
Effect of Predisposition
45
55
Age of Onset
65
61
Risk Factors Must Also Be Evaluated in
Light of Individual Predisposition to
Disease
Normal vs. Abnormal is Not a Numeric
Value or Even a Population Average
It is a Level That Produces An End Organ Effect in An
Individual
Question 4: How Much Myocardium Will
Become at Risk in the Future and How
Soon Will It Occur?
Factors that Affect Risk May or May Not
Be Modifiable
Diabetes - Increases Mortality Risk
 Equivalent
to Having a Previous MI in a Non-
Diabetic
 Risk is Worse in Type 1 DM
 Extensive Disease is More Likely
 Outcomes are Worse in Diabetics for Any Given
Extent of Disease
• If Present with Unstable Angina – More Likely to Have an
MI
• If Have an MI – Twice as Likely to Die
66
Relative Risk of Mortaltiy with CAD and DM
3.00
2.50
Relative Risk
2.00
1.50
DM
1.00
0.50
0.00
1
2
3
4
5
6
7
8
9
10
Smoking
 Converts
Minor Plaque Ruptures into Major Events
• Effect is Primarily on Thrombosis Leg of the Triad
 Active
Smokers Have Highest Risk
 Risk Persists into Older Ages
 Quitters Have Reduced Risk
• Some Studies Suggest Relative Risk Post MI is Lower in
Quitters Than Lifelong Nonsmokers
• Reason: Major Risk Factor Leading to Events Has Been
Removed
68
Hazard Function for Smoking - Post Bypass
Cass Data
Hazard Function
10
8
Never Smoked
6
Quit Smoking
4
Current Smokers
2
0
1month
5
10
15
Duration
Myers et al., J Am Coll Cardiol, 1999; 33:488-98.
Adjusted Hazard Ratio for All-Cause Death
Patients With Acute Myocardia Infarction
2.5
Hazard Ratio
2
1.5
Multivariate Hazard
Ratio
1
0.5
0
None
Former
Quitter
Persistent
Smoking Status
Kinjo et al., Circ J, 2005; 69:7-12.
Lipids
 Multiple
Studies Have Demonstrated Increased
Risk with Elevated Lipids
 Control Clearly Reduces Risk
 Reduction in Acute Event Rates Occurs At
Minimum within Months
• May Occur Within Weeks or Sooner
 Cholesterol/HDL
Measure
71
Ratio is the Best Single Lipid
Relative Risk
Relative Risk By Factor
3.5
3
2.5
2
1.5
1
0.5
0
Relative Risk
Lp(a)
Homocyst
TC
LDL
Apo B
TC:HDL
Factor
Clin Chem, 47;2001.
Relative Risk of Mortality with Hyperlipidemia
Multivariate Studies
3
Relative Risk
2.5
2
1.5
Relative Risk
1
0.5
0
1
2
3
Studies
4
Hypertension
 Multiple
Potential Adverse Effects
• Progression of Atherosclerosis
• Mechanical Stress That May Destabilize Plaques
• Development or Progression of LVH
• Synergistic Effect with Diabetes
 Effects
Greater with Systolic BP
 Pulse Pressure is Important
 Overall Relative Risk is Modest in Most Studies –
Probably Maximum of 1.3-1.4
74
Type of Therapy
 Choice
of CABG v PTCI is Still Somewhat
Controversial
• Some Data Suggests That Outcome is Better with CABG
for Three Vessel and Left Main Disease
– Especially if High Risk with Reduced EF
– Diabetics
– Older Individuals
 Outcomes
are Probably Equivalent for One and Two
Vessel Disease
 Benefit of CABG for Diabetics Continues to 10 Years
75
Type of Therapy — Invasive
 Stents
Clearly Improve Short-Term Outcomes
• Reduced Restenosis Rate
• Restenosis is Reduced Further with Drug Eluting Stents
(DES)
– DES is Associated with Late Stent Thrombosis (Rare)
– No Real Survival Benefit of DES vs Bare Metal Stents
• Limited Benefit Long Term
– Most Adverse Outcomes Result from Progression of Disease in
Vessels without a Stent
76
Type of Therapy — Invasive
 Outcomes
Better with Use of Internal Mammary
Artery (LIMA)
• Hazard Ratio – 1.34 with a Vein Graft Alone
–Data Suggests Two IMA is Better Than One (HR=0.81)
• Now Standard of Care for Bypass
 Radial
Arteries also Superior to Vein Grafts
• May Not Be as Good as Using Both LIMA and RIMA
Type of Therapy — Non-Invasive
Benefit of Medical Therapy – Multiple Studies
 Different Types – Benefit Additive
 Clear
• Statins
• Beta-Blockers
• ACE Inhibitors
• Aspirin/Platelet Agents
• Anticoagulation
78
For Stable CAD w Multivessel Disease
and Good EF - Mortality Outcomes are
Similar for Medical Therapy, PTCI and
CABG
More Interventions with Med Rx and PTCI
New Biomarkers
 C-Reactive
Protein (CRP)
 B-Natriuretic Peptide (BNP)
 Troponin
 WBC Count
 Microalbuminuria
 Cystatin C
 Midregional Proadrenomedullin (MR-proADM)
 Fibrinogen
 IL-6
80
New Biomarkers
 Individually
Have Shown Some Increase in Hazard
Ratios in Multivariate Analysis
 For the Most Part the Effect on the Disease
Classification Has Been Modest
 Combinations of Markers Have Been Tried with
Mixed Results
• Some Combos Have Shown Some Improvement of
Risk Assessment
 B-Natriuretic
Peptide Appears to Be the Best of the
Current Group
81
B-Natriuretic Peptide
 Peptide
Hormone Released from Ventricles in
Response to Myocyte Stretch
 Associated with Regional or Global Ventricular
Dysfunction
 Provides Value Independent of EF
 Found to Be a Predictor of Long-Term Increase in
Mortality in Multiple Scenarios
• Stable Coronary Disease (RR 2.4)
• Acute Coronary Syndromes (RR 2.4)
• Myocardial Infarction
82
Relative Risk by NT-proBNP Levels
Mean Age 59
3.00
2.50
2.00
1.50
Relative Risk
1.00
0.50
0.00
< 64
64-169
170-455
> 455
BNP Levels
Kragelund et al., N Engl J Med, 2005; 352:666-75.
25-Hydroxyvitamin D
 Has a Variety of Effects
• Smooth Muscle Cell Proliferation
• Reduces Inflammation
• Vascular Calcification
• Renin-Angiotensin System
• Blood Pressure
 Low Levels are Associated with:
• Increasing Age
• Female Sex
• Non-White Race
• Diabetes
• Hypertension
• Current Smoking
• Lower Physical Activity
• Winter Season
84
25-Hydroxyvitamin D
 Deficiency
was Present in 22% of the NHANES III
Population Age 18 up (16,603)
 Self Reported CV Disease is Higher with Lower
Levels in NHANES III
• RR=1.20
 Relative
Risk of MI is Increased Comparing Lowest
to Highest Quartile Levels
• RR=2.09
 Multiple
Studies Show an Increase in All-Cause
and CV Mortality (Highest v Lowest Quartiles)
When Controlling for Other Risk Factors
85
Mortality By 25-Hydroxyvitamin D Level ng/ml (nmol/L)
1.4
1.2
Relative Risk
1
0.8
All Cause
CV
0.6
0.4
0.2
0
>32.1(80.1)
24.4(60.9)32.1(80.1)
17.8(44.4)24.3(60.7)
< 17.8(44.4)
Level
Melamed et al., Arch Intern Med, 2008; 168:1629-37.
All Cause Mortality By 25 Hydroxyvitamin D Level ng/ml(nmol/L)
2.5
Hazard Ratio
2
1.5
All Cause
1
0.5
0
23.6(58.9)33.5(83.6)
14.6(36.4)22.8(56.9)
10.4(26.0)16.8(41.9)
5.8(14.5)-10.1(25.2)
Level
Dobnig et al., Arch Intern Med, 2008; 168:1340-9.
Exercise Tolerance and Heart Rate Recovery
 Important
Considerations in Long-Term Prognosis
 Survival Rate Decreases in Proportion to Reduction
of Exercise Duration and VO2 Max
 HR Recovery Adds Additional Information to That
Supplied by Exercise Tolerance
88
Renal Insufficiency
 Even
Mild Renal Insufficiency (Serum Creatinine >
1.4 mg/dl-1.5 mg/dl/123.8 umol/L-132.6 umol/L) is
Associated with a Worsened Outcome with CAD
• Common Finding in the Elderly
 Outcome is Worse with Overt Renal Failure
 Increased Risk Occurs in Multiple Scenarios
• Chronic Stable Angina
• Acute Coronary Syndrome
• Myocardial Infarction
• CABG and PTCI
89
Left Ventricular Hypertrophy (LVH)
 Associated
with Coronary Disease Itself and
Comorbid Conditions Like Hypertension
 In CAD, Increases Risk Compared to Those
Without LVH
• Relative Risk - 1.5-1.8 Range
 Certain
Treatments May Decrease LV Mass
• Unclear if Reducing Mass Reduces Risk
90
Ventricular Arrhythmias
 Ventricular
Fibrillation in the Setting of an Acute
Event Does Not Reduce Long-Term Survival
• Provided No Ongoing Arrhythmias
 Sustained
Ventricular Tachycardia, Even in the
First 24 Hours, is an Adverse Prognostic Indicator
• Associated with Larger Infarcts, LV Aneurysm
• Non-Sustained VT is a Much Weaker Predictor of Adverse
Outcome
91
Ventricular Arrhythmias
 Mortality
Risk is Increased with Even Relatively
Few PVCs Present Beyond the Setting of the Acute
Event
• Outcome Depends Heavily on Presence of Ongoing
Ischemia and Especially Status of Ventricular Function
• No Good Evidence That Treatment Affects Survival
Atrial Fibrillation
 Incident
AF Occurs in 5-13% of Acute Infarctions in
Recent Studies (Higher in Older Ones)
• New AF has a Higher Risk than Chronic AF
 Older
Age, Heart Failure, Elevated Heart Rate,
Hypertension Increased the Risk of Developing AF
 AF Increases the Risk of Stroke and In-Hospital
Mortality Post MI
 AF Increases Long-Term Mortality
• Even When Controlling for Co-Morbid Conditions
• RR is in the 1.25-1.35 Range
93
Peripheral or Cerebrovascular Disease
 Indicators
of Diffuse Vascular Involvement
 Outcomes are Worse for Those With CAD and
Peripheral or Cerebrovascular Disease
• RR Approximately 1.5
 Diffuse
Vascular Disease is Associated with Risk
Factor Profiles That Magnify Risk
• Diabetes
• Smoking
94
Homocysteine
 Data
is Mixed
• Retrospective Studies Suggested Very High Relative Risk
• Prospective Studies – Generally Less Impressive
 Overall
Association with Increased Risk is Probably
Mild to Moderate
 Other Factors
• Technical Problems with Assay
• Difficulties with Collection
• Expensive
 Does
Risk
95
Not Appear That Lowering Level Reduces
Lipoprotein (a)
Play a Large Role in Determining Level –
Important in Some Groups
 Homology with Plasminogen
 Risk Tied to LDL Cholesterol Levels
 Difficult to Treat
 Genetics
• Does Not Respond to Statins
• Benefit – Estrogens, Nicotinic Acid
 Relatively
Weak Predictor
• May Be More Important in Select Cases
96
3.5
3
2.5
2
1.5
1
0.5
0
D
L
B
TC
:H
o
Ap
LD
L
ys
t
H
om
oc
TC
)
Relative Risk
Lp
(a
Relative Risk
Relative Risk By Factor
Factor
Clin Chem, 47;2001.
Where the Questions Fit
Future Rate of
Progression
4
Initial Progression
Slope
3
1, 2
Baseline Amount of
Disease
45
55
Age of Onset
65